Cellular immunity. humoral immunity

Humoral immunity is based on the synthesis of antibodies.

Antibodies (specific immunoglobulins)- these are proteins related to. synthesized by cells of the lymphoid system in response to the appearance of antigens in the internal environment of the body. They, performing the main biological function, enter into a specific relationship with antigens, which is called the formation of an immune complex.

Attention! All antibodies are Ig, but not all Ig are antibodies.

Ig molecules are composed of interconnected chains:

Heavy H-chains (from English heavy) with a large molecular weight;

since there are 5 types of H-chains, immunoglobulins are divided into

5 classes:

Mechanism of humoral immunity

humoral immunity represented by B-lymphocytes, whose main function is to become plasma cells that produce antibodies.

According to the scheme of formation of lymphocytes, the B-lymphocyte is formed from a stem cell in the bone marrow, where it subsequently remains for life (unlike the T-lymphocyte, which necessarily passes through the thymus). Already in the bone marrow B-lymphocyte matures and has an antigen-recognizing (recognize - English recognize) receptor, namely IgM.

The second sign maturity B-lymphocyte is the presence on its surface IgD.

Then B-lymphocytes enter the bloodstream. Such cells in an older child are approximately 1/3 of the total number of lymphocytes. Within one day ~ 108 new B-lymphocytes appear in the peripheral blood.

Each B-lymphocyte has an antigen-recognizing immunoglobulin receptor that can “capture”, “come into contact” with only one antigen that is close to it. Since there are a lot of antigens in nature, up to 8 different B-lymphocytes simultaneously exist in human blood.

Immunoglobulins can be located on the B-lymphocyte, but can detach from it and circulate independently in the blood.

However, no matter where the Ig is located, once the antigen enters the body, the corresponding immunoglobulin (antibody) creates an antigen-antibody immune complex to inactivate the antigen. At the same time, such an Ig activates complement, which tones the process of phagocytosis. As a result, the antigen is destroyed.

In response to the destruction of the antigen, the required number of specific plasma cells is formed from B-lymphocytes. At the same time, various immunoglobulins are produced - after Ig M, Ig G is formed, after which - Ig A and Ig E. Attention! When different types of antibodies are formed, their antigenic specificity for a particular antigen remains identical. The degree of specificity for different types of Ig is different: the most specific is Ig G, less specific is Ig A, and even less specific is Ig M.

According to recent studies, plasma cells produce thousands of antibody molecules per second.

Thus, the stage of anti-antigenic activity consists of 2 phases:

The first phase - an gene independent - occurs in the bone marrow, where B-lymphocytes with antigen-recognizing Ig M are formed;

The second phase - avtigenzavisimy - begins with the formation of plasma cells that secrete specific antibodies AGAINST the antigen.

Attention! Rg6ta of B-lymphocytes is often associated with T-lymphocytes-helpers. If the latter are involved in the formation of antibodies by B-lymphocytes, this is called a T-dependent immune response.

Antigens, depending on which lymphocytes take part in their destruction, are divided into 2 groups:

Thymus-dependent antigens are those antigens to which the immune response occurs with the obligatory participation of T-lymphocytes-helpers and macrophages;

Thymus-independent antigens are those antigens for which Ig production is carried out only by B-cells, without the participation of T-lymphocytes.

A characteristic feature of the T-dependent immune response is that it leaves an immunological memory. As a rule, after the production of antibodies, after a few days, most plasma cells die.

If B-lymphocytes work "without the help" of T-helper lymphocytes, this is a T-independent immune response.

Modern methods for diagnosing the state of humoral immunity

The number of B-cells in the bloodstream, which in children 7-14 years old is:

Absolute number - = 500 cells/µl;

They make up 25% of the total number of all lymphocytes.

The total concentration of immunoglobulins in the blood serum, which is normally 10-20 g / l.

Interpretation of these analyzes: a decrease in normative data is a possible sign of a deficiency in humoral immunity.

The level of serum immunoglobulins (normative data for Bucleus - see "Appendix No. 6"), as well as their condition in the lymph nodes, the mucous membrane of the gastrointestinal tract and various secretions of the body. The indicators of the results obtained in various diseases, the pathogenesis of which is the pathology of the immune system, are interpreted in different ways.

It follows from the above that both humoral and cellular immunity are characterized by the so-called immunological memory. This memory is characterized by high accuracy. It is manifested by the ability to "recognize" the antigen upon repeated contact and respond to it with an accelerated and enhanced, compared with the first contact, immunological reaction of the type of secondary IMMUNE response. Interestingly, low doses of antigen induce memory in T cells, while high doses form memory in B cells.

In general, immunological memory during the formation of Ig by B-lymphocytes requires the mandatory presence of T-lymphocytes.

The ability of cells to exhibit immunological memory can persist in the body from several months to decades. Sometimes antibodies may not be detected at all during the study, but the repeated intake of a specific antigen causes a rapid increase in their number. Over time, memory cells tend to involute.

Interesting data: the presence of memory in T-cells gives rise to the opinion that without the thymus in an adult, immunological memory will still manifest itself if necessary; however, scientific experiments on the study of cellular memory in adult animals have shown that when the thymus is removed, T-memory is not restored in them.

The maximum production of antibodies with the introduction of the antigen occurs on the 10-14th day. In the presence of a memory cell, this process begins earlier - by about 4-5 days. This principle underlies vaccination, when memory cells are artificially created.

