What is innate immunity - mechanisms and types. Factors of innate immunity

Cells that mediate innate immune responses (for example, NK cells or natural killer cells) are the first line of defense against cancer cells and infectious agents.
The innate immune system, which is a collection of various cellular receptors, enzymes and interferons with antiviral properties, is characterized by the fact that for the development of nonspecific immune reactions it does not require preliminary (primary) contact with an infectious agent.

Moreover, the intensity of the nonspecific immune response does not change even if there is a repeated encounter with the same pathogen. The innate immune system is configured to recognize and subsequently respond to nonspecific components of microorganisms. These components are predetermined, and the set of these characteristics does not depend on how many times the immune system encounters a given pathogen.
There are remarkably close similarities between the innate immune systems of a wide variety of animals. This indicates that the valuation system is the most ancient nonspecific immunity is of vital importance. There was a time when the innate immune system in vertebrates was considered archaic and outdated, but today there is no doubt that the state of innate immunity in many ways depends on the functioning of the acquired immune system. Indeed, the nonspecific (innate) immune response determines the effectiveness of the specific (acquired) immune response. It is now generally accepted that the innate immune system initiates and optimizes specific (acquired) immune responses, which develop more slowly.
Natural antibodies
Natural antibodies are always present in the body, and their formation does not require external stimuli. Their constant presence is necessary because these antibodies are directed against the most common damaging agents most often found in our environment. Natural antibodies are not only the product of an effectively functioning immune system, but are also capable of activating immune responses. After a microbial or viral agent is recognized by the body, the production of specific antibodies begins, which are already one of the components of the acquired immune system.
Compliment system. Recognition (or so-called marking ) infectious or malignant cells by attaching specific antibodies to them is often combined with activation of a compliment. The complement system is part of the nonspecific system (congenital) immunity and provides primary (incomplete) protection against infectious agents. The complement system has three main functions:
1) Opsonization . This term implies the attachment of complement proteins to a damaged or infected cell, which must be destroyed and removed from the body.
2) Chemotaxis . Chemical signals that attract immune cells to the infectious focus.
3) Membranotopic damage complex (MPC) . It is formed specifically to destroy opsonized cells. To simplify somewhat, we can say that MPC is a set of complement proteins that disrupt the integrity of the lipid membrane of a foreign cell. As a result of this, fluid begins to flow intensively into the cell until the cell membrane bursts like an inflated balloon. Some types of bacteria and cancer cells manage to destroy MPC if its formation occurs slowly enough. Therefore, the rate of formation of MPC is of fundamental importance.
It is important to recall that animal cell membranes are formed by two layers of lipids and a single-molecule protein layer. In this case, the cell can be compared to the smallest drop of liquid enclosed inside a vesicle, the walls of which are built from two layers of fat molecules. This structure allows many viruses to use part of the cell membrane of the host cell to create an additional protective shell. This becomes possible when the cell dies and the viruses come out. By using fragments of the cell membrane to create an outer shell, viruses thereby protect their vulnerable genetic apparatus, represented by sections of ribonucleic acid (RNA) or deoxyribonucleic acid (DNA). The additional lipid membrane also helps viruses to “disguise” themselves as normal, albeit very small, cells, and thereby avoid immune attack. Viruses that can create an additional shell from the lipid membrane of the host cell belong to the group of so-called. enveloped viruses Below is a short list of enveloped and non-enveloped viruses (Table 3). The list of enveloped viruses is a kind of quintessence of the causative agents of the most dangerous viral infections today.

Table 3

ENVELOPED AND NON-ENVELOPETED VIRUSES

Shell

Non-sheathed

Comparative characteristics of the main types of immunological recognition

Abbreviations

BCR -- antigen recognition receptor of B-lymphocytes (B-cell reseptor)

TCR -- antigen recognition receptor of T-lymphocytes (T-cell receptor)

TLR -- Toll-like receptor

Characteristics of theories of immunity

The theory of "environmental depletion"

The theory of "environmental depletion", proposed by Louis Pasteur in 1880, was one of the first attempts to explain the cause of acquired immunity. Immunity resulting from

once suffered from a disease, is explained by the fact that the microbes completely used the substances necessary for their life that were in the body before the disease, and therefore did not multiply in it again, just as they stop multiplying on an artificial nutrient medium after long-term cultivation in it.

The receptor theory of immunity, proposed by Chauveau, dates back to the same time, according to which the retardation of bacterial growth was explained by the accumulation in the body of special metabolic products that prevent

further proliferation of microbes. Although the receptor theory of immunity, as well as the “environmental depletion” hypothesis, were speculative, they still to some extent reflected objective reality. Chauveau's hypothesis already contained hints about the possibility of the appearance, as a result of infection or immunization, of some new substances that inhibit the activity of microbes in the event of secondary infection. These, as was shown later, are antibodies.

Exile theory

The first clear description of a smallpox clinic was given by the Muslim physician Rhazes (9th century). Not only was he the first to differentiate smallpox from measles and other infectious diseases, but he also confidently argued that recovery from smallpox caused long-term immunity. To explain this phenomenon, he proposed a theory of immunity, which is the first in the literature known to us. It was believed that smallpox affected the blood, and Rhazes argued that the disease was associated with fermentation of the blood, which helps get rid of the “excess moisture” characteristic, in his opinion, of the blood of young people. He believed that smallpox pustules, which appear on the skin and then burst with the flow of fluid, are a mechanism that rids the body of excess moisture in the blood. He explained the subsequent long-term immunity of a person who had been ill to smallpox by such processes of “expulsion,” “liberation” of blood from excess moisture. Re-infection, according to Rhazes, is impossible, since there is no substrate for infection. It is also impossible to infect old people whose blood has been “dried up” by the aging process.

Thus, Rhazes' concept explained not only acquired, but also natural immunity.

In the 11th century, Avicina proposed another theory, which 500 years later was developed by the Italian physician Girolamo Fracastro in his book “On Contagion” (1546).

The difference between the concepts of Rhazes and Fracastro in the substrate of the “expelled substance”: with Rhazes, excess moisture is expelled, and with Fracastro, the remains menstrual blood mother.

In each case, the essence of the disease was seen in the decay of the impurity and its expulsion through pustules, which results in lifelong immunity based on the absence in the body of a substrate for the occurrence of the disease during a new infection.

Phagocytic theory of immunity

The founder was I.I. Mechnikov, it was the first experimentally substantiated theory of immunity. First expressed in 1883 in Odessa, it was later successfully developed in Paris by I.I. Mechnikov and his many collaborators and students. Mechnikov argued that the ability of motile cells of invertebrate animals to absorb food particles, i.e. participate in digestion, there is actually their ability to absorb in general everything “foreign” that is not characteristic of the body: various microbes, inert particles, dying parts of the body. Humans also have amoeboid motile cells - macrophages and neutrophils. But they “eat” a special kind of food - pathogenic microbes.

