Specific humoral factors. Humoral factors of nonspecific resistance

1. « Complement"- a complex of protein molecules in the blood that destroy cells or mark them for destruction (from lat. Complementum-supplement). Different fractions (particles) of complement circulate in the blood, denoted by the symbols C1, C2, C3 ... C9, etc. Being in a dissociated state, they are inert complement precursor proteins. The assembly of complement fractions into a single whole occurs when pathogenic microbes are introduced into the body. Once formed, the complement looks like a funnel and is able to lyse (destroy) bacteria or mark them for destruction by phagocytes.

In healthy people, the complement level varies slightly, but in sick people it can rise or fall sharply.

2. Cytokines- small peptide information molecules interleukins and interferons. They regulate intercellular and intersystem interactions, determine cell survival, stimulation or suppression of their growth, differentiation, functional activity and apoptosis (natural cell death). They ensure the coordination of the action of the immune, endocrine and nervous systems under normal conditions and in pathology.

The cytokine is released on the surface of the cell (in which it was) and interact with the receptor next to another cell. Thus, a signal is transmitted to trigger further reactions.

a) Interleukins(INL or IL) - a group of cytokines synthesized mainly by leukocytes (for this reason, the ending "-leukin" was chosen). Also produced by monocytes and macrophages. There are different classes of interleukins from 1 to 11, etc.

b) Interferons (INF) These are low molecular weight proteins containing a small amount of carbohydrates (from English interfere - I prevent reproduction). There are 3 serological groups α, β and γ. α-IFN is a family of 20 polypeptides produced by leukocytes, β-IFN is a glycoprotein produced by fibroblasts. γ - IFN is produced by T-lymphocytes. Differing in structure, they have the same mechanism of action. Under the influence of the infectious principle, they are secreted by many cells at the site of the entrance gate of infection, the concentration of INF increases many times over in a matter of hours. Its protective effect against viruses is reduced to the inhibition of RNA or DNA replication. Type I INF associated with healthy cells protects them from the penetration of viruses.

3. Opsonins These are acute phase proteins. Enhance phagocytic activity, settle on phagocytes and facilitate their binding to a/g coated with immunoglobulin (IgG and IgA) or complement .

Immunogenesis

Antibody formation is called immunogenesis and depends on the dose, frequency and method of administration of a / g.

Cells that provide an immune response are called immunocompetent, originate from hematopoietic stem cell that are produced in the red bone marrow. Leukocytes, platelets and erythrocytes are also formed there, as well as the precursors of T and B - lymphocytes.

Along with the above cells, the precursors of T- and B-lymphocytes are cells of the immune system. For maturation, T - lymphocytes are sent to the thymus.

B - lymphocytes initially mature in the red bone marrow, and complete maturation in the lymphatic vessels and nodes. B - lymphocytes comes from the word "bursa" - a bag. In the bursa of Fabricius, birds develop cells similar to human B-lymphocytes. In humans, the organ that produces B-lymphocytes has not been found. T and B - lymphocytes are covered with villi (receptors).

Storage of T - and B - lymphocytes is carried out in the spleen. This whole process occurs without the introduction of antigen. Renewal of all blood cells and lymph occurs constantly.

The process of formation of Jg can be continued if the penetration of a/g into the body occurs.

In response to the introduction of a/g, macrophages react. They determine the foreignness of a / g, then phagocytize and if the macrophages fail, the formed histocompatibility complex (MHC) (a \ g + macrophage), this complex releases the substance interleukin I(INL I) order, this substance acts on T-lymphocytes, which differentiate into 3 types of Tk (killers), Th (T-helpers), Ts (T-suppressors).

Th allocate INL II order, which affects the transformation of B-lymphocytes and the activation of Tk. After such activation, B - lymphocytes are transformed into plasma cells, from which Jg (M, D, G, A, E,) is ultimately obtained.

The process of producing Jg occurs if a person falls ill for the first time.

If re-infection with the same species of microbe occurs, the Jg production pattern is reduced. In this case, the remaining JgG on B-lymphocytes immediately combine with a/g and transform into plasma cells. T - the system remains, not involved. Simultaneously with the activation of B-lymphocytes during re-infection, a powerful complement assembly system is activated.

