- the distance from the reference point to the specific values \u200b\u200bof the indicators of the evaluated objects is determined.
In this method, the integrated assessment indicator takes into account not only the absolute values \u200b\u200bof the compared partial indicators, but also their proximity to the best values.
The following mathematical analogy is proposed to calculate the value of the indicator of a comprehensive assessment of an enterprise.
Each facility is viewed as a point in n-dimensional Euclidean space; point coordinates - values \u200b\u200bof indicators used for comparison. The concept of a benchmark is introduced - an enterprise in which all indicators have the best values \u200b\u200bamong a given set of enterprises. As a reference, you can also take a conditional object, in which all indicators correspond to the recommended or standard values. The closer the enterprise is to the benchmark indicators, the shorter its distance to the benchmark point and the higher the rating. The highest rating is given to the company with the lowest value of the complex assessment.
For each analyzed enterprise, the value of its rating is determined by the formula
where x ij - coordinates of matrix points - standardized indicators of the j-th enterprise, which are determined by the ratio of the actual values \u200b\u200bof each indicator with the reference according to the formula
X ij \u003d a ij: a ij max
where a ij max is the reference value of the indicator.
It is necessary to pay attention to the validity of the distances between the values \u200b\u200bof the indicators of a particular object of research and the standard. Certain aspects of activity have a different impact on the financial condition and production efficiency. Under these conditions, weighting factors are introduced; they attach importance to certain indicators. To obtain a comprehensive assessment, taking into account the weight coefficients, use the formula
where k 1 ... k n - weight coefficients of indicators, determined by expert assessments.
Based on this formula, the coordinate values \u200b\u200bare squared and multiplied by the corresponding weight factors; the summation is performed over the columns of the matrix. The received subradical sums are arranged in descending order. In this case, the rating score is established by the maximum distance from the origin, and not by the minimum deviation from the reference enterprise. The highest rating is given to the company with the highest overall result in all indicators.
1. The results of financial and economic activities are presented in the form of an initial matrix, in which the reference (best) values \u200b\u200bof indicators are distinguished.
2. A matrix is \u200b\u200bcompiled with standardized coefficients calculated by dividing each actual indicator by the maximum (reference) coefficient. The reference values \u200b\u200bof indicators are equal to one.
3. A new matrix is \u200b\u200bcompiled, where for each enterprise the distance from the coefficient to the reference point is calculated. The obtained values \u200b\u200bare summarized for each enterprise.
4. Enterprises are ranked in descending order of rating. The highest rating is given to the company with the lowest score.
PLAN
1. Definition of the concept of "immunity".
2. The history of the formation of immunology.
3. Types and forms of immunity.
4. Mechanisms of nonspecific resistance and their characteristics.
5. Antigens as inducers of acquired antimicrobial
immunity, their nature and properties.
6. Antigens of microorganisms and animals.
1. Definition of the concept of "immunity".
ImmunityIs a set of protective and adaptive reactions and adaptations aimed at maintaining the constancy of the internal environment (homeostasis) and protecting the body from infectious and other genetically alien agents.
Immunity is a universal biological phenomenon for all organic forms of matter, multicomponent and diverse in its mechanisms and manifestations.
The word "immunity" comes from the Latin word " immunitas "- immunity.
Historically, it is closely related to the concept of immunity to pathogens of infectious diseases, tk. the doctrine of immunity (immunology) - originated and formed at the end of the 19th century in the depths of microbiology, thanks to the research of Louis Pasteur, Ilya Ilyich Mechnikov, Paul Ehrlich and other scientists.
Introduction. The main stages of the development of immunology.
ImmunologyIs the science of the structure and function of the immune system of the organism of animals, including humans and plants, or the science of the patterns of immunological reactivity of organisms and methods of using immunological phenomena in the diagnosis of therapy and prevention of infectious and immune diseases.
Immunology arose as part of microbiology as a result of the practical application of the latter for the treatment of infectious diseases. Therefore, infectious immunology developed first.
Since its inception, immunology has closely interacted with other sciences: genetics, physiology, biochemistry, and cytology. At the end of the 20th century, it became an independent functional biological science.
Several stages can be distinguished in the development of immunology:
Infectious (L. Pasteur and others), when the study of immunity to infections began. Non-infectious, after K. Landsteiner's discovery of blood groups and
the phenomenon of anaphylaxis by S. Richet and P. Porter.
Cellular-humoral, which is associated with the discoveries made by Nobel Prize winners:
II Mechnikov - developed the cellular theory of immunity (phagocytosis), P. Ehrlich - developed the humoral theory of immunity (1908).
F. Burnet and N. Ierne - created the modern clonal-selective theory of immunity (1960).
P. Medavar - discovered the immunological nature of allograft rejection (1960).
Molecular genetic, characterized by outstanding discoveries that have been awarded the Nobel Prize:
R. Porter and D. Edelman - deciphered the structure of antibodies (1972).
Ts. Melstein and G. Koehler - developed a method for producing monoclonal antibodies based on their hybrids (1984).
S. Tonegawa - revealed the genetic mechanisms of somatic recombination of immunoglobulin genes as the basis for the formation of a variety of antigen-recognizing receptors of lymphocytes (1987).
R. Zinkernagel and P. Dougherty - revealed the role of MHC molecules (large histocompatibility complex) (1996).
Jean Dosset and his co-workers discovered the system of human antigens and leukocytes (histocompatibility antigens) - HLA, which made it possible to perform tissue typing (1980).
Russian scientists made a significant contribution to the development of immunology: I. I. Mechnikov (theory of phagocytosis), N. F. Gamaleya (vaccines and immunity), A. A. Bogomolets (immunity and allergy), V. I. Ioffe (anti-infective immunity) , P. M. Kosyakov and E. A. Zotikov (isoserology and isoantigens), A. D. Ado and I. S. Gushchin (allergies and allergic diseases),
R. V. Petrov and R. M. Khaltov (immunogenetics, cell interaction, artificial antigens and vaccines, new immunomodulators), A. A. Vorobiev (toxoids and immunity in infections), B. F. Semenov (anti-infective immunity), L V. Kovalchuk, B. V. Pinechin, A. N. Cheredeev (assessment of the immune status), N. V. Medunitsyn (vaccines and cytotoxins), V. Ya. Arlon, A. A. Yarilin (hormones and thymus function) and many others.
In Belarus, the first doctoral dissertation on immunology "Reactions of transplant immunity in vivo and in vitro in various immunogenetic systems" was defended in 1974 by DK Novikov.
Belarusian scientists make a certain contribution to the development of immunology: I. I. Generalov (abzymes and their clinical significance), N. N. Voitenyuk (cytokines), E. A. Dotsenko (ecology of bronchial asthma), V. M. Kozin (immunopathology and immunotherapy for psoriasis), D.K. Novikov (immunodeficiencies and allergies), V.I. Novikova (immunotherapy and assessment of the immune status in children), N.A.Skepian (allergic diseases), L.P. Titov (pathology of the complement system) , M. P. Potaknev (cytokines and pathology), S. V. Fedorovich (professional allergy).
Immunology studies the structure and function of the immune system, its response to pathogens, the consequences of the immune response and how it can be influenced.
Immunology - (from Latin immunis - free, liberated, freed from anything + Greek privilege - knowledge) - biomedical science, which studies the body's reactions to foreign structures (antigens), the mechanisms of these reactions, their manifestations, the course and outcome in norm and pathology, developing methods of research and treatment based on these reactions.
SUBJECT OF STUDYING IMMUNOLOGY
The structure of the immune system;
Patterns and mechanisms of development of immune reactions;
Mechanisms for control and regulation of immune responses;
Diseases of the immune system and its dysfunction;
Conditions and patterns of development of immunopathological reactions and methods of their correction;
The ability to use the reserves and mechanisms of the immune system in the fight against infectious and non-infectious diseases;
Immunological problems of reproduction;
Immunological problems of organ and tissue transplantation.
MAIN TASKS Immunology has become: the study of the molecular mechanisms of immunity - both congenital and acquired, the development of new vaccines and methods for the treatment of allergies, immunodeficiencies, and oncological diseases.
1.2. Immunology as a definite area of \u200b\u200bresearch arose from the practical need to combat infectious diseases. It is often divided into classic (old) and modern (new). This division is conditional, since the new immunology grew out of the classical one that made vaccinations against smallpox, rabies, anthrax, etc.
Several stages can be distinguished in the development of immunology:
Infectious (L. Pasteur and others), when the study of immunity to infections began.
There is evidence that the first smallpox vaccinations were carried out in China a thousand years before the birth of Christ. Inoculation The contents of smallpox pustules to healthy people in order to protect them from the acute form of the disease then spread to India, Asia Minor, Europe, the Caucasus and Russia.
Inoculation was replaced by the method vaccinations (from Lat. "vacca" - cow), developed at the end of the 18th century. by the English doctor E. Jenner. He vaccinated an 8-year-old boy D. Phipps with vaccinia, and then, 1.5 months later, infected him with smallpox, as was done during inoculation.
The boy did not get sick. After 1.5 months E. Jenner re-inoculated him, and again the boy remained healthy. In 1880louis Pasteur's article on protecting chickens from cholera by immunizing them with a pathogen with reduced virulence is published.
In 1881... Pasteur conducts a public experiment to inoculate 27 sheep with the anthrax vaccine, and in 1885 successfully tests a rabies vaccine on a boy bitten by a rabid dog.
In 1890... German physician Emil von Bering, together with Shibasaburo Kitasato, showed that antitoxins are formed in the blood of people who have had diphtheria or tetanus, which provide immunity to these diseases both for those who have been ill and for those to whom such blood will be transfused. In the same year, on the basis of these discoveries, a method of treatment with blood serum was developed.
Non-infectious, after K. Landsteiner's discovery of blood groups and
the phenomenon of anaphylaxis by S. Richet and P. Porter.
In 1900... Austrian doctor - immunologist Karl Landsteiner discovered human blood groups, for which he was awarded the Nobel Prize in 1930.
In 1904 g. the famous chemist Svante Arrhenius proved the reversibility of the antigen-antibody interaction and laid the foundations for immunochemistry.
Cellular-humoral, which is associated with the discoveries made by Nobel Prize winners:
II Mechnikov - developed the cellular theory of immunity (phagocytosis), P. Ehrlich - developed the humoral theory of immunity (1908).
F. Burnet and N. Ierne - created the modern clonal-selective theory of immunity (1960).
P. Medavar - discovered the immunological nature of allograft rejection (1960).
In 1883 Russian biologist - immunologist Ilya Mechnikov made the first report on the phagocytic theory of immunity. It was Mechnikov who stood at the origins of the knowledge of cellular immunity. Mechnikov showed that in the human body there are special amoeboid mobile cells - neutrophils and macrophages, which absorb and digest pathogenic microorganisms. It was to them that he gave the primary role in protecting the body.
In 1891 g. an article by the German pharmacologist Paul Ehrlich is published, in which he uses the term "antibody" to denote antimicrobial substances in the blood.
A new stage in the development of immunology is associated primarily with the name of the outstanding Australian scientist M. Burnet (Macfarlane Burnet; 1899-1985). Considered immunity as a reaction aimed at differentiating everything "ours" from everything "alien". It was Burnet who drew attention to the lymphocyte as the main participant in a specific immune response, giving it the name "immunocyte". It was Burnet who predicted, and the Englishman Peter Medavar and the Czech Milan Hasek experimentally confirmed the state opposite to immune reactivity - tolerance. It was Burnet who pointed out the special role of the thymus in the formation of the immune response. And finally, Burnet remained in the history of immunology as the creator of the clonal selection theory of immunity (Fig. B.9). The formula for this theory is simple: one clone of lymphocytes is capable of responding only to one specific antigenic specific determinant.
Molecular genetic, characterized by outstanding discoveries that have been awarded the Nobel Prize:
A great contribution to the formation of modern immunology was also made by Robert Koch (Robert Koch; 1843-1910), who discovered the causative agent of tuberculosis and described the skin tuberculin reaction; Jules Bordet (1870-1961), who made an important contribution to the understanding of complement-dependent lysis of bacteria; Rodney Porter (1917-1985) and Gerald Edelman (Gerald Edelman; 1929), who studied the structure of antibodies; George Snell, Baruj Benacerraf and Jean Dausset, who described the major histocompatibility complex in animals and humans and discovered the immune response genes
A brief historical outline of the development of immunology
Ancient world and Middle Ages
1000 BC - the first inoculations of the contents of smallpox papules to healthy people in order to protect them from the acute form of the disease were carried out in China, and then spread to India, Europe, Asia Minor, and the Caucasus.
First vaccines
Since 1701, variolation (vaccination against smallpox) has spread in Constantinople, from where it spreads to Europe. In 1722, the Prince and Princess of Wales inoculated two of their daughters with smallpox, which set a royal example for the inhabitants of England. In London in 1746 a special hospital of St. Pancras was opened, in which smallpox was inoculated to everyone. On October 12, 1768, one of the best doctors - inoculators, Thomas Dimsdale, vaccinated Empress Catherine II and her son Paul. In 1796, after thirty years of research, Edward Jenner tried vaccinating people with vaccinia on an 8-year-old boy, and then on 23 more people. In 1798 he published the results of his research. Jenner developed a medical technique for smallpox vaccination, which he called vaccination (from Latin vaccus - cow).
Immunological revolution
In 1880 an article by Louis Pasteur was published on the protection of chickens from cholera by immunizing them with a pathogen with reduced virulence.
In 1881 Pasteur conducted a public experiment to inoculate 27 sheep with an anthrax vaccine, and in 1885 successfully tested a rabies vaccine on a boy bitten by a rabid dog. These events mark the dawn of infectious immunology and the beginning of the era of vaccination. In 1890, the German physician Emil von Bering, together with Sibasaburo Kitasato, showed that antitoxins are formed in the blood of people who have had diphtheria or tetanus, which provide immunity to these diseases both for those who have been ill and for those to whom such blood will be transfused. In the same year, on the basis of these discoveries, a method of treatment with blood serum was developed. The work of these scientists laid the foundation for the study of the mechanisms of humoral immunity. In 1883 the Russian biologist and immunologist Ilya Mechnikov made the first report on the phagocytic theory of immunity. It was Mechnikov who stood at the origins of the knowledge of cellular immunity. Mechnikov showed that in the human body there are special amoeboid mobile cells - neutrophils and macrophages, which absorb and digest pathogenic microorganisms. It was to them that he gave the primary role in protecting the body.
In 1891, an article by Paul Ehrlich was published, in which he used the term "antibody" to denote antimicrobial substances in blood. In parallel with Mechnikov, Ehrlich developed his theory of the body's immune defense. Ehrlich noted that the main property of antibodies is their pronounced specificity. Two theories - phagocytic (cellular) and humoral - at the time of their emergence stood on antagonistic positions. In 1908, Mechnikov and Ehrlich shared the Nobel Prize in Medicine, and later it turned out that their theories complemented each other.
In 1900, the Austrian doctor - immunologist Karl Landsteiner discovered human blood groups. In 1904, the famous chemist Svante Arrhenius proved the reversibility of the antigen - antibody interaction and laid the foundations for immunochemistry. In 1913, the American Association of Immunologists was organized. Breakthrough in theoretical immunologyVirologist Frank McFarlane Burnet became the author of the clonally selective theory of immunity and the discoverer of the phenomenon of immunotolerance.
The study of immunoglobulins began with the work on electrophoresis of blood proteins by Arne Tiselius in 1937. Then, during the 40s-60s. classes and isotypes of immunoglobulins were discovered, and in 1962 Rodney Porter proposed a model of the structure of immunoglobulin molecules, which turned out to be universal for immunoglobulins of all isotypes and is absolutely correct to this day of our knowledge.
60s - early 80s - the stage of isolating all kinds of factors - humoral mediators of the immune response from cell culture supernatants. From the mid-1980s to the present, methods of molecular cloning, transgenic mice and mice with the removal of specified genes (knokout) have entered immunology.