Features of maturation, purpose and mechanism of action of 5 classes of immunoglobulins.

After all, this phrase has to be heard quite often, especially within the walls of a medical facility. In this article, we will take a closer look at what humoral immunity is.

Disputes about how our immune system works began to arise back in the 19th century between such great scientists as Ilya Mechnikov and Paul Erlich. But, before delving into the classification of immunity and its differences among themselves, let's remember what human immunity is.

What is human immunity?

If a person's immunity decreases, then this is the cause of various diseases, ailments, inflammatory and infectious processes in the body.

Immunity is regulated in the human body at two levels - cellular and molecular. It is thanks to the increase in the body's defenses that the existence and life of a multicellular organism, that is, a person, became possible. Prior to this, only single-celled individuals functioned.

The mechanism of the emergence of immunity

After we realized that without immunity, a person would constantly get sick and, as a result, would not be able to exist in this world, since his cells were constantly eaten by infections and bacteria. Now, back to the scientists - Mechnikov and Erlich, whom we talked about above.

There was a dispute between these two scientists about how the human immune system works (the dispute dragged on for several years). Mechnikov tried to prove that human immunity works exclusively at the cellular level. That is, all the body's defenses are manifested by the cells of the internal organs. The scientist Ehrlich made a scientific assumption that the body's defenses are manifested at the level of blood plasma.

As a result of numerous scientific studies and a huge number of days and years spent on experiments, a discovery was made:

Human immunity functions at the cellular and humoral levels.

For these studies, Ilya Mechnikov and Paul Ehrlich received the Nobil Prize.

Specific and non-specific immune response

The way our body reacts to pathogenic negative factors surrounding a person is called the immunity mechanism. What does this mean - let's take a closer look.

Today, specific and non-specific reactions of the body to environmental factors are classified.

A specific reaction is one that is directed to one particular pathogen. For example, a person once in childhood had chickenpox and after that he developed immunity to this disease.

This means that if a person has developed specific immunity, then he can be protected from negative factors throughout his life.

Nonspecific immunity is a universal protective function of the human body. If a person has nonspecific immunity, then his body immediately reacts to most viruses, infections, as well as foreign organisms that penetrate cells and internal organs.

A little about cellular immunity

To move on to the consideration of humoral immunity, let's first consider cellular immunity.

In our body, cells such as phagocytes are responsible for cellular immunity. Thanks to cellular immunity, we can be reliably protected from the penetration of various viruses and infections into the body.

Lymphocytes, which act as the body's defenses, are formed in the human bone marrow. After these cells are fully mature, they move from the bone marrow to the thymus or thymus. It is for this reason that in many sources you can find such a definition as T-lymphocytes.

T-lymphocytes - classification

Cellular immunity provides protection to the body through active T-lymphocytes. In turn, T-lymphocytes are divided into:

• T-killers- that is, these are cells in the human body that are able to completely destroy and fight viruses and infections (antigens);
• T-helpers- these are "smart" cells that are immediately activated in the body and begin to produce specific protective enzymes in response to the penetration of pathogenic microorganisms;
• T-suppressors- they block the response of cellular immunity (of course, if there is such a need). T-suppressors are used in the fight against autoimmune diseases.

humoral immunity

Humoral immunity consists entirely of proteins that fill the human blood. These are cells such as interferons, C-reactive protein, an enzyme called lysozyme.

How does humoral immunity work?

The action of humoral immunity occurs through a large number of different substances that are aimed at inhibiting and destroying microbes, viruses and infectious processes.

All substances of humoral immunity are usually classified into specific and nonspecific.

Consider nonspecific factors of humoral immunity:

• Blood serum (the infection enters the bloodstream - the activation of C-reactive protein begins - the infection is destroyed);
• The secrets secreted by the glands - affect the growth and development of microbes, that is, they do not allow them to develop and multiply;
• Lysozyme is an enzyme that is a kind of solvent for all pathogenic microorganisms.

Specific factors of humoral immunity are represented either by B-lymphocytes. These beneficial substances are produced by the internal organs of a person, in particular, the bone marrow, Peyer's patches, the spleen, and also the lymph nodes.

Most of the humoral immunity is formed during the development of the child in the womb and then transferred to the baby through breast milk. Some immune cells can be laid down during a person's life through vaccination.

Summary!

Immunity is the ability of our body to protect us (that is, internal organs and important vital systems) from the penetration of viruses, infections and other foreign objects.

Humoral immunity is built according to the type of constant formation in the human body of special antibodies that are necessary for an enhanced fight against infections and viruses that enter the body.

Humoral and cellular immunity are one common link, where one element cannot exist without the other.

FGOU VPO Moscow State Academy of Veterinary Medicine and Biotechnology named after V.I. K.I. Scriabin"

on the topic: "Humoral immunity"

Performed:

Moscow 2004

Introduction

ANTIGENS

antibodies, structure and function of immunoglobulins

THE SYSTEM OF COMPLEMENT COMPONENTS

alternate activation path

classic activation path

cytokines

interleukins

interferons

tumor necrosis factors

colony stimulating factors

other biologically active substances

acute phase proteins

• normal (natural) antibodies

bacteriolysins

inhibitors of enzymatic activity of bacteria and viruses

properdin

other substances...