Tk have antiviral protection. Responsible for cellular immunity: they destroy tumor cells, transplanted cells, mutated cells of their own body, participate in HRT. Unlike NK cells, killer T cells specifically recognize a certain antigen and kill only cells with that antigen.

NK-cells. natural killers, natural killers(English) Natural killer cells (NK cells)) are large granular lymphocytes with cytotoxicity against tumor cells and cells infected with viruses. NK cells are considered as a separate class of lymphocytes. NK are one of the most important components of cellular innate immunity, they carry out nonspecific protection. They do not have T-cell receptors, CD3, or surface immunoglobulins.

Ts - T-suppressors (English regulatory T cells, suppressor T cells, Treg) or regulatory T- lymphocytes. Their main function is to control the strength and duration of the immune response through the regulation of the function of T-helpers and T k. At the end of the infectious process, it is necessary to stop the transformation of B-lymphocytes into plasma cells, Ts suppress (inactivate) the production of B-lymphocytes.

Specific and non-specific immune defense factors always act simultaneously.

Diagram of the production of immunoglobulins

Antibodies

Antibodies (a \ t) are specific blood proteins, another name for immunoglobulins, formed in response to the introduction of a / g.

A / t associated with globulins, and changed under the action, a \ g are called immunoglobulins (J g) they are divided into 5 classes: JgA, JgG, JgM, JgE, JgD. All of them are necessary for the response of the immune system. JgG has 4 subclasses JgG 1-4. .This immunoglobulin makes up 75% of all immunoglobulins. Its molecule is the smallest, therefore it penetrates the mother's placenta, and provides natural passive immunity to the fetus. In primary disease, JgG is formed and accumulated. At the beginning of the disease, its concentration is low, with the development of the infectious process and the amount of JgG increases, with recovery, the concentration decreases and remains in the body in a small amount after the disease, providing immunological memory.

JgM first appear during infection and immunization. They have a large molecular weight (the largest molecule). It is formed during household repeated infection.

JgA found in the secrets of the mucous membranes of the respiratory tract and digestive tract, as well as in colostrum, saliva. Participate in antiviral protection.

JgE responsible for allergic reactions, participate in the development of local immunity.

JgD found in small amounts in human serum, has not been studied enough.

Jg structure

The simplest JgE, JgD, JgA

Active centers bind to a / g, the valency of a / t depends on the number of centers. Jg + G are divalent, JgM is 5-valent.

Humoral factors of non-specific defense of the body include normal (natural) antibodies, lysozyme, properdin, beta-lysines (lysines), complement, interferon, virus inhibitors in blood serum and a number of other substances that are constantly present in the body.

Antibodies (natural). In the blood of animals and humans that have never been ill and have not been immunized before, substances are found that react with many antigens, but in low titers, not exceeding dilutions of 1:10 ... 1:40. These substances were called normal or natural antibodies. They are believed to result from natural immunization with various microorganisms.

L and o c and m. Lysosomal enzyme is present in tears, saliva, nasal mucus, secretion of mucous membranes, blood serum and extracts of organs and tissues, in milk; a lot of lysozyme in the protein of chicken eggs. Lysozyme is resistant to heat (inactivated by boiling), has the ability to lyse live and killed mostly gram-positive microorganisms.

The method for determining lysozyme is based on the ability of serum to act on a culture of micrococcus lysodecticus grown on oblique agar. Suspension of the daily culture is prepared according to the optical standard (10 IU) in physiological saline. The test serum is diluted sequentially with saline 10, 20, 40, 80 times, etc. An equal volume of microbial suspension is added to all test tubes. The tubes are shaken and placed in a thermostat for 3 hours at 37°C. Accounting for the reaction produced by the degree of clarification of the serum. The titer of lysozyme is the last dilution in which complete lysis of the microbial suspension occurs.

S ecretor n y and mm u n o g lo b l and N A. Constantly present in the contents of the secrets of the mucous membranes, mammary and salivary glands, in the intestinal tract; It has strong antimicrobial and antiviral properties.

