Basic concepts

IMMUNITY (IMMUNITY) is a general biological phenomenon, the essence of which is long-term self-maintenance within an individual organism of a balance between genetically "one's own" and "not one's own" in an alien environment. IMMUNE SYSTEM (IMMUNE SYSTEM) specializes in the implementation of the mechanisms of this phenomenon. In order to understand the fundamentals of the science of IMMUNOLOGY, it is necessary to study the defense mechanisms aimed at eliminating "not one's own" and the regulatory processes that form the internal homeostasis of "one's own" in the body. Immunity can be innate and adaptive (acquired, specific). Failure of one or more components of the immune system can lead to the development of immunodeficiencies and the loss of the ability to defend against infection. Disorders of regulation in the functioning of this system contribute to the development of autoimmune diseases, allergies and the growth of tumors. The importance of the very existence of the immune system is illustrated by the emergence in the last 20 years of a new disease - AIDS (acquired immunodeficiency syndrome), in which all possible variants of disorders of the immune system are observed.

ANTIGEN (ANTIGEN) is a macromolecule containing foreign or self information, which is the basis for triggering a specific immune response; on the other hand, it should be borne in mind that any antigen often serves as an immunobiological marker for researchers. The total number of different antigens is estimated at 10 18 . A complete antigen molecule consists of an information part (low molecular weight antigenic determinants, epitopes, haptens) and a carrier part (macromolecular protein). The isolated informational part is not immunogenic in itself, i.e. unable to induce an immune response.

ANTIBODY or IMMUNOGLOBULIN is a type of immune system molecule. Antibodies and antigen recognition receptors can bind the corresponding antigens.

LYMPHOCYTES are the main cells of the immune system. Essentially, the immune system is a hierarchical collection of lymphoid cells (1013). Exist T-, B- and NK lymphocytes. T cells differentiate in the thymus and play a key role in all aspects of the specific immune response. B-lymphocytes differentiate in the bone marrow and are the precursors of plasma cells - antibody producers. NK cells (natural killers) are involved in non-specific cytotoxicity against intracellularly located pathogens. Other cells (macrophages, dendritic cells, neutrophils, eosinophils, mast cells, etc.) are also involved in many immune processes, but their participation is rather indirect, i.e. they are attracted by lymphocytes to implement the functions of the immune (lymphoid) system.

strategic function The immune system is the implementation of the genetic program of the individual development of the body from birth to death in a foreign environment.

Tactical features:

1. Protection from "not one's own" (infection, transplant).

2. Elimination of the modified "own" (tumors, damaged, aging cells).

3. Regulation of growth and development of cells and tissues.

The main partners of the immune system are central nervous system, endocrine system and liver, which are most important for ensuring the regulation of homeostasis.

The functional organization of the immune system can be seen in organ, cellular and molecular levels. There are two types of organs of the immune system, central (or primary) and peripheral (or secondary). BONE MARROW(bone marrow) - the central organ in which all cells of the immune system are born and B-lymphocytes mature (B-lymphopoiesis or B-commitment). THYMUS(thymus) - the central organ in which T-lymphocytes differentiate (T-lymphopoiesis or T-commitment) and which is also general coordinating for the entire immune system.

In peripheral organs, lymphocytes encounter antigens and their specific antigen-dependent differentiation occurs. This process is called immune response(immune response), the essence of which is the creation of a whole "army" of specifically reacting lymphocytes and specific antibodies that carry out effector reactions to destroy this particular antigen. There are T-cell and B-cell (humoral) pathways of the immune response.

Peripheral organs include:

q Lymph nodes, lymphatic ducts and spleen;

q Lymphoid tissue associated with mucous membranes, mucosae (Mucous-Associated Lymphoid Tissue - MALT), which is located at five levels. The first two levels - the Eustachian tube (Tube-Associated Lymphoid Tissue - TALT) and the nasopharynx (Nasal-Associated Lymphoid Tissue - NALT) - are represented by various tonsils; the next level is bronchi (Bronchus-Associated Lymphoid Tissue - BALT) and mammary glands(among women); the fourth level - the upper sections of the gastrointestinal tract (Gut-Associated Lymphoid Tissue - GALT) - contain lymphoid tissue of the stomach and Peyer's patches small intestine, the fifth level is the lower sections of the gastrointestinal tract and the genitourinary system - the appendix, the solitary follicles of the large intestine and the lymphoid tissue of the genitourinary system;

q Lymphoid tissue associated with the skin (Skin-Associated Lymphoid Tissue - SALT).

A great contribution to the development of immunology from Edward Jenner to the present day was made by such scientists as L.Pasteur, I.I. Mechnikov, P. Ehrlich, N.F. Gamaleya, F.McFarlane Burnet, N.K. .V.Vasiliev, S.Tonegawa and others.

