Mechanisms, determination of humoral immunity tests. What is immunity

Humans have two types of immunity - cellular and humoral immunity. Both types of immunity perform different functions, but are closely related to each other. Therefore, the division of both types is relative. Humoral immunity is the ability to exclude infections due to antibodies. They are present in blood plasma, mucous membranes of the organs of vision, and saliva.

This type of immunity is developed in the womb and passes to the fetus through the placenta. Antibodies are supplied to the child during the first months of life through mother's milk. Milk protects the child from the intense influence of multiple types of microbes and microorganisms. Breastfeeding is a key factor in the development of the baby’s immune system.

The body's protective function against infectious diseases is carried out in this way: When an antigen for a specific disease is remembered. If the infection enters the body again, the antibodies recognize it and destroy the pathogenic organisms. During vaccinations, a drug is administered to subsequently recognize the antigen and absorb it.

Humoral and cellular immunity: features of functions

Cellular immunity protects against viral diseases caused by pathogenic fungi and tumors. This species directly takes part in the rejection of various foreign tissues, allergic responses and is produced by phagocytes. These cells protect the body by absorbing (phagocytosis) foreign substances, particles, and microorganisms. Granulocytes and monocytes are present in the blood to a greater extent.

The former are considered a type of leukocytes and provide the body's defenses. They are the first to notice the inflammatory process.

The second type of leukocytes refers to large blood cells. Monocytes protect against viruses and infections, absorb blood clots, protect against the formation of thrombosis, and fight tumors. Immune defense requires the process of phagocytosis (absorption), when a foreign substance is absorbed by phagocytes.

Both immunities cannot exist and function one without the other. Their difference lies in functionality. When humoral immunity fights directly against microorganisms, then cellular immunity fights fungus, cancer and various microbes. For normal functioning of the immune system, 2 types of immunity are important.

To increase protection, you should constantly take vitamins and lead a healthy lifestyle. Also, decreased immunity is characterized by constant lack of sleep and stress on the body. In the latter cases, you will need to take drugs that regulate the immune system. Immunity is one of the factors of well-being. When the functioning of the immune system is not maintained normally, all microbes and infections will constantly attack the body.

Immunity restoration

To regenerate weak immune defenses, it is initially necessary to find out the root cause of the failures. Violation of specific parts of the immune system is considered the source of certain diseases. Weak resistance of the body to infections may also indicate problems with the immune system. Treatment of diseases that have weakened the immune system contributes to its rapid recovery. These diseases include diabetes and chronic diseases.

Lifestyle changes are considered one of the best ways to solve the question of how to increase humoral immunity.

The method covers:

quitting smoking and alcohol;
adherence to sleep and wakefulness;
playing sports and walking in the fresh air;
hardening of the body;
balanced diet with vitamins.

Humoral immunity can be effectively restored by taking vitamins, traditional medicine and special medications. Any means to restore the immune system are prescribed by an immunologist in the exact dosage, according to the instructions. Taking vitamins and minerals is especially beneficial in the spring. Berry fruit drinks, honey, rose hips, and aloe can restore immunity.

Taking medications and vitamins to increase any type of immunity will not give results when the main factor in its reduction is not detected or eliminated. Pharmaceuticals are prescribed by a doctor. Self-medication is prohibited.

Mechanism of humoral immunity

The basis for the implementation of humoral immunity is the mechanism of influence of substances that destroy pathogenic bacteria through the blood. Such elements are divided into groups - specific (Engerix helps) and non-specific. Conditions of a nonspecific nature include innate immune cells that suppress microorganisms.

The group includes:

Blood serum;
Secrets of glands that suppress the formation of bacteria;
Lysozyme enzyme. The antibacterial agent destroys chemicals. relationships in the structure of the wall of pathogenic organisms;
Mucin enters the glands that secrete saliva. These are carbohydrates and proteins called glycoproteins. The unusual composition allows the main glycoproteins of mucus to protect the cell layers from the effects of toxic substances;
Properdin is a blood serum protein from the globulin group, responsible for blood clotting;
Cytokines are small peptide signal (control) molecules. They transmit signals between these cells. There are a couple of groups, the main one of which is interferons;
Interferons (autogenous glycoproteins) are protein substances that have general protective properties. If the inflammatory process begins, they give a signal. In addition to this ability, they suppress pathogens. There are a number of types of autogenous glycoproteins. Alpha and Beta arise during viral infection, and Gamma is formed due to immune cells.