Properdin (from Latin pro and perdere - prepare for destruction). Described in 1954 in the form of a polymer as a factor of nonspecific protection and cytolysin. It is present in normal blood serum in an amount up to 25 mcg / ml. It is a whey protein (beta-globulin) with a molecular weight

220,000. Properdin takes part in the destruction of microbial cells, the neutralization of viruses. Properdine acts as part of the properdine system: properdine complement and divalent magnesium ions. Native properdin plays a significant role in non-specific complement activation (alternative activation pathway).

L and z and n s. Serum proteins that have the ability to lyse (dissolve) some bacteria and red blood cells. The blood serum of many animals contains beta-lysins, which cause lysis of the culture of hay bacillus, as well as many pathogenic microbes.

Laktoferrin. Non-heminic glycoprotein with iron-binding activity. Binds two atoms of ferric iron, competing with microbes, as a result of which the growth of microbes is suppressed. It is synthesized by polymorphonuclear leukocytes and grape cells of the glandular epithelium. It is a specific component of the secretion of glands - salivary, lacrimal, milk, respiratory, digestive and genitourinary tracts. Lactoferrin is a factor of local immunity that protects epithelial integument from microbes.

Complement. A multicomponent system of proteins in blood serum and other body fluids that play an important role in maintaining immune homeostasis. It was first described by Buchner in 1889 under the name "alexin" - a thermolabile factor, in the presence of which microbes are lysed. The term "complement" was introduced by Erlich in 1895. Complement is not very stable. It was noted that specific antibodies in the presence of fresh blood serum can cause hemolysis of erythrocytes or lysis of a bacterial cell, but if the serum is heated at 56 ° C for 30 minutes before the reaction, then lysis will not occur. It turned out that hemolysis (lysis) occurs after calculation of the presence of complement in fresh serum.The greatest amount of complement is contained in the serum of the guinea pig.

The complement system consists of at least nine different serum proteins, designated C1 to C9. C1, in turn, has three subunits - Clq, Clr, Cls. The activated form of complement is indicated by a dash above (c).

There are two ways of activation (self-assembly) of the complement system - classical and alternative, differing in trigger mechanisms.

In the classical activation pathway, complement component C1 binds to immune complexes (antigen + antibody), which include successively subcomponents (Clq, Clr, Cls), C4, C2, and C3. The C4, C2, and C3 complex ensures the fixation of the activated C5 component of the complement on the cell membrane, and then they are switched on through a series of C6 and C7 reactions, which contribute to the fixation of C8 and C9. As a result, damage to the cell wall or lysis of the bacterial cell occurs.

In an alternative way of complement activation, the activators themselves are the viruses, bacteria, or exotoxins themselves. The alternative activation pathway does not involve components C1, C4 and C2. Activation begins from the C3 stage, which includes a group of proteins: P (properdin), B (proactivator), proactivator convertase C3, and inhibitors j and H. In the reaction, properdin stabilizes C3 and C5 convertases, therefore this activation pathway is also called the properdin system. The reaction begins with the addition of factor B to C3, as a result of a series of successive reactions, P (properdin) is inserted into the complex (C3 convertase), which acts as an enzyme on C3 and C5, "and the complement activation cascade begins with C6, C7, C8 and C9, resulting in damage to the cell wall or cell lysis.

Thus, the complement system serves as an effective defense mechanism of the body, which is activated as a result of immune responses or by direct contact with microbes or toxins. Let us note some biological functions of activated complement components: they participate in the regulation of the process of switching immunological reactions from cellular to humoral and vice versa; Cell-bound C4 promotes immune attachment; C3 and C4 enhance phagocytosis; C1 and C4, binding to the surface of the virus, block the receptors responsible for the introduction of the virus into the cell; C3a and C5a are identical to anaphylactoxins, they act on neutrophil granulocytes, the latter secrete lysosomal enzymes that destroy foreign antigens, provide directed migration of macrophages, cause smooth muscle contraction, and increase inflammation.

It has been established that macrophages synthesize C1, C2, C3, C4 and C5; hepatocytes - C3, Co, C8; liver parenchyma cells - C3, C5 and C9.

In terferon. Separated in 1957. English virologists A. Isaacs and I. Linderman. Interferon was originally considered as an antiviral protection factor. Later it turned out that this is a group of protein substances, the function of which is to ensure the genetic homeostasis of the cell. Bacteria, bacterial toxins, mitogens, etc. act as inducers of interferon formation, in addition to viruses. agents; (3-interferon, or fibroblastic, which is produced by fibroblasts treated with viruses or other agents. Both of these interferons are classified as type I. Immune interferon, or y-interferon, is produced by lymphocytes and macrophages activated by non-viral inducers.