Cells of the immune system

All cells related to the immune system and attracted by it to provide effector reactions can be functionally divided into four groups:

1. ANTIGEN-PRESENTING CELLS:

macrophages, dendritic cells types 1 and 2, B-lymphocytes;

2. REGULATORY CELLS:

T-inductors, T-helpers types 1, 2 and 3, T-regulators type 1;

3. EFFECTOR CELLS:

plasma cells (differentiating from B-lymphocytes);

cytotoxic T cells with the CD8+ phenotype (or T-killers);

inflammatory effector T cells with a CD4+ phenotype (or T lymphocytes responsible for delayed-type hypersensitivity);

neutrophils, eosinophils, basophils, mast cells, natural killer (NK-cells), macrophages.

4. MEMORY CELLS:

memory T cells with the CD8+ phenotype; memory T cells with the CD4+ phenotype;

long-lived plasma cells; Memory B cells.

CD nomenclature ("Cluster of Differentiation"), based on monoclonal technology, which was developed Nobel laureates(1984) G.J.F. Kohler (Switzerland) and C. Milstein (Argentina/Great Britain), allows identifying cells with respect to their origin, stage of differentiation, functional state, etc. (see Table 1). This technology has undoubtedly proved to be revolutionary in immunological and related fields of research.

MAIN ID CD MARKERS

CELLS OF THE IMMUNE SYSTEM

Lymphocytes are the main cells of the immune system. distinctive features:

1. Permanent "patrol" recycling by blood flow, lymph flow, interstitial spaces and secretions.

2. Ability recognize, i.e. interact with "self" and "non-self" according to the "ligand - receptor" principle.

3. Clonal organization(McF. Burnet) and the ability to form network elements (N.K. Jerne).

4. Ability to continuous rearrangements in your genome at any age in connection with the needs of the formation of a specific response to the pathogen.

5. Skill memorize about the fact of meeting with any antigen and provide in the future an express highly effective response to it.

CLONE(a clone) - is a group of lymphocytes committed to a specific antigen. Before encountering this antigen, each lymphocyte clone is called naive. Apparently in human body Initially, there are tens of millions of clones of T- and B-lymphocytes. After encountering the appropriate antigen and as a result of the immune response, the committed lymphocyte becomes primed.

1.3. Molecules of the immune system

To carry out the necessary functions, the cells of the immune system have a complex molecular organization of their receptors and are capable of producing a number of molecules.

1. ANTIGEN PRESENTING, ANTIGEN RECOGNIZING AND ANTIGEN BINDING MOLECULES. The set of these molecules is unique for each organism, for each lymphocyte clone, and for each specific immune response. These include:

Antigen-recognizing immunoglobulin receptors of B-cells (B cellular receptors - BCR);

free immunoglobulins: IgM, IgG, IgA, IgE, IgD;

antigen-recognizing T-cell receptors (T cellular receptors - TCR);

antigen-presenting molecules: leukocyte antigens of the major histocompatibility complex (Human leukocyte antigens - HLA I and II) and CD1 molecules (a, b, c, d, e).

2. ADHESIVE MOLECULES mediate interactions between cells and ligands in direct contact:

a superfamily of immunoglobulin-like molecules;

integrins;

selectins;

mucins (mucin-like vascular addressins);

· a superfamily of receptors for tumor necrosis factors and nerve growth factor - TNF/NGF (or molecules that mediate apoptosis);

Link family (components of the extracellular matrix).

3. IMMUNOCYTOKINES are hormones of the immune system, acting more often with para- and autocrine, less often with endocrine effects:

interleukins (Interleukins - ILs);

colony-stimulating factors (CSFs);

interferons (Interferons - IFNs);

tumor necrosis factors (TNFs);

chemokines (Chemokines), etc.

4. ASSEMBLY GROUP OF VARIOUS IMMUNE INFLAMMATOR MEDIATORS includes complement proteins, "acute phase", prostanoids and leukotrienes, proteolytic enzymes, etc.

Immunoglobulins M, G, A, E and D are effector molecules of the humoral immune response. The immunoglobulin molecule is a glycoprotein; protein chains include hundreds amino acid sequences; the carbohydrate component is 2-12%. The IgG molecule (see Fig. 1) consists of two identical lungs(light-L) and two identical heavy (heavy - H) chains (chains). Light chains are of two types: (light - λ and χ, heavy - five (α, γ, δ, ε, μ) Light and heavy chains contain repeating homologous sequences and form peculiar coils (domains). There are constant (constant) (CL, CH1, CH2 and CH3) and variable domains (VL and vh). The hypervariable regions of the variable domains form antigen-binding sites or active sites. The immunoglobulin molecule can also be divided into Fc fragment (a fragment crystalline), which is responsible for non-specific effector activity , and 2 Fab-fragment (fragment antigen-binding), that contain antigen-binding sites . The chemical nature of antibodies was studied in detail by the Nobel laureates (1972) G.M.Edelman (USA) and R.R.Porter (Great Britain).