In the works of James Govans of the 60s of the XX century. shows the role of lymphocytes in the body. In the middle of the XX century. a team led by American geneticist and immunologist George Snell conducted experiments with mice, which led to the discovery of a major histocompatibility complex and the laws of transplantation.
In 2011, the French immunologist Jules Hoffmann received the Nobel Prize in Physiology or Medicine for his work “on the study of innate immunity activation”.
In the 21st century, the main tasks of immunology have become: the study of the molecular mechanisms of immunity - both innate and acquired, the development of new vaccines and methods for the treatment of allergies, immunodeficiencies, and oncological diseases.
Subject, goals and objectives of immunology
Depending on the method and object of knowledge, immunology can be divided into general and specific. General immunology studies the processes of "immunity at the molecular, cellular and organismic levels, genetics and evolution of immunity, regulation of immunity at all levels. Private immunology studies methods and methods of prevention, diagnosis and treatment of infectious diseases (immunoprophylaxis, vaccinology); malignant tumors (immuno-oncology); conditions conducive to the transplantation of foreign organs and tissues (transplant immunology); perverse reactions to antigens (allergology, immunopathology); the effect of environmental factors on the immune system (ecological immunology).
Immunology tasks:
1. study of the immune system of a healthy person;
2.Study of the role of IP in the pathogenesis of infectious and non-infectious diseases
3.development of unified and informative methods for assessing the immune status
4. development of new highly effective immunoactive drugs and optimal schemes for their use.
The main subject research in immunology is the knowledge of the mechanisms of formation of a specific immune response of the organism to all foreign and antigenic compounds.
The most characteristic features of the immune system that distinguish it from other body systems are the following:
1. The ability to differentiate everything "ours" from everything "alien";
2. Creation of memory from primary contact with foreign antigenic material;
3. Clonal organization of immunocompetent cells, manifested in the ability of an individual cell clone to respond to only one of the many antigenic determinants.
General characteristics of the immune system of mammals
The organs of the immune system are usually divided into central (or primary) and peripheral (or secondary), based not so much on their location in the body, but on the degree of their importance in maintaining the normal state of this system. Red bone marrow and thymus (thymus gland) are referred to the primary organs of the immune system due to the fact that it is in them that the main stages of development that make up the immune system arise and pass. The same organs in which these cells carry out only some stages of their development and are temporarily localized in the course of the circulation throughout the body inherent in these cells are considered secondary. Those in the immune system are the spleen, lymph nodes and lymphoid clusters not separated from the surrounding tissues by connective tissue membranes: tonsils and adenoids of the nasopharynx, as well as specific lymphoid formations in the intestinal walls, called Peyer's patches.
The immune system, due to the mobility of its constituent cells, is distributed throughout the body. The cells referred to it, which are originally blood cells, are able to penetrate the walls of the capillaries and move between the cells of other tissues, which makes the internal environment almost anywhere in the body accessible to the immune system. Specifically, the cells of the immune system are considered to be all blood leukocytes, conventionally divided into 5 groups: monocytes, neutrophils, eosinophils, basophils and lymphocytes. Under normal physiological conditions, the ability to move from the bloodstream to tissues is possessed by basophils (after penetrating into the tissue, they are called mast cells) and monocytes, which are converted during such movements into the so-called tissue macrophages. In the secondary lymphoid organs, lymphocytes are also able to pass from the blood to the tissue, some of which can then return to the bloodstream. Lymphocytes are usually divided based on the places of their primary formation into T-lymphocytes (the main stages of maturation in the thymus pass) and B-lymphocytes (in mammals, they mostly mature in the red bone marrow).
The third component of the immune system is the molecules secreted by its cells, since some of them are able to function as independently acting agents during the implementation of protective reactions. A typical example of such molecules are immunoglobulins secreted by B-lymphocytes (also called antibodies), which are capable of specifically interacting with specific foreign antigens without any influence from other components of the immune system. In addition to immunoglobulins, it is customary to consider molecules that are inherent in the immune system, and substances that regulate the activity of both the cells of the immune system and some other cells of the body, most often they are called: cytokines, lymphokines and interleukins.
The structure and characteristics of the central and peripheral organs of the immune system
Bone marrow (central) localized in the inner cavity of tubular bones and is a tissue union of the reticular stroma, densely packed hematopoietic and lymphoid cells, as well as a branched network of capillaries. The main purpose is the production of blood cells and lymphocytes. The development of the cellular elements of the bone marrow begins from the hematopoietic stem cell (HSC), which gives rise to six germs of differentiation:
1) megakaryocytic, resulting in the formation of platelets;
2) erythroid, with the formation of non-nuclear, oxygen-carrying red blood cells; 3) granulocytic, from which are formed: basophils, eosinophils, neutrophils; these cells are directly involved in the processes of inflammation and phagocytosis and are participants in the form of protection against pathogens; 4) monocyte-macrophage-formation of monocytes migrating into the blood; final mature forms - tissue macrophages are localized in various organs and tissues;
5) T-cell-formation of a precursor of T-cells;
6) B-cell; B-cell differentiation is characterized by almost complete completeness.
Thymus (thymus) - a lymphoepithelial organ located in most mammals in the upper part of the chest cavity above the heart; consists of two lobes, dividing into smaller lobules. The organ as a whole and individual lobules are enclosed in a connective tissue capsule, the internal cavity of which includes an epithelial network filled with lymphocytes (thymocytes). Lobule - two layers: the cortex with a dense packing of small thymocytes and the medullary substance (medullary layer), where the number of thymocytes is reduced.
The peculiarity of the thymus organization is the presence of two elementary structural and histological units: follicle clarke
(as if separate "bricks" from which the cortical layer is built; densely packed lymphocytes and macrophages and dendritic cells located among them are surrounded by epithelial cells, which together creates an elementary structural and histological unit) and hassal's body
(in the medullary zone, lymphocyte-free round clusters of epithelial cells; the functional purpose of the bodies is unclear).
Birds' Bag of Fabricius plays the role of a central organ of immunity, being a supplier of B-cells for the periphery, is a place of active formation of antibody producers. It is a lymphoepithelial organ located in the back of the cloaca. The lumen of the bag is lined with a cylindrical epithelium. Nodules (lobules) are located behind the epithelial layer. The bark is mainly represented by a dense accumulation of small lymphocytes. The lighter medulla includes large lymphocytes, plasma cells, macrophages, granulocytes, and reticular cells.
Spleen (periphery) - a large organ located in the upper, left side of the peritoneum. Outside, the organ is surrounded by a connective tissue capsule, from which supporting partitions - trabeculae - extend into the organ. A characteristic feature of the structure is the presence of two sections - red (the place of localization of a large number of erythrocytes, as well as macrophages, megakaryocytes, granulocytes, lymphocytes) and white pulp (accumulation of lymphocytes around an eccentrically located arterial canal). There are no clear boundaries between the white and red pulp, and a partial cellular exchange occurs between them. T- and B-lymphocytes are localized in the white pulp. T cells are located around arterioles, forming periarterial muffs. B cells are part of the germinal centers, which are located in the border zone. The red pulp also contains lymphocytes and plasma cells. However, they do not form morphologically formed clusters in this zone.
The lymph nodesare truly lymphoid formations. They are located in the form of grains along the lymphatic vessels; are formed as a result of the accumulation of mesenchymal cells around the blood vessels. The outer layer of the mesenchyme differentiates into a connective tissue capsule, from which partitions extend into the node. Directly under the capsule is the marginal sinus, where the lymph flows through the vessels carrying the lymph. From the marginal sinus, lymph enters the intermediate sinuses, which penetrate the entire thickness of the node, and is collected in the outflowing lymph vessel, which eventually carries it into the thoracic duct. The outlet of the vessel is called the knot gate. Blood vessels pass through the gate into the node. In the lymph node, the cortical layer and the medulla located in the center of the node are distinguished. The cortical layer of the node is the place of concentration of B cells. The medulla is represented by relatively poorly packed lymphocytes, plasma cells, free macrophages and stromal reticular cells. The area between the cortex and the medulla is where T cells are concentrated.
Lymphoid tissuelocalized in the walls of the digestive, respiratory and urogenital tracts. It is referred to as lymphoid tissue associated with mucous membranes. The tissue is presented either in the form of diffuse infiltration, or in the form of nodular accumulations, devoid of a closed connective tissue case. Functions: concentrates antigen, provides contact with antigen of various types of cells, transports cellular structures of lymphoid tissue to the necessary parts of the body and eliminates foreign antigens. Distinguish between loose lymphoid tissue - in which reticular fibers, reticular cells and fixed macrophages dominate; and dense - lymphocytes, plasma cells and free macrophages.
The concept of immunity. Natural immunity. Active and passive forms of immunity.
Immunity is the body's immunity to infectious diseases, as well as to agents and substances that have antigenic properties foreign to the body.
Immune reactions are of a protective, adaptive nature and are aimed at freeing the body from foreign antigens that enter it from the outside and violate the constancy of its internal environment. Protective in nature, immune responses, for one reason or another, can be perverted and directed to some of their own, normal, unchanged components of cells and tissues, resulting in autoimmune diseases. Immune reactions can cause increased sensitivity of the body to certain antigens - allergies, anaphylaxis. There are the following types of immunity : Natural and artificial. Natural immunity can be congenital and acquired. With natural innate immunity, a person is from birth immune to one or another disease. Acquired natural is called the immunity that appears after the transfer of any infectious disease. Children who have had measles, mumps, whooping cough acquire natural immunity against these diseases, that is, they do not get sick with them again. In the blood of a person, after infection with pathogens of any disease, special protective substances appear, which are called antibodies or immune substances. They either destroy the causative agents of this disease, or sharply weaken their effect, and this creates favorable conditions for phagocytosis. The acquired natural immunity lasts for several months or years.
Actively acquired natural immunity arises after an infectious disease. This is the strongest, lasting immunity, which is sometimes maintained throughout life. Actively acquired artificial immunity occurs as a result of vaccination with live weakened or killed vaccines (microbial preparations). Such immunity develops within 1-2 weeks after vaccination and is maintained for a relatively long time - for years and tens of years. Passivelyacquired natural immunity is the immunity of the fetus or newborn, which receives antibodies from the mother through the placenta or in breast milk. Passively acquired artificial immunity is created by introducing into the body immunoglobulins obtained from actively immunized people or animals. Such immunity is established quickly - a few hours after the introduction of immune serum or immunoglobulin and lasts a short time for 3-4 weeks, since the body seeks to get rid of foreign serum. All types of immunity associated with the formation of antibodies are called specific, since antibodies act only against a certain type of microorganism or toxins.
TO non-specific defense mechanisms include skin and mucous membranes, which are practically impermeable to microbes, lysozyme (bactericidal substance of the skin and mucous membranes), inflammation reaction, bactericidal properties of blood tissue fluid, phagocytosis reactions.
Artificial immunity and its role in the fight against infectious diseases. The concept of vaccines and sera used for the prevention of infectious diseases
Artificial immunity is immunity that is created as a result of activation of the immune system or artificial immunization. Distinguish between passive and active artificial immunity. Passive immunity arises from the introduction into the body of specific serums, interferons and their mixtures, interleukins, immunoglobulins, bone marrow cells, monocytes, lymphocytes, which are artificially activated in vitro. Passive immunity is created in case of primary or severe secondary immunodeficiency. Active immunity is created by activating the immune response mechanisms. For this, vaccines, inducers of interleukins, interferons, activators of phagocytosis and complement systems, and natural killer mechanisms are used. With active immunization, the body itself produces interferons, antibodies, interleukins and other factors of immunity. The vaccine contains weakened or killed viruses or bacteria. A primary immune response develops, and after ingestion of an unweakened pathogen, a secondary response is provided, which contributes to an easy course of the disease and rapid recovery.
Vaccines and serums are used as active or passive immunostimulants. Such drugs are especially effective if used not only for treatment, but also for the prevention of infectious diseases. Vaccines
are produced directly from microorganisms that cause infections, or from their antigens. The vaccine helps the body produce antibodies on its own to fight off viruses or infections. Depending on the origin, vaccines are divided into:
Corpuscular vaccines (such drugs are made from killed germs that cause the disease),
Attenuated vaccines (produced on the basis of weakened microorganisms),
· Chemical vaccines, in which antigens are created in a laboratory by chemical means (in particular, vaccines against hepatitis B).
Serums are blood plasma without fibrinogen. Serum is obtained by natural plasma clotting or by calcium ions, which precipitate fibrinogen. With the introduction of serum, the formation of the immune system also occurs. Serum is usually made from animal blood, but in some cases, serum based on human blood - immunoglobulins (or gamma globulins) - is most effective. γ-globulins do not cause allergic reactions. Serums contain ready-made antibodies, which are used if the body cannot produce them on its own due to a strong immunodeficiency, for the treatment and prevention of viral or bacterial infections (but not in an acute form). Serums can be used after organ transplantation to prevent organ transplantation. Serums are also used to form a person's immunity to infection if he has to come into contact with people who are already sick or carriers of certain viruses.
Constitutive and inducible defense mechanisms of mammals against infection.
Distinctive features of constitutive (congenital) births
shieldmechanisms are their constant presence in the body
regardless of the effect of destabilizing factors and the absence
pronounced specificity, that is, the similarity of manifestation during action
various factors. Defense mechanisms of this kind are capable of one
temporarily protect the body from a number of factors is practically
after birth. In the same time inducible defense reactions
are absent in the body initially, arise during life in re-
as a result of contact with a specific destabilizing factor and
give a pronounced specificity, that is, they only protect against
factor that caused the manifestation of this mechanism.
It can be assumed that constitutive defense mechanisms are the first barrier or echelon of protection against biological aggression, and inducible - the second, since they, as a rule, are included only when the first barrier is overcome to one degree or another.
TO constitutiveprotective barriers are traditionally includenot-
permeability of integuments, lysozyme, hydrolytic enzymes and
hydrochloric acid of the gastrointestinal tract, interferon, inflammation
lenia, phagocytosis, the complement system and others present in
blood humoral factors of constitutive protection.
Inducible defense mechanisms are all forms of immune
responses based on the specific recognition of foreign anti-
genes. As a rule, their implementation takes much longer
nothing, than for the manifestation of constitutive factors of protection, as well as the obligation
the participation of immunocompetent cells is essential. The main and
the most studied among them are: response to thymus-dependent
antigens, leading to the appearance of specific antibodies and
the corresponding cells of the immune memory; action of T-killers, limited
determined by the molecules of the main histocompatibility complex;
delayed-type hypersensitivity; hypersensitivity
immediate type.
The protective function of the skin and mucous membranes of mammals.
Skin itself (dermis) represented by dense fibrous co-
the only fabric that distinguishes itself availability
a large amount of dense intercellular substance... The main
the components of this substance are collagen and elastin proteins,
filling fibers, and filling the space between these fibers
polysaccharide hyaluronic acid. This combination creates a durable
dense and at the same time tensile mechanical barrier on a way
seeking to penetrate the inside of microorganisms. Available in the skin sweat glands in addition to fulfilling its core thermoregulatory function play an essential role in formation of the protective properties of the skin... The presence in the sweat fluid of small amounts of low molecular weight organic compounds (lactic acid, some amino acids, uric acid and urea) and its acidity (pH 5.5) are unfavorable for bacteria and fungi. The synergy of these secrets as a whole gives the skin surface bactericidal sv-va, which is experimentally confirmed by the death of saprotrophic bacteria placed on the surface of clean skin within 1 hour after application. The importance of sebaceous secretion should also be emphasized. as a water-repellent agent, because microorganisms that get on the surface of the skin with water (for example, when swimming in natural reservoirs) are removed when water flows from non-wetted skin. At the same time, the same fatty secretion protects the skin from drying out and subsequent cracking, which would drastically reduce its protection. The mucous membranes are provided. protectionorganism in a slightly different way. Due to the almost complete absence of intercells in the composition of the epithelial tissues forming the mucous membranes. ve-va the mechanical strength of the mucous membranes is extremely low and mucosal cells are easily damaged by external factors. However, their high regenerative capacity allows compensation
seize the resulting damage, and the layer secreted by these cells
slime hinders direct the effect of micro-mov on cells. Permanent removal of allocated secrets as a result of pass-
draining or activity found in some mucous membranes
membranes of ciliary cells promotes and removal of trapped
surface of particles.Since the process of such removal, as a rule, is prolonged in time, most of the secretions of the mucous membranes are composed of bactericidal substances. This is most pronounced in the mucous membranes. respiratory tract and eyes, where in the composition of the secreted mucus is present. means. number of lysozyme - acetylmuramidase, substrate
for which is one of the main components of the cage. walls
bacteria — peptidoglycan murein. Also present in mucus
nosepolysaccharide substances possess some antivirus
action.