Evolution has preserved the absorptive capacity of amoeboid cells from unicellular animals to higher vertebrates, including humans. However, the function of these cells in highly organized ones has become different - it is the fight against microbial aggression.

It was found that the capture and digestion of pathogenic agents by phagocytes is not the only factor in the body’s defense. There are microbes, such as viruses, for which phagocytosis itself is not as important as in bacterial infections, and only preliminary exposure to antibodies to viruses can facilitate their capture and destruction.

I.I. Mechnikov emphasized one side of the cellular defense reaction - the phagocytic one. Subsequent development of science has shown that the functions of phagocytic cells are more diverse: in addition to phagocytosis, they are involved in the production of antibodies, interferon, lysozyme and other substances that are of great importance in the formation of immunity. Moreover, it has been established that not only cells take part in immune reactions lymphoid tissue, but also others. Interferon can be produced by all cells.

The glycoprotein fragment of secretory antibodies is produced by epithelial cells of the mucous membranes. Simultaneously with the phagocytic theory of immunity, the humoral direction developed, which main role in protection against infection, it was devoted to body fluids and juices (blood, lymph, secretions), which contain substances that neutralize microbes and their metabolic products.

Humoral and receptor theories of immunity

The humoral theory of immunity was created by many major researchers, so it is unfair to associate it only with the name of P. Ehrlich, although many fundamental discoveries related to antibodies belong to him.

J. Fodor (1887) and then J. Nuttall (1888) reported bactericidal properties blood serum. G. Buchner (1889) established that this property depends on the presence in the serum of special thermolabile “protective substances”, which he called alexins. J. Bordet (1898), who worked in the laboratory of I.I. Mechnikov, presented facts indicating the participation in the cytocidal effect of two serum substrates with different properties - thermolabile complement and thermostable antibody. Of great importance for the formation of the theory of humoral immunity was the discovery by E. Bering and S. Kitazato (1890) of the ability of immune sera to neutralize tetanus and diphtheria toxins, and by P. Ehrlich (1891) of antibodies neutralizing toxins of plant origin (ricin, abrin). In immune sera obtained from guinea pigs resistant to cholera vibrio, R. Pfeiffer (1894) discovered antibodies that dissolved microbes; the introduction of these sera to non-immune animals gave them resistance to Vibrio cholerae. The discovery of antibodies that agglutinate microbes (Gruber and Durham, 1896), as well as antibodies that precipitate their waste products (Kraus, 1897), confirmed the direct effect of humoral factors on microbes and their waste products. The production of serum by E. Roux (1894) for the treatment of a toxic form of diphtheria finally strengthened the idea of ​​the role of humoral factors in protecting the body from infection.

It seemed to supporters of cellular and humoral immunity that these directions were in sharp, irreconcilable contradiction. However further development science has shown that there is a close interaction between cellular and humoral immunity factors. For example, humoral substances such as opsonins, agglutinins and other antibodies promote phagocytosis: by attaching to pathogenic microbes, they make them more accessible to capture and digestion by phagocytic cells. In turn, phagocytic cells take part in cooperative cellular interactions leading to the production of antibodies.

From a modern perspective, it is clear that both the cellular and humoral theories of immunity correctly reflected its individual aspects, i.e. were one-sided and did not cover the phenomenon as a whole. Recognition of the value of both theories was the simultaneous award in 1908 of I.I. Mechnikov and P. Ehrlich Nobel Prize for outstanding achievements in the development of immunology.

Instructive and selective theories of immunity

In the most concise form, all hypothetical constructions that have appeared since the time of P. Ehrlich regarding the phenomenon of immunological specificity can be divided into two groups: instructive and selective.

Instructional theories considered the antigen as a passive material - a matrix on which the antigen-binding region of antibodies is formed. According to this theory, all antibodies have the same sequence of amino acid residues. The differences relate to the tertiary structure and arise during the final formation of the antibody molecule around the antigen. From an immunological point of view, they did not explain, firstly, why the amount of antibodies in molar terms is significantly greater than the amount of antigen that penetrated the body, and, secondly, they did not answer the question of how immunological memory is formed. Theories contradict modern facts immunology and molecular biology and are of historical interest only.

Selective theories of antibody variability have proven more fruitful. All selective theories are based on the idea that the specificity of antibodies is predetermined, and the antigen acts only as a selection factor for immunoglobulins corresponding in specificity.

In 1955, a version of the selective theory was put forward by N. Erne. According to his ideas, antibodies of the most diverse specificity are constantly present in the body. The antibody, after interaction with the corresponding antigen, is absorbed by phagocytic mononuclear cells, which leads to the active production of antibodies of the original specificity by these cells.

A special place in immunology is occupied by the clonal selection theory of immunity by M.F. Burnet (1959). It states that during the differentiation of lymphocytes from a hematopoietic stem cell and during a parallel process

In the process of mutational changes in the genes responsible for the synthesis of antibodies, clones arise that are capable of interacting with an antigen of one specific specificity. As a result of such interaction, a clone selected for specificity is formed, which either secretes antibodies of a given specificity or provides a strictly specific cellular response. The clonal selection principle of organization of the immune system, put forward by Burnet, has now been fully confirmed. The disadvantage of the theory is the idea that the diversity of antibodies arises only due to the mutation process.

The basic principle of selection of specific clones is preserved in the germline theory of L. Hood et al. (1971). However, the authors see the root cause of the diversity of clones not in the increased mutability of immunoglobulin genes, but in their original embryonic pre-existence. The entire set of V genes that control the variable region of immunoglobulins is initially presented in the genome and is passed on from generation to generation without changes. During the development of B cells, recombination of immunoglobulin genes occurs, so that a single maturing B cell is capable of synthesizing immunoglobulin of one specificity. Such a monospecific cell becomes the source of a clone of B cells that produce immunoglobulin of a specific specificity.

Ehrlich's theory. Study of the antigen-antibody reaction

immunological recognition antigen phagocytic

Ehrlich first introduced immunological study statistical method - a method for titrating antibodies and antigens. Secondly, the article declared that the specificity of antibodies and their reactions are based on the laws of structural chemistry. Thirdly, it proposed a theory of antibody formation, which has had strong influence on immunological thinking for many years to come.