Each B-lymphocyte expresses B cell antigen recognition receptor(an antigen-recognizing receptor - BCR), which consists of monomeric immunoglobulins IgM and IgD, has clonal heterogeneity and is associated with CD79a and CD79b molecules necessary for signal transmission into the cell. Along with these molecules, there is also a co-receptor complex (CD19, CD21(CR2), CD81) designed to recognize HLA II.

Each T-lymphocyte expresses T cell antigen recognition receptor(an antigen-recognizing receptor - abTCR), which consists of two chains, a and b, and has one of the co-receptors - CD4 (in T-helpers) or CD8 (in cytotoxic T-lymphocytes). These invariant CD4 and CD8 co-receptors are required for recognition of HLA II or HLA I, respectively. Each TCR chain, like an immunoglobulin molecule, has variable and constant domains, which provides clonal heterogeneity of antigen recognition receptors. Another molecule (CD3) is closely associated with the TCR and serves to conduct the signal into the cell. CD3 consists of 5 invariant proteins (e,g,d,x,h). Another type of antigen recognition receptor, gdTCR, is expressed on a small subset of T cells. These gdT cells, whose role is not yet fully understood, appear to function similarly to NK cells, but they also have some clonal heterogeneity.

Histocompatibility molecules were discovered by Nobel laureates (1980) B.Benacerraf (USA), J.Dausset (France) and G.D.Snell (USA). These molecules play a critical role in many immune processes, including antigenic peptide loading and presentation. HLA molecules are divided into class I (A, B, C, E, F, G) and class II (DR, DP, DQ) depending on their structure and function. The expression of HLA I takes place on almost all cells (with the exception of syncytiotrophoblast), performing the function of mutual information of cells within the body about autologousness; HLA II expression is observed almost exclusively on cells of the immune system: B-lymphocytes, macrophages, endotheliocytes, activated T-cells, etc.

Non-HLA CD1 molecules (a, b, c, d and e), which, by analogy with HLA I, consist of an a-chain and b2-microglobulin, are also involved in the processes of loading antigens, but of a non-protein nature (phospholipids, lipopolysaccharides).

There is an association between the inheritance of certain HLA genes and a high risk of developing certain diseases. For example, more than 90% of patients with ankylosing spondylitis, a severe autoimmune pathology of the spine, have the HLA-B27 gene.

Since HLA determines histocompatibility, it is necessary that the donor and recipient of an organ or tissue transplant have an HLA match. The HLA patient chart is called "full house" ("full house") and includes data on two alleles of each type of molecule (eg, HLA-A, HLA-B, HLA-DR, etc.). HLA sensitization in the past (during blood transfusions, transplants or pregnancy) can lead to acute transplant rejection or thrombocytopenia during blood transfusion, so mandatory testing for the presence of anti-HLA antibodies is necessary. HLA typing can serve as an additional criterion for the diagnosis of diseases such as ankylosing spondylitis, diabetes, celiac disease, hemochromatosis, psoriasis, and narcolepsy, in which a high degree of association with certain HLA haplotypes is known.

Immune responses are a process of interaction of cells of the immune system, which is induced by an antigen and leads to the formation of effector cells and molecules that destroy this antigen. Immune responses are always specific, but not an isolated process that occurs only in the peripheral organs of the immune system. It is usually accompanied by natural immune response like phagocytosis, complement activation, NK cells, etc.

At least three types of cells are involved in the initial stages of the immune response: a macrophage (as well as a dendritic cell), a T- and a B-lymphocyte. In general, all cells involved in this process can be divided, as mentioned above, into antigen-presenting, regulatory, effector, and memory cells. There are four types of immune responses:

1. T-cell response with the formation of inflammatory T-cells;

2. T-cell response with the formation of cytotoxic T-cells;

3. Simple B-cell (humoral) response with IgM synthesis;

4. Extended B-cell (humoral) response

with sequential formation of antibodies of different classes.

T cell responses are regulated T-helpers type 1 and lead to the formation

1) effector CD4+ T-cells of inflammation

2) cytotoxic CD8+ T-lymphocytes, as well as their corresponding memory T-cells.

With a simple humoral response, only IgM is formed without the formation of immune memory. The extensive humoral response is regulated T-helpers type 2 and ends with the formation of plasma cells (producers of antibodies of classes M, G, A and E) and memory B-lymphocytes. Switching to the synthesis of certain isotypes of antibodies is partially controlled by T helper type 1. With the exception of a latent induction period, immune responses last on average about 3 weeks, with a maximum tension on the 1st week.