The role of normal human microflora in protection against infection.
Normal microflora plays an important role in protecting the body from pathogenic microbes, for example, by stimulating the immune system, taking part in metabolic reactions. At the same time, this flora can lead to the development of infectious diseases. The role of normal microflora in infections Most infectionscaused by representatives of the normal microflora is opportunistic. In particular, intestinal anaerobes (eg, bacteroids) can cause abscesses to form after penetration into the intestinal wall as a result of trauma or surgery; The main causative agents of frequently recorded post-influenza pneumonia are considered micro-we living in the nasopharynx of any person. The number of such lesions is so great that it seems that doctors are more likely to deal with endogenous rather than exogenous infections, that is, with pathology induced by endogenous microflora. Lack of clear delineation between opportunistic microbes and commensals gives reason to believe that unlimited colonization by any kind of bacteria that can survive in the human body can lead to the development of infectious pathology. But this position is relative - different members of microbial communities exhibit pathogenic properties of different orders (some bacteria are more likely to cause damage than others). For example, despite the diversity of the intestinal microflora, peritonitis caused by the breakthrough of bacteria into the abdominal cavity is caused by only a few types of bacteria. The leading role in the development of such lesions is played not by the virulence of the pathogen itself, but by the state of the protective systems of the macroorganism; thus, in persons with immunodeficiencies, weakly virulent or avirulent microorganisms (candidates, pneumocysts) can cause severe, often fatal lesions. Normal microflora is competition for pathogenic; the mechanisms of suppressing the growth of the latter are quite diverse. Main mechanism- selective binding by normal microflora of surface cell receptors, especially epithelial. These properties are especially pronounced in bifidobacteria and lactobacilli; the antibacterial potential is formed by the secretion of acids, alcohols, lysozyme, bacteriocins and other substances. Normal microflora is a non-specific stimulant ("Irritant") of the immune system; the absence of a normal microbial biocenosis causes numerous disorders in the immune system. Normal intestinal microflora plays a huge role in metabolic body processes and maintaining their balance. Intestinal bacteria take part in inactivation toxic products of endo- and exogenous origin. Acids and gases released during the vital activity of intestinal microbes have a beneficial effect on intestinal peristalsis and its timely emptying.
Development and characteristics of mammalian phagocytic cells
Phagocytes - cells of the immune system that protect the body by absorbing (phagocytosis) harmful foreign particles, bacteria, as well as dead or dying cells. The main phagocytic cells of the mammalian body are divided into micro- and macrophages.
Monoblasts, when exposed to humoral factors such as monocyte-macrophage colony-stimulating factor (M-CSF) and partially interleukin-6 (IL-6), are converted into promonocytes, and those into monocytes. This stage of development has an average duration of 50-60 hours, but monocytes enter the bloodstream after another 13-26 hours. It is believed that monocytes are directly in the blood for no more than 4 days, and most of them on the second day move through the walls of the capillaries, turning into tissue macrophages. The lifespan of macrophages varies depending on where they are located, but in most cases they exist for about 40 days. Mature macrophages are distinguished by the presence on their surface of specific molecules necessary for the manifestation of functions characteristic of macrophages. Since one of their main functions is phagocytosis, macrophages have receptors that bind bacterial lipopolysaccharides, the most pronounced of which is the CD14 molecule. A distinctive feature of macrophages is their ability to move actively, which is due to the special properties of their cytoskeleton and the presence on their surface of another group of specialized molecules - receptors for chemokines. The main phagocytic cells among microphages are neutrophils - the largest group of all leukocytes, in a healthy adult, their number is about 70% of the total number of white blood cells. Their lifespan is not long - 2–3 days, and after leaving the red bone marrow, they remain in the bloodstream for only 8–10 hours, and then move into tissues, where they die either in the process of fighting against foreign agents or by the mechanism of apoptosis. Eosinophils in the body is much less - from 0.5 to 2% of the total number of leukocytes. They develop similarly to neutrophils, but their development is most sensitive to IL-5, known as the growth and differentiation factor of eosinophils. Basophils are the smallest group of granulocytes - their number in mammals is estimated as 0.2–0.5% of the total number of leukocytes. These are highly granular cells with granules with different contents stained with basic dyes. The transformation of basophils into mast cells occurs as a result of the penetration of the first through the walls of the capillaries both in the secondary lymphoid organs and in the epithelium in contact with the environment and its underlying layers, or in the skin itself. Mast cells are large in comparison with basophils, the number of granules in them increases, and their surface acquires a villous structure.
Phagocytosis process. Mechanisms of inactivation of microorganisms by phagocytes. Incomplete phagocytosis, its significance in the development of the infectious process
Conventionally, the whole process is usually divided into several stages. The first of these is the chemotactic movement of the phagocytic cell to the phagocytic object. Attractants for phagocytes can be both substances released by a foreign agent that has penetrated the internal environment, and substances that have appeared in the tissue fluid as a result of the effect of a foreign agent on the cells of the body. In particular, when bacterial cells are destroyed, a short peptide consisting of formyl-methionine, leucine and phenylalanine appears in the tissue fluid, which is the initiator of protein synthesis in prokaryotes and is completely unusual for eukaryotic cells. Among the most typical chemoattractants of their own origin are inflammatory mediators, products of activation of the complement system (C3a and C5a), substances formed when the blood coagulation system starts (thrombin, fibrin), cytokines secreted by various blood cells. For these substances, there are specific receptors on the surface of phagocytic cells, the attachment to which of an active agent causes a change in the protein G bound to the receptors, which leads to the launch of a number of processes. In particular, the susceptibility of cells to various activating factors increases, the secretory activity of phagocytes increases, but the main thing in relation to chemotaxis is the rearrangement of the cytoskeleton and, as a consequence, the polarization of the cell. The cell turns from rounded to triangular, in the part of the cytoplasm facing towards the movement, the number of organelles decreases and a network of microfilaments consisting of F-actin appears, the contraction of which determines the movement of the entire cell in the desired direction. A greater amount of integrins appear on the membrane in this part of the cell - specific molecules for enhancing the adhesion of a moving cell on the walls of the capillaries of the circulatory system, and the production of cathepsins, collagenase and elastase by phagocytes increases, which facilitate penetration through the basement membranes underlying the epithelium. It is thanks to such changes that phagocytic cells can quickly move from the blood to the site of tissue damage, i.e., the potential penetration of foreign agents. Some pathogenic microorganisms acquired in the course of joint evolution with the host the ability to withstand the inactivating effect of phagocytes and maintain viability, being in phagolysosomes - incomplete phagocytosis. The mechanisms contributing to this survival are not the same in different types of pathogens, but it is clearly shown that some bacteria are capable of producing catalase, thereby reducing the bactericidal effect of oxygen-dependent inactivation pathways.
Characterization of inflammation as a protective reaction of the body
Inflammation is a protective and adaptive local reaction of the whole organism that occurs in response to the impact of a harmful agent. Inflammation protects against harmful factors in the form of the formation of a kind of barrier. Due to the inflammatory reaction, the focus of damage is delimited from the whole organism; white blood cells rush to it, carrying out phagocytosis. Inflammation includes three most important components: alteration - a change up to damage to cells and tissues, exudation - the release of fluid and blood cells from the vessels and proliferation - cell multiplication and tissue proliferation. Depending on the predominance of one of them, three main forms of inflammation are distinguished: alterative, exudative, and proliferative. Alternative - when cell damage predominates, it occurs more often in the heart, liver, kidneys. Exudative inflammation - with it, changes in the vessels in the focus of inflammation prevail, which leads to a sharp increase in the permeability of the walls of the vessels, the liquid part of the blood and leukocytes leave the vessels into the surrounding tissue; fluid accumulating in the focus is called exudate. Proliferative - characterized by the predominance of the reproduction of cellular elements, which is manifested by the formation of nodules (granulomas), thickenings in the tissue.
The complement system, ways of its activation and mechanism of action.
Complement is a collective term for a system of about 20 proteins, many of which are precursors of enzymes (proenzymes). The main acting factors of this system are 11 proteins, designated C1-C9, B and D. All of them are normally present among blood plasma proteins, as well as among proteins that have leaked from capillaries into tissue spaces. The proenzymes are not normally active, but they can be activated in the so-called classical way. Complement is the main humoral component of the innate immune response. In humans, this mechanism is activated by the binding of complement proteins to carbohydrates on the surface of microbial cells, or by binding of complement to antibodies that have attached to these microbes. The signal in the form of a complement attached to the cell membrane triggers rapid reactions aimed at destroying such a cell. The speed of these reactions is due to the enhancement arising from the sequential proteolytic activation of complement molecules, which are themselves proteases. After the complement proteins have attached to the microorganism, their proteolytic action is triggered, which, in turn, activates other proteases of the complement system, and so on. There are three ways to activate complement: classical, lectin and alternative. Lectin and alternative pathways for complement activation are responsible for the nonspecific response of innate immunity without the participation of antibodies. In vertebrates, complement is also involved in specific immune responses, and its activation usually occurs along the classical pathway. Classic way complement activation is an immunologically mediated process initiated by antibodies. Immunological specificity is provided by the interaction of antibodies with antigens of bacteria, viruses and cells. The antigen-antibody reaction is associated with a change in the configuration of the immunoglobulin, which leads to the formation of a binding site for Clq on the Fc fragment near the hinge region. Immunoglobulins can bind to C1. C1 activation occurs exclusively between two Fc fragments. Therefore, the activation cascade can be induced even by one IgM molecule. In the case of IgG antibodies, the proximity of two antibody molecules is necessary, which imposes severe restrictions on the density of antigen epitopes. In this regard, IgM is a much more effective initiator of cytolysis and immune opsonization than IgG. The process of complement activation itself can be divided into certain stages: 1- recognition of immune complexes and the formation of C1; 2 - formation of C3-convertase and C5-convertase; 3 - formation of a thermostable complex C5b, 6.7; 4 - membrane perforation. The classical path works more precisely, since this way any foreign cell is destroyed. When alternative way antibodies are not involved in the activation of the complement system. The functional main difference of the alternative response is the speed of the response to the pathogen. If the classical pathway of complement activation takes time for the accumulation of specific antibodies, then an alternative pathway develops immediately after the penetration of the pathogen. The initiator of the process is C3b covalently bound to the cell surface. The sequence of reactions caused directly by microorganisms, leading to the degradation of C3 and regulated by factor I and factor H, is called "alternative pathway of complement activation". The complement component C3, abundantly present in the plasma, is constantly broken down into C3a and C3b. The internal thioether bond in the native C3 molecule is susceptible to spontaneous hydrolysis. This constant, low-level, spontaneous activation of C3 in plasma is termed "blank", and it maintains a low plasma C3b concentration. In serum, most C3b is inactivated by hydrolysis, but some C3b covalently binds to host cells or invaded pathogens. The connection of C3b with the pathogen is especially important, since contact with a foreign surface determines a set of reactions that lead to further accumulation of C3b: in a cell-bound state, C3b is able to non-covalently interact on the surface with factor B. The resulting C3bB becomes a substrate for serum protease - serine esterase ( factor D). Factor D cleaves a small fragment of Ba from factor B. The large Bb fragment remains linked to C3b. The resulting C3bBb ~ complex on the surface of the pathogen dissociates very quickly unless it is stabilized by binding with properdin (factor P) and the formation of the C3bBbP ~ complex, which is a surface-bound C3 convertase of the alternative pathway. Since the convertase is localized on the surface of the pathogen, the resulting C3b molecules will bind there. The result of the chain of reactions of the alternative pathway of complement activation is the accumulation of two essential factors of nonspecific protection: opsonin C3b and inflammatory factors: C3a and C5b. The СЗbВb complex is stabilized by properdin; in the absence of the latter, the СЗbВb complex is rapidly destroyed. The activation of the alternative complement pathway is initiated by cells infected with certain viruses, many gram-positive and gram-negative bacteria, trypanosomes, leishmanias, many fungi, heterologous erythrocytes, polysaccharides, dextran sulfate, as well as complexes of IgG, IgA or IgE with an antigen. The development of B-lymphocytes during the entire postembryonic period occurs in the bone marrow. Under the influence of the cellular marrow microenvironment and the humoral factors of the bone marrow, B-lymphocytes are formed from the lymphoid stem cell. The early stages of B-lymphocyte development depend on direct contact with stromal elements. Later stages of B-lymphocyte development proceed under the influence of humoral factors of the bone marrow. The interaction of the earliest precursors of B cells (early pro-B lymphocytes) with stromal elements is carried out using surface adhesive molecules CD44, c-kit, and SCF. As a result of these contacts, there is an increase in the proliferation of B-lymphocytes and their transition to the next stage of development - late pro-B-cells. The IL-7 receptor is expressed on the surface of late pro-B cells. Under the influence of IL-7, produced by stromal elements, pro-B-lymphocytes proliferate and differentiate into early pre-B-cells, characterized by the presence of an immunoglobulin m-polypeptide chain in their cytoplasm. These cells have the morphology of large lymphoid cells. Subsequently, these cells are transformed into small pre-B-lymphocytes, in some of which light chains of immunoglobulins are detected in the cytoplasm in addition to the m-heavy polypeptide chain. At the next stage of development of B-lymphocytes, the expression of surface monomeric immunoglobulins M. These structures are the antigen-recognizing receptors of B-cells. The antigenic specificity of the receptors is genetically determined. At the next stage of B-lymphocyte development, the cells are oriented towards the synthesis of antibodies of a certain class. B-lymphocytes appear, which express, along with IgM, molecules of the IgA or IgG class. Next, expression on IgD cells occurs. With the expression of immunoglobulins D on lymphocytes, the stage of antigen-independent maturation of B cells is completed. Thus, on mature B-lymphocytes, surface Ig-molecules can be represented by the following classes: 1) IgM, IgD; 2) IgM, IgA, IgD; 3) IgM, IgG, IgD. Moreover, all immunoglobulins presented on the same B-cell have the same idiotype, since they are encoded by the same VH and VL genes. Expression of MHC molecules on B-lymphocytes is observed starting from the pro-B-cell stage. These antigens are expressed on all mature B cells. Receptors for the complement C3 component (RC3b) and the Ig Fc fragment (RFc) are first found in small numbers on immature B cells. Lectin (mannose) pathway for activating the complement system uses Mannose Binding Lectin (MBL), a C1q-like protein in the classical activation pathway that binds to mannose residues and other sugars on the membrane to recognize a variety of pathogens. MBL is a whey protein belonging to the group of colletins proteins, which is synthesized mainly in the liver and can activate the complement cascade by directly binding to the surface of the pathogen. In serum, MBL forms a complex with MASP-I and MASP-II (Mannan-binding lectin Associated Serine Protease, MBL-binding serine proteases). MASP-I and MASP-II are very similar to the C1r and C1s of the classical activation pathway. When several active sites of MBL bind in a certain way to oriented mannose residues on the phospholipid bilayer of a pathogen, MASP-I and MASP-II are activated and cleave the C4 protein into C4a and C4b, and the C2 protein into C2a and C2b. C4b and C2a then combine on the surface of the pathogen to form C3 convertase, and C4a and C2b act as chemoattractants for cells of the immune system.