HUMORAL IMMUNE RESPONSE

List of used literature

Introduction

To humoral immune components include a wide variety of immunologically active molecules, from simple to very complex, which are produced by immunocompetent and other cells and are involved in protecting the body from foreign or its defective:

immunoglobulins,

cytokines,

complement system,

acute phase proteins

enzyme inhibitors that inhibit the enzymatic activity of bacteria,

virus inhibitors,

numerous low molecular weight substances that are mediators of immune reactions (histamine, serotonin, prostaglandins and others).

Of great importance for the effective protection of the body are also the saturation of tissues with oxygen, the pH of the environment, the presence of Ca 2+ and Mg 2+ and other ions, trace elements, vitamins, etc.

All these factors function interrelatedly with each other and with the cellular factors of the immune system. Thanks to this, the precise direction of immune processes is maintained and, ultimately, the genetic constancy of the internal environment of the body.

Antigens

BUT An antigen is a genetically alien substance (protein, polysaccharide, lipopolysaccharide, nucleoprotein) that, when introduced into the body or formed in the body, can cause a specific immune response and interact with antibodies and antigen-recognizing cells.

An antigen contains several distinct or repetitive epitopes. An epitope (antigenic determinant) is a distinctive part of an antigen molecule that determines the specificity of antibodies and effector T-lymphocytes in an immune response. The epitope is complementary to the active site of an antibody or T-cell receptor.

Antigenic properties are associated with the molecular weight, which should be at least tens of thousands. Hapten is an incomplete antigen in the form of a small chemical group. The hapten itself does not cause the formation of antibodies, but it can interact with antibodies. When a hapten combines with a large molecular protein or polysaccharide, this complex compound acquires the properties of a full-fledged antigen. This new complex substance is called the conjugated antigen.

Antibodies, structure and functions of immunoglobulins

BUT
antibodies are immunoglobulins produced by B-lymphocytes (plasma cells). Immunoglobulin monomers consist of two heavy (H-chains) and two light (L-chains) polypeptide chains linked by a disulfide bond. These chains have constant (C) and variable (V) regions. Papain cleaves immunoglobulin molecules into two identical antigen-binding fragments - Fab (Fragment antigen binding) and Fc (Fragment cristallizable). The active center of antibodies is the antigen-binding site of the Fab-fragment of immunoglobulin, formed by the hypervariable regions of the H- and L-chains; binds antigen epitopes. The active center has specific complementary sites to certain antigenic epitopes. The Fc fragment can bind complement, interact with cell membranes, and is involved in the transfer of IgG across the placenta.

Antibody domains are compact structures held together by a disulfide bond. So, in IgG, there are: V - domains of light (V L) and heavy (V H) chains of the antibody, located in the N-terminal part of the Fab fragment; C-domains of constant regions of light chains (C L); C domains of heavy chain constant regions (C H 1, C H 2, C H 3). The complement binding site is located in the C H 2 domain.

Monoclonal antibodies are homogeneous and highly specific. They are produced by a hybridoma - a population of hybrid cells obtained by fusion of an antibody-forming cell of a certain specificity with an "immortal" myeloma cell.

There are such properties of antibodies as:

affinity (affinity) - the affinity of antibodies to antigens;

Avidity is the strength of the antibody-antigen bond and the amount of antigen bound by the antibody.

Antibody molecules are extremely diverse, primarily associated with variable regions located in the N-terminal regions of the light and heavy chains of the immunoglobulin molecule. The rest of the sections are relatively unchanged. This makes it possible to isolate the variable and constant regions of the heavy and light chains in the immunoglobulin molecule. Separate parts of the variable regions (the so-called hypervariable regions) are particularly diverse. Depending on the structure of the constant and variable regions, immunoglobulins can be divided into isotypes, allotypes and idiotypes.

The isotype of antibodies (class, subclass of immunoglobulins - IgM, IgG1, IgG2, IgG3, IgG4, IgA1, IgA2, IgD, IgE) is determined by the C-domains of heavy chains. Isotypes reflect the diversity of immunoglobulins at the species level. When animals of one species are immunized with the blood serum of individuals of another species, antibodies are formed that recognize the isotype specificity of the immunoglobulin molecule. Each class of immunoglobulins has its own isotype specificity, against which specific antibodies can be obtained, for example, rabbit antibodies against mouse IgG.

Availability allotypes due to genetic diversity within a species and concerns structural features of the constant regions of immunoglobulin molecules in individuals or families. This diversity is of the same nature as the differences in people according to the blood groups of the ABO system.

The antibody idiotype is determined by the antigen-binding sites of the Fab fragments of the antibodies, ie the antigenic properties of the variable regions (V-regions). An idiotype consists of a set of idiotopes - antigenic determinants of the V-regions of an antibody. Idiotypes are regions of the variable portion of an immunoglobulin molecule that are themselves antigenic determinants. Antibodies obtained against such antigenic determinants (anti-idiotypic antibodies) are able to distinguish between antibodies of different specificity. Anti-idiotypic sera can detect the same variable region on different heavy chains and in different cells.

According to the type of heavy chain, 5 classes of immunoglobulins are distinguished: IgG, IgM, IgA, IgD, IgE. Antibodies belonging to different classes differ from each other in many respects in terms of half-life, distribution in the body, ability to fix complement and bind to the surface Fc receptors of immunocompetent cells. Since all classes of immunoglobulins contain the same heavy and light chains, as well as the same heavy and light chain variable domains, the above differences should be due to the constant regions of the heavy chains.