There are several main stages of immune responses:

· Antigen endocytosis, its processing and loading onto HLA I or II molecules for presentation to lymphocytes.

· Recognition of antigenic peptide/HLA I or II complex and other stimuli.

· Signal transduction and activation of a cellular clone.

Clonal expansion or proliferation.

Maturation of effector and memory cells.

effector activity.

exogenous antigens are presented in complex with HLA II molecules to naive CD4+ T cells ( HLA II mediated pathway). First, these antigens are endocytosed and fragmented by proteolytic enzymes in endosomes (lysosomes). At the same time, HLA II molecules associated with chaperones (calnexin and invariant chain Ii) are synthesized and assembled in the endoplasmic reticulum. The II chain is required to protect the groove of the HLA molecule until the antigenic peptide is loaded here. Then the HLA II/Ii-chain complex is transported through the Golgi apparatus to endosomes, where the Ii-chain is lost, and additional HLA-DM and, probably, HLA-DO molecules begin to play the role of protecting the groove. Finally, the antigenic peptide is loaded into the groove of the HLA II molecule and this complex is expressed on the cell surface.

Endogenous or intracellular antigens of microbial origin loaded onto HLA I molecules ( HLA I mediated pathway) for presentation to naive CD8+ T cells. First, unlike exogenous antigens, such cytoplasmic antigens migrate to the cytosol, where they are cleaved into a large proteolytic complex, the proteasome. Thereafter, the antigenic peptide is transported through a "tunnel" of TAP-1/TAP-2 molecules into the endoplasmic reticulum. At the same time, the HLA I molecule is assembled here, the groove of which (by analogy with the Ii chain in HLA II) is "protected" by chaperones (first calnexin, then calreticulin), and the folding of the entire HLA I molecule is subsequently stabilized by additional molecules (tapazine, etc.). .). After the antigenic peptide is loaded onto the HLA I groove, this complex is transported to the cell surface.

Non-protein antigens, probably loaded onto non-HLA antigen-presenting CD1 molecules.

In general, macrophages and B cells are involved, respectively, in the T-cell or humoral immune response via the HLA II-mediated pathway, and the two types of dendritic cells are capable of cross-presentation. The type 1 dendritic cell processes endogenous antigens along the HLA I pathway to trigger a T cell response, and the type 2 dendritic cell processes exogenous antigens along the HLA II pathway and triggers a B cell response.

Recognition(recognition) proceeds within a few hours. However, with violations of cell migration and intercellular interactions, it can be longer. This may lead to a slowdown in the overall immune response to the pathogen. Clinical manifestations this stage are fever, muscle weakness, loss of appetite and drowsiness. For the most part, they are due to the systemic effects of cytokines, which will be discussed in more detail below.

In order for a specific immune response to a specific antigen to start, it is necessary that the T- and B-lymphocytes of the corresponding clone meet with the antigen-presenting cell. Some bacterial antigens (T-independent antigens) are recognized by BCR B cells and do not require help from T helpers. Most native antigens (so-called T-dependent antigens) are recognized by " full program"naïve CD4+ T helper type 1 and CD8+ T cells (to trigger a T cell response or T-helper pathways 1), as well as naive CD4+ T-helper type 2 (to trigger a humoral response or T-helper pathways 2). Interestingly, priming of CD8+ T cells requires the participation of CD4+ T helpers 1.

During recognition, lymphocytes perceive three types of obligatory signals, one specific and two non-specific:

1. Antigenic peptide/HLA I or II.

2. Cytokines.

3. Costimulatory molecules.

The antigenic peptide loaded onto HLA I or II as a result of processing serves specific signal. This simultaneous "double" recognition of "self" (HLA proteins) and "non-self" (foreign antigen) was discovered by Nobel laureates (1996) P.C. Doherty (Australia, USA) and R.M. Zinkernagel (Switzerland) and turned out to be a fairly universal phenomenon. Secreted cytokines and expressed costimulatory molecules are two essential non-specific signals. Moreover, to ensure reliable physical contact of cells, the interaction of such adhesive molecules as LFA-1, ICAM-1, ICAM-2, ICAM-3 is also necessary.

Cytokines play one of the key roles in the nonspecific regulation of the immune response. T- and B-lymphocytes receive cytokine signals from antigen-presenting cells, NK cells, mast cells etc. The reverse signal from lymphocytes, for example, secreted IFNg, promotes the reexpression of HLA I/II on antigen-presenting cells. Cytokines acting in the early stages of the immune response can be divided into two groups depending on its direction:

1. IL12, IL2, IL18, IFNg, TNFa/b (for type 1 T-helper pathway).

2.IL4(for T-helper path type 2).