General characteristics of the immune response to thymus-dependent antigens, its stages and the final result.
As a rule, activation of T-helpers - Th is required to trigger an immune response (for most antigens). Antigens, the response to which develops with the help of Th, are called thymus-dependent, and the response itself is a thymus-dependent immune response.
Thymus-dependent antigens are called, the formation of antibodies against which requires complex cooperation of macrophages, T- and B-lymphocytes.
The immune response to these antigens is characterized by the following stages.
4) transmission of information about the antigen to the third group of immunocompetent cells (either to specialized macrophages - the so-called cellular type of immune response, implemented by T-helper subtype 1, or to B-lymphocytes - a type of immune response leading to the production of antibodies specific to the antigen that caused the immune response and implemented by T-helpers of subtype 2);
Development and characteristics of antigen-presenting cells, their localization in the body
Antigen-presenting (presenting) cells (APCs) - capture antigens, process them and present the corresponding antigenic determinants to other immunocompetent cells. There are two types of antigen-presenting cells: "professional" and "non-professional". "Professional" antigen-presenting cells very efficiently capture antigen by phagocytosis or receptor-mediated endocytosis and then present a fragment of this antigen on their membrane in a complex with molecules of the major histocompatibility complex II class. T cells recognize this complex on the membrane and interact with it. The antigen-presenting cells then produce additional co-stimulatory molecules, which leads to activation of the T cell. The expression of these co-stimulatory molecules is a characteristic feature of "professional" antigen-presenting cells. There are several main types of "professional" antigen-presenting cells: dendritic cells , which are the most important antigen-presenting cells. Activated dendritic cells are particularly effective activators of helper T cells because co-stimulatory molecules such as protein B7 are present on their surface. Macrophages which are CD4-positive cells and therefore can be infected with human immunodeficiency virus. B-lymphocytes , which carry on their surface (as a B-cell receptor) and secrete specific antibodies, and can also capture the antigen that binds to the B-cell receptor, process it and present it in a complex with the molecules of the major histocompatibility complex II class. In relation to other types of antigens, B-lymphocytes are inactive as antigen-presenting cells. Some activated epithelial cells. Dendritic cells, like macrophages and lymphocytes, are of hematopoietic origin. Dendritic cells are localized in the epithelium of the intestine, urogenital tract, airways, lungs, in the epidermis of the skin (Langerhans cells) and interstitial spaces. “Non-professional »Antigen-presenting cells normally do not contain class II major histocompatibility complex molecules, but synthesize them only in response to stimulation with certain cytokines, for example, γ-interferon. Non-professional antigen-presenting cells include:
Fibroblasts of the skin
Epithelial cells of the thymus
Epithelial cells of the thyroid gland
Glial cells
Β-cells of the pancreas
Vascular endothelial cells
Antigen-presenting cells are present mainly in the skin, lymph nodes, spleen and thymus.
Antigen processing, its role in the development of the immune response
Antigen processing.The expression of HLA class I and II molecules presenting the antigen is regulated by three genetic HLA loci - TAP, DM, and LMP, which determine their interaction with antigens. The molecules HLA-LMP 2 and HLA-LMP 7, which are expressed under the influence of gamma-interferon, are the first to be included in the processing system of various exogenous antigens. They trigger proteolysis in proteosomes and regulate the size and specificity of peptides to bind to HLA molecules. The proteosome is an enzymatic complex of 24 protein subunits. Two chains of HLA class II molecules are synthesized in the endoplasmic reticulum, temporarily connecting to the third, invariant Ii (CD74) chain, which prevents them from binding to autopeptides. Then this complex is transferred to endosomes, where it binds to the corresponding peptide-antigen 9-25 amino acids long, displacing the invariant Ii chain. By fusing the endosome with the membrane, HLA-DR molecules are expressed with a peptide antigen on the cell surface. The displacement of the peptide of the invariant chain and its replacement with a specific peptide-antigen is carried out by special proteins of the HLA-DM locus, which catalyze this process. Class I MHC molecules are constantly synthesized in the endoplasmic reticulum of the cell and are stabilized by the calnexin protein. Endogenous and viral antigens are preliminarily cleaved in the proteosome into peptides of 8-11 amino acid residues. When binding to the antigen-peptide, calnexin is cleaved off, and MHC molecules are transported by transport proteins HLA-TAP (transporter of antigen processing) to the cell surface, where this complex is presented to T-suppressors / killers. The structural features of MHC class II molecules, in contrast to MHC class I, are such that they provide the binding of more polymorphic peptides-antigens. MHC molecules acquire a stable three-dimensional shape on cells only after they are bound by fold-sites of the corresponding peptides. The presented complex "MHC molecule-peptide" remains on the cell (macrophage, etc.) for several weeks, which allows other cells, in particular T-lymphocytes, to interact with it. Specific allelic specificities of MHC molecules come into association with a specific peptide-antigen, which ensures antigen recognition. For example, a peptide of the herpes virus binds to the HLA-DQA 1 * 0501 / DQB 1 * 2001 haplotype, but not to another one that differs only by 15 amino acid residues.
T-lymphocytes, their development and localization. T-helper cells and their role in the development of the immune response to thymus-dependent antigens
The thymus provides optimal conditions for the development of all subpopulations of T lymphocytes from bone marrow progenitors to mature forms with full TCR. Epithelial cells play a key role in the microenvironment of T-lymphocytes in the thymus. They provide the necessary conditions for the differentiation of T-lymphocytes. The foci of extrathymic development of T cells existing in the body (for example, in the intestine) do not provide such an effect in full. The pool of naive T-lymphocytes leaving the thymus decreases with age. At this time, the immune system "uses" the memory T cells formed in the body. One of the key problems of the adaptive immune system in old age is the ability to adequately respond to new antigens that the body has not previously encountered (for example, “new” infectious diseases are more severe than at a young age, and more often lead to complications and death) ... The main stages of the development of T-lymphocytes in the thymus (T-cell immunopoiesis) in accordance with a genetically determined program and in the absence of antigenic stimulation have been determined: the formation of clone-specific antigen-recognizing receptors capable of recognizing antigenic peptides in combination with autologous HLA molecules; rejection of T-cells specific to autoantigens; expression of coreceptor molecules CD4 or CD8 with the formation of subpopulations of T-helpers and CTLs, as well as natural (natural) regulatory T-cells (Treg). Differentiation in the thymus is accompanied by a change in surface markers of T-lymphocytes. It includes the following stages: migration of T-cell precursors from the bone marrow; rearrangement of TCR genes and formation of a full-fledged receptor; positive and negative selection of T cells; the formation of mature subpopulations of CD4 + and CD8 + T-lymphocytes; emigration of mature T cells from the thymus. Early lymphoid progenitors (CD34, CD38, CD45RA, CD117, CD7, CD44), formed in the fetal liver and later in the bone marrow, enter the thymus parenchyma by diapedesis through postcapillary venules with high endothelium located in the cortico-medullary junction, and move to the outer layers of the cortex, and then migrate again to the area of \u200b\u200bthe corticomedullary junction. When cells migrate, their differentiation occurs.
If the antigen capable of causing proliferation (increase in the number) of B cells was added to a cell suspension consisting of macrophages, T-lymphocytes and B-lymphocytes, then a well-pronounced proliferative response from B cells was observed. If the cell suspension consisted only of T - and B-lymphocytes, the proliferative response of the latter was not recorded. If the antigen was added to a suspension consisting only of macrophages, kept for some time, and then, having freed the suspension from excess antigen, mixed it with T and B lymphocytes, a pronounced proliferation of B cells was observed.
More detailed studies of the role of macrophages in these processes not only confirmed their initiating role, but also made it possible to describe the mechanism of their participation in the formation of the immune response. The information obtained in this way formed the basis for the now generally accepted scheme of three-cooperative cellular interaction during the development of the immune response to thymus-dependent antigens.
According to this scheme, the body responding to the penetration of the antigen occurs:
1) perception and processing of information contained in the antigen by cells of the macrophage system;
2) transmission of this information to cells of the lymphocytic system, namely to T-lymphocytes-helpers (T-helpers);
3) activation of the T-helpers who have perceived information and their proliferation;
4) transmission of information about the antigen to the third group of immunocompetent cells (either to specialized macrophages - the so-called cellular type of immune response, implemented by T-helpers of subtype 1, or to B-lymphocytes - a type of immune response leading to the production of antibodies specific to the antigen that caused the immune response and implemented by T-helpers of subtype 2);
5) activation of the cells of the third group that have received the information and either the destruction by activated macrophages of their own cells altered by the action of the antigen (cell-type immune response), or the formation by activated B-lymphocytes of a set of antibodies that specifically interact with the antigen that caused the immune response (antibody-producing type of immune response).
B-lymphocytes, their development and localization. Plasma cells and antibody production
On mature cells, these molecules have a high density and are easily detected. Mature B-lymphocytes are characterized by the presence of surface IgD, a high density of receptors for the C3 component of complement and the Fc-fragment of Ig, the ability to transform into blast forms under the influence of B-mitogens (LPS, PWM), and the ability to transform under the influence of antigens into antibody-forming cells.
Immunological memory. Primary and secondary immune response
Immunological memory is the ability of the immune system to respond more quickly and efficiently to an antigen (pathogen) with which the body had prior contact.
The immune system has two truly amazing properties: specific recognition and immune memory. The latter is understood as the ability to develop a qualitatively and quantitatively more effective immune response upon repeated contact with the same pathogen. According to this, a distinction is made between primary and secondary immune responses. The primary immune response is realized at the first contact with an unfamiliar antigen, and the secondary - at the second contact. The secondary immune response is more perfect, as it is carried out at a qualitatively higher level due to the presence of preformed immune factors reflecting genetic adaptation to the pathogen (there are already ready-made genes for specific immunoglobulins and antigen-recognizing T-cell receptors). Indeed, healthy people do not get sick twice with many infectious diseases, since when reinfected, a secondary immune response is realized, in which there is no prolonged inflammatory phase, and immune factors - specific lymphocytes and antibodies - immediately enter the work.
The secondary immune response is characterized by the following features:
one . Earlier development, sometimes even lightning fast.
2. A lower dose of antigen required to achieve an optimal immune response.
3. An increase in the strength and duration of the immune response due to the more intense production of cytokines (TD 1 or more than 2 profiles, depending on the nature of the pathogen).
4 . Strengthening of cellular immune responses due to the more intense formation of specific T - type 1 helpers and cytotoxic T - lymphocytes.
five . Strengthening the formation of antibodies due to the formation of more T - type 2 helper cells and plasma cells.
6. Increasing the specificity of recognition of immunogenic peptides by T - lymphocytes by increasing the affinity of their antigen - specific receptors.
7. An increase in the specificity of the synthesized antibodies due to the initial production of IgG of high affinity / avidity.
It should be noted that the impossibility of forming an effective immune memory is one of the characteristic symptoms of human immunodeficiency diseases. So, in patients with hypoimmunoglobulinemia, the phenomenon of multiple episodes of the so-called. children's infections, since after the transferred infectious diseases, a protective antibody titer is not formed. Patients with defects in cellular immunity also do not form immune memory for T - dependent antigens, which is manifested by the absence of seroconversion after infections and vaccinations, however, the total concentration of immunoglobulins in their blood serum may be normal.
The nature of the interactions of antigen-presenting cells, T- and B-lymphocytes during the development of the immune response to thymus-dependent antigens, the role of surface antigens (proteins of the main histocompatibility complex and others) in these interactions
Antigen-presenting cells are present mainly in the skin, lymph nodes, spleen and thymus. These include macrophages, dendritic cells, follicular process cells of the lymph nodes and spleen, Langerhans cells, M cells in the lymphatic follicles of the digestive tract, and epithelial cells of the thymus gland. These cells capture, process and present Ag (epitope) on their surface to other immunocompetent cells, produce cytokines, and secrete prostaglandin E2, which suppresses the immune response. Dendritic cells come from the bone marrow and form a population of long-lived cells that trigger and modulate the immune response. In the bone marrow, their precursors form a subpopulation of CD34 + cells, which are able to differentiate into Langerhans cells for the epithelium and dendritic cells for the internal environment. Immature and non-dividing dendritic cell precursors inhabit many tissues and organs. Dendritic cells have a stellate shape and, at rest, carry a relatively small number of MHC molecules on the surface. Unlike Langerhans cells, interstitial dendritic cells are able to stimulate Ig synthesis by B-lymphocytes. Varieties of DC: - myeloid - originate from monocytes. They can be considered as a type of macrophage specializing in the presentation of Ar to T-lymphocytes; - lymphoid cells originate from a common lymphoid progenitor cell, from which T- and B-lymphocytes also develop. Interaction of T- and B-lymphocytes.In the primary immune response, the only effective APCs for T-lymphocytes are DCs. But in the case of activation of a T-lymphocyte by Ar represented by DCs, adjacent B-lymphocytes will also be involved in the immune response. In this case, two options for the interaction of T- and B-lymphocytes are possible:
B-lymphocytes with their immunoglobulin receptor bind soluble Ag, absorb it by endocytosis, process it inside themselves and expose Ag fragments as part of complexes with MHC-II and MHC-I molecules on the surface. T-lymphocyte TCR binds Ar on the B-lymphocyte surface, acting as APC; in addition, all necessary and sufficient coreceptor relationships between T- and B-lymphocytes are established. This interaction occurs in the T-dependent zones of the peripheral lymphoid tissue at the beginning of the development of the immune response.
The B-lymphocyte recognizes its own Ar, but the T-lymphocyte, which recognizes the Ar on another APC and is activated by interaction with this other APC, will be nearby. In this case, the T-B interaction may be limited by the interaction of T-lymphocyte cytokines with the receptor for these cytokines on the B-lymphocyte, and the interaction of membrane molecules between them may or may not occur to some extent (at least in the primary immune response ). But with a secondary immune response, the membrane molecule of the B-lymphocyte CD40 necessarily interacts with the membrane molecule of the T-lymphocyte CD40L, since without this interaction there is no switching of the class of immunoglobulins from IgM to others, and the secondary response of B2-lymphocytes is characterized by the obligatory switching of the class of immunoglobulins with IgM for IgG, IgA or IgE. These T-B interactions already take place in the B-cell zones - in the follicles of the lymphoid organs. Major histocompatibility complex (MHC) antigens are a group of surface proteins from various cells in the body that play a key role in cell-mediated immune responses. Molecules encoded by MHC bind to peptide antigens, as a result of which these antigens are recognized by specific receptors of T and B lymphocytes. Cytotoxic T-lymphocytes (T-killers) recognize target cells only if they have MHC class I antigens of their own genotype on their surface. In the case when the cells interacting in the immune response carry different MHC alleles, the immune response develops not against the presented foreign antigen (for example, viral or bacterial), but against different MHC antigens. This phenomenon underlies the fact that MHC antigens provide recognition in the body of "friend" and "alien".
The concept of antigens. General properties of antigens. Complete and incomplete antigens.
Antigens are substances that are structurally foreign to a particular organism (high molecular weight compounds - proteins and polysaccharides) that can cause an immune response.
The main properties of antigens:
- foreignness.The concept of antigens cannot be separated from the concept of foreignness. We use the term antigen, meaning its foreignness in relation to a given organism. For example, for a person, a protein of an animal or another person will be antigen.
Foreignness is determined by the molecular weight, size and structure of the biopolymer, its macromolecularity and structural rigidity.
- antigenicity.The antigenicity of proteins is a manifestation of their foreignness, and its specificity depends on the amino acid sequence of proteins, secondary, tertiary and quaternary (i.e., on the general conformation of the protein molecule) structure, on the surface located determinant groups and terminal amino acid residues. Colloidal state and solubility are essential properties of antigens.
- immunogenicity.Immunogenicity is the ability to induce an immune response with the formation of antibodies, that is, to form immunity. The concept of immunogenicity refers mainly to microbial antigens that provide the formation of immunity, that is, immunity to infections.