IgG - the main class of immunoglobulins found in blood serum (80% of all immunoglobulins) and tissue fluids. It has a monomeric structure. It is produced in large quantities during the secondary immune response. Antibodies of this class are able to activate the complement system and bind to receptors on neutrophils and macrophages. IgG is the main opsonizing immunoglobulin in phagocytosis. Since IgG is able to cross the placental barrier, it plays a major role in protecting against infections during the first weeks of life. The immunity of newborns is also enhanced due to the penetration of IgG into the blood through the intestinal mucosa after the entry of colostrum containing large amounts of this immunoglobulin. The content of IgG in the blood depends on antigenic stimulation: its level is extremely low in animals kept in sterile conditions. It rises rapidly when the animal is placed under normal conditions.

IgM makes up about 6% of serum immunoglobulins. The molecule is formed by a complex of five linked monomeric subunits (pentamer). IgM synthesis begins before birth. These are the first antibodies produced by developing B-lymphocytes. In addition, they are the first to appear in a membrane-bound monomeric form on the surface of B-lymphocytes. It is believed that IgM in the phylogenesis of the immune response of vertebrates appeared earlier than IgG. Antibodies of this class are released into the blood during the early stages of the primary immune response. The binding of the antigen to IgM causes the attachment of the Clq component of the complement and its activation, which leads to the death of microorganisms. Antibodies of this class play a leading role in removing microorganisms from the bloodstream. If a high level of IgM is found in the blood of newborns, then this usually indicates intrauterine infection of the fetus. In mammals, birds and reptiles, IgM is a pentamer, in amphibians it is a hexamer, and in most bony fish it is a tetramer. At the same time, there were no significant differences in the amino acid composition of the constant regions of IgM light and heavy chains of different classes of vertebrates.

IgA exists in two forms: in the blood serum and in the secrets of the exocrine glands. Serum IgA is approximately 13% of the total content of immunoglobulins in the blood. Dimeric (predominant), as well as tri- and tetrameric forms are presented. IgA in the blood has the ability to bind and activate complement. Secretory IgA (slgA) is the main class of antibodies in the secretions of exocrine glands and on the surface of mucous membranes. It is represented by two monomeric subunits associated with a special glycoprotein - the secretory component. The latter is produced by cells of the glandular epithelium and ensures the binding and transport of IgA to the secretions of the exocrine glands. Secretory IgA blocks the attachment (adhesion) of microorganisms to the surface of the mucous membranes and its colonization by them. slgA may also play the role of an opsonin. High levels of secretory IgA in mother's milk protect the mucous membranes of the infant's digestive tract from intestinal infections. When comparing various secrets, it turned out that the maximum level of slgA was found in tears, and the highest concentrations of the secretory component were found in the lacrimal glands.

IgD is less than 1% of the total content of immunoglobulins in the blood serum. Antibodies of this class have a monomeric structure. They contain a large amount of carbohydrates (9-18%). This immunoglobulin is characterized by extremely high sensitivity to proteolysis and a short plasma half-life (about 2.8 days). The latter may be due to the large length of the hinge region of the molecule. Almost all IgD, together with IgM, is located on the surface of blood lymphocytes. It is believed that these antigen receptors can interact with each other, controlling the activation and suppression of lymphocytes. It is known that the sensitivity of IgD to proteolysis increases after binding to an antigen.

Plasma cells secreting IgD have been found in the tonsils. They are rarely found in the spleen, lymph nodes and lymphoid tissues of the intestine. Immunoglobulins of this class are the main membrane fraction on the surface of B-lymphocytes isolated from the blood of patients with leukemia. Based on these observations, it was hypothesized that IgD molecules are receptors on lymphocytes and may be involved in the induction of immunological tolerance.

IgE is present in the blood in trace amounts, accounting for only 0.002% of all immunoglobulins in the blood serum. Like IgG and IgD, it has a monomeric structure. It is produced mainly by plasma cells in the mucous membranes of the digestive tract and respiratory tract. The content of carbohydrates in the IgE molecule is 12%. When injected subcutaneously, this immunoglobulin lingers in the skin for a long time, binding to mast cells. Subsequent interaction of the antigen with such a sensitized mast cell leads to its degranulation with the release of vasoactive amines. The main physiological function of IgE is apparently the protection of the mucous membranes of the body by local activation of blood plasma factors and effector cells due to the induction of an acute inflammatory reaction. Pathogenic microbes capable of breaking through the line of defense formed by IgA will bind to specific IgE on the surface of mast cells, as a result of which the latter will receive a signal to release vasoactive amines and chemotactic factors, and this in turn will cause an influx of circulating IgG, complement, neutrophils. and eosinophils. It is possible that local production of IgE contributes to protection against helminths, since this immunoglobulin stimulates the cytotoxic effect of eosinophils and macrophages.