It is worth considering the concept of the complement system - protein complexes that perform the function of neutralizing bacteria. The complement system includes up to twenty proteins with their own serial number (C1, C2, C3 and others).

Immunology

Specific response is a single factor. For example, in childhood a child suffered from smallpox. As an adult, he will no longer suffer from this disease, since immunity has already developed. This also applies to all those vaccinations that a person received at an early age.

The nonspecific form involves multi-purpose innate protection, including the body’s response to infection entering the body.

Humoral immune response is the synthesis of antibodies by B cells in response to the appearance of pathogenic organisms in the human body. As the humoral immune response develops from the stage of antigen detection to more intense antibody production, 2 main actions occur:

transition of antibody synthesis from one type to another;
increasing the strength of binding of the active zones of antibodies with reactive groups of the antigen.

The place of formation is considered to be follicles with an additional membrane or places of concentration of B-lymphocytes in lymphoid tissue. Antigen detection occurs at the periphery of the follicle. A subpopulation of T lymphocytes enters the process and assists in the production of antibodies. B lymphocytes begin to divide rapidly.

Immunoglobulin genes are switched, and the number of possible mutations increases. On the plane of lymphocytes, different types of immunoglobulins of class G appear. B-cell clones at the sites of reproduction are selected based on the high degree of affinity of their receptors. Cells with an increased degree of affinity differentiate into:

plasma cells;
cells that store information about previously active antigens.

The participation of the resulting antibodies is expressed in 3 forms:

reaction of neutralization of microorganisms;
enhanced phagocytic activity;
activation of a complex of complex proteins.

During their existence in the host's body, pathogens enter the extracellular environment. Presence in body fluids can be long (if we talk about extracellular pathogenic bacteria) or shorter when the body is affected by intracellular microorganisms.

During normal immune activity, infectious agents, toxic substances present outside the host cells, are exposed to the following immunoglobulins:

An effector molecule is a small molecule whose concentration regulates the activity of a protein molecule;
B lymphocytes are capable of producing antibodies in two forms - membrane-bound and secreted (soluble).

Why does immunity decrease?

A decrease in the functioning of the immune system has specific prerequisites that indicate health problems. They are relatively divided into a number of groups:

Wrong lifestyle:

poor nutrition;
a painful condition that occurs when there is insufficient intake of vitamins in the body compared to their consumption;
a condition characterized by low levels of hemoglobin or red blood cells in the blood;
excess or lack of physical activity;
sleep disturbances;
drinking alcohol, smoking;
bad ecology;
poisoning of the body by emissions.

Immunity may decrease due to diseases:

pathologies of the circulatory system;
diarrhea due to impaired absorption (impaired digestive and transport function of the small intestine);
rapid and sharp decline in kidney and liver function;
self-poisoning of the body with nitrogenous compounds such as urea, uric acid, creatinine and indican;
HIV infection;
immunodeficiencies of congenital and acquired nature;
oncological diseases;
long-term antibacterial treatment;
chemotherapy;
helminths.

There is no need to self-medicate, since increasing immunity is not an easy task. In this regard, medical supervision is needed.

Comprehensive study of humoral immunity

An immunogram is a list of characteristics that are deciphered based on the results of a blood test. In this way, you can learn about the functioning of the immune system. However, with the procedure it is impossible to know the disease factor. Finding out whether there is immunity to a specific disease will also not work.

The immune system has a complex mechanism. Therefore, characteristics are assessed not only by number, but by their compliance and dynamics. As a rule, the following characteristics are indicated in the immunogram:

Lymphocyte count;
T-lymphocytes (recognize the antigen and communicate to B-lymphocytes);
T helper cells (the main function of which is to enhance the adaptive immune response);
Natural killer cells (large granular lymphocytes that are part of the innate immune system);
B lymphocytes (having received information, they secrete antibodies);
The level of immunoglobulins that destroy pathogenic microorganisms;
Marker of cell death.

Foreign elements captured by antibodies that should soon dissolve. When a very large number of them accumulate, this is a criterion for autoimmune diseases. That is, the body does not recognize its cells and forms antibodies to attack (increased blood sugar, damage to the myelin sheath of the nerve fibers of the brain and spinal cord, inflammatory disease of the connective tissue of the joints).