The immediate practical side of Ehrlich's research was that it showed how to quantify diphtheria toxin and antitoxin, which made it possible to create rational basis for immunotherapy, which was important in those years. At the same time, Ehrlich introduced many terms into the young field of immunology that later became generally accepted. He argued that an antibody is an independent type of molecule that initially exists in the form of receptors (side chains) on the surface of cells and has a special chemical conformation that ensures a specific interaction with the complementary configuration on the antigen molecule. He believed that both antigen and antibodies have functional domains, each of which has a haptophore group that ensures chemical interaction as a result of mutual correspondence like a “lock and key”, i.e., similar to the enzyme-substrate interaction, which is such Emil Fischer described it with a figurative metaphor. The antigenic toxin molecule also has a separate toxophore group, the destruction of which turns it into a toxoid that retains the ability to specifically interact with the antibody. Ehrlich set the units for quantification toxin and antitoxin and believed that the valence of the latter is approximately 200. Due to the variability of titration curves for various drugs toxin, Ehrlich suggested that they are a mixture of not only toxin and toxoid, but also other substances with different affinities for the antibody receptor. It was also assumed that the antibody molecule has different domains, one of which is responsible for attachment to the antigen, and others provide secondary biological phenomena such as agglutination, precipitation and complement fixation. For several decades, antibodies with different biological activities were considered various types molecules, until the unitary theory of Hans Zinser triumphed, according to which the same antibody can cause a variety of biological effects.

Ehrlich's theory of antigen-antibody interaction was based on the principles of structural organic chemistry of those days. Ehrlich not only believed that the specificity of an antibody depends on chemical composition and configuration of the molecule, but considered the interaction of antigen with antibody an irreversible reaction based on the formation of strong chemical bonds a certain type, later called covalent. According to Svante Arrhenius and Thorvald Madsen, the toxin-antitoxin interaction is highly reversible and resembles the neutralization of a weak acid by a weak alkali. This idea was further developed in the book “Immunochemistry” written by Arrhenius in 1907, which gave the name to the new branch of immunology. Corresponding to Ehrlich, these researchers argued that the antigen-antibody interaction is strictly stoichiometric and obeys the law of mass action. However, it was soon discovered that the ratio between antigen and antibodies that participate in the reaction can vary greatly, and finally, in the late twenties and early thirties, Marak and Heidelberger put forward the position that antigen and antibodies are multivalent and can therefore form a “lattice” "containing antigen and antibodies in different proportions.

Ehrlich believed that antibodies are macromolecules whose specificity for antigen and complement depends on the presence of certain stereochemical configurations that are complementary to similar structures of the antigen, which ensures a specific interaction between them. In his opinion, antibodies are a natural component of the body that plays the role of a specific receptor on the surface membrane of cells, where they normally perform the same physiological functions, as hypothetical receptors for nutrients or as receptors for medicines, the existence of which Ehrlich argued in his later theories of chemotherapy. One of Ehrlich's postulates was that the antigen specifically selects the corresponding antibody receptors, which then detach from the surface of the cells. This leads to condenser overproduction of receptors, which accumulate in the blood in the form of circulating antibodies. The brilliant theory proposed by Ehrlich had a deep and lasting influence and - especially in Germany - determined the development of ideas in the most different areas medicine. However, in the following decades, two events occurred in immunology that cast doubt on Ehrlich's theory. The first of these was a stream of studies showing that antibodies could be produced against huge amount a variety of completely harmless natural substances. In addition, in the twenties, data appeared from F. Obermayer and E. P. Pick, then significantly developed by Karl Landsteiner, according to which antibodies can be formed against almost any artificial chemical compound, if it is attached as a hapten to a carrier protein. After this, it began to seem incredible that the body could produce specific antibodies against such a huge number of foreign and even artificially created structures.

General theory of immunity

Significant contributions to the development of general immunology were made experimentally - theoretical research M.F. Burnet (1972) - the author of the clonal selection theory of antibody formation. This theory contributed to the study immunocompetent cells, their role in the specific recognition of antigens, the production of antibodies, the emergence of immunological tolerance, allergies.

Despite some progress in the study of specific and nonspecific factors and mechanisms of immunity, many aspects of it are still far from being revealed. It is not known why for some infections

(measles, smallpox, mumps, tularemia, etc.) the body is capable of forming intense and long-lasting immunity, but in relation to other infections, the immunity acquired by the body is short-lived, and is the same in

antigenically, the type of microbe can cause recurrent diseases over relatively short periods of time. The reasons for the low efficiency are also unknown immune factors and in relation to bacterial carriage, as well as chronic and latent infections, for example, the herpes simplex virus, which for a long time, and sometimes for life, can persist in the body and cause periodic exacerbations of infection, while other diseases end in sterile immunity. It has not been established why, in some cases, factors and mechanisms of immunity are able to eliminate infectious process and free the body from pathogenic agents, and in other cases, for many years, a state of a kind of equilibrium is established between the microbe and the body, periodically disrupted in one direction or the other (tuberculosis).

Apparently, there is no single mechanism of immunity and liberation of the body from microbes that is universal for all infections. Features of pathogenesis various infections are also reflected in the characteristics of the mechanisms that provide immunity, however, there are general principles, characterizing the method of protection against microbes and other foreign antigenic substances.

This provides a basis for building general theory immunity. The identification of two aspects of immunity - cellular and humoral - is justified by methodological and pedagogical considerations. However, none of these approaches provides sufficient grounds for creating a theory of immunity that would comprehensively reflect the essence of the observed phenomena. Both cellular and humoral factors, artificially isolated, characterize only certain aspects of the phenomenon, but not the entire process as a whole. In the construction of a modern theory of immunity, general physiological factors and mechanisms should also find a place: increased temperature, secretory-excretory and enzymatic functions, neurohormonal influences, metabolic activity, etc. Molecular, cellular and general physiological reactions that provide protection of the body from microbes and other foreign antigenic substances must be presented as a single, interconnected, evolutionarily developed and genetically determined system. Hence, it is natural that the genetic determination of the immune response to a foreign antigen, as well as newly acquired factors and mechanisms, should be taken into account when constructing a modern theory of immunity.

Immune reactions not only perform a special function of protection against microbes and their metabolic products, but also have another, more diverse physiological function. Immune reactions also take part in liberating the body from various non-microbial antigenic substances that penetrate through the respiratory and digestive tract, through damaged skin, as well as artificially administered for medical purposes (blood serum, drugs). To all these substrates, which are genetically different from the recipient’s antigens, the body responds with a complex of specific and nonspecific cellular, humoral and general physiological reactions that contribute to their destruction, rejection and elimination.

The importance of immune reactions has also been proven in preventing the occurrence of malignant tumors viral etiology.

A hypothesis has been put forward (M.F. Burnet 1962; R.V. Petrov 1976) that the body’s immune system carries out the function of overseeing the genetic constancy of the population somatic cells. Specific and nonspecific defense reactions play an important role in the preservation of life on earth.

However, the perfection of immune reactions, like all others, is relative, and under certain conditions they can also cause harm. For example, the body responds to the repeated intake of large doses of foreign protein with a violent and rapid reaction, which can end fatal. Relative imperfection can also characterize such a powerful protective reaction as inflammation, which, if localized in the vital important body sometimes leads to large and irreparable tissue destruction.