Immunogenicity depends on a number of reasons (molecular weight, mobility of antigen molecules, shape, structure, ability to change).
- specificity.Antigen specificity refers to the features that distinguish some antigens from others.
Antigen as the root cause of the development of the immune process has been of interest to immunologists since ancient times, when immunology was born. However, it was only thanks to the research of Karl Landsteiner in the 1920s and 1930s that conditions developed for studying the subtle nature of antigen specificity. Simple organic compounds were taken as antigenic material - haptens ... By themselves, these compounds are not capable of causing an immunological response. The presence of foreignness at a low molecular weight deprives them of immunogenicity. In this case, the complex of the hapten with the carrier protein is immunogenic.
Otherwise haptens are known as incomplete antigens.... As a rule, they have a small molecular weight and are not recognized by the immune incompetent and cells. Haptens can be simple or complex; simple haptens interact with antibodies in the body, but are not able to react with them in vitro; complex haptens interact with antibodies in vivo and in vitro. Haptens can become immunogenic by binding to a high molecular weight carrier that has its own immunogenicity.
Depending on the origin, antigens are classified into exogenous, endogenous, and autoantigens.
Exogenous antigens enter the body from the environment by inhalation, ingestion or injection. Such antigens enter antigen-presenting cells by endocytosis or phagocytosis and are then processed into fragments. The antigen-presenting cells then present the fragments to the helper T cells (CD4 +) on their surface through the type II major histocompatibility complex (MHC II) molecules.
Endogenousantigens are produced by cells of the body during natural metabolism or as a result of viral or intracellular bacterial infection. The fragments are then presented on the cell surface in a complex with the proteins of the main histocompatibility complex of the first type MHC I. If the presented antigens are recognized by cytotoxic lymphocytes, T cells secrete various toxins that cause apoptosis or lysis of the infected cell. To prevent cytotoxic lymphocytes from killing healthy cells, autoreactive T-lymphocytes are excluded from the repertoire during selection for tolerance.
Autoantigens are normal proteins or protein complexes that are recognized by the immune system in patients with autoimmune diseases. Such antigens should not normally be recognized by the immune system, but due to genetic factors or environmental conditions, immunological tolerance to such antigens may be lost in such patients.
Types of antigenic specificity.
1) species specificity - I mean the presence of antigens characteristic of all individuals of the species and uncharacteristic for organisms of other species;
2) heterospecificity - antigenic specificity, due to the presence of antigens common to representatives of different types.
3) group specificity - differences in antigens of groups of individuals within a species, for example, the division of people by antigens of erythrocytes into the so-called blood groups;
4) type specificity - a concept that practically coincides with group specificity, but is used for types of microorganisms;
5) functional specificity - similarity in antigenic determinants of molecules that perform the same function in different organisms. such molecules have not only similar determinants, but also those by which species or group specificity manifests itself, due to which it is possible to distinguish, for example, enzymes with the same substrate specificity formed in organisms of animals of different species;
6) stage specificity - a concept related to embryogenesis: we are talking about molecules that appear only at a certain stage of embryonic development and are absent at other stages of ontogenesis. The identification of such antigens allows one to determine the stage of development with high accuracy, especially when morphological and anatomical differentiation of stages is difficult or impossible;
7) pathological specificity - the presence of antigens that are not typical for the body in normal conditions and appear only in pathology. their detection opens up new possibilities for diagnosing a number of diseases (for example, malignant changes) and monitoring the condition of patients during therapy;
8) hapten specificity - the properties of complex antigens, determined by a specific hapten. It is important in the development of immune responses to low molecular weight substances, in particular to antibiotics or aniline dyes, to which people of certain professions may be allergic. To identify the antigenic specificity of any of the types, appropriate suspensions of antibodies or immunoglobulins are used.
Haptens- these are antigens of an organic nature related to lipids and polysaccharides.
Dependence of antigenic properties on molecular structure.
The antigenicity of a molecule is determined by its ability to induce an immune response in a particular organism. Antigenicity refers to the ability of molecules to be recognized by the receptors of immunocompetent cells individually, i.e. this property determines the specificity of the immune response. Most antigens (mainly of a protein nature) are capable of causing the formation of immunological memory. This is important in relation to antigens of microorganisms that cause immunity to infection - how immunogenic a particular vaccine is.
The degree of antigenicity depends on a number of factors. The size and molecular weight of the antigen is of great importance. The higher the molecular weight of a molecule, the stronger its antigenic properties.
Antigenic determinant
Antigenic determinant [Greek. anti - against and genes - generative; lat. determinantis - limiting, determining] - the structural part of the antigen, to which the antibody binds. Hell. consists of several amino acids (usually 6-8), forming a spatial structure characteristic of a given protein. In one protein, consisting of several hundred amino acids, there are several (5-15) different A. Special programs have been developed to predict the localization of protein ADs recognized in the course of the humoral immune response, which makes it possible to use not whole proteins for immunization, but short peptides that contain AD.
Determinants can be extremely diverse in shape and charge distribution and contribute to the development of a fairly diverse response of the humoral immune response.
Antigens: valence
Antigen valence is the number of antibody binding sites. This value can vary significantly depending on the structure of the antigen, its size, and the type of animal from which the antibodies were obtained.
Antigens usually carry many determinants. The larger the antigen molecule, the more it contains a determinant, the higher its valence. Antigens usually carry determinants of varying specificity. As a result, antibodies of different specificity are formed upon the introduction of most antigens.
Classification of antigens by origin. Types of antigen specificity
Antibodies are specific gamma globulins of blood serum formed in response to the introduction of antigens or as a result of natural contact of the body with substances of an antigenic nature (bacteria, toxins, proteins of various origins, polysaccharides, polysaccharide-protein complexes, etc.). For the production of a significant amount of antibodies, it is sufficient for a small amount of antigen to enter the body. The main structural unit (monomer) of an immunoglobulin of any class consists of two identical light (L - from English light) and two identical heavy (H - from English heavy) polypeptide chains held together by disulfide bonds. Light chains contain 2 homologous regions, and heavy ones, depending on the class of immunoglobulin, 4-5 homologous regions, consisting of about 110 amino acid residues and having globular structures connected by a disulfide bond and having autonomous functions. Such structures are called domains. Antigen-binding sites of immunoglobulins are formed by the N-terminal sequences of light and heavy chains, i.e. variable domains of these chains (V-domains). Several (3-4) hypervariable regions are distinguished within the V-domains. The structure of the remaining domains is constant, therefore they are called constant, or C-domains. Light chains contain one C-domain, heavy chains contain 3-4 C-domains. Under the influence of papain, immunoglobulin molecules (monomers) are cleaved to form two Fab fragments (fragment antigen binding) that bind the antigen, and one Fc fragment (fragment crystallizable, constant), which is the C-terminal part of the molecule, easily forming crystals. Fc fragments within the same class are identical (constant), regardless of the specificity of the immunoglobulins. They ensure the interaction of antigen-antibody complexes with complement proteins, phagocytes, eosinophils, basophils and mast cells. IgG, IgD and IgE molecules are represented by monomers, IgM - by pentamers; IgA molecules in blood are monomers, in saliva and secretions of mucous membranes - dimers. Immunoglobulin M (lgM) is formed at an early stage of the immune response and indicates an acute infectious process. In the IgM molecule, five subunits are connected by a J-chain (from the English joining - binding), as a result of which the molecule has 10 antigen-binding centers ..
Immunoglobulin A (lgA) is found on the surface of mucous membranes, in colostrum, milk, saliva and lacrimal fluid. It contains a secretory component that is synthesized in epithelial cells and protects it from degradation by proteolytic enzymes. Immunoglobulin E (lgE) has the form of a monomer (L-H) 2 -subunit and a molecular weight of about 190,000. It is found in blood serum in trace amounts. Possesses high homocytotropic activity, i.e. firmly binds to mast cells of connective tissue and blood basophils. The interaction of cell-bound IgE with a related antigen causes degranulation of mast cells, the release of histamine and other vasoactive substances, which leads to the development of immediate hypersensitivity. Previously, IgE antibodies were called reagins. Immunoglobulin D (lgD) exists in the form of a monomeric antibody with a molecular weight of about 180,000. Its concentration in blood serum is 0.03-0.04 g / l. lgD is present as a receptor on the surface of B-lymphocytes.
FunctionsFandb- andFc-parts of an immunoglobulin molecule
Immunoglobulin molecules of all five classes consist of polypeptide chains: two identical heavy H chains and two identical light chains - L, connected by disulfide bridges. Accordingly, each class of immunoglobulins, i.e. M, G, A, E, D, there are five types of heavy chains: μ (mu), γ (gamma), α (alpha), ε (epsilon) and Δ (delta), differing in antigenicity. Light chains of all five classes are common and are of two types: κ (kappa) and λ (lambda); L-chains of immunoglobulins of various classes can join (recombine) with both homologous and heterologous H-chains. However, in the same molecule there can only be identical L-chains (κ or λ). Both in the H- and in the L-chains there is a variable - V region, in which the amino acid sequence is not constant, and a constant - C region with a constant set of amino acids. In light and heavy chains, NH2- and COOH-terminal groups are distinguished.
When processing γ-globulin mercaptoethanoldisulfide bonds are destroyed and the immunoglobulin molecule breaks down into separate polypeptide chains. When exposed to a proteolytic enzyme papain the immunoglobulin is cleaved into three fragments: two non-crystallizing fragments containing determinant groups to the antigen and called Fab-fragments I and II and one crystallizing Fc-fragment. FabI and FabII fragments are similar in properties and amino acid composition and differ from the Fc fragment; Fab and Fc fragments are compact formations interconnected by flexible sections of the H chain, due to which immunoglobulin molecules have a flexible structure.
Papain splits an immunoglobulin molecule into two identical Fab - fragment (Fragment antigen binding), each of which has one antigen-binding center and Fc fragment(Fragment crystallizable)unable to bind antigen.
Pepsin cleaves the molecule elsewhere, cutting off the pFc "fragment from a large 5S fragment called F (ab") 2, since, like the parent antibody, it is bivalent with respect to antigen binding. The pFc "fragment is the C-terminal portion of the Fc region, the heavy chain portion of the Fab fragment is designated Fd.
Studies have shown that one part of the antibody (Fab-fragment) is designed to bind to the antigen, while the other part (Fc-fragment) interacts with cells of the immune system: neutrophils, macrophages and other mononuclear phagocytes that carry receptors for the Fc-fragment on their surface. Therefore, if antibodies have contacted pathogenic microorganisms, they can also interact with phagocytes with their Fc-fragment. Due to this, the cells of the pathogen will be destroyed by these phagocytes. In fact, antibodies act in this case as mediator molecules.
27.
Classes of mammalian immunoglobulins. Structural and functional differences between immunoglobulins of different classes
(IgG) make up about 80% of serum immunoglobulins, with a pier. weighing 160,000. They are formed at the height of the primary immune response and with repeated administration of the antigen (secondary response). IgGs have a high rate of binding to antigen, especially of a bacterial nature. This determines the ability of IgG to participate in the protective reactions of bacteriolysis. IgG is the only class of antibodies that cross the placenta into the fetus. Some time after the birth of the child, its content in the blood serum falls and reaches a minimum concentration by 3-4 months, after which it begins to increase due to the accumulation of its own IgG, reaching the norm by the age of 7 years. Of all the classes of immunoglobulins, IgG is synthesized most in the body. About 48% of IgG is contained in tissue fluid, into which it diffuses from the blood. IgG, like immunoglobulins of other classes, undergoes catabolic degradation, which occurs in the liver, macrophages, and the inflammatory focus under the action of proteinases.
(IgM) the first to begin to be synthesized in the body of the fetus and the first to appear in the blood serum after immunization of people with most antigens. They constitute about 13% of serum immunoglobulins at an average concentration of 1 g / l. In terms of molecular weight, they are significantly superior to all other classes of immunoglobulins. This is due to the fact that IgM are pentamers, that is, they consist of 5 subunits, each of which has a molecular weight close to IgG. IgM belongs to most of the normal antibodies - isohemagglutinins, which are present in the blood serum in accordance with the belonging of people to certain blood groups. These allotypic IgM variants play an important role in blood transfusion. They do not cross the placenta and have the highest avidity. When interacting with antigens in vitro, they cause agglutination, precipitation or complement binding. In the latter case, activation of the complement system leads to the lysis of corpuscular antigens.
(IgA) are found in blood serum and in secretions on the surface of mucous membranes. Serum contains IgA monomers with a sedimentation constant of 7S at a concentration of 2.5 g / L. This level is reached by 10 years of age. Serum IgA is synthesized in the plasma cells of the spleen, lymph nodes and mucous membranes. They do not agglutinate and do not precipitate antigens, are unable to activate complement by the classical pathway, as a result of which they do not lyse antigens.
Secretory immunoglobulins of the IgA class (SlgA) differ from serum by the presence of a secretory component, it is synthesized by cl. secretory epithelium and can f-th as their receptor, and attaches to IgA during the passage of the latter through epithelial cells. Secretory IgA plays an essential role in local immunity, since it prevents the adhesion of microorganisms to the epithelial cells of the mucous membranes of the mouth, intestines, respiratory and urinary tract.
IgD Not clarified. They are found on the surface of B-lymphocytes and in serum.
IgE Immediate hypersensitivity is realized by the release of mediators by mast cells and basophils after antigen attachment. The main defense against helminthic invasion is by the release of enzymes from eosinophils. Does not fix complement.
IgG Major antibodies in secondary immune response. Opsonize bacteria, promote the activation of phagocytosis. They fix the complement, promoting the lysis of bacteria. Neutralizes bacterial toxins and viruses. Pass through the placenta.
IgA Secretory IgA prevents the adhesion of bacteria and viruses to mucous membranes. Does not fix complement.
IgMThe first to be synthesized when the antigen hits. They fix the complement and do not cross the placenta. Antigenic receptors on the surface of B-lymphocytes.
Genetic mechanisms of formation of specificity of immunoglobulins and switching of cells to the synthesis of immunoglobulins of a certain class
The structure of Ig molecules is characterized by unique genetic coding. It was proved by molecular genetics that the structure of the Ig molecule is controlled by a large number of genes that have a fragmentary organization, form three groups, are located on three different chromosomes and are inherited independently. The first group of genes codes for the primary structure of the λ-type light chain, the second for the κ-type light chain, and the third for all types of heavy chains (α, δ, ε, γ and μ). The genes belonging to each group are located on the corresponding chromosome in close proximity to each other, located sequentially and separated by introns. The DNA region encoding the structure of the λ-type light chain contains 2 V-segments (control the structure of the V-domains) and 4 C-segments (control the structure of the C-domains). Between the C- and V-segments there is a J-segment (from the English join - connecting). The κ-type light chain is encoded by several hundred V-segments of DNA, 4 J-segments and one C-segment. The group of genes that control the structure of heavy chains has an even more complex structure. Along with the V-, C- and J-segments of DNA, they include 20 D-segments (from the English divercity - diversity). In addition, there is an M-segment that encodes the biosynthesis of the membrane-associated region of the receptor Ig molecule. Maturation of pre-B-lymphocytes is accompanied by rearrangements in their genetic apparatus. There is an arbitrary approach of individual DNA fragments and the assembly of common functional genes within the corresponding chromosomes. This process is called splicing (from the English splicing - splicing, joining). Missing DNA regions are excluded from further reading. From functional genes, pro-mRNA is subsequently transcribed, and then the final mRNA encoding the primary amino acid sequence of the L- and H-chains of the Ig molecule. In parallel with splicing, point mutations and non-template extension of oligonucleotides can occur in individual regions of the V-segments of immunoglobulin genes. These sections of DNA are called hypermutable regions. Splicing and mutation processes in Ig genes are random. They occur in each lymphocyte independently and are unique, which increases the diversity of V-domains and ultimately the structure of paratopes and idiotypic antigenic determinants of the Ig molecule in an infinite number of times. Therefore, B-lymphocytes, specific to almost any antigen, always exist in the body or at any time may appear. This thesis forms the basis of the molecular genetic theory of the origin of the diversity of antibody specificities. In the process of the primary immune response, the multiplication of B-lymphocytes is also accompanied by recombination rearrangements within the immunoglobulin genes, but already within the C-segments. This is manifested by a sequential change in the Ig class: at the early stages of differentiation, B-lymphocytes synthesize Ig of classes M and D, at later stages - classes G, A or E (rarely).