At the end of the 19th century, there was a serious debate over the structure of the immune system between the two great scientists Ilya Mechnikov and Paul Ehrlich for several years. Mechnikov argued that the body’s struggle is waged at the cellular level, and Ehrlich - that it’s all about the protective properties of blood plasma. Defending their positions, scientists discovered two components of the body's internal defense - cellular and humoral immunity, for which they were awarded the Nobel Prize.

Humoral immunity is one of the mechanisms for realizing the protective properties of the body in a liquid environment. In contrast, humoral protects extracellular spaces.

The division into cellular and humoral immunity is very arbitrary, since this is an interconnected system.

The principle of action of humoral immunity

Humoral immunity acts through various substances that can suppress the proliferation of microbes.

These substances, called humoral immune factors, are divided into two broad categories: specific and nonspecific factors.

Nonspecific factors of humoral immunity

Nonspecific factors are substances that do not have a clear specialization, but have a depressing effect on microbes in general.

These include:

extracts from body tissues;
blood serum and proteins circulating in it (interferons increase the resistance of cells to the action of viruses, C-reactive protein causes immune reactions, marking foreign objects for their subsequent destruction, proteins of the complement system are activated under the influence of participants in the immune reaction);
gland secretions can inhibit the growth of microbes;
lysozyme is an enzyme with antibacterial properties that dissolves the walls of microorganisms.

Specific factors of humoral immunity

Specific factors are antibodies or, in other words, immunoglobulins. They are produced by B lymphocytes.

Lymphocytes are white blood cells. B lymphocytes are formed in adult mammals, including humans, in the red bone marrow, spleen, lymph nodes, and Peyer's patches.

They react to antigens - foreign substances, which in this case have entered the blood or other fluids inside the body, which our body considers dangerous, block them, and phagocytes, killer cells, absorb them. Antibodies are specialized for specific antigens.

Antibodies arise in the body in various ways. The first part is passed on to the child in utero from the mother; this is a legacy of the evolution of the human species and its struggle for survival. The second part is transmitted through breast milk after birth; these are some of the antibodies that the mother was able to accumulate during her life.

Over time, the body begins to produce antibodies on its own from stem cells or after vaccination. Antibodies can be injected into a sick person. This is resorted to if there is an urgent need, because it takes some time to produce antibodies.

Moreover, during illness, the formation of antibodies occurs unevenly over time. There are two phases:

inductive (latent) phase - the first day, antibodies are released in small quantities;
productive phase - 10-15 days with a peak on the 4th day, there is a wave-like increase in their synthesis with a gradual decrease.

The body has immune memory. Some antigens are remembered for a lifetime, others for a while. When a familiar antigen reappears, antibodies appear in large quantities within the first two days, and the person either does not get sick at all or suffers the disease faster and easier than the first time.

It is on the phenomenon of immune memory that the system of revaccinations with certain periods of time between vaccinations is built.

Humoral immunity is the means by which the body protects itself from infection by producing antibodies that target foreign material in the bloodstream that is considered potentially harmful.
It is part of the adaptive immune system that is activated in response to a specific threat, as opposed to the innate immune system, which is constantly active but less effective.
Another part of the adaptive system is cellular or cell-mediated immunity, in which cells release toxins to kill invaders or attack directly, without the participation of antibodies. Together, humoral and cellular immunity are designed to protect the body from a variety of threats that can compromise it.

Working mechanisms

This form of immunity begins in specialized white blood cells known as B cells produced in the bone marrow. They recognize antigens, which are certain molecules, such as certain proteins, on the surface of a virus or bacteria.
There are different B cells dedicated to responding to a specific antigen.
The B cell will multiply, creating a huge number of individuals that release antibodies designed to attach to an antigen on the infecting organism; they essentially turn into little antibody factories in the blood, floating around to capture as many invaders as possible.
Once these antibodies are marked, the invaders will be destroyed by other immune cells.
When the invader is removed, many of the B cells created to fight that particular threat will die, but some will remain in the bone marrow and act as a "memory" of that attack.
Humans are born with a set of innate immune responses that are designed to recognize broad types of cells and organisms, but humoral immunity is acquired through exposure to viruses and bacteria. Over time, the body accumulates more “memories” of previous attacks by harmful microorganisms.