The function of individual protective factors can not only be weakened, but also changed. If normally immune reactions are aimed at destroying foreign agents - bacteria, toxins, viruses, etc., then in pathology these reactions begin to act against one’s own normal, unchanged cells and tissues.

Thus, immune reactions, protective in nature, can, under certain conditions, be the cause and pathological conditions: allergies, autoimmune processes and etc.

A protective reaction or immunity is the body's response to external danger and irritants. Many factors in the human body contribute to its defense against various pathogens. What is innate immunity, how does the body’s defense occur and what is its mechanism?

Innate and acquired immunity

The very concept of immunity is associated with the evolutionarily acquired ability of the body to prevent foreign agents from entering it. The mechanism for combating them is different, since the types and forms of immunity differ in their diversity and characteristics. According to its origin and formation, the protective mechanism can be:

• congenital (nonspecific, natural, hereditary) - protective factors in the human body that were formed evolutionarily and help fight foreign agents from the very beginning of life; This type of protection also determines the species-specific immunity of humans to diseases that are characteristic of animals and plants;
• acquired - protective factors that are formed during life, can be natural and artificial. Natural protection is formed after exposure, as a result of which the body is able to acquire antibodies to this dangerous agent. Artificial protection involves the introduction of ready-made antibodies (passive) or a weakened form of the virus (active) into the body.

Properties of innate immunity

A vital property of innate immunity is the constant presence of natural antibodies in the body, which provide the primary response to invasion pathogenic organisms. Important property The natural response is the compliment system, which is a complex of proteins in the blood that provide recognition and primary defense against foreign agents. This system performs following functions:

• opsonization is the process of attaching elements of the complex to a damaged cell;
• chemotaxis - a set of signals through a chemical reaction that attracts other immune agents;
• membranotropic damage complex - complement proteins that destroy the protective membrane of opsonized agents.

The key property of the natural response is primary protection, as a result of which the body can receive information about foreign cells that are new to it, as a result of which an already acquired response is created, which, in the event of further encounters with similar pathogens, will be ready for a full fight, without the involvement of other protective factors (inflammation, phagocytosis, etc.) .

Formation of innate immunity

Every person has nonspecific protection; it is genetically fixed and can be inherited from parents. A specific feature of humans is that they are not susceptible to a number of diseases characteristic of other species. Plays an important role in the formation of innate immunity. intrauterine development And breast-feeding after birth. The mother passes on important antibodies to her child, which lay the foundation for his first defenses. Violation of the formation of natural defenses can lead to an immunodeficiency state due to:

• exposure to radiation;
• chemical agents;
• pathogens during fetal development.

Factors of innate immunity

What is innate immunity and what is its mechanism of action? A set of general factors of innate immunity are designed to create a certain line of defense for the body against foreign agents. This line consists of several protective barriers that the body builds on the way pathogenic microorganisms:

1. The skin epithelium and mucous membranes are the primary barriers that have colonization resistance. Due to the penetration of the pathogen, an inflammatory reaction develops.
2. The lymph nodes– an important defense system that fights the pathogen before it enters the circulatory system.
3. Blood – when an infection enters the blood, a systemic inflammatory response develops, which involves the use of special blood cells. If the microbes do not die in the blood, the infection spreads to the internal organs.

Innate immune cells

Depending on the defense mechanisms, there is a humoral and cellular response. The combination of humoral and cellular factors creates a unified defense system. Humoral defense is the body’s response in the liquid environment, the extracellular space. Humoral factors of innate immunity are divided into:

• specific - immunoglobulins that are produced by B-lymphocytes;
• nonspecific - gland secretions, blood serum, lysozyme, i.e. liquids with antibacterial properties. TO humoral factors include the compliment system.

Phagocytosis is the process of uptake of foreign agents and occurs through cellular activity. The cells that participate in the body's response are divided into:

• T-lymphocytes are long-lived cells that are divided into lymphocytes with different functions (natural killers, regulators, etc.);
• B lymphocytes – produce antibodies;
• neutrophils - contain antibiotic proteins, have chemotaxis receptors, and therefore migrate to the site of inflammation;
• eosinophils – participate in phagocytosis and are responsible for neutralizing helminths;
• basophils - responsible for an allergic reaction in response to irritants;
• monocytes are special cells that turn into different types macrophages (bone tissue, lungs, liver, etc.), have many functions, incl. phagocytosis, activation of compliment, regulation of the inflammation process.

Stimulators of innate immune cells

Latest Research WHO shows that in almost half of the world's population, important immune cells - natural killer cells - are in short supply. Because of this, people are more often susceptible to infectious, oncological diseases. However, there are special substances that stimulate the activity of killer cells, these include:

• immunomodulators;
• adaptogens (general strengthening substances);
• transfer factor proteins (TP).

TB is most effective; stimulators of innate immune cells of this type were found in colostrum and egg yolk. These stimulants are widely used in medicine; they have been isolated from natural sources, therefore transfer factor proteins are now freely available in the form medical supplies. Their mechanism of action is aimed at restoring damage in the DNA system, establishing immune processes of the human species.

Video: innate immunity

MECHANISMS OF INNATE IMMUNITY

Innate immunity is the earliest protective mechanism both in evolutionary terms (it exists in almost all multicellular organisms) and in terms of response time, developing in the first hours and days after the penetration of foreign material into the internal environment, i.e. long before the adaptive immune response develops. A significant portion of pathogens are inactivated by the innate mechanisms of immunity, without bringing the process to the development of an immune response with the participation of lymphocytes. And only if the mechanisms of innate immunity cannot cope with pathogens penetrating the body, lymphocytes are included in the “game”. At the same time, the adaptive immune response is impossible without the involvement of innate immune mechanisms. In addition, innate immunity plays a major role in the removal of apoptotic and necrotic cells and the reconstruction of damaged organs. In the mechanisms of the body's innate defense, the most important role is played by primary receptors for pathogens, the complement system, phagocytosis, endogenous antibiotic peptides and protection factors against viruses - interferons. The functions of innate immunity are schematically presented in Fig. 3-1.

RECEPTORS FOR “ALIEN” RECOGNITION

Microorganisms are present on the surface repeating molecular carbohydrate and lipid structures, which in the vast majority of cases are absent on the cells of the host body. Special receptors that recognize this “pattern” on the surface of the pathogen - PRR (Pattern Recognition Receptors–PPP receptor) - allow innate immune cells to detect microbial cells. Depending on the location, soluble and membrane forms of PRR are distinguished.

Circulating (soluble) receptors for pathogens - serum proteins synthesized by the liver: lipopolysaccharide binding protein (LBP - Lipopolysaccharide Binding Protein), complement system component C1q and acute phase proteins MBL and C-reactive protein(SRB). They directly bind microbial products in body fluids and provide the possibility of their absorption by phagocytes, i.e. are opsonins. In addition, some of them activate the complement system.