However, at the next stages of the immune response (clonal expansion, maturation of effectors, switching the synthesis of antibody isotypes), other cytokines are involved in the process.

Costimulatory molecules also play an important role in the nonspecific regulation of the immune response (see Table. 2.).

Introduction

Immunity is understood as a set of biological phenomena aimed at preserving the internal environment and protecting the body from infectious and other genetically alien agents. There are the following types of infectious immunity:

antibacterial

antitoxic

antiviral

antifungal

antiprotozoal

Infectious immunity can be sterile (no pathogen in the body) or non-sterile (pathogen in the body). Innate immunity is present from birth, it can be specific and individual. Species immunity - immunity of one species of animal or person to microorganisms, disease-causing in other species. It is genetically determined in humans as a biological species. Species immunity is always active. Individual immunity is passive (placental immunity). Nonspecific protective factors are as follows: skin and mucous membranes, lymph nodes, lysozyme and other enzymes of the oral cavity and gastrointestinal tract, normal microflora, inflammation, phagocytic cells, natural killers, complement system, interferons. Phagocytosis.

I. The concept of the immune system

The immune system is the totality of all lymphoid organs and accumulations of lymphoid cells in the body. Lymphoid organs are divided into central ones - thymus, bone marrow, Fabricius' sac (in birds) and its analogue in animals - Peyer's patches; peripheral - spleen, lymph nodes, solitary follicles, blood and others. Its main component is lymphocytes. There are two main classes of lymphocytes: B-lymphocytes and T-lymphocytes. T cells are involved in cellular immunity, regulation of B-cell activity, delayed-type hypersensitivity. The following subpopulations of T-lymphocytes are distinguished: T-helpers (programmed to induce the reproduction and differentiation of other types of cells), suppressor T-cells, T-killers (secrete cytotoxic lymphokines). The main function of B-lymphocytes is that, in response to an antigen, they are able to multiply and differentiate into plasma cells that produce antibodies. B - lymphocytes are divided into two subpopulations: 15 B1 and B2. B-cells are long-lived B-lymphocytes derived from mature B-cells as a result of antigen stimulation with the participation of T-lymphocytes.

The immune response is a chain of successive complex cooperative processes that occur in the immune system in response to the action of an antigen in the body. There are primary and secondary immune responses, each of which consists of two phases: inductive and productive. Further, the immune response is possible in the form of one of three options: cellular, humoral and immunological tolerance. Antigens by origin: natural, artificial and synthetic; by chemical nature: proteins, carbohydrates (dextran), nucleic acids, conjugated antigens, polypeptides, lipids; by genetic relation: autoantigen, isoantigens, alloantigen, xenoantigens. Antibodies are proteins synthesized under the influence of an antigen.

II. Cells of the immune system

Immunocompetent cells are cells that make up the immune system. All of these cells originate from a single ancestral stem cell in the red bone marrow. All cells are divided into 2 types: granulocytes (granular) and agranulocytes (non-granular).

The granulocytes are:

neutrophils

eosinophils

basophils

For agranulocytes:

macrophages

lymphocytes (B, T)

Neutrophil granulocytes or neutrophils, segmented neutrophils, neutrophilic leukocytes- a subspecies of granulocytic leukocytes, called neutrophils because, when stained according to Romanovsky, they are intensely stained with both acidic dye eosin and basic dyes, in contrast to eosinophils stained only with eosin, and from basophils stained only with basic dyes.

Mature neutrophils have a segmented nucleus, that is, they belong to polymorphonuclear leukocytes, or polymorphonuclear cells. They are classical phagocytes: they have adhesiveness, mobility, the ability to chemostaxis, as well as the ability to capture particles (for example, bacteria).

Mature segmented neutrophils are normally the main type of leukocytes circulating in human blood, accounting for 47% to 72% of the total number of blood leukocytes. Another 1-5% are normally young, functionally immature neutrophils, which have a rod-shaped solid nucleus and do not have the nuclear segmentation characteristic of mature neutrophils - the so-called stab neutrophils.

Neutrophils are capable of active amoeboid movement, extravasation (emigration outside the blood vessels), and chemotaxis (preferential movement towards sites of inflammation or tissue damage).

Neutrophils are capable of phagocytosis, and they are microphages, that is, they are able to absorb only relatively small foreign particles or cells. After phagocytosis of foreign particles, neutrophils usually die, releasing a large amount of biologically active substances that damage bacteria and fungi, increase inflammation and chemotaxis of immune cells in the focus. Neutrophils contain a large amount of myeloperoxidase, an enzyme that is able to oxidize the chloride anion to hypochlorite, a strong antibacterial agent. Myeloperoxidase, as a heme-containing protein, has a greenish color, which determines the greenish hue of the neutrophils themselves, the color of pus and some other secretions rich in neutrophils. Dead neutrophils, together with cellular debris from tissues destroyed by inflammation and pyogenic microorganisms that caused inflammation, form a mass known as pus.