Interferon takes part in the regulation of various mechanisms of the immune response: it enhances the cytotoxic effect of sensitized lymphocytes and K-cells, has anti-proliferative and antitumor effects, etc. Interferon has specific tissue specificity, i.e., it is more active in the biological system in which it is produced, protects cells from viral infection only if it acts on them before contact with the virus.

The process of interaction of interferon with sensitive cells includes several stages: adsorption of interferon on cell receptors; induction of an antiviral state; development of viral resistance (filling of interferon-induced RNA and proteins); pronounced resistance to viral infection. Therefore, interferon does not directly interact with the virus, but prevents the penetration of the virus and inhibits the synthesis of viral proteins on cellular ribosomes during the replication of viral nucleic acids. Interferon also has radiation-protective properties.

I n g i b i to r y. Nonspecific antiviral substances of a protein nature are present in normal native blood serum, secretions of the epithelium of the mucous membranes of the respiratory and digestive tracts, in extracts of organs and tissues. They have the ability to suppress the activity of viruses in the blood and fluids outside the sensitive cell. Inhibitors are divided into thermolabile (they lose their activity when the blood serum is heated to 60 ... 62 ° C for 1 hour) and thermostable (withstand heating up to 100 ° C). Inhibitors have universal virus-neutralizing and anti-hemagglutinating activity against many viruses.

Inhibitors of tissues, secretions and excretions of animals have been found to be active against many viruses: for example, secretory inhibitors of the respiratory tract have antihemagglutinating and virus-neutralizing activity.

Bactericidal activity of blood serum (BAS). Fresh human and animal blood serum has pronounced bacteriostatic properties against a number of pathogens of infectious diseases. The main components that inhibit the growth and development of microorganisms are normal antibodies, lysozyme, properdin, complement, monokines, leukins and other substances. Therefore, BAS is an integrated expression of the antimicrobial properties of humoral nonspecific defense factors. BAS depends on the state of health of animals, the conditions of their maintenance and feeding: with poor maintenance and feeding, serum activity is significantly reduced.

Throughout the path of evolution, a person comes into contact with a huge number of pathogenic agents that threaten him. In order to resist them, two types of defensive reactions have formed: 1) natural or non-specific resistance, 2) specific protective factors or immunity (from lat.

Immunitas - free from anything).

Nonspecific resistance is due to various factors. The most important of these are: 1) physiological barriers, 2) cellular factors, 3) inflammation, 4) humoral factors.

Physiological barriers. Can be divided into external and internal barriers.

external barriers. Intact skin is impervious to the vast majority of infectious agents. Constant desquamation of the upper layers of the epithelium, the secrets of the sebaceous and sweat glands contribute to the removal of microorganisms from the surface of the skin. When the integrity of the skin is violated, for example, with burns, infection becomes the main problem. In addition to the fact that the skin serves as a mechanical barrier to bacteria, it contains a number of bactericidal substances (lactic and fatty acids, lysozyme, enzymes secreted by the sweat and sebaceous glands). Therefore, microorganisms that are not part of the normal microflora of the skin quickly disappear from its surface.

Mucous membranes are also a mechanical barrier to bacteria, but they are more permeable. Many pathogenic microorganisms can penetrate even through intact mucous membranes.

The mucus secreted by the walls of internal organs acts as a protective barrier that prevents bacteria from "attaching" to epithelial cells. Microbes and other foreign particles captured by the mucus are removed mechanically - due to the movement of the cilia of the epithelium, with coughing and sneezing.

Other mechanical factors contributing to the protection of the surface of the epithelium include the washing out effect of tears, saliva, and urine. Many fluids secreted by the body contain bactericidal components (hydrochloric acid in gastric juice, lactoperoxidase in breast milk, lysozyme in lacrimal fluid, saliva, nasal mucus, etc.).

The protective functions of the skin and mucous membranes are not limited to non-specific mechanisms. On the surface of the mucous membranes, in the secrets of the skin, mammary and other glands, there are secretory immunoglobulins that have bactericidal properties and activate local phagocytic cells. The skin and mucous membranes are actively involved in antigen-specific reactions of acquired immunity. They are considered independent components of the immune system.