Rice. 3-1. Functions of innate immunity. Legend: PAMP (PathogenAssociated Molecular Patterns)- molecular structures of microorganisms, HSP (Heat Shock Proteins)- proteins heat shock, TLR (Toll-Like Receptors), NLR (NOD-Like Receptors), RLR (RIG-Like Receptors)- cellular receptors

- SRB, binding phosphorylcholine to the cell walls of a number of bacteria and unicellular fungi, opsonizes them and activates the complement system along the classical pathway.

- MBL belongs to the collectin family. Having an affinity for mannose residues exposed on the surface of many microbial cells, MBL triggers the lectin pathway of complement activation.

- Lung surfactant proteins- SP-A And SP-D belong to the same molecular family of collectins as MBL. They are likely to be important in the opsonization (binding of antibodies to the cell wall of a microorganism) of the pulmonary pathogen - a unicellular fungus Pneumocystis carinii.

Membrane receptors. These receptors are located on both the outer and inner membrane structures of cells.

- TLR(Toll-Like Receptor- Toll-like receptor; those. similar to the Drosophila Toll receptor). Some of them directly bind pathogen products (mannose receptors of macrophages, TLRs of dendritic and other cells), others work in conjunction with other receptors: for example, the CD14 molecule on macrophages binds bacterial lipopolysaccharide (LPS) complexes with LBP, and TLR-4 interacts with CD14 and transmits the corresponding signal into the cell. A total of 13 have been described in mammals various options TLR (humans have only 10 so far).

Cytoplasmic receptors:

- NOD receptors(NOD1 and NOD2) are located in the cytosol and consist of three domains: the N-terminal CARD domain, the central NOD domain (NOD - Nucleotide Oligomerization Domain- nucleotide oligomerization domain) and the C-terminal LRR domain. The difference between these receptors is the number of CARD domains. The NOD1 and NOD2 receptors recognize muramyl peptides - substances formed after the enzymatic hydrolysis of peptidoglycan, which is part of cell wall all bacteria. NOD1 recognizes mesodiaminopimelic acid-terminated muramyl peptides (meso-DAPs), which are produced only from peptidoglycan of Gram-negative bacteria. NOD2 recognizes muramyl dipeptides (muramyl dipeptide and glycosylated muramyl dipeptide) with terminal D-isoglutamine or D-glutamic acid, resulting from peptidoglycan hydrolysis of both Gram-positive and Gram-negative bacteria. In addition, NOD2 has an affinity for L-lysine-terminated muramyl peptides, which are found only in Gram-positive bacteria.

- RIG-similarreceptors(RLR, RIG-Like Receptors): RIG-I (Retinoic acid-Inducible Gene I), MDA5 (Melanoma Differentiation-associated Antigen 5) and LGP2 (Laboratory of Genetics and Physiology 2).

All three receptors encoded by these genes have similar chemical structure and are localized in the cytosol. The RIG-I and MDA5 receptors recognize viral RNA. The role of the LGP2 protein is still unclear; perhaps it acts as a helicase, binding to double-stranded viral RNA, modifies it, which facilitates subsequent recognition using RIG-I. RIG-I recognizes single-stranded RNA with 5-triphosphate, as well as relatively short (<2000 пар оснований) двуспиральные РНК. MDA5 различает длинные (>2000 base pairs) double-stranded RNA. There are no such structures in the cytoplasm of a eukaryotic cell. The contribution of RIG-I and MDA5 to the recognition of specific viruses depends on whether these microorganisms produce the appropriate forms of RNA.

CONDUCTING SIGNALS FROM TOLL-LIKE RECEPTORS

All TLRs use the same circuitry to transmit the activation signal to the nucleus (Figure 3-2). After binding to a ligand, the receptor attracts one or more adapters (MyD88, TIRAP, TRAM, TRIF), which ensure signal transmission from the receptor to the serine-threonine kinase cascade. The latter cause activation of NF-kB transcription factors (Nuclear Factor of k-chain B-lymphocytes), AP-1 (Activator Protein 1), IRF3, IRF5 and IRF7 (Interferon Regulatory Factor), which translocate into the nucleus and induce the expression of target genes.

All adapters contain a TIR domain and bind to the TIR domains of TOLL-like receptors (Toll/Interleukin-1 Receptor, as well as the receptor for IL-1) through homophilic interaction. All known TOLL-like receptors, with the exception of TLR3, transmit signals through the MyD88 adapter (MyD88-dependent pathway). The binding of MyD88 to TLR1/2/6 and TLR4 occurs through the additional adapter TIRAP, which is not required in the case of TLR5, TLR7 and TLR9. The MyD88 adapter is not involved in signal transmission from TLR3; TRIF (MyD88-independent pathway) is used instead. TLR4 uses both MyD88-dependent and MyD88-independent signal transduction pathways. However, the binding of TLR4 to TRIF occurs through the additional adapter TRAM.

Rice. 3-2. Signaling pathways from Toll-like receptors (TLRs). TLR3, TLR7, TLR9 indicated in the figure are intracellular endosomal receptors; TLR4 and TLR5 are monomeric receptors embedded in the cytoplasmic membrane. Transmembrane dimers: TLR2 with TLR1 or TLR2 with TLR6. The type of ligand recognized by dimers depends on their composition

MyD88-dependent pathway. The MyD88 adapter consists of an N-terminal DD domain (Death Domain- death domain) and the C-terminal TIR domain associated with the receptor via homophilic TIR-TIR interaction. MyD88 recruits IRAK-4 kinases (Interleukin-1 Receptor-Associated Kinase-4) and IRAK-1 through interaction with their analogous DD domains. This is accompanied by their sequential phosphorylation and activation. IRAK-4 and IRAK-1 then dissociate from the receptor and bind to the adapter TRAF6, which in turn recruits the TAK1 kinase and ubiquitin ligase complex (not shown in Figure 3-2), resulting in TAK1 activation. TAK1 activates two groups of targets:

IκB kinase (IKK), consisting of the subunits IKKα, IKKβ and IKKγ. As a result, the transcription factor NF-kB is released from the IκB protein that inhibits it and is translocated into the cell nucleus;

A cascade of mitogen-activated protein kinases (MAP kinases) that promotes the activation of AP-1 group transcription factors. The composition of AP-1 varies and depends on the type of activating signal. Its main forms are c-Jun homodimers or c-Jun and c-Fos heterodimers.

The result of activation of both cascades is the induction of the expression of antimicrobial factors and inflammatory mediators, including tumor necrosis factor alpha TNFa (TNFa), which, acting on cells in an autocrine manner, induces the expression of additional genes. In addition, AP-1 initiates the transcription of genes responsible for proliferation, differentiation and regulation of apoptosis.