Complement system

Complement is a complex complex of proteins and glycoproteins (about 20), which, like the proteins involved in the processes of blood coagulation, fibrinolysis, form cascade systems of effective protection of the body from foreign cells. This system is characterized by a rapid, multiply enhanced response to the primary antigenic signal due to a cascade process. The product of one reaction serves as a catalyst for the next. The first data on the existence of the complement system were obtained at the end of the 19th century. when studying the mechanisms of protecting the body from bacteria penetrating into it and the destruction of foreign cells introduced into the blood. These studies have shown that the body responds to the penetration of microorganisms and foreign cells with the formation of antibodies capable of agglutinating these cells without causing their death. The addition of fresh serum to this mixture caused the death (cytolysis) of the immunized subjects. This observation was the impetus for intensive research aimed at elucidating the mechanisms of lysis of foreign cells.

A number of components of the complement system are denoted by the symbol "C" and a number that corresponds to the chronology of their discovery. There are two ways to activate a component:

without antibodies - alternative

with the participation of antibodies - classic

Alternative way to activate the computerelement

The first pathway of complement activation, caused by foreign cells, is phylogenetically the oldest. A key role in the activation of complement in this way is played by C3, which is a glycoprotein consisting of two polypeptide chains. Under normal conditions, the internal thioether bond in C3 is slowly activated as a result of interaction with water and trace amounts of proteolytic enzymes in blood plasma, leading to the formation of C3b and C3a (C3 fragments). In the presence of Mg 2+ ions, C3b can form a complex with another component of the complement system, factor B; then the last factor is cleaved by one of the blood plasma enzymes - factor D. The resulting C3bBb complex is a C3-convertase - an enzyme that cleaves C3 into C3a and C3b.

Some microorganisms can activate C3Bb convertase with the formation of a large amount of C3 cleavage products by binding the enzyme to the carbohydrate regions of their surface membrane and thereby protecting it from the action of factor H. Then another protein properdin interacts with convertase, increasing the stability of its binding. Once C3 is cleaved by convertase, its internal thioether bond is activated and the reactive C3b derivative covalently binds to the membrane of the microorganism. One C3bBb active center allows a large number of C3b molecules to bind to the microorganism. There is also a mechanism that inhibits this process under normal conditions: in the presence of factors I and H, C3b is converted to C3bI, the latter being cleaved to the final inactive C3c and C3d peptides under the influence of proteolytic enzymes. The next activated component, C5, interacts with membrane-bound C3b, becomes a substrate for C3bBb and is cleaved to form a short C5a peptide, while the C5b fragment remains fixed on the membrane. Then C5b sequentially adds C6, C7 and C8 to form a complex that facilitates the orientation of molecules of the last C9 component on the membrane. This leads to the deployment of C9 molecules, their penetration into the bilipid layer and polymerization into a ring-shaped "membrane attack complex" (MAC). The C5b-C7 complex wedged into the membrane allows C8 to come into direct contact with the membrane, cause disorganization of its regular structures and, finally, lead to the formation of helical transmembrane channels. The emerging transmembrane channel is completely permeable to electrolytes and water. Due to the high colloid osmotic pressure inside the cell, Na + and water ions enter it, which leads to the lysis of a foreign cell or microorganism.

In addition to the ability to lyse cells with foreign information, complement also has other important functions:

a) due to the presence on the surface of phagocytic cells of receptors for C3b and C33, adhesion of microorganisms is facilitated;

b) small peptides C3a and C5a (“anaphylatoxins”) formed during complement activation:

stimulate the chemotaxis of neutrophils to the place of accumulation of objects of phagocytosis,

activate oxygen-dependent mechanisms of phagocytosis and cytotoxicity,

cause the release of inflammatory mediators from mast cells and basophils,

cause the expansion of blood capillaries and increase their permeability;

c) proteinases that appear during complement activation, despite their substrate specificity, are able to activate other blood enzyme systems: the coagulation system and the kinin formation system;

d) complement components, interacting with insoluble antigen-antibody complexes, reduce the degree of their aggregation.

Classical complement activation pathway

The classical pathway is initiated when an antibody bound to a microbe or other cell carrying foreign information binds and activates the first component of the Clq cascade. This molecule is multivalent in relation to antibody binding. It consists of a central collagen-like rod that branches into six peptide chains, each of which terminates in an antibody-binding subunit. According to electron microscopy, the entire molecule resembles a tulip. Its six petals are formed by the C-terminal globular regions of polypeptide chains, collagen-like regions are twisted in each subunit into a three-helix structure. Together, they form a stem-like structure due to the association in the region of the N-terminal region by disulfide bonds. The globular regions are responsible for interaction with antibodies, and the collagen-like region is responsible for binding to the other two C1 subunits. To combine three subunits into a single complex, Ca 2+ ions are needed. The complex is activated, acquires proteolytic properties and participates in the formation of binding sites for other components of the cascade. The process ends with the formation of MAC.

Antigen-specific antibodies can complement and enhance the ability of natural immune mechanisms to initiate acute inflammatory responses. A smaller part of the complement in the body is activated through an alternative pathway, which can be carried out in absence of antibodies. This nonspecific pathway of complement activation is important in the destruction of aging or damaged body cells by phagocytes, when the attack begins with nonspecific sorption of immunoglobulins and complement on the damaged cell membrane. However, the classical pathway of complement activation in mammals is prevalent.

Cytokines

Cytokines are proteins mainly of activated cells of the immune system that provide intercellular interactions. Cytokines include interferons (IFN), interleukins (IL), chemokines, tumor necrosis factors (TNF), colony stimulating factors (CSF), growth factors. Cytokines act according to the relay principle: the effect of a cytokine on a cell causes the formation of other cytokines by it (cytokine cascade).