One of the most important physiological barriers is the normal microflora of the human body, which inhibits the growth and reproduction of many potentially pathogenic microorganisms.

internal barriers. Internal barriers include the system of lymphatic vessels and lymph nodes. Microorganisms and other foreign particles that have penetrated the tissues are phagocytized on the spot or delivered by phagocytes to the lymph nodes or other lymphatic formations, where an inflammatory process develops aimed at destroying the pathogen. If the local reaction is insufficient, the process extends to the following regional lymphoid formations, which represent a new barrier to the penetration of the pathogen.

There are functional histohematic barriers that prevent the penetration of pathogens from the blood into the brain, reproductive system, and eyes.

The membrane of each cell also serves as a barrier to the penetration of foreign particles and molecules into it.

Cellular factors. Among the cellular factors of nonspecific protection, the most important is phagocytosis - the absorption and digestion of foreign particles, incl. and microorganisms. Phagocytosis is carried out by two populations of cells:

I. microphages (polymorphonuclear neutrophils, basophils, eosinophils), 2. macrophages (blood monocytes, free and fixed macrophages of the spleen, lymph nodes, serous cavities, liver Kupffer cells, histiocytes).

In relation to microorganisms, phagocytosis can be complete when bacterial cells are completely digested by the phagocyte, or incomplete, which is typical for diseases such as meningitis, gonorrhea, tuberculosis, candidiasis, etc. In this case, pathogens remain viable inside phagocytes for a long time, and sometimes they breed in them.

In the body, there is a population of lymphocyte-like cells that have natural cytotoxicity with respect to “target” cells. They are called natural killers (NK).

Morphologically, NK are large granular lymphocytes, they do not have phagocytic activity. Among human blood lymphocytes, the content of EC is 2 - 12%.

Inflammation. When the microorganism is introduced into the tissue, an inflammatory process occurs. The resulting damage to tissue cells leads to the release of histamine, which increases the permeability of the vascular wall. The migration of macrophages increases, edema occurs. In the inflammatory focus, the temperature rises, acidosis develops. All this creates unfavorable conditions for bacteria and viruses.

Humoral protective factors. As the name itself indicates, humoral protective factors are found in body fluids (blood serum, breast milk, tears, saliva). These include: complement, lysozyme, beta-lysins, acute phase proteins, interferons, etc.

Complement is a complex complex of blood serum proteins (9 fractions), which, like the proteins of the blood coagulation system, form cascade systems of interaction.

The complement system has several biological functions: it enhances phagocytosis, causes bacterial lysis, and so on.

Lysozyme (muramidase) is an enzyme that cleaves glycosidic bonds in the peptidoglycan molecule, which is part of the bacterial cell wall. The content of peptidoglycan in gram-positive bacteria is higher than in gram-negative ones, therefore, lysozyme is more effective against gram-positive bacteria. Lysozyme is found in humans in lacrimal fluid, saliva, sputum, nasal mucus, etc.

Beta-lysins are found in the blood serum of humans and many animal species, and their origin is associated with platelets. They have a detrimental effect primarily on gram-positive bacteria, in particular on anthracoid.

Acute phase proteins are the common name for some plasma proteins. Their content increases dramatically in response to infection or tissue damage. These proteins include: C-reactive protein, serum amyloid A, serum amyloid P, alpha1-antitrypsin, alpha2-macroglobulin, fibrinogen, etc.

Another group of acute phase proteins are proteins that bind iron - haptoglobin, hemopexin, transferrin - and thereby prevent the reproduction of microorganisms that need this element.

During infection, microbial waste products (such as endotoxins) stimulate the production of interleukin-1, which is an endogenous pyrogen. In addition, interleukin-1 acts on the liver, increasing the secretion of C-reactive protein to such an extent that its concentration in blood plasma can increase 1000 times. An important property of C-reactive protein is the ability to bind with the participation of calcium with some microorganisms, which activates the complement system and promotes phagocytosis.

Interferons (IF) are low molecular weight proteins produced by cells in response to the penetration of viruses. Then their immunoregulatory properties were revealed. There are three types of IF: alpha, beta, belonging to the first class, and interferon gamma, belonging to the second class.