MyD88-independent pathway. Signal transmission occurs through the TRIF or TRIF:TRAM adapter and leads to the activation of TBK1 kinase, which in turn activates the transcription factor IRF3. The latter induces the expression of type I interferons, which, like TNF-α in the MyDSS-dependent pathway, affect cells autocrinely and activate the expression of additional genes (interferon response genes). Activation of various signaling pathways upon TLR stimulation likely directs the innate immune system to fight a particular type of infection.

Comparative characteristics of innate and adaptive mechanisms of resistance are given in Table. 3-1.

There are subpopulations of lymphocytes with properties “intermediate” between those of non-clonotypic innate immune mechanisms and clonotypic lymphocytes with a wide variety of antigen receptors. They do not proliferate after antigen binding (i.e., clonal expansion does not occur), but the production of effector molecules is immediately induced in them. The response is not very specific and occurs faster than the “true lymphocytic” one; immune memory is not formed. These lymphocytes include:

Intraepithelial γδT lymphocytes with rearranged genes encoding TCRs of limited diversity bind ligands such as heat shock proteins, atypical nucleotides, phospholipids, MHC-IB;

B1 lymphocytes of the abdominal and pleural cavities have rearranged genes encoding BCRs of limited diversity that exhibit broad cross-reactivity with bacterial antigens.

NATURAL KILLERS

A special subpopulation of lymphocytes is natural killer cells (NK cells, natural killer cells). They differentiate from a common lymphoid progenitor cell and in vitro capable of spontaneously, i.e. without prior immunization, kill some tumor cells, as well as virus-infected cells. NK cells are large granular lymphocytes that do not express lineage markers of T and B cells (CD3, CD19). In the circulating blood, normal killer cells make up about 15% of all mononuclear cells, and in tissues they are localized in the liver (the majority), the red pulp of the spleen, and mucous membranes (especially the reproductive organs).

Most NK cells contain azurophilic granules in the cytoplasm, where the cytotoxic proteins perforin, granzymes and granulysin are deposited.

The main functions of NK cells are the recognition and elimination of cells infected with microorganisms, altered as a result of malignant growth, or opsonized by IgG antibodies, as well as the synthesis of cytokines IFN, TNFa, GM-CSF, IL-8, IL-5. In vitro When cultured with IL-2, NK cells acquire a high level of cytolytic activity towards a wide range of targets, turning into so-called LAK cells.

General characteristics of NK cells are presented in Fig. 3-3. The main markers of NK cells are CD56 and CD16 (FcγRIII) molecules. CD16 is the receptor for the Fc portion of IgG. NK cells have receptors for IL-15, the growth factor of NK cells, as well as IL-21, a cytokine that enhances their activation and cytolytic activity. Adhesion molecules play an important role, ensuring contact with other cells and the intercellular matrix: VLA-5 promotes adhesion to fibronectin; CD11a/CD18 and CD11b/CD18 ensure attachment to endothelial molecules ICAM-1 and ICAM-2, respectively; VLA-4 - to the endothelial molecule VCAM-I; CD31, a homophilic interaction molecule, is responsible for diapedesis (exit through vascular wall into the surrounding tissue) NK cells through the epithelium; CD2, the sheep red blood cell receptor, is an adhesion molecule that

Rice. 3-3. General characteristics of NK cells. IL15R and IL21R are receptors for IL-15 and IL-21, respectively

interacts with LFA-3 (CD58) and initiates the interaction of NK cells with other lymphocytes. In addition to CD2, on NK cells person Some other T-lymphocyte markers are also detected, in particular CD7 and the CD8a homodimer, but not CD3 and TCR, which distinguishes them from NKT lymphocytes.

In terms of their effector functions, NK cells are close to T lymphocytes: they exhibit cytotoxic activity against target cells using the same perforin-granzyme mechanism as CTLs (see Fig. 1-4 and Fig. 6-4), and produce cytokines - IFNγ, TNF, GM-CSF, IL-5, IL-8.

The difference between natural killer cells and T lymphocytes is that they lack a TCR and recognize the antigen-

MHC in a different (not entirely clear) way. NK cells do not form immune memory cells.

On NK cells person there are receptors belonging to the KIR family (Killer-cell Immunoglobulin-like Receptors), capable of binding MHC-I molecules of their own cells. However, these receptors do not activate, but rather inhibit, the killer function of normal killer cells. In addition, NK cells have immunoreceptors such as FcyR and express the CD8 molecule, which has an affinity for

At the DNA level, KIR genes are not rearranged, but at the level of the primary transcript, alternative splicing occurs, which provides a certain diversity of variants of these receptors in each individual NK cell. Each normal killer cell expresses more than one KIR variant.

H.G. Ljunggren And K. Karre in 1990 they formulated a hypothesis "missing self"(“lack of self”), according to which NK cells recognize and kill cells of their body with reduced or impaired expression of MHC-I molecules. Since subnormal expression of MHC-I occurs in cells during pathological processes, e.g. viral infection, tumor degeneration, NK cells are able to kill virus-infected or degenerated cells of their own body. Hypothesis "missing self" shown schematically in Fig. 3-4.

COMPLEMENT SYSTEM

Complement is a system of serum proteins and several cell membrane proteins that perform 3 important functions: opsonization of microorganisms for their further phagocytosis, initiation of vascular inflammatory reactions and perforation of membranes of bacterial and other cells. Complement components(Table 3-2, 3-3) are designated by the letters of the Latin alphabet C, B and D with the addition of an Arabic numeral (component number) and additional lowercase letters. The components of the classical pathway are designated by the Latin letter “C” and Arabic numerals (C1, C2 ... C9); for complement subcomponents and cleavage products, lowercase Latin letters are added to the corresponding designation (C1q, C3b, etc.). Activated components are marked with a line above the letter, inactivated components with the letter “i” (for example, iC3b).

Rice. 3-4. Hypothesis "missing self" (lack of one’s own). The figure shows three types of interaction between NK cells and targets. There are two types of recognition receptors on NK cells: activating and inhibitory. Inhibitory receptors distinguish MHC-I molecules and inhibit the signal from activating receptors, which, in turn, detect either MHC-I molecules (but with lower affinity than inhibitory receptors) or MHC-like molecules: a - the target cell does not express activation ligands, and lysis does not occur; b - the target cell expresses activation ligands, but does not express MHC-I. Such a cell undergoes lysis; c - target cells contain both MHC-I molecules and activation ligands. The outcome of the interaction depends on the balance of signals coming from activating and inhibitory NK cell receptors

Complement activation(Fig. 3-5). Normally, when the internal environment of the body is “sterile” and pathological decay of its own tissues does not occur, the level of activity of the complement system is low. When microbial products appear in the internal environment, the complement system is activated. It can occur through three pathways: alternative, classical and lectin.