The following mechanisms of action of cytokines are distinguished:

Intracrine mechanism - the action of cytokines inside the producer cell; binding of cytokines to specific intracellular receptors.

The autocrine mechanism is the action of a secreted cytokine on the secreting cell itself. For example, IL-1, -6, -18, TNFα are autocrine activating factors for monocytes/macrophages.

Paracrine mechanism - the action of cytokines on nearby cells and tissues. For example, IL-1, -6, -12, -18, TNFα produced by macrophages activate T-helpers (Th0), recognizing the antigen and MHC of the macrophage (Scheme of autocrine-paracrine regulation of the immune response).

The endocrine mechanism is the action of cytokines at a distance from the producing cells. For example, IL-1, -6 and TNFα, in addition to auto and paracrine effects, can have a distant immunoregulatory effect, a pyrogenic effect, induction of the production of acute phase proteins by hepatocytes, symptoms of intoxication, and multiorgan damage in toxic-septic conditions.

Interleukins

At present, the structure and functions of 16 interleukins have been isolated, studied, their serial numbers are in the order of receipt:

Interleukin-1. Produced by macrophages, as well as AGP cells. It triggers the immune response by activating T-helpers, plays a key role in the development of inflammation, stimulates myelopoiesis and the early stages of erythropoiesis (later it suppresses, being an antagonist of erythropoietin), is a mediator of the interaction between the immune and nervous systems. Inhibitors of IL-1 synthesis are prostaglandin E2, glucocorticoids.

Interleukin-2. Produce activated T-helpers. It is a growth and differentiation factor for T-lymphocytes and NK cells. Participates in the implementation of antitumor resistance. Inhibitors are glucocorticoids.

Interleukin-3. They produce activated T-helpers, such as Th1 and Th2, as well as B-lymphocytes, bone marrow stromal cells, brain astrocytes, keratinocytes. Growth factor for mast cells of the mucous membranes and enhances their release of histamine, a regulator of the early stages of hematopoiesis, suppresses the formation of NK cells under stress.

Interleukin-4. Stimulates the proliferation of B-lymphocytes activated by antibodies to IgM. It is produced by T-helpers of the Th2 type, on which it has a stimulating differentiation effect, affects the development of hematopoietic cells, macrophages, NK cells, basophils. Promotes the development of allergic reactions, has anti-inflammatory and antitumor effects.

Interleukin-6. It is produced by lymphocytes, monocytes/macrophages, fibroblasts, hepatocytes, keratinocytes, mesanglial, endotholial and hematopoietic cells. According to the spectrum of biological action, it is close to IL-1 and TNFα, participates in the development of inflammatory, immune reactions, and serves as a growth factor for plasma cells.

Interleukin-7. Produced by stromal cells of the bone marrow and thymus (fibroblasts, endothelial cells), macrophages. It is the main lymphopoietin. Promotes the survival of pre-T cells, causes antigen-dependent reproduction of T-lymphocytes outside the thymus. Deletion of the IL-7 gene in animals leads to the devastation of the thymus, the development of total lymphopenia and severe immunodeficiency.

Interleukin-8. They form macrophages, fibroblasts, hepatocytes, T-lymphocytes. The main target of IL-8 is neutrophils, on which it acts as a chemoattractant.

Interleukin-9. Produced by T-helper type Th2. Supports the proliferation of activated T-helpers, affects erythropoiesis, mast cell activity.

Interleukin-10. It is produced by T-helper type Th2, T-cytotoxic and monocytes. Suppresses the synthesis of cytokines by T-cells of the Th1 type, reduces the activity of macrophages and their production of inflammatory cytokines.

Interleukin-11. Formed by fibroblasts. Causes the proliferation of early hematopoietic precursors, prepares stem cells to perceive the action of IL-3, stimulates the immune response and the development of inflammation, promotes the differentiation of neutrophils, the production of acute phase proteins.

Specific immune protection is mainly provided by lymphocytes, which do this in two ways: cellular or humoral. Cellular immunity is provided by immunocompetent T-lymphocytes, which are formed from stem cells migrating from the red bone marrow into the thymus. , T-lymphocytes create most of the lymphocytes of the blood itself (up to 80%), and also settle in the peripheral organs of immunogenesis (primarily in the lymph nodes and spleen), forming thymus-dependent zones in them, which become active points of proliferation (reproduction) T lymphocytes outside the thymus. Differentiation of T-lymphocytes occurs in three directions. The first group of daughter cells is capable of reacting with it and destroying it when it encounters a “foreign” protein-antigen (the causative agent of the disease, or its own mutant). Such lymphocytes are called T-killerash (“killers”) and are characterized by the fact that they are capable of lysis (destruction by dissolving cell membranes and n Protein binding) target cells (carriers of antigens). Thus, T-killers are a separate branch of stem cell differentiation (although their development, as will be described below, is regulated by G-helpers) and are designed to create, as it were, a primary barrier in the antiviral and antitumor immunity of the body.