Alpha-interferon, produced by leukocytes, has antiviral, antitumor and antiproliferative effects. Beta-IF, secreted by fibroblasts, has a predominantly antitumor and antiviral effect. Gamma-IF, a product of T-helpers and CD8+ T-lymphocytes, is called lymphocytic or immune. It has an immunomodulatory and weak antiviral effect.

The antiviral effect of IF is due to the ability to activate the synthesis of inhibitors and enzymes in cells that block the replication of viral DNA and RNA, which leads to suppression of virus reproduction. The mechanism of antiproliferative and antitumor action is similar. Gamma-IF is a polyfunctional immunomodulatory lymphokine that affects the growth, differentiation and activity of cells of different types. Interferons inhibit the reproduction of viruses. It has now been established that interferons also have antibacterial activity.

Thus, the humoral factors of nonspecific protection are quite diverse. In the body, they act in combination, providing a bactericidal and inhibitory effect on various microbes and viruses.

All of these protective factors are non-specific, since there is no specific response to the penetration of pathogenic microorganisms.

Specific or immune protective factors are a complex set of reactions that maintain the constancy of the internal environment of the body.

According to modern ideas, immunity can be defined "as a way to protect the body from living bodies and substances that bear signs of genetically alien information" (RV Petrov).

The concept of "living bodies and substances bearing signs of genetically alien information" or antigens may include proteins, polysaccharides, their complexes with lipids, and high-polymer preparations of nucleic acids. All living things consist of these substances, therefore, the properties of antigens are possessed by animal cells, elements of tissues and organs, biological fluids (blood, blood serum), microorganisms (bacteria, protozoa, fungi, viruses), exo- and endotoxins of bacteria, helminths, cancer cells and etc.

The immunological function is performed by a specialized system of cells of tissues and organs. This is the same independent system as, for example, the digestive or cardiovascular system. The immune system is a collection of all lymphoid organs and cells of the body.

The immune system consists of central and peripheral organs. The central organs include the thymus (thymus or thymus gland), the pouch of Fabricius in birds, the bone marrow, and possibly Peyer's patches.

The peripheral lymphoid organs include lymph nodes, spleen, appendix, tonsils, and blood.

The central figure of the immune system is the lymphocyte, it is also called the immunocompetent cell.

In humans, the immune system consists of two parts that cooperate with each other: the T-system and the B-system. The T-system carries out a cell-type immune response with the accumulation of sensitized lymphocytes. The B-system is responsible for the production of antibodies, i.e. for a humorous response. In mammals and humans, no organ has been found that would be a functional analogue of the bag of Fabricius in birds.

It is assumed that this role is performed by the aggregate of Peyer's patches of the small intestine. If the assumption that Peyer's patches are analogous to the bag of Fabricius is not confirmed, then these lymphoid formations will have to be attributed to peripheral lymphoid organs.

It is possible that in mammals there is no analogue of the Fabricius bag at all, and this role is performed by the bone marrow, which supplies stem cells for all hematopoietic lineages. Stem cells leave the bone marrow into the bloodstream, enter the thymus and other lymphoid organs, where they differentiate.

Cells of the immune system (immunocytes) can be divided into three groups:

1) Immunocompetent cells capable of a specific response to the action of foreign antigens. This property is possessed exclusively by lymphocytes, which initially possess receptors for any antigen.

2) Antigen-presenting cells (APCs) are capable of differentiating self and foreign antigens and presenting the latter to immunocompetent cells.

3) Antigen-nonspecific defense cells that have the ability to distinguish their own antigens from foreign ones (primarily from microorganisms) and destroy foreign antigens using phagocytosis or cytotoxic effects.

1. Immunocompetent cells

Lymphocytes. The precursor of lymphocytes, as well as other cells of the immune system, is the pluripotent stem cell of the bone marrow. During the differentiation of stem cells, two main groups of lymphocytes are formed: T- and B-lymphocytes.

Morphologically, a lymphocyte is a spherical cell with a large nucleus and a narrow layer of basophilic cytoplasm. In the process of differentiation, large, medium and small lymphocytes are formed. The most mature small lymphocytes capable of amoeboid movements predominate in the lymph and peripheral blood. They constantly recirculate in the bloodstream, accumulate in lymphoid tissues, where they participate in immunological reactions.