- Alternative activation path. It is initiated directly by the surface molecules of microbial cells [factors of the alternative pathway are designated by letters: P (properdin), B and D].

Rice. 3-5. Activation of the complement system and formation of the membrane attack complex. For explanations, see the text and also the table. 3-2, 3-3. Activated components, according to international agreement, are underlined

◊ Of all the proteins of the complement system, C3 is the most abundant in blood serum - its normal concentration is 1.2 mg/ml. In this case, there is always a small but significant level of spontaneous cleavage of C3 with the formation of C3a and C3b. Component C3b is opsonin, i.e. it is capable of covalently binding both to the surface molecules of microorganisms and to receptors on phagocytes. In addition, “settled” on the cell surface, C3b binds factor B. This, in turn, becomes a substrate for serum serine protease - factor D, which splits it into fragments Ba and Bb. C3b and Bb form an active complex on the surface of the microorganism, stabilized by properdin (factor P).

◊ The C3b/Bb complex serves as a C3 convertase and significantly increases the level of C3 cleavage compared to spontaneous ones. In addition, after binding to C3, it cleaves C5 into fragments C5a and C5b. Small fragments C5a (the strongest) and C3a are complement anaphylatoxins, i.e. mediators of the inflammatory response. They create conditions for the migration of phagocytes to the site of inflammation, cause degranulation of mast cells, and contraction of smooth muscles. C5a also causes increased expression on CR1 and CR3 phagocytes.

◊ With C5b, the formation of a “membrane attack complex” begins, causing perforation of the membrane of microorganism cells and their lysis. First, the C5b/C6/C7 complex is formed and inserted into the cell membrane. One of the subunits of the C8 component, C8b, joins the complex and catalyzes the polymerization of 10-16 C9 molecules. This polymer forms a non-collapsing pore in the membrane with a diameter of about 10 nm. As a result, the cells become unable to maintain osmotic balance and lyse.

- Classical and lectin pathways are similar to each other and differ from the alternative mode of activation of C3. The main C3 convertase of the classical and lectin pathways is the C4b/C2a complex, in which C2a has protease activity, and C4b covalently binds to the surface of microbial cells. It is noteworthy that the C2 protein is homologous to factor B, even their genes are located nearby in the MHC-III locus.

◊ When activated via the lectin pathway, one of the acute phase proteins - MBL - interacts with mannose on the surface of microbial cells, and MBL-associated serine protease (MASP - Mannose-binding protein-Associated Serine Protease) catalyzes the activation cleavage of C4 and C2.

◊ The serine protease of the classical pathway is C1s, one of the subunits of the C1qr 2 s 2 complex. It is activated when at least 2 C1q subunits bind to the antigen-antibody complex. Thus, the classical pathway of complement activation links innate and adaptive immunity.

Complement component receptors. There are 5 types of receptors for complement components (CR - Complement Receptor) on various cells of the body.

CR1 is expressed on macrophages, neutrophils and erythrocytes. It binds C3b and C4b and, in the presence of other stimuli for phagocytosis (binding of antigen-antibody complexes through FcyR or when exposed to IFNu, a product of activated T-lymphocytes), has a permissive effect on phagocytes. CR1 of erythrocytes, through C4b and C3b, binds soluble immune complexes and delivers them to macrophages of the spleen and liver, thereby ensuring blood clearance of immune complexes. When this mechanism is disrupted, immune complexes precipitate - primarily in the basement membranes of the vessels of the glomeruli of the kidneys (CR1 is also present on the podocytes of the glomeruli of the kidneys), leading to the development of glomerulonephritis.

CR2 of B lymphocytes binds the degradation products of C3 - C3d and iC3b. This increases the susceptibility of the B lymphocyte to its antigen by 10,000-100,000 times. The same membrane molecule - CR2 - is used as its receptor by the Epstein-Barr virus, the causative agent of infectious mononucleosis.

CR3 and CR4 also bind iC3b, which, like the active form of C3b, serves as an opsonin. If CR3 is already bound to soluble polysaccharides such as beta-glucans, binding of iC3b to CR3 alone is sufficient to stimulate phagocytosis.

C5aR consists of seven domains that penetrate the cell membrane. This structure is characteristic of receptors coupled to G proteins (proteins capable of binding guanine nucleotides, including GTP).

Protecting your own cells. The body's own cells are protected from the destructive effects of active complement thanks to the so-called regulatory proteins of the complement system.

C1 -inhibitor(C1inh) disrupts the bond of C1q to C1r2s2, thereby limiting the time during which C1s catalyzes the activation cleavage of C4 and C2. In addition, C1inh limits the spontaneous activation of C1 in the blood plasma. At genetic defect dinh develops hereditary angioedema. Its pathogenesis consists of chronically increased spontaneous activation of the complement system and excessive accumulation of anaphylactics (C3a and C5a), causing edema. The disease is treated with replacement therapy with the drug dinh.

- C4 -binding protein- C4BP (C4-Binding Protein) binds C4b, preventing the interaction of C4b and C2a.

- DAF(Decay-Accelerating Factor- degradation accelerating factor, CD55) inhibits convertases of the classical and alternative pathways of complement activation, blocking the formation of the membrane attack complex.

- Factor H(soluble) displaces factor B from the complex with C3b.

- Factor I(serum protease) cleaves C3b into C3dg and iC3b, and C4b into C4c and C4d.

- Membrane cofactor protein MCP(Membrane Cofactor Protein, CD46) binds C3b and C4b, making them available to factor I.

- Protectin(CD59). Binds to C5b678 and prevents subsequent binding and polymerization of C9, thereby blocking the formation of the membrane attack complex. With a hereditary defect in protectin or DAF, paroxysmal nocturnal hemoglobinuria develops. In such patients, episodic attacks of intravascular lysis of their own red blood cells by activated complement occur and hemoglobin is excreted by the kidneys.

PHAGOCYTOSIS

Phagocytosis- a special process of absorption by a cell of large macromolecular complexes or corpuscular structures. "Professional" phagocytes in mammals there are two types of differentiated cells - neutrophils and macrophages, which mature in bone marrow from HSCs and have a common intermediate progenitor cell. The term “phagocytosis” itself belongs to I.I. Mechnikov, who described the cells involved in phagocytosis (neutrophils and macrophages) and the main stages of the phagocytic process: chemotaxis, absorption, digestion.