The other two populations of T-lymphocytes are called T-helpers and T-suppressors and carry out cellular immune protection through the regulation of the level of functioning of T-lymphocytes in the humoral immunity system. T-helpers ("helpers") in the event of the appearance of antigens in the body contribute to the rapid reproduction of effector cells (executors of immune defense). There are two subtypes of helper cells: T-helper-1, which secrete specific interleukins of type 1L2 (hormone-like molecules) and β-interferon and are associated with cellular immunity (promote the development of T-helpers) T-helper-2 secrete interleukins of the type IL 4-1L 5 and interact predominantly with T-lymphocytes of humoral immunity. T-suppressors are able to regulate the activity of B and T-lymphocytes in response to antigens.

humoral immunity

humoral immunity provide lymphocytes that differentiate from brain stem cells not in the thymus, but in other places (in the small intestine, lymph nodes, pharyngeal tonsils, etc.) and are called B-lymphocytes. Such cells make up to 15% of all leukocytes. At the first contact with the antigen, T-lymphocytes that are sensitive to it multiply intensively. Some of the daughter cells differentiate into immunological memory cells and at the level of lymph nodes in the £-zones turn into plasma cells, then they are able to create humoral antibodies. T-helpers contribute to these processes. Antibodies are large protein molecules that have a specific affinity for a particular antigen (based on the chemical structure of the corresponding antigen) and are called immunoglobulins. Each immunoglobulin molecule is composed of two heavy and two light chains of disulfide bonds linked to each other and capable of activating cell membranes of antigens and attaching a complement to them (contains 11 proteins capable of providing lysis or dissolution of cell membranes and binding protein binding of antigen cells) . Blood plasma complement has two activation pathways: classical (from immunoglobulins) and alternative (from endotoxins or toxic substances and from drugs). There are 5 classes of immunoglobulins (lg): G, A, M, D, E, differing in functional features. So, for example, lg M habitually first included in the immune response to an antigen activates complement and promotes uptake of this antigen by macrophages or cell lysis; lg A is located in the cities of the most probable penetration of antigens (lymph nodes of the gastrointestinal tract, in the lacrimal, salivary and sweat glands, in the adenoids, in mother's milk, etc.) which creates a strong protective barrier, contributing to the phagocytosis of antigens; lg D promotes the proliferation (reproduction) of lymphocytes during infections, T-lymphocytes "recognize" antigens with the help of gamma globulin included in the membrane, forming an antibody, binding links, the configuration of which corresponds to the three-dimensional structure of antigenic deterministic groups (haptens or low molecular weight substances that can bind to proteins antibodies, transferring the properties of antigen proteins to them), as a key corresponds to a lock (G. William, 2002; G. Ulmer et al., 1986). Antigen-activated B- and T-lymphocytes multiply rapidly, are included in the body's defense processes and die en masse. At the same time, not many of the activated lymphocytes turn into B- and T-memory cells, which have a long lifespan and, upon re-infection of the body (sensitization), B- and T-memory cells “remember” and recognize the structure of antigens and quickly turn into effector (active) cells and stimulate lymph node plasma cells to produce appropriate antibodies.

Repeated contact with certain antigens can sometimes give hyperergic reactions, accompanied by increased capillary permeability, increased blood circulation, itching, bronchospasm, etc. Such phenomena are called allergic reactions.

Nonspecific immunity, due to the presence in the blood of "natural" antibodies, which often occur when the body comes into contact with the intestinal flora. There are 9 substances that together form a protective complement. Some of these substances are able to neutralize viruses (lysozyme), the second (C-reactive protein) suppress the vital activity of microbes, the third (interferon) destroy viruses and suppress the reproduction of their own cells in tumors, etc. Nonspecific immunity is also caused by special cells, neutrophils and macrophages, capable of phagocytosis, i.e. to the destruction (digestion) of foreign cells.

Specific and non-specific immunity is divided into innate (transmitted from the mother), and acquired, which is formed after a disease in the process of life.

In addition, there is the possibility of artificial immunization of the body, which is carried out either in the form of vaccination (when a weakened pathogen is introduced into the body and this causes the activation of protective forces before the formation of the corresponding antibodies), or in the form of passive immunization, when the so-called vaccination against a specific disease is done by introducing serum (blood plasma that does not contain fibrinogen, or its coagulation factor, but has ready-made antibodies against a specific antigen). Such vaccinations are given, for example, against rabies, after being bitten by poisonous animals, and so on.

As V. I. Bobritskaya (2004) testifies, in the blood there are up to 20 thousand of all forms of leukocytes in 1 mm3 of blood, and in the first days of life their number grows, even up to 30 thousand in 1 mm3, which is associated with the resorption of hemorrhage decay products in the baby's tissue, which usually occur at birth. After 7-12 first days of life, the number of leukocytes decreases to 10-12 thousand in I mm3, which persists during the first year of a child's life. Further, the number of leukocytes gradually decreases and at the age of 13-15 it is set at the level of adults (4-8 thousand in 1 mm 3 of blood). In children of the first years of life (up to 7 years), lymphocytes are exaggerated among leukocytes, and only at 5-6 years their ratio levels off. In addition, children under 6-7 years old have a large number of immature neutrophils (young, rods - nuclear), which causes relatively low defenses of the body of young children against infectious diseases. The ratio of different forms of leukocytes in the blood is called the leukocyte formula. With age in children, the leukocyte formula (Table 9) changes significantly: the number of neutrophils increases, while the percentage of lymphocytes and monocytes decreases. At 16-17 years old, the leukocyte formula takes on a composition characteristic of adults.