T- and B-lymphocytes are not differentiated using light microscopy, but are clearly distinguished from each other in surface structures and functional activity. B-lymphocytes carry out a humoral immune response, T-lymphocytes - a cellular one, and also participate in the regulation of both forms of the immune response.

T-lymphocytes mature and differentiate in the thymus. They make up about 80% of all blood lymphocytes, lymph nodes, are found in all tissues of the body.

All T-lymphocytes have surface antigens CD2 and CD3. CD2 adhesion molecules cause the contact of T-lymphocytes with other cells. CD3 molecules are part of the lymphocyte receptors for antigens. There are several hundred of these molecules on the surface of each T-lymphocyte.

T-lymphocytes maturing in the thymus differentiate into two populations, the markers of which are the surface antigens CD4 and CD8.

CD4 make up more than half of all blood lymphocytes, they have the ability to stimulate other cells of the immune system (hence their name - T-helpers - from the English. Help - help).

The immunological functions of CD4+ lymphocytes begin with the presentation of an antigen by antigen-presenting cells (APCs). The receptors of CD4+ cells perceive the antigen only if the cell's own antigen (antigen of the major tissue compatibility complex of the second class) is simultaneously on the surface of the APC. This “double recognition” serves as an additional guarantee against the occurrence of an autoimmune process.

Tx after exposure to the antigen proliferate into two subpopulations: Tx1 and Tx2.

Th1s are mainly involved in cellular immune responses and inflammation. Th2 contribute to the formation of humoral immunity. During the proliferation of Th1 and Th2, some of them turn into immunological memory cells.

CD8+ lymphocytes are the main type of cells with cytotoxic activity. They make up 22 - 24% of all blood lymphocytes; their ratio with CD4+ cells is 1:1.9 – 1:2.4. The antigen-recognizing receptors of CD8+ lymphocytes perceive the antigen from the presenting cell in combination with the MHC class I antigen. MHC antigens of the second class are present only on the APC, and antigens of the first class on almost all cells, CD8+-lymphocytes can interact with any cells of the body. Since the main function of CD8+ cells is cytotoxicity, they play a leading role in antiviral, antitumor, and transplantation immunity.

CD8+-lymphocytes can play the role of suppressor cells, however, recently it has been found that many types of cells can suppress the activity of cells of the immune system, so CD8+-cells are no longer called suppressors.

The cytotoxic effect of a CD8+ lymphocyte begins with the establishment of contact with the “target” cell and the entry of cytolysin proteins (perforins) into the cell membrane. As a result, holes with a diameter of 5–16 nm appear in the membrane of the “target” cell, through which enzymes (granzymes) penetrate. Granzymes and other lymphocyte enzymes inflict a lethal blow on the “target” cell, which leads to cell death due to a sharp rise in the intracellular level of Ca2+, activation of endonucleases, and destruction of cell DNA. The lymphocyte then retains the ability to attack other “target” cells.

Natural killers (NKs) are close to cytotoxic lymphocytes in their origin and functional activity, but they do not enter the thymus and are not subjected to differentiation and selection, do not participate in specific reactions of acquired immunity.

B-lymphocytes make up 10-15% of blood lymphocytes, 20-25% of lymph node cells. They provide the formation of antibodies and are involved in the presentation of the antigen to T-lymphocytes.

The body is protected from antigens by two groups of factors:

1. Factors that provide nonspecific resistance (resistance) of the body to antigens, regardless of their origin.

2. Specific immunity factors that are directed against specific antigens.

Nonspecific resistance factors include:

1. mechanical

2. physical and chemical

3. immunobiological barriers.

1) Mechanical barriers created by the skin and mucous membranes mechanically protect the body from the penetration of antigens (bacteria, viruses, macromolecules) into it. The same role is played by mucus and the ciliated epithelium of the upper respiratory tract (which free the mucous membranes from foreign particles that have fallen on them).