Neutrophils make up a significant part of peripheral blood leukocytes - 60-70%, or 2.5-7.5x10 9 cells in 1 liter of blood. Neutrophils are formed in the bone marrow, being the main product of myeloid hematopoiesis. They leave the bone marrow at the penultimate stage of development - the rod form, or at the last stage - the segmented form. A mature neutrophil circulates for 8-10 hours and enters the tissue. The total lifespan of a neutrophil is

2-3 days. Normally, neutrophils do not leave the vessels in peripheral tissues, but they are the first to migrate (i.e., undergo extravasation) to the site of inflammation due to the rapid expression of adhesion molecules - VLA-4 (ligand on the endothelium - VCAM-1) and integrin CD11b/CD18 (ligand on endothelium - ICAM-1). Exclusive markers CD66a and CD66d (carcinoembryonic antigens) were identified on their outer membrane. Figure 3-6 shows the participation of neutrophils in phagocytosis (migration, engulfment, degranulation, intracellular killing, degradation, exocytosis and apoptosis) and the main processes occurring in these cells upon activation (by chemokines, cytokines and microbial substances, in particular PAMPs) - degranulation , the formation of reactive oxygen species and the synthesis of cytokines and chemokines. Apoptosis of neurophils and their phagocytosis by macrophages can be considered an important component of the inflammatory process, since their timely removal prevents the destructive effect of their enzymes and various molecules on surrounding cells and tissues.

Rice. 3-6. The main processes occurring in neutrophils (NF) during their activation and phagocytosis

Monocytes and macrophages. Monocytes are an “intermediate form”; in the blood they constitute 5-10% of total number leukocytes. Their purpose is to become resident macrophages in tissues (Fig. 3-7). Macrophages are localized in certain areas of lymphoid tissue: medullary cords of lymph nodes, red and white pulp of the spleen. Monocyte-derived cells are present in almost all non-lymphoid organs: Kupffer cells in the liver, microglia nervous system, alveolar macrophages, Langerhans cells of the skin, osteoclasts, macrophages of the mucous membranes and serous cavities, interstitial tissue of the heart, pancreas, mesangial cells of the kidneys (not shown in the figure). Macrophages help maintain homeostasis by clearing the body of senescent and apoptotic cells and repairing tissue after infection and injury. Macrophages

Rice. 3-7. Heterogeneity of cells derived from monocytes. Tissue macrophages (TMCs) and dendritic cells (DCs) are derived from peripheral blood monocytes (MNs).

mucous membranes play a leading role in protecting the body. To implement this function, they have a set of recognition receptors, oxygen-dependent and oxygen-independent mechanisms for killing microorganisms. Macrophages of the alveolar and intestinal mucosa play a significant role in protecting the body from infection. The former “work” in a relatively opsonin-poor environment, so they express a large number of pattern recognition receptors, including scavenger receptors, mannose receptors, β-glucan-specific receptors, Dectin-1, etc. During a microbial infection, a large number of inflammatory monocytes additionally migrate to the site of microbial penetration , capable of differentiating into different cell lineages depending on the cytokine environment.

Introduction

The development of immunology occurred unevenly, and practical achievements were significantly ahead of theoretical ones.

For a long time, immunity was considered as protection only from infectious agents, and immunology was a branch of infectious pathology. Major discoveries, made in the second half of the twentieth century, made it possible to expand the scope of “old classical immunology,” which was considered only in terms of immunity to infectious diseases.

These include: the discovery of immunological tolerance, the major histocompatibility complex and its functions, deciphering the molecular genetic mechanisms of transplantation immunity and a wide range of antigen recognition receptors of B- and T-lymphocytes and immunoglobulins, obtaining monoclonal antibodies, the creation of clonal selection theory, etc. It was found that the function of the immune system is to protect against any foreign genetic information, which can be represented not only by infectious agents, but also by mutationally changed own cells, as well as products of foreign genes.

This function is aimed at maintaining phenotypic homeostasis during the individual life of the organism. The successes achieved in studying the mechanisms of the lymphoid apparatus of adaptive immunity have relegated the study of innate immunity factors to the background. It was only at the end of the twentieth century that receptors for innate immune cells were discovered, explaining how they recognize foreign objects and develop an immune response.

This mechanism is basic and is constantly in an active state, and if necessary, it activates the lymphoid system of adaptive, more specific immunity.

The purpose of this work was to familiarize ourselves with new literature sources on the factors and mechanisms of innate immunity in order to get an idea of ​​its role and significance in the overall immune response.

Factors of innate immunity

The term “immunity” comes from the Latin word “ummunitas” which means exemption from any duties. This term entered medicine in the second half of the 20th century - initial period active development of vaccination methods to protect people from infectious diseases.

Immunity is a way of protecting the body from all antigens - foreign substances both exogenous and endogenous nature: the biological meaning is to ensure the genetic integrity of individuals, species during their individual life.

Protection from a foreign antigen [AG] entering the body from outside is manifested by certain reactions that are either relatively “nonspecific” in nature in relation to the antigen that caused them, or are strictly specific. “Nonspecific” protective mechanisms are phylogenetically earlier and can be considered as precursors of specific reactions. This is confirmed by the fact that there are also transitional forms.

Immunity is divided into innate and acquired. By innate immunity we mean a system of pre-existing protective factors of the body, as hereditarily determined. If there is a need to protect the body, for example when it gets into infectious agent, first of all, the factors of innate immunity enter the battle.

These factors begin to be synthesized in the first hours. Innate immunity also has relative specificity in recognizing “foreign”, the ability to organize inflammation, and the ability to “include” adaptive immune factors in the immune response.

What factors and systems are included in the “arsenal” of innate immunity?

These are, first of all, mechanical barriers and physiological factors that prevent the penetration of infectious agents into the body. These include intact skin, various secretions that cover epithelial cells and prevent contact between a variety of pathogens and the body. Factors of natural resistance include saliva, tears, urine, sputum and other body fluids that help eliminate microbes. This is where epithelial cells and villi are exfoliated from the surface of the skin. epithelial cells respiratory tract .

Natural factors of resistance include physiological functions such as sneezing, vomiting, diarrhea, which also contribute to the elimination of pathogenic agents from the body. This should also include physiological factors such as body temperature, oxygen concentration, and hormonal balance. This last factor is of great importance for the immune response. For example, increasing the production of corticosteroids suppresses inflammatory processes and reduces the body's resistance to infection.

Further, we can distinguish chemical and biochemical reactions, suppressing infection in the body. Factors of “nonspecific” protection with such an effect include waste products of the sebaceous glands containing antimicrobial factors in the form of fatty acids; the enzyme lysozyme, which is found in various secretions of the body and has the ability to destroy gram-positive bacteria; low acidity some physiological secrets that prevent the colonization of the body by various microorganisms.

immunity cell innate plasma

Factors of innate immunity

Humoral Cellular

Bactericidal substances; Microphages (neutrophils);

properdin; lysozyme; macrophages (monocytes);

complement system; dendritic cells;

cationic proteins; SRB; normal killers.

low density peptides;

cytokines; interleukins.

Fig.1.1. Factors of innate immunity: humoral and cellular.