Paratope and epitope. The nature of the antigen-antibody interaction. Affinity and Avidity
Epitope, or antigenic determinant - a part of an antigen macromolecule that is recognized by the immune system (antibodies, B-lymphocytes, T-lymphocytes). The part of the antibody that recognizes the epitope is called paratope. Although epitopes usually refer to molecules that are foreign to a given organism (proteins, glycoproteins, polysaccharides, etc.), the regions of their own molecules recognized by the immune system are also called epitopes.
Antigen - antibody reaction - the specific interaction of antibodies with the corresponding antigens, as a result of which antigen - antibody complexes (immune complexes) are formed. Often the end result of this reaction is the binding of toxins, immobilization of virulent bacteria, and neutralization of viruses.
The reaction a \\ r - a \\ m proceeds in two phases, which differ from each other in mechanism and speed. 1. specific connection of the active center of the antibody with the corresponding groups of the antigen or hapten. 2. nonspecific phase - a visually observed reaction.
Antigen-antibody binding is reversible; bond strength, called affinity, can be quantified by determining the association constant. There is also a term avidityantibodies, which is used to describe the total strength of the interaction of a multivalent antibody with a polydeterminant antigen.
IgM and IgG avidity is very important in diagnosis and allows for retrospective analysis of viral diseases. So, for example, a high avidity of primary IgM indicates an acute phase of the disease and recent - from one to one and a half months - infection. Trace IgM concentrations can persist in the body, in some cases, for up to two years.
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. Obtaining sera for immunological reactionsinvitro.
Monoclonal antibodies
Antitoxic serum is obtained by repeated immunization (hyperimmunization) of horses, from which a sufficiently large amount of blood can be obtained. Immunization is carried out first with toxoid, then toxin. Blood serum is purified from ballast proteins by fermentation and dialysis (anti-diphtheria, anti-tetanus, anti-botulinum, anti-gangrenous.)
Antibacterial serums are obtained by hyperimmunizing horses with appropriate vaccines. The use of antibacterial serums is limited due to their low effectiveness.
* material for obtaining heterologousimmunoglobulins are serum or blood plasma of hyperimmunized animals.
* material for cooking homologousimmunoglobulins serves human blood plasma.
Agglutinating serumsobtained by immunizing animals with microbes may contain antibodies against related microbes, that is, they are polyvalent. To increase the specificity of the sera, group antibodies are removed from them by Castellani adsorption, using group antigens. The resulting sera are called adsorbed... Leaving antibodies to only one antigen, monoreceptor sera are obtained.
Monoclonal antibodies - a / t produced by immune cells belonging to the same cell clone, that is, originating from one plasma progenitor cell. MAs can be generated against almost any natural antigen (mainly proteins and polysaccharides) that the antibody will specifically bind. They can then be used to detect (detect) this substance or purify it. MA are widely used in biochemistry, molecular biology, and medicine. used to treat melanoma, breast cancer.
Agglutination and precipitation. Agglutination and precipitation reactions used in biology and medicine
Agglutination reactions
These reactions involve antigens in the form of particles (microbial cells, erythrocytes and other corpuscular antigens), which are glued together by antibodies and precipitate. Three components are needed to formulate the agglutination reaction (RA): 1) antigen (agglutinogen); 2) antibody (agglutinin) and 3) electrolyte (isotonic sodium chloride solution). positive result
- presence of flakes agglutinate,
negative
- no agglutinate flakes
Expanded agglutination reaction (RA). To determine AT in the patient's blood serum, put extended agglutination reaction (RA)... For this, a diagnosticum is added to a series of dilutions of blood serum - a suspension of killed microorganisms or particles with adsorbed Ag. The maximum dilution giving agglutination Ag is called the serum titer.
Indicative agglutination reaction (RA)To identify the isolated microorganisms, put an approximate RA on the slides. To do this, a culture of the pathogen is added to a drop of standard diagnostic antiserum (dilution 1:10, 1:20). If the result is positive, a detailed reaction is set with increasing dilutions of the antiserum. The reaction considered positive if agglutination is observed in dilutions close to the titer of the diagnostic serum.
Direct hemagglutination reactions. The simplest of these reactions is erythrocyte agglutination, or hemagglutination, used to determine blood groups in the AB0 system. To determine agglutination (or its absence), standard antisera with anti-A and anti-B-agglutinins are used. The reaction is called direct, since the investigated Ag are natural components of erythrocytes.
Precipitation reactionIs the formation and precipitation of a complex of a soluble molecular antigen with antibodies in the form of a turbidity called a precipitate. It is formed by mixing antigens and antibodies in equivalent amounts. The precipitation reaction is put in test tubes (ring precipitation reaction), in gels, nutrient media, etc.
The precipitation reaction allows you to determine the presence of an unknown antigen in the test material by adding a known antibody or using a known antigen - an unknown antibody. Precipitation is better recorded if the antigen is layered in a test tube on the antibody. In this case, the appearance of a precipitate in the form of a ring is observed - ring precipitation. Ring precipitation is carried out in special test tubes. Agar precipitation makes it possible to determine the toxigenicity of diphtheria cultures.
In forensic research, precipitation is used to establish the species of blood, organs and tissues using specific precipitating sera.
Immunoelectrophoresis, its main varieties
Immunoelectrophoresis (IEF) - a method for studying the antigenic composition of biological materials, combining electrophoresis and immunodiffusion. First described by Grabar and Williams in 1953, the method was modified in 1965.
A sample of antigenic material is separated by electrophoresis in gel (agarose), as a result of which the characteristic zones are formed. Further, in parallel to the electrophoresis zones, precipitating antiserum is introduced, antigens and antiserum diffuse towards each other, and precipitation lines appear at the meeting point of the antiserum with the antigen, and they form an arc. After immunodiffusion and elution of non-precipitated molecules from the gel, the gel is stained with special dyes (amido black 10B, azocarmine B, and other dyes, staining proteins in the case of protein antigens or Sudan black B in the case of lipoprotein antigens). There are also a number of modifications of the IEF method (using a pure antigen, using a monospecial antiserum, the Osserman method, the Geremans IEF method. Using this method in clinical immunology, the concentration of Ig and identifiers of myeloma proteins is determined.
Counter immunoelectrophoresis can be used to detect antigens migrating in agar to a positively charged electrode. It is used to identify antigens of the hepatitis B virus and corresponding antibodies, antibodies to DNA in systemic lupus erythematosus, autoantibodies to soluble nuclear antigens in collagenoses, and antibodies (precipitins) to Aspergillus in allergic bronchopulmonary aspergillosis.
Rocket electrophoresis-This is a quantitative method involving the introduction of antigen into a gel containing antibodies. The precipitation line is rocket-shaped, the length of which is determined by the concentration of the antigen. Like counter electrophoresis, this is a fast method, but here again the antigen must travel to the positively charged electrode. Thus, rocket electrophoresis is suitable for proteins such as albumin, transferrin and ceruloplasmin, while the concentration of immunoglobulins is usually determined by simple radial immunodiffusion.
One of the most successful options for rocket electrophoresis is two-dimensional or cross-over immunoelectrophoresis Laurella. In this case, at the first stage, the mixture of antigens is electrophoretically separated in an agarose gel, then the separated proteins are forced to diffuse again in the gel under the influence of an electric field in another
Types of immunoelectrophoresis A - simple immunoelectrophoresis; B - counter immunoelectrophoresis; B - rocket immunoelectrophoresis; D - two-dimensional immunoelectrophoresis.
Immunofluorescence methods
Immunofluorescence consists in the use of fluorochrome-labeled antibodies, more precisely, the immunoglobulin fraction of IgG antibodies. An antibody labeled with a fluorochrome forms an antigen-antibody complex with an antigen, which becomes available for observation under a microscope in UV rays that excite fluorochrome luminescence. Direct immunofluorescence is used to study cellular antigens, detect the virus in infected cells, and detect bacteria and rickettsia in smears. So, for the diagnosis of rabies, the prints of pieces of the brain of animals suspected of carrying a virus are treated with luminescent rabies serum. With a positive result, lumps of bright green color are detected in the cytoplasm of nerve cells. Express diagnostics of influenza, parainfluenza and adenovirus infection is based on the detection of viral antigens in the cells of imprints from the nasal mucosa.
The method of indirect immunofluorescence is more widely used. based on the detection of an antigen-antibody complex using luminescent immune serum against IgG antibodies and used to detect not only antigens, but also titration of antibodies. The method has found application in serodiagnostics of herpes, cytomegaly, and Lassa fever. Preparations with layered test blood serum are placed in a thermostat at t ° 37 ° for the formation of immune complexes, and then, after washing off unbound reagents, these complexes are detected with labeled luminescent serum against human globulins. Using labeled immune sera against IgM or IgG antibodies, it is possible to differentiate the type of antibodies and detect an early immune response by the presence of IgM antibodies.
Radioimmunoassay
Radioimmunological method based on the use of a radioisotope label of antigens or antibodies. It is the most sensitive method for the determination of antigens and antibodies, it is used to determine hormones, medicinal substances and antibiotics, to diagnose bacterial, viral, rickettsial, protozoal diseases, to study blood proteins, tissue antigens. It was originally developed as a specific method for measuring the level of hormones circulating in the blood. The test system was a hormone (antigen) labeled with a radionuclide and an antiserum to it. If a material containing the desired hormone is added to such an antiserum, then it will bind part of the antibodies; with the subsequent introduction of the labeled titrated hormone, a reduced amount of it will bind to the antibodies compared to the control. The result is evaluated by comparing the curves of the bound and unbound radioactive label. This type of method is called competitive reaction. There are other modifications of the radioimmunoassay method.
Radioimmunoassay. The principle of radioimmunoassay (RIA) is based on the detection of an antigen-antibody complex, in which one of the immunoreagents has been labeled with a radioactive isotope. Iodine isotopes (I-125 and I-131) are commonly used. The reaction is accounted for in decreasing or increasing radioactivity (depending on the RIA technique) using special ionizing radiation counters. The method is highly sensitive, but is gradually being replaced by enzyme immunoassay, given the non-safety of working with radioactive isotopes and the need for sophisticated recording equipment.
A type of immunoelectrophoresis is radioimmunophoresis.In this case, after electrophoretic separation of antigens, a groove cut parallel to the movement of antigens in the gel is poured first a radioactive iodine-labeled immune serum against the antigens to be determined, and then an immune serum against IgG antibodies, which precipitates the formed antibody complexes with antibodies. All unbound reagents are washed out, and the antigen-antibody complex is detected by autoradiography.
Linked immunosorbent assay
Immunoassay, or enzyme-immunological, methods are based on the use of antibodies conjugated with enzymes, mainly horseradish peroxidase or alkaline phosphatase. To detect the binding of labeled antibodies to the antigen, a substrate degraded by an enzyme attached to lgG is added, staining in yellow-brown (peroxidase) or yellow-green (phosphatase). They also use enzymes that decompose not only the chromogenic, but also the lumogenic substrate. In this case, with a positive reaction, a glow appears. Like immunofluorescence, the enzyme immunoassay is used to detect antigens in cells or to titrate antibodies on antigen-containing cells.
The most popular type of enzyme immunoassay is immunosorption. The antigen is sorbed on a solid carrier, which can be cellulose, polyacrylamide, dextran and various plastics. Most often the surface of the micropanel wells serves as a carrier. The test blood serum is added to the wells with the adsorbed antigen, then the enzyme-labeled antiserum and the substrate. Positive results are taken into account by changing the color of the liquid medium. To detect antigens, antibodies are sorbed onto the carrier, then the test material is introduced into the wells and the reaction is developed with an enzyme-labeled antimicrobial serum. The introduction of avidin and biotin into the reaction system helps to increase the sensitivity of immunofluorescent and enzyme immunoassay.
Enzyme-linked immunosorbent assay (ELISA). In the methods of enzyme-linked immunosorbent assay, enzyme-labeled immunoreagents are used. The most widely used solid-phase ELISA. As a solid phase, polystyrene or polyvinyl plates or beads are used, on which antigens or antibodies are adsorbed. To detect antibodies, a known antigen is adsorbed in the wells of a polystyrene plate. Then the test serum is introduced, in which they want to detect antibodies to this antigen. After incubation, the wells are washed to remove unbound proteins and anti-immunoglobulin antibodies labeled with an enzyme are added to them. After incubation and washing, enzyme-specific substrate and chromogen are added to the wells to record the end products of substrate degradation. The presence and amount of antibodies is judged by the change in color and color intensity of the solution. ELISA methods have high sensitivity and specificity and are most widely used among immunological methods of clinical and laboratory diagnostics.Immunoblotting
Immunoblotting are used to detect antibodies to individual antigens or to "recognize" antigens by known sera. The method consists of 3 stages: separation of biological macromolecules (for example, a virus) into individual proteins using polyacrylamide gel electrophoresis; transferring the separated proteins from the gel to a solid support (blot) by applying a polyacrylamide gel plate to activated paper or nitrocellulose (electroblottang); detection of the proteins in question on the substrate using direct or indirect enzyme immunoassay. As a diagnostic method, immunoblotting is used in HIV infection. Detection of antibodies to one of the proteins of the outer envelope of the virus is of diagnostic value.
Immunoblotting
After separation of a complex mixture of proteins by electrophoresis in polyacrylamide or agarose gel, they can be transferred from the gel to a microporous nitrocellulose membrane. Further, non-specifically membrane bound antigens can be identified using labeled antibodies. This method is widely used. For example, it is used to identify components of neurofilaments that have been previously separated in a polyacrylamide gel in the presence of sodium dodecyl sulfate (SDS). Of course, if the antigen is irreversibly denatured by SDS, then this technique cannot be used. If the antiserum proteins are separated by isoelectrofocusing and then transferred (this is called blotting) to the membrane, then using the labeled antigen it is possible to establish the so-called antiserum spectrotype, i.e. determine the isotype of antibodies interacting with a given antigen.
reactions involving a compliment.
Complement system - a complex of complex proteins constantly present in the blood. This is a cascade system of proteolytic enzymes, designed for humoral protection of the body from the action of foreign agents, it is involved in the implementation of the body's immune response.
Complement - a system of proteins, which includes about 20 interacting components: C1 (a complex of three proteins), C2, C3, ..., C9, factor B, factor D and a number of regulatory proteins. All these components are soluble proteins circulating in the blood and tissue fluid. Complement proteins are synthesized primarily in the liver. Most of them are inactive until they are triggered either by an immune response (involving antibodies) or by a directly invading microorganism.
Reactions involving complement are based on the activation of complement as a result of its attachment to the antigen-antibody complex. If the antigen-antibody complex is not formed, then the complement is attached to the erythrocyte-anti-erythrocyte antibody complex, thereby causing hemolysis (destruction) of erythrocytes (radial hemolysis reaction). It is used to diagnose infectious diseases, in particular syphilis.
RSK refers to complex serological reactions, in which, in addition to antigen, antibody and complement, the hemolytic system is also involved, revealing the results of the reaction.
RSC proceeds in two phases:
the first - interaction of antigen with antibody with the participation of complement and
second - Revealing the degree of complement binding using the hemolytic system. This system consists of sheep erythrocytes and hemolytic serum. Erythrocytes are processed - sensitized by adding serum to them at a temperature of 37 ° C for 30 minutes. Lysis of sensitized sheep erythrocytes occurs only if complement is attached to the hemolytic system. In the absence of it, erythrocytes do not change. RSK results depend on the presence of antibodies in the studied serum. If the serum contains antibodies homologous to the antigen used in the reaction, then the resulting antigen-antibody complex binds, binds the complement. When a hemolytic system is added, hemolysis will not occur in this case, since all the complement is spent on the specific bond of the antigen-antibody complex. Erythrocytes remain unchanged, therefore the absence of hemolysis in the test tube is recorded as a positive CSC. In the absence of antibodies corresponding to the antigen in the serum, the specific antigen-antibody complex is not formed and the complement remains free. When a hemolytic system is added, the complement is attached to it and causes hemolysis of erythrocytes. The destruction of red blood cells, their hemolysis characterizes a negative reaction.