An increase in the proportion of neutrophils in the blood is called relative neutrophilia, or relative neutrophilic leukocytosis. An increase in the absolute number of neutrophils in the blood is called absolute neutrophilosis. A decrease in the proportion of neutrophils in the blood is called relative neutropenia. A decrease in the absolute number of neutrophils in the blood is referred to as absolute neutropenia.

Neutrophils play a very important role in protecting the body from bacterial and fungal infections, and a relatively lesser role in protecting against viral infections. In antitumor or anthelmintic protection, neutrophils practically do not play a role.

The neutrophil response (infiltration of the focus of inflammation with neutrophils, an increase in the number of neutrophils in the blood, a shift in the leukocyte formula to the left with an increase in the proportion of "young" forms, indicating an increase in the production of neutrophils by the bone marrow) is the very first response to bacterial and many other infections. Neutrophil response at acute inflammation and infections are always preceded by a more specific lymphocytic. In chronic inflammations and infections, the role of neutrophils is insignificant and the lymphocytic response predominates (infiltration of the focus of inflammation with lymphocytes, absolute or relative lymphocytosis in the blood).

Eosinophilic granulocytes or eosinophils, segmented eosinophils, eosinophilic leukocytes- a subspecies of granulocytic blood leukocytes.

Eosinophils are so named because, when stained according to Romanovsky, they are intensely stained with the acidic dye eosin and do not stain with basic dyes, unlike basophils (stain only with basic dyes) and neutrophils (they absorb both types of dyes). Also, a distinguishing feature of an eosinophil is a bilobed nucleus (in a neutrophil it has 4-5 lobes, and in a basophil it is not segmented).

Eosinophils are capable of active amoeboid movement, extravasation (penetration beyond the walls of blood vessels) and chemotaxis (predominant movement towards the focus of inflammation or tissue damage).

Also, eosinophils are able to absorb and bind histamine and a number of other mediators of allergy and inflammation. They also have the ability to release these substances when needed, similar to basophils. That is, eosinophils are able to play both pro-allergic and protective anti-allergic roles. The percentage of eosinophils in the blood increases in allergic conditions.

Eosinophils are less numerous than neutrophils. Most of the eosinophils do not remain in the blood for long and, getting into the tissues, stay there for a long time.

The normal level for a person is considered to be 120-350 eosinophils per microliter.

Basophilic granulocytes or basophils, segmented basophils, basophilic leukocytes- a subspecies of granulocytic leukocytes. They contain a basophilic S-shaped nucleus, often not visible due to the overlap of the cytoplasm with histamine granules and other allergomediators. Basophils are so named for the fact that, when stained according to Romanovsky, they intensively absorb the main dye and do not stain with acidic eosin, in contrast to eosinophils that stain only with eosin, and from neutrophils that absorb both dyes.

Basophils are very large granulocytes: they are larger than both neutrophils and eosinophils. Basophil granules contain large amounts of histamine, serotonin, leukotrienes, prostaglandins, and other mediators of allergy and inflammation.

Basophils are actively involved in the development of immediate-type allergic reactions (anaphylactic shock reactions). There is a misconception that basophils are precursors of mast cells. Mast cells are very similar to basophils. Both cells are granulated and contain histamine and heparin. Both cells also release histamine when bound to IgE. This similarity has led many to speculate that mast cells are the basophils in tissues. In addition, they share a common precursor in the bone marrow. However, basophils leave the bone marrow already mature, while mast cells circulate in an immature form, only eventually entering the tissues. Thanks to basophils, the poisons of insects or animals are immediately blocked in the tissues and do not spread throughout the body. Basophils also regulate blood clotting with the help of heparin. However, the original statement is still true: basophils are direct relatives and analogues of tissue mast cells, or mast cells. Like tissue mast cells, basophils carry immunoglobulin E on the surface and are capable of degranulation (release of the contents of the granules into the external environment) or autolysis (dissolution, cell lysis) upon contact with an allergen antigen. During degranulation or lysis of the basophil, a large amount of histamine, serotonin, leukotrienes, prostaglandins and other biologically active substances are released. This determines the observed manifestations of allergy and inflammation when exposed to allergens.

Basophils are capable of extravasation (emigration outside the blood vessels), and they can live outside the bloodstream, becoming resident tissue mast cells (mast cells).

Basophils have the ability to chemotaxis and phagocytosis. In addition, apparently, phagocytosis is neither the main nor the natural (carried out under natural physiological conditions) activity for basophils. Their only function is instant degranulation, leading to increased blood flow, increased vascular permeability. an increase in the influx of fluid and other granulocytes. In other words, the main function of basophils is to mobilize the remaining granulocytes to the focus of inflammation.