Invasion of the body always leads to inflammation. Acute inflammation is usually generated by antigen-antibody reactions in which plasma complement activation begins a few hours after immunological damage, reaches its peak after 24 hours, and fades after 42-48 hours. Chronic inflammation is associated with the influence of antibodies on the T-lymphocyte system, habitually manifests itself through the age characteristic of the leukocyte formula

1-2 days and peaks in 48-72 hours. At the site of inflammation, the temperature always rises (due to vasodilation); swelling occurs (in acute inflammation due to the release of proteins and phagocytes into the intercellular space, in chronic inflammation - infiltration of lymphocytes and macrophages is added); pain occurs (associated with increased pressure in the tissues).

They are very dangerous for the body and often lead to fatal consequences, since the body actually becomes unprotected. There are 4 main groups of such diseases: primary or secondary immune deficiency, dysfunction; malignant diseases, infections of the immune system. Among the latter known is the herpes virus and threateningly spreading in the world, including in Ukraine, the anti-HIV virus or anmiHTLV-lll/LAV, which causes acquired immunodeficiency syndrome (AIDS or AIDS). The clinic is based on viral damage to the T-helper (Th) chain of the lymphocytic system, which leads to a significant increase in the number of T-suppressors (Ts) and a violation of the Th / Ts ratio, which becomes 2:1 instead of 1:2, resulting in a complete cessation production of antibodies and the body dies from any infection.

To date, a wide range of types of human immune systems has been identified, among which it is necessary to distinguish cellular and humoral. The interaction of both types ensures the recognition and destruction of foreign microorganisms. The presented publication will help to consider the features and principles of operation of the extracellular defense system in more detail.

What is humoral immunity?

humoral immunity - this is the protection of the human body from the regular entry into the internal environment of foreign pathogens of infections and diseases. Protection is carried out by means of proteins soluble in internal fluids, human blood - antigens (lysozyme, interferon, reactive protein).

The principle of operation is the regular formation of substances that contribute to the prevention and spread of viruses, bacteria, microbes, regardless of what kind of microorganism has entered the internal environment, dangerous or harmless.

The humoral link of immunity includes:

• Blood serum - it contains C - a reactive protein, the activity of which is aimed at eliminating pathogenic microbes;
• Secrets of the glands that prevent the development of foreign bodies;
• Lysozyme - stimulates the dissolution of bacterial cell walls;
• Mucin - a substance aimed at protecting the shell of the cellular element;
• Properdin - responsible for blood clotting;
• Cytokines are a combination of proteins secreted by tissue cells;
• Interferons - perform signaling functions, announcing the appearance of foreign elements in the internal environment;
• Complementary system - the total number of proteins that contribute to the neutralization of microbes. The system includes twenty proteins.

Mechanisms

The mechanism of humoral immunity is a process during which a protective reaction is formed, aimed at preventing the penetration of viral microorganisms into the human body. The state of health and vital activity of a person depends on how the process of protection proceeds.

The process of protecting the body consists of the following steps:

• There is a formation of B - a lymphocyte, which is formed in the bone marrow, where the lymphoid tissue matures;
• Next, the process of antigen exposure to plasma cells and memory cells is carried out;
• Antibodies of extracellular immunity recognize foreign particles;
• Antibodies of the acquired immune defense are formed.

The mechanisms of the immune system are divided into:

Specific - the action of which is aimed at the destruction of a specific infectious agent;

Non-specific — differ in the universal character of orientation. The mechanisms recognize and fight any foreign antibodies.

Specific Factors

Specific factors of humoral immunity are produced by B-lymphocytes, which are formed in the bone marrow, spleen, and lymph nodes within two weeks. Presented antigens react to the appearance of foreign particles in body fluids. Specific factors include antibodies and immunoglobulins (Ig E, Ig A, Ig M, Ig D). The action of lymphocytes in the human body is aimed at blocking foreign particles, after this process phagocytes come into action, which eliminate viral elements.

Stages of antibody formation:

• Latent phase (inductive) - during the first days, the elements are produced in small quantities;
• Productive phase - the formation of particles occurs within two weeks.

Non-specific factors

The list of nonspecific factors of humoral immunity is represented by the following substances:

• Elements of tissue cells;
• Blood serum and the protein elements contained in it, which stimulate the resistance of cells to pathogens;
• Secrets of the internal glands - help to reduce the number of bacteria;
• Lysozyme is a substance that has an antibacterial effect.

Indicators of humoral immunity

The action of humoral immunity is carried out by developing the elements necessary to protect the body. The general condition and viability of the human body depends on the amount of antibodies obtained and the correct functioning of them.

If it is necessary to determine the parameters of the extracellular immune system, it is required to conduct a comprehensive blood test, the results of which determine the total number of formed particles and possible violations of the immune system.

Cellular and humoral immunity

Favorable functioning of extracellular immunity is ensured only through interaction with cellular defenses. The functions of the immune systems differ, but there are similar characteristics. They have an effective effect on the internal system of the human body.

difference between humoral and cellular immunity lies in their object of influence. Cellular functions directly in the cells of the body, preventing the reproduction of foreign microorganisms, and humoral affects viruses and bacteria in the extracellular space. One immune defense system cannot exist without the other.

Of great importance in the life of every person is the viability of his internal environment. Strengthening the immune defense and will help protect the human body from pathogenic bacteria and viruses.