Hemolysis reaction... Under the influence of antibodies and complement, a cloudy suspension of erythrocytes turns into a bright red transparent liquid - lacquer blood due to the release of hemoglobin. The reaction is widely used in laboratory serological practice as an indicator of complement adsorption in the formulation of a diagnostic complement fixation test (CSC). Local hemolysis reaction in the gel (Erne reaction). This reaction is one of the variants of hemolysis. It allows you to determine the number of antibody-producing cells in the lymphoid organs. The presence of cells secreting hemolytic antibodies - hemolysins, is determined by the hemolysis plaques that appear in an agar gel containing erythrocytes, when the lymphoid tissue and complement under investigation are added to them. Plaque formation is observed only around those cells that secrete antibodies to erythrocytes or to the antigen that was previously adsorbed on them.
Bacteriolysis reaction... The bacteriolysis reaction consists in the fact that when a specific immune serum is combined with the corresponding live bacteria homologous to it in the presence of complement, microbial lysis occurs. The bacteriolysis reaction can be observed both in vitro (in vitro) and in the animal body (in vivo). This reaction use when diagnosing cholera. When staging a bacteriolysis reaction in test tubes, a vibrio culture isolated from a patient, a specific anti-cholera immune serum and complement are combined. The results are taken into account after a two-hour incubation at 37 ° C by inoculating material taken from a test tube on meat-peptone agar.
Neutralization reactions, opsonization reaction
Neutralization (from lat. neuter - neither one nor the other) - the interaction of acids with bases, as a result of which salts and water are formed. Neutralization reactions are often exothermic. For example, the reaction of sodium hydroxide and hydrochloric acid:
НСl + NaOH \u003d NaCl + Н 2 О
In ionic form, the equation is written as follows:
H + + OH - \u003d H 2 O.
However, there are also endothermic neutralization reactions, such as the reaction of sodium bicarbonate (baking soda) and acetic acid. Opsonization means the facilitation of phagocytosis of microorganisms and other materials after the attachment of opsonins to them. Opsonization. This is an immunological reaction that changes the surface properties of pathogenic microorganisms so that they become more susceptible to phagocytosis. Specific opsonins are antibodies directed against bacterial surface antigens that promote phagocytosis by coating the bacterial cell. The activity of specific opsonins is enhanced by some complement components, although the corresponding antibodies themselves may also exhibit little opsonizing activity. The ability to bind to tissue cells is apparently very pronounced in IgE, which in humans are responsible for various hypersensitivity reactions; it is possible that this ability is determined by the activity of the Fc fragment in the molecule.
Anaphylaxis, anaphylactic shock, serum sickness. The mechanism of immediate hypersensitivity. Allergies and allergens
Anaphylaxis is a life-threatening systemic hypersensitivity reaction to an allergen ( allergic reaction immediate type). Manifestations of anaphylaxis: respiratory distress - syndrome, itching, urticaria, edema of the mucous membranes, disorders of the gastrointestinal tract (nausea, vomiting, pain, diarrhea), vascular collapse. Any allergen can cause an anaphylactic reaction, but the most significant are the following: antisera, hormones, pollen extracts, Hymenoptera poison (hymenoptera), food, drugs, especially antibiotics; diagnostic tools. Clinical forms of anaphylactic reactions: anaphylactic shock, Quincke's edema, urticaria, generalized erythema. Symptoms of the disease: chills, dizziness, fear of death, a feeling of heaviness in the chest, tachycardia, decreased blood pressure, puffiness of the face, itchy skin, rash like urticaria, laryngeal edema, bronchospasm, nausea, vomiting, abdominal pain, loose stools.
Anaphylactic shockor anaphylaxis- the allergic district is slowed down. type, a state of sharply increased sensitivity of the body, which develops with repeated administration of the allergen. The primary cause of anaphylactic shock was the penetration of poison into the human body. The pathogenesis is based on an immediate hypersensitivity reaction. The general and most significant sign of shock is an acute decrease in blood flow with impaired peripheral and then central circulation under the influence of histamine and other mediators abundantly secreted by cells. The skin becomes cold, moist and cyanotic. In connection with a decrease in blood flow in the brain and other organs, anxiety, darkening of consciousness, shortness of breath appear, and urination is disturbed. Serum sickness is a condition that develops during treatment with immune sera of animal origin. It is an immune response to the introduction of foreign serum proteins, which consists in the formation of a large number of antibodies binding them by the plasmocytes of the bang's orgma. This p-tion yavl. a special case of type III hypersensitivity. Human antibodies bind foreign proteins, forming immune complexes. In this case, phagocytosis and complement-dependent lysis of antigen-antibody complexes occurs slowly, allowing them to have a damaging effect on the body. Allergy is an inadequate reaction of the body to various substances, which manifests itself in direct contact with them. They talk about allergies when the immune system comes into play and the body responds with a violent reaction and exaggerated protection to substances that are quite harmless in themselves. That is, allergy is an increased sensitivity, an altered response of the human body to the effects of certain factors - allergens.
Delayed type hypersensitivity and mechanisms of its development
Currently, according to the mechanism of development, it is customary to distinguish 4 types of allergic reactions (hypersensitivity). All these types of allergic reactions, as a rule, rarely occur in their pure form, more often they coexist in various combinations or move from one type of reaction to another type. In this case, types I, II and III are due to antibodies, are and belong to immediate hypersensitivity reactions (HNT)... Type IV reactions are caused by sensitized T cells and belong to delayed-type hypersensitivity reactions (HRT)... The fourth (IV) type of reactions is delayed-type hypersensitivity or cell-mediated hypersensitivity. Delayed-type reactions develop in a sensitized body 24-48 hours after contact with an allergen. In type IV reactions, the role of antibodies is played by sensitized T-lymphocytes. Ag, contacting with Ag-specific receptors on T-cells, leads to an increase in the number of this population of lymphocytes and their activation with the release of mediators of cellular immunity - inflammatory cytokines. Cytokines cause the accumulation of macrophages and other lymphocytes, involve them in the process of the destruction of hypertension, resulting in inflammation. Clinically, this is manifested by the development of hyperergic inflammation: a cellular infiltrate is formed, the cellular basis of which is mononuclear cells - lymphocytes and monocytes. The cellular type of reaction underlies the development of viral and bacterial infections (contact dermatitis, tuberculosis, mycoses, syphilis, leprosy, brucellosis), some forms of infectious-allergic bronchial asthma, transplant rejection and antitumor immunity.
Immunology is the science of the specific reactions of the body to the introduction of substances and structures alien to the body. Initially, immunology was considered as the science of the body's immunity to bacterial infections, and since its inception, immunology has developed as an applied field of other sciences (human and animal physiology, medicine, microbiology, oncology, cytology).
Over the past 40 years, immunology has become an independent fundamental biological science.
The history of development .
The first stage of development: first information in the 5th century BC e. In ancient times, mankind was defenseless against infectious diseases (plague, smallpox). The epidemics claimed many lives. The first immunological observations date back to ancient Greece. The Greeks noticed that people who have had smallpox are not susceptible to re-infection. In ancient China, smallpox scabs were taken, rubbed and allowed to smell. This method was used by the Persians and Turks and was called variolation method... It spread to Europe as well.
In 18th century England, it was noticed that milkmaids serving sick cows rarely fell ill with smallpox. On this basis, Jeer in 1796 developed a safe way to prevent smallpox by inoculating a person with cowpox. This method was further improved: the variola virus was added to the vaccinia virus. Thanks to the complete vaccination of the population, smallpox was eliminated. However, the birth of immunology as a science dates back to the early 80s of the 19th century and is associated with the discovery of Pasteur microorganisms, pathogens... Studying chicken pox, Pasteur came to the conclusion that microbes lose their ability to cause death of animals due to changes in biological properties and suggested that it is possible to prevent infectious diseases by weakened smallpox microbes.
In 1884, Mechnikov formulated phagocytosis theory... This was the first experimentally proven theory of immunity. He introduced the concept cellular immunity... Ehrlich believed that the basis of immunity are substances that suppress foreign objects. Later it turned out that both were right.
At the end of the 19th century. The following discoveries were made: Leffler and Roux showed that microbes release exotoxins, which, when administered to animals, cause the same diseases as the microbe itself. During this period, antitoxic sera for various infections (antidiphtheria, anti-tetanus) were obtained. Buckner found that microbes do not multiply in the fresh blood of mammals, since it has bactericidal properties, which are caused by the substance alexin (complement).
AT - agglutinins were discovered in 1896. In 1900 Ehrlich created the theory of AT formation.
Second phase begins from the beginning to the middle of the 20th century. This stage begins with the discovery of Langsteiner Ar (sensitized T cells) groups A, B, 0, which determine the human blood group, and in 1940 Langsteiner and Wiener discovered Ar on erythrocytes, which they called the Rh factor. In 1902 Richet and the Porter opened allergy phenomenon. In 1923, Ramon discovered the possibility of converting highly toxic bacterial exotoxins into non-toxic substances under the influence of pharmacoline.
Stage three mid 20th century to our time. It begins with Burnet's discovery of the body's tolerance to its own Ar. In 1959, Burnet developed a clonal selection theory of AT formation. Porter discovered the molecular structure of AT.
The immune system along with other systems (nervous, endocrine, cardiovascular) ensures the constancy of the internal environment of the body (homeostasis). There are 3 components in the immune system:
- cellular,
- humoral.
- gene.
Cellular component is in 2 forms - organized (- lymphoid cells that are part of the thymus, bone marrow, spleen, tonsils, lymph nodes) and unorganized (free lymphocytes circulating in the blood).
The cellular component is not homogeneous: T and B cells. The molecular component is Ig, which are produced by B-lymphocytes. 5 classes of Ig are known: G, D, M, A, E. At present, the structure of Ig of various classes has been established; Ig G is predominant in human serum (70-75% of the total amount of Ig).
In addition to Ig, the molecular component includes immunomodiators (cytokines), which are secreted by various cells of the immune system (macrophages and lymphocytes).
Cytokines are not constantly released, interact with surface receptors of cells and regulate the strength and duration of the immune response. The genetic component includes many genes that determine Ig synthesis. Each of the 4 AT protein chains is encoded by 2 structural genes.
PENZA STATE UNIVERSITY
Department "Microbiology, Epidemiology and Infectious Diseases"
Discipline : Medical Microbiology
Lecture
Lecture topic: INTRODUCTION TO IMMUNOLOGY. TYPES OF IMMUNITY. NON-SPECIFIC PROTECTION FACTORS
Goal:
To get acquainted with the types and forms of immunity, to study non-specific factors of the body's defense.
Plan:
Review questions:
- Describe the stages of development of immunology.
- What forms and types of immunity do you know?
- What non-specific factors of the body's defense do you know?
- Describe the complement system.
Literature for preparation:
Vorobiev A.A., Bykov A.S., Pashkov E.P., RybakovaA. M ... Microbiology (Textbook) .- M: Medicine, 1998.
Medical Microbiology (Handbook), ed. V.I. Pokrovsky, D.K. Pozdeeva. - M: GOETAR, "Medicine", 1999.
Microbiology with virology and immunology / Under the editorship of L.B. Borisov, A.M. Smirnova.-M., 1994
Microbiology and Immunology / Edited by A.A. Vorobyov. - M., 1999
Guide to laboratory studies in microbiology / Ed. LB Borisova. - M., 1984.
Virology. In 3 vols. / Edited by B. Filsz, D. Naip. - M, 1989.
Mesrovianu L., Punescu E. Physiology of bacteria.- Bucharest: Publishing house of the Academy of Sciences RPRD960.
Viral, chlamydial and mycoplasma diseases. V.I. Kozlova and others - M .: "Avicenna", 1995.
Lecturer Mitrofanova N.N.
1. History of the development of immunology
Immunology (from Latin immunity - immunity, immunity, logos - science) is a science that studies the ways and mechanisms of the body's defense against genetically foreign substances in order to maintain homeostasis.
In case of violation of homeostasis, infectious diseases, autoimmune reactions, and oncological processes develop.
The main function of the immune system is to recognize and destroy alien, genetically modified cells that have penetrated from the outside or formed in the body itself.
The development of immunology as a science can be divided into three stages.
1. The first stage (protoimmunology) is associated with the empirical development of infectious immunology
2. The second stage is the completion of the formation of classical immunology, the extension of the basic provisions of immunity to non-infectious processes (transplant and antitumor immunity) and the creation of a unified general biological theory of immunity.
3. The third stage - molecular genetic - (from the middle of the 20th century) the development of molecular and cellular immunology, immunogenetics.
The origins of the doctrine of immunity go back to ancient times and are associated with the observation that many, primarily children's, diseases, such as measles, chickenpox, mumps, etc., are not repeated. During this period, variolation methods were used to create immunity. After the introduction of a new method of protection against smallpox by the English rural doctor E. Jenner, a method of vaccination appeared. E. Jenner is sometimes called the "progenitor" of immunology.
However, having received a vaccine to protect against smallpox, he did not formulate general principles for creating immunity against any other infection.
The development of immunology began with the work of the outstanding French scientist L. Pasteur (1881). He and his students found methods of weakening (attenuating) the virulent properties of microorganisms, created vaccines with their help and explained the mechanism of formation of immunity when vaccines are administered. II Mechnikov (1882) discovered the phenomenon of phagocytosis and formulated the cellular (phagocytic) theory of immunity. At the same time, the French researchers E. Roux and A. Yersin (1888) established the ability of the causative agent of diphtheria to secrete a special toxin, to neutralize which the German scientist E. Bering and the Japanese researcher S. Kitazato (1890) developed a method for producing anti-diphtheria antitoxic immune serum. In Russia, such a serum was prepared by G.N. Gabrichevsky (1894). Antitoxic sera were obtained for the treatment of botulism, gas anaerobic infection, etc. A humoral theory of immunity emerged, the founder of which was the German researcher P. Ehrlich.
The period of active specific prevention of infectious diseases began. New vaccines were obtained from weakened living microorganisms for the prevention of tuberculosis (1919), plague (1931), yellow fever (1936), tularemia (1939), poliomyelitis (1954), etc. A method for the preparation of toxoids was developed, which tetanus. New methods of diagnostics of infectious diseases based on the interaction of antigen - antibody have been introduced.
In the 40s of the XX century, a new direction in immunology began to develop, associated with organ and tissue transplants. It is called transplant immunity. Its study was initiated by the work of J. Bordet and N. Ya. Chistovich (colleagues of II Mechnikov), who established that foreign erythrocytes and serum stimulate the production of antibodies. K. Landsteiner (1900) discovered blood groups and developed the theory of tissue isoantigens.
The English scientist P. Medovar (1945) put forward the postulate that immunity protects not only from microorganisms, but also from cells or tissues of a genetically foreign organism. It was clearly stated that the process of rejection of transplanted foreign tissues is due to immunological mechanisms. New ideas about malignant neoplasms, specific tumor antigens [Zilber LA, 1944], antitumor immunity, new methods of treating tumors and allergies have emerged.
P. Medovar et al. (1953) and the Czech researcher M. Hasek (1960), while studying transplant immunity, independently of each other discovered the phenomenon of immunological tolerance as a manifestation of tolerance for an alien, genetically different from "our own". Australian scientist F.M. Burnet and colleagues (1949) found that tolerance can be induced artificially by introducing a foreign antigen to an animal before birth. For this teaching, P. Medovar and M. Burnet were awarded the title of Nobel Prize laureates.