Monocyte - a large mature single-nuclear leukocyte of the agranulocyte group with a diameter of 18-20 microns with an eccentrically located polymorphic nucleus with a loose chromatin network and azurophilic granularity in the cytoplasm. Like lymphocytes, monocytes have an unsegmented nucleus. Monocyte is the most active phagocyte in peripheral blood. An oval-shaped cell with a large, bean-shaped, chromatin-rich nucleus (which makes it possible to distinguish them from lymphocytes that have a rounded dark nucleus) and a large amount of cytoplasm, in which there are many lysosomes.

In addition to the blood, these cells are always present in large numbers in the lymph nodes, alveolar walls, and sinuses of the liver, spleen, and bone marrow.

Monocytes are in the blood for 2-3 days, then they go into the surrounding tissues, where, having reached maturity, they turn into tissue macrophages - histiocytes. Monocytes are also precursors of Langerhans cells, microglial cells, and other cells capable of processing and presenting antigen.

Monocytes have a pronounced phagocytic function. These are the largest peripheral blood cells, they are macrophages, that is, they can absorb relatively large particles and cells or a large number of small particles and, as a rule, do not die after phagocytization (the death of monocytes is possible if the phagocytosed material has any cytotoxic properties for the monocyte). In this they differ from microphages - neutrophils and eosinophils, capable of absorbing only relatively small particles and, as a rule, dying after phagocytosis.

Monocytes are able to phagocytize microbes in an acidic environment when neutrophils are inactive. By phagocytizing microbes, dead leukocytes, damaged tissue cells, monocytes cleanse the site of inflammation and prepare it for regeneration. These cells form a delimiting rampart around indestructible foreign bodies.

Activated monocytes and tissue macrophages:

participate in the regulation of hematopoiesis (hematopoiesis)

take part in the formation of a specific immune response of the body.

Monocytes, leaving the bloodstream, become macrophages, which, along with neutrophils, are the main "professional phagocytes". Macrophages, however, are much larger and live longer than neutrophils. Macrophage precursor cells, monocytes, after leaving the bone marrow, circulate in the blood for several days, and then migrate to tissues and grow there. At this time, the content of lysosomes and mitochondria increases in them. Near the inflammatory focus, they can multiply by division.

Monocytes are capable, having emigrated to tissues, to turn into resident tissue macrophages. Monocytes are also able, like other macrophages, to process antigens and present antigens to T-lymphocytes for recognition and learning, that is, they are antigen-presenting cells of the immune system.

Macrophages are large cells that actively destroy bacteria. Macrophages in large quantities accumulate in the foci of inflammation. Compared to neutrophils, monocytes are more active against viruses than bacteria, and are not destroyed during the reaction with a foreign antigen, therefore, pus does not form in the foci of inflammation caused by viruses. Also, monocytes accumulate in the foci of chronic inflammation.

Monocytes secrete soluble cytokines that affect the functioning of other parts of the immune system. Cytokines secreted by monocytes are called monokines.

Monocytes synthesize the individual components of the complement system. They recognize an antigen and convert it into an immunogenic form (antigen presentation).

Monocytes produce both factors that enhance blood coagulation (thromboxanes, thromboplastins) and factors that stimulate fibrinolysis (plasminogen activators). Unlike B and T lymphocytes, macrophages and monocytes are not capable of specific antigen recognition.

T-lymphocytes, or T cells- lymphocytes that develop in mammals in the thymus from precursors - prethymocytes, entering it from the red bone marrow. In the thymus, T-lymphocytes differentiate by acquiring T-cell receptors (TCRs) and various co-receptors (surface markers). They play an important role in the acquired immune response. They provide recognition and destruction of cells carrying foreign antigens, enhance the action of monocytes, NK cells, and also take part in switching immunoglobulin isotypes (at the beginning of the immune response, B cells synthesize IgM, later switch to the production of IgG, IgE, IgA).

Types of T-lymphocytes:

T-cell receptors are the main surface protein complexes of T-lymphocytes responsible for the recognition of processed antigens associated with molecules of the major histocompatibility complex on the surface of antigen-presenting cells. The T cell receptor is associated with another polypeptide membrane complex, CD3. The functions of the CD3 complex include signal transduction into the cell, as well as stabilization of the T-cell receptor on the membrane surface. The T cell receptor can be associated with other surface proteins, TCR receptors. Depending on the coreceptor and the functions performed, two main types of T cells are distinguished.

T-helpers

T-helpers - T-lymphocytes, the main function of which is to enhance the adaptive immune response. They activate T-killers, B-lymphocytes, monocytes, NK-cells by direct contact, as well as humorally, releasing cytokines. The main feature of T-helpers is the presence of the CD4 co-receptor molecule on the cell surface. T-helper cells recognize antigens when their T-cell receptor interacts with an antigen associated with molecules of the major histocompatibility complex of class II.