2) Enzymes, hydrochloric (hydrochloric) acid of gastric juice, aldehydes and fatty acids of sweat and sebaceous glands of the skin are the physico-chemical barrier that destroys antigens entering the body. There are few microbes on clean and undamaged skin, because. sweat and sebaceous glands constantly secrete on the surface of the skin substances that have a bactericidal effect (acetic, formic, lactic acid).

The stomach is a barrier to orally penetrating bacteria, viruses, antigens, because. they are inactivated and destroyed under the influence of the acidic contents of the stomach (pH 1.5-2.5) and enzymes. In the intestine, the factors are enzymes, bacteriocins formed by the normal intestinal microflora, as well as trypsin, pancreatin, lipase, amylase, and bile.

3) Immunobiological protection is carried out by phagocytic cells that absorb and digest microparticles with antigenic properties, as well as the complement system, interferon, protective blood proteins.

I. Phagocytosis discovered and studied by I.I. Mechnikov, is one of the main powerful factors that ensure the body's resistance, protection from foreign and foreign substances, including microbes.

To phagocytic cells I.I. Mechnikov classified macrophages and microphages.

There is currently single mononuclear phagocytic system .

It includes:

1. tissue macrophages (alveolar, peritoneal, etc.)

2. Langerhans cells (white process epidermocytes) and Granstein cells (skin epidermocytes)

3. Kupffer cells (stellate reticuloendotheliocytes).

4. epithelial cells.

5. neutrophils and eosinophils of the blood, etc.

The process of phagocytosis has several stages:

1) the approach of the phagocyte to the object (chemotaxis)

2) adsorption of the object on the surface of the phagocyte

3) absorption of the object

4) digestion of the object.

Absorption of a phagocytosed object (microbe, antigens, macromolecules) is carried out by invagination of the cell membrane with the formation of a phagosome containing the object in the cytoplasm. The phagosome then fuses with the cell's lysosome to form the phagolysosome, in which the object is digested with the help of enzymes.

In the event that all stages pass and the process ends with the digestion of microbes, phagocytosis is called completed.

If the absorbed microbes do not die, and sometimes even multiply in phagocytes, then such phagocytosis is called unfinished.

The activity of phagocytes is characterized by:

1. Phagocytic indicators are estimated by the number of bacteria absorbed or digested by one phagocyte per unit of time.

2. Opsonophagocytic index is the ratio of phagocytic indices obtained with serum containing opsonins and control.

II. Humoral protective factors:

1) Platelets - humoral protective factors play an important role in immunity, releasing biologically active substances

(histamine, lysozyme, lysins, Leukins, prostaglandins, etc.), which are involved in the processes of immunity and inflammation.

2) The complement system is a complex complex of blood serum proteins, which is usually in an inactive state and

activated during the formation of the antigen-antibody complex.

Complement functions are diverse, it is an integral part of many immunological reactions aimed at freeing the body from microbes and other foreign cells and antigens.

3) Lysozyme is a proteolytic enzyme that is synthesized by macrophages, neutrophils and other phagocytic cells. The enzyme is found in blood, lymph, tears, milk,

sperm, on the mucous membranes of the urogenital tract, respiratory tract and gastrointestinal tract. Lysozyme destroys the cell wall of bacteria, which leads to their lysis and promotes phagocytosis.

4) Interferon is a protein that is synthesized by cells of the immune system and connective tissue.

There are three types of it:

Interferons are constantly synthesized by cells. Their production increases sharply when the body is infected with viruses, as well as

when exposed to interferon inducers (interferonogens).

Interferon is widely used as a prophylactic and therapeutic agent for viral infections, neoplasms and immunodeficiencies.

5) Protective proteins of blood serum are acute phase proteins, opsonins, properdin, b-lysine, fibronectin.

Acute phase proteins include:

a) C - reactive

b) Properdin is a normal serum globulin that promotes complement activation and thus participates in many immunological reactions.

c) Fibronectin is a universal protein in blood plasma and tissue fluids that synthesizes macrophages and provides antigen opsonization and cell binding to foreign substances.

d) lysine - blood serum proteins that are synthesized by platelets and damage the cytoplasmic membrane of bacteria.

Specific protection directed against a specific antigen is carried out by a complex of special forms of immune system response:

1. antibody formation

2. immune phagocytosis

3. killer function of lymphocytes

4. allergic reactions occurring in the form of immediate hypersensitivity (ITH) and