The patterns of inheritance of antigenic specificity, genetic control of the immune response, genetic aspects of tissue incompatibility during transplantation and problems of homeostasis of somatic cells of a macroorganism are being studied by a new branch of immunology - immunogenetics.
The development of immunology continues, and at the present stage the organization of the immune system has been studied, the role of the thymus in the formation of cell populations (T- and B-lymphocytes), the mechanisms of their functioning, cooperative relationships between the main cells of the immune system have been identified, the structure of antibodies has been established (D. Edelman, R . Porter).
New phenomena of cellular immunity have been discovered (cytopathogenic effect, allogeneic inhibition, the phenomenon of blast transformation, etc.).
The doctrine of hypersensitivity and immunodeficiency was created.
The forms of the immune response and factors of nonspecific protection were studied.
Theories of immunity have been developed.
The creation of a unified general biological theory of immunity opened the way to its use in the fight for healthy longevity, taking as a basis the powerful natural resources of constitutional protection in the fight against infectious and many other diseases of humans and animals.
2. Factors and mechanisms of immunity
Immunity (from Latin immunitas - inviolable, protected, liberation, getting rid of the disease) is a system of biological protection of the internal environment of a multicellular organism (homeostasis) from genetically foreign substances of exogenous and endogenous nature.
This system ensures the structural and functional integrity of organisms of a particular species throughout their life. Genetically foreign substances ("not our own") enter the body from the outside in the form of pathogenic microorganisms and helminths, their toxins, proteins and other components, sometimes in the form of transplanted tissues or organs. Outdated, mutated or damaged cells of one's own organism can become "alien".
The functions of the defense system, called the immune system, are the recognition of such foreign agents and a specific response to them.
2.1. Types and forms of immunity
Immunity is a multicomponent and diverse phenomenon in its mechanisms and manifestations. Two main defense mechanisms are known.
The first is due to the action of congenital, constitutive factors of nonspecific resistance (from lat.r esistentia - resistance) and is controlled by genetic mechanisms (innate, species immunity). They provide a non-selective response to the foreign agent. This means that the properties of such an agent do not matter. So, for example, a person is immune to the causative agents of dog distemper, chicken cholera, and animals are insensitive to Shigella, gonococcus and other microorganisms pathogenic for humans.
The second is determined by defense mechanisms that occur with the participation of the lymphatic system. They underlie the formation of individual adaptive (acquired) immunity acquired during life. Such immunity is characterized by the development of specific responses of the immune system to a specific foreign agent (i.e., it is inducible) in the form of the formation of immunoglobulins or sensitized lymphocytes. These factors are highly active and specific.
Depending on the methods of formation, several forms of acquired individual immunity are distinguished.
Acquired immunity can be formed as a result of an infectious disease, and then it is called natural active (post-infectious). Its duration ranges from several weeks and months (after dysentery, gonorrhea, etc.) to several years (after measles, diphtheria, etc.). Sometimes it can occur as a result of latent infection or carriage (for example, by "household" immunization for meningococcal infection). There are types of acquired immunity:
Antimicrobial is produced after a bacterial infection (plague, typhoid fever, etc.);
Antitoxic is formed as a result of the transferred toxicoinfection (tetanus, botulism, diphtheria, etc.);
Antiviral - after viral infections (measles, mumps, poliomyelitis, etc.);
Antiprotist - after infections caused by protozoa;
Antifungal - after fungal diseases.
In some cases, after an infectious disease, the macroorganism is completely freed from pathogens. Such immunity is called sterile. Immunity, in which pathogens persist indefinitely in the body of clinically healthy people who have undergone the disease, is called non-sterile.
Acquired immunity is transmitted from mother to child through the placenta during intrauterine development and is provided by immunoglobulins. It is called natural passive (transplacental). Its duration is 3-4 months, but it can be prolonged with breastfeeding of children, since antibodies are also contained in mother's milk. The importance of such immunity is great. It ensures the immunity of infants to infectious diseases.
Acquired artificial immunity arises from immunization. There are active and passive forms of artificial immunity. Active artificial immunity develops after the introduction into the body of weakened or killed microorganisms or their neutralized toxins. At the same time, an active restructuring takes place in the body of warm-blooded animals, aimed at the formation of substances that have a detrimental effect on the pathogen and its toxins, there is a change in the properties of cells that destroy microorganisms and their metabolic products. The duration of this immunity is from 1 to 3-7 years.
Passive artificial immunity occurs when ready-made antibodies are introduced into the body, which are contained in the sera of animals specially immunized with certain types of pathogens (immune sera), or they are obtained from the sera of people who have been ill (immunoglobulins). This type of immunity occurs immediately after the introduction of antibodies, but lasts only 15-20 days, then the antibodies are destroyed and removed from the body.
2.2. Factors of nonspecific resistance
Factors of nonspecific resistance (protection), which provide a nonselective response to an antigen and are the most stable form of immunity, are due to innate biological characteristics of the species. They react to a foreign agent in a stereotyped manner and regardless of its nature. The main mechanisms of nonspecific defense are formed under the control of the genome during the development of the organism and are associated with a wide range of natural physiological reactions - mechanical, chemical and biological.
Among the factors of nonspecific resistance are:
unresponsiveness of macroorganism cells to pathogenic microorganisms and toxins, due to the genotype and associated with the absence on the surface of such cells of receptors for the adhesion of the pathogenic agent;
barrier function of the skin and mucous membranes, which is provided by the rejection of skin epithelial cells and active movements of the cilia of the ciliated epithelium of the mucous membranes. In addition, it is due to the release of exosecretions of the sweat and sebaceous glands of the skin, specific inhibitors, lysozyme, the acidic environment of gastric contents and other agents. Biological factors of protection at this level are due to the destructive effect of the normal microflora of the skin and mucous membranes on pathogenic microorganisms;
temperature reaction, at which the reproduction of most pathogenic bacteria stops. For example, the resistance of chickens to the causative agent of anthrax (B. anthracis) is due to the fact that their body temperature is in the range 41-42 ° C, at which bacteria are not capable of self-reproduction;
cellular and humoral factors of the body.
In the case of the penetration of pathogens into the body, humoral factors are included, which include proteins of the complement system, properdin, lysines, fibronectin, the cytokine system (interleukins, interferons, etc.). Vascular reactions develop in the form of a rapid local edema in the focus of damage, which detains microorganisms and does not allow them to enter the internal environment. The acute phase proteins appear in the blood - C-reactive protein and mannan-binding lectin, which have the ability to interact with bacteria and other pathogens. In this case, their capture and absorption by phagocytic cells is enhanced, i.e., opsonization of pathogens occurs, and these humoral factors play the role of opsonins.
Cellular factors of nonspecific defense include mast cells, leukocytes, macrophages, natural (natural) killer cells (NK cells, from the English "natural killer").
Mast cells are large tissue cells that contain cytoplasmic granules containing heparin and biologically active substances such as histamine and serotonin. During degranulation, mast cells secrete special substances that mediate inflammatory processes (leukotrienes and a number of cytokines). Mediators increase the permeability of the vascular walls, which allows complement and cells to exit into the tissues of the lesion. All this inhibits the penetration of pathogens into the internal environment of the body. NK cells are large lymphocytes that do not have T- or B-cell markers and are able to kill tumor and virus-infected cells spontaneously, without prior contact. In peripheral blood, they account for up to 10% of all mononuclear cells. NK cells are localized mainly in the liver, red pulp of the spleen, and mucous membranes.
Leukocytes contain powerful bactericidal factors and provide primary or pre-immune phagocytosis of microbial cells. Such leukocytes are called phagocytes (phagocytic cells). They are represented by monocytes, polymorphonuclear neutrophils and macrophages.
Phagocytosis - a biological phenomenon based on the recognition, capture, absorption and processing of foreign substances by a eukaryotic cell. The objects for phagocytosis are microorganisms, the body's own dying cells, synthetic particles, etc. Phagocytes are polymorphonuclear leukocytes (neutrophils, eosinophils, basophils), monocytes and fixed macrophages - alveolar, peritoneal, Kupffer cells, dendritic cells of the spleen Langerhans and others.
In the process of phagocytosis (from the Greek.phago - I devour, cytos - cells), there are several stages (Fig.15.1):
Approach of a phagocyte to a foreign corpuscular object (cell);
Adsorption of an object on the phagocyte surface;
Absorption of the object;
Destruction of the phagocytosed object.
The first phase of phagocytosis is carried out by positive chemotaxis.
Adsorption occurs by binding a foreign object to phagocyte receptors.
The third phase is carried out as follows.
The phagocyte envelops the adsorbed object with its outer membrane and draws (invaginates) it into the cell. Here a phagosome is formed, which then fuses with the lysosomes of the phagocyte. A phagolysosome is formed. Lysosomes are specific granules containing bactericidal enzymes (lysozyme, acid hydrolases, etc.).
Special enzymes are involved in the formation of active free radicals O2 and H 2 O 2.
At the final stage of phagocytosis, the absorbed objects are lysis to low molecular weight compounds.
Such phagocytosis proceeds without the participation of specific humoral protective factors and is called pre-immune (primary) phagocytosis. It is this variant of phagocytosis that was first described by II Mechnikov (1883) as a factor of nonspecific defense of the organism.
The result of phagocytosis is either the death of foreign cells (complete phagocytosis), or the survival and proliferation of captured cells (incomplete phagocytosis). Incomplete phagocytosis is one of the mechanisms of long-term persistence (experience) of pathogenic agents in a macroorganism and chronicity of infectious processes. Such phagocytosis often occurs in neutrophils and ends with their death. Incomplete phagocytosis was detected in tuberculosis, brucellosis, gonorrhea, yersiniosis and other infectious processes.
An increase in the speed and efficiency of the phagocytic reaction is possible with the participation of nonspecific and specific humoral proteins, which are called opsonins. These include proteins of the complement system C3b and C4 b , proteins of the acute phase, IgG, IgM, etc. Opsonins have a chemical affinity for some components of the cell wall of microorganisms, bind to them, and then such complexes are easily phagocytosed because phagocytes have special receptors for opsonin molecules. The cooperation of various opsonins of blood serum and phagocytes constitutes the opsonophagocytic system of the body. Evaluation of the opsonic activity of blood serum is carried out by determining the opsonic index or opsonophagocytic index, which characterize the effect of opsonins on the absorption or lysis of microorganisms by phagocytes. Phagocytosis, in which specific (IgG, IgM) opsonin proteins are involved, is called immune.
Complement system (lat. complementum - supplement, means of replenishment) is a group of blood serum proteins that take part in nonspecific defense reactions: cell lysis, chemotaxis, phagocytosis, activation of mast cells, etc. Complement proteins belong to globulins or glycoproteins. They are produced by macrophages, leukocytes, hepatocytes and make up 5-10% of all blood proteins.
The complement system is represented by 20-26 blood serum proteins, which circulate in the form of separate fractions (complexes), differ in physical and chemical properties and are designated by the symbols C1, C2, C3 ... C9, etc. The properties and functions of the main 9 components of complement are well studied ...
In the blood, all components circulate in an inactive form, in the form of coenzymes. The activation of complement proteins (i.e., the assembly of fractions into a single whole) is carried out by specific immune and nonspecific factors in the process of multistage transformations. Moreover, each component of the complement catalyzes the activity of the next. This ensures the sequence, the cascade of the entry of the complement components into the reaction.
The proteins of the complement system are involved in the activation of leukocytes, the development of inflammatory processes, the lysis of target cells and, by attaching to the surface of the cell membranes of bacteria, are able to opsonize (“dress”) them, stimulating phagocytosis.
There are 3 known ways to activate the complement system: alternative, classical and lectin.
The most important component of complement is C3, which is cleaved by the convertase formed by any activation pathway into C3 and C3 fragments.b. Fragment SZ b participates in the formation of C5-convertase. This is the initial stage in the formation of the membranolytic complex.
In an alternative pathway, complement can be activated by polysaccharides, bacterial lipipolysaccharides, viruses and other antigens without the participation of antibodies. The initiator of the process is the SZ componentb , which binds to the surface molecules of microorganisms. Further, with the participation of a number of enzymes and the protein properdin, this complex activates the C5 component, which attaches to the membrane of the target cell. Then a membrane-attacking complex (MAC) of C6 – C9 components is formed on it. The process ends with membrane perforation and lysis of microbial cells. It is this way of starting a cascade of complementary proteins that takes place at the early stages of the infectious process, when specific immunity factors (antibodies) have not yet been developed. In addition, the SZ componentb by binding to the surface of bacteria, it can act as an opsonin, enhancing phagocytosis.
The classical pathway of complement activation is triggered and proceeds with the participation of an antigen-antibody complex. IgM molecules and some IgG fractions in the antigen-antibody complex have special sites that can bind the C1 component of the complement. The C1 molecule consists of 8 subunits, one of which is an active protease. It participates in the cleavage of the C2 and C4 components with the formation of the C3-convertase of the classical pathway, which activates the C5 component and ensures the formation of the membrane-attacking complex C6-C9, as in the alternative pathway.
The lectin pathway of complement activation is due to the presence in the blood of a special calcium-dependent sugar-binding protein - mannan-binding lectin (MSL). This protein is able to bind mannose residues on the surface of microbial cells, which leads to the activation of a protease that cleaves components C2 and C4. This triggers the formation of a membrane-lysing complex, as in the classical complement activation pathway. Some researchers consider this path as a variant of the classical path.
In the process of cleavage of the C5 and C3 components, small fragments C5a and C3a are formed, which serve as mediators of the inflammatory reaction and initiate the development of anaphylactic reactions with the participation of mast cells, neutrophils and monocytes. These components are called complement anaphylatoxins.
The activity of complement and the concentration of its individual components in the human body can increase or decrease in various pathological conditions. There may be hereditary deficiencies. The complement content in animal sera depends on the species, age, season and even time of day.
The highest and most stable level of complement was noted in guinea pigs; therefore, native or lyophilized blood serum of these animals is used as a source of complement. The proteins of the complement system are very labile. They are quickly destroyed when stored at room temperature, exposed to light, ultraviolet rays, proteases, solutions of acids or alkalis, removing Ca ++ and Mg ++ ions. Heating the serum at 56 ° C for 30 minutes leads to the destruction of complement, and this serum is called inactivated.
The quantitative content of complement components in the peripheral blood is determined as one of the indicators of the activity of humoral immunity. In healthy individuals, the content of the C1 component is 180 μg / ml, C2 - 20 μg / ml, C4 - 600 μg / ml, C3 - 13 001 μg / ml.
Inflammation as the most important manifestation of immunity develops in response to damage to tissues (primarily integumentary) and is aimed at localizing and destroying microorganisms that have entered the body. The inflammatory response is based on a complex of humoral and cellular factors of nonspecific resistance. Clinically, inflammation is manifested by redness, swelling, pain, localized fever, dysfunction of the damaged organ or tissue.
The central role in the development of inflammation is played by vascular reactions and cells of the mononuclear phagocyte system: neutrophils, basophils, eosinophils, monocytes, macrophages and mast cells. When cells and tissues are damaged, in addition, various mediators are released: histamine, serotonin, prostaglandins and leukotrienes, kinins, acute phase proteins, including C-reactive protein, etc., which play an important role in the development of inflammatory reactions.
Bacteria that have entered the body after damage and their waste products activate the blood coagulation system, the complement system and the cells of the macrophage-mononuclear system. The formation of blood clots occurs, which prevents the spread of pathogens with blood and lymph and prevents the generalization of the process. When the complement system is activated, a membrane attacking complex (MAC) is formed, which lyses microorganisms or opsonizes them. The latter enhances the ability of phagocytic cells to absorb and digest microorganisms.
The nature of the course and outcome of the inflammatory process depend on many factors: the nature and intensity of the action of a foreign agent, the form of the inflammatory process (alternative, exudative, proliferative), its localization, the state of the immune system, etc. If the inflammation does not end within a few days, it becomes chronic and then immune inflammation develops with the participation of macrophages and T-lymphocytes.