T-killers

T-helpers and T-killers form a group of effector T-lymphocytes directly responsible for the immune response. At the same time, there is another group of cells, regulatory T-lymphocytes, whose function is to regulate the activity of effector T-lymphocytes. By modulating the strength and duration of the immune response through the regulation of T-effector cell activity, regulatory T-cells maintain tolerance to the body's own antigens and prevent the development of autoimmune diseases. There are several mechanisms of suppression: direct, with direct contact between cells, and distant, carried out at a distance - for example, through soluble cytokines.

γδ T-lymphocytes

γδ T-lymphocytes are a small population of cells with a modified T-cell receptor. Unlike most other T cells, whose receptor is formed by two α and β subunits, the T cell receptor of γδ lymphocytes is formed by γ and δ subunits. These subunits do not interact with peptide antigens presented by MHC complexes. It is assumed that γδ T-lymphocytes are involved in the recognition of lipid antigens.

B-lymphocytes(B cells, from bursa fabricii birds, where they were first discovered) is a functional type of lymphocytes that play an important role in providing humoral immunity. Upon contact with an antigen or stimulation from T cells, some B lymphocytes transform into plasma cells capable of producing antibodies. Other activated B-lymphocytes turn into memory B-cells. In addition to producing antibodies, B cells perform many other functions: they act as antigen-presenting cells and produce cytokines and exosomes.

In human and other mammalian embryos, B-lymphocytes are formed in the liver and bone marrow from stem cells, while in adult mammals, only in the bone marrow. Differentiation of B-lymphocytes takes place in several stages, each of which is characterized by the presence of certain protein markers and the degree of genetic rearrangement of immunoglobulin genes.

There are the following types of mature B-lymphocytes:

Actually B-cells (also called "naive" B-lymphocytes) are non-activated B-lymphocytes that have not been in contact with the antigen. They do not contain Gall's bodies, scattered monoribosomes in the cytoplasm. They are polyspecific and have low affinity for many antigens.

Memory B-cells are activated B-lymphocytes that have again passed into the stage of small lymphocytes as a result of cooperation with T-cells. They are a long-lived clone of B-cells, provide a rapid immune response and produce a large amount of immunoglobulins upon repeated administration of the same antigen. They are called memory cells because they allow the immune system to "remember" the antigen for many years after its action has ceased. Memory B cells provide long-term immunity.

Plasma cells are the last step in the differentiation of antigen-activated B cells. Unlike other B cells, they carry few membrane antibodies and are able to secrete soluble antibodies. They are large cells with an eccentrically located nucleus and a developed synthetic apparatus - a rough endoplasmic reticulum occupies almost the entire cytoplasm, and the Golgi apparatus is also developed. They are short-lived cells (2-3 days) and are quickly eliminated in the absence of the antigen that caused the immune response.

A characteristic feature of B cells is the presence of surface membrane-bound antibodies related to IgM classes and IgD. In combination with other surface molecules, immunoglobulins form an antigen-recognizing receptor complex responsible for antigen recognition. Also on the surface of B-lymphocytes are MHC class II antigens that are important for interaction with T-cells, and on some clones of B-lymphocytes there is a CD5 marker that is common with T-cells. Receptors for complement components C3b (Cr1, CD35) and C3d (Cr2, CD21) play a role in B cell activation. It should be noted that CD19, CD20 and CD22 markers are used to identify B-lymphocytes. Fc receptors have also been found on the surface of B-lymphocytes.

natural killers- large granular lymphocytes with cytotoxicity against tumor cells and cells infected with viruses. Currently, NK cells are considered as a separate class of lymphocytes. NKs perform cytotoxic and cytokine-producing functions. NK is one of the most important components of cellular innate immunity. NKs are formed as a result of the differentiation of lymphoblasts (common precursors of all lymphocytes). They do not have T-cell receptors, CD3, or surface immunoglobulins, but usually carry CD16 and CD56 markers on their surface in humans, or NK1.1/NK1.2 in some strains of mice. About 80% of NKs carry CD8.

These cells were called natural killer cells because, according to early ideas, they did not require activation to kill cells that did not carry major histocompatibility complex type I markers.

The main function of NK is the destruction of body cells that do not carry MHC1 on their surface and are thus inaccessible to the action of the main component of antiviral immunity - T-killers. A decrease in the amount of MHC1 on the cell surface may be due to the transformation of the cell into a cancer cell or the action of viruses such as papillomavirus and HIV.

Macrophages, neutrophils, eosinophils, basophils and natural killers provide an innate immune response that is non-specific.