Long-term protection of the body from harmful effects

Humoral immunity can provide long-term immunity to many infectious agents. When the body is attacked by an agent, such as a virus, that it has not encountered before, it must start from scratch and usually takes several days to mount an effective immune response. During this time, the virus can multiply unchecked, causing an infection that can cause unpleasant and possibly dangerous symptoms. Only when the body has produced large quantities of suitable antibodies can it fight off the infection.
If, however, he encounters this virus again, he will usually be much better prepared, thanks to the retention of B cells created in response to the previous attack, and he will be able to immediately work to eliminate the invader.
Graft.
People can be injected with dead or inactivated forms of a dangerous virus or bacteria, which will stimulate humoral immunity without creating any threat to the body.
If at some point in the future that person is exposed to the agent, an immediate immune response should follow, eliminating it before it can cause serious damage.
Vaccination is more effective for some types of infection. Unfortunately, some viruses mutate quickly, causing changes in compounds on their surfaces that the humoral immune system uses to recognize them. This is why it is necessary to constantly develop new vaccines. People vaccinated against the rapidly mutating virus may be immune to a new strain that emerges next year because the chemicals on its surface have changed and will not be recognized by the body's B cell antigens.

Federal State Educational Institution of Higher Professional Education "Moscow State Academy of Veterinary Medicine and Biotechnology named after. K.I. Scriabin"

on the topic: “Humoral immunity”

Performed:

Moscow 2004

Introduction

ANTIGENS

antibodies, structure and functions of immunoglobulins

COMPLEMENT COMPONENT SYSTEM

alternative activation pathway

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 defective substances:

immunoglobulins,

cytokines,

complement component system,

acute phase proteins,

enzyme inhibitors that suppress the enzymatic activity of bacteria,

virus inhibitors,

numerous low-molecular 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, microelements, vitamins, etc.

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

Antigens

A antigen is a genetically foreign substance (protein, polysaccharide, lipopolysaccharide, nucleoprotein), capable, when introduced into the body or when formed in the body, to cause a specific immune response and interact with antibodies and antigen-recognizing cells.

An antigen contains several different or repeated 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 the antibody or T-cell receptor.

Antigenic properties are associated with the molecular weight, which must be at least tens of thousands. Hapten is a defective antigen in the form of a small chemical group. The hapten itself does not cause the formation of antibodies, but 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 conjugated antigen.

Antibodies, structure and functions of immunoglobulins

A
antibodies are immunoglobulins produced by B lymphocytes (plasma cells). Immunoglobulin monomers consist of two heavy (H-chain) and two light (L-chain) polypeptide chains linked by a disulfide bond. These chains have constant (C) and variable (V) regions. Papain splits immunoglobulin molecules into two identical antigen-binding fragments - Fab (Fragment antigen binding) and Fc (Fragment crystallizable). The active center of antibodies is the antigen-binding region of the Fab fragment of an immunoglobulin, formed by hypervariable regions of the H- and L-chains; binds antigen epitopes. The active center contains specific complementary regions to certain antigenic epitopes. The Fc fragment can bind complement, interacts 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. Thus, in IgG there are: V – domains of the light (V L) and heavy (V H) chains of the antibody, located in the N-terminal part of the Fab fragment; C-domains of light chain constant regions (CL); C-domains of the constant regions of heavy chains (CH 1, C H 2, C H 3). The complement-fixing region is located in the CH2 domain.

Monoclonal antibodies are homogeneous and highly specific. They are produced by a hybridoma - a population of hybrid cells obtained by merging an antibody-producing cell of a certain specificity with an “immortal” myeloma cell.

The following properties of antibodies are distinguished:

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

avidity – the strength of the bond between an antibody and an antigen and the amount of antigen bound by antibodies.

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 remaining areas are relatively unchanged. This makes it possible to isolate the variable and constant regions of the heavy and light chains in the immunoglobulin molecule. Individual portions of the variable regions (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 antibody isotype (class, subclass of immunoglobulins - IgM, IgG1, IgG2, IgG3, IgG4, IgA1, IgA2, IgD, IgE) is determined by the C-domains of the heavy chains. Isotypes reflect the diversity of immunoglobulins at the species level. When animals of one species are immunized with the blood serum of an individual of another species, antibodies are formed that recognize the isotype specificities of the immunoglobulin molecule. Each class of immunoglobulins has its own isotype specificity, against which specific antibodies can be obtained, for example, rabbit anti-mouse IgG antibodies.

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

The idiotype of antibodies is determined by the antigen-binding centers of the Fab fragments of antibodies, that is, the antigenic properties of the variable regions (V-regions). The idiotype consists of a set of idiotopes - antigenic determinants of the V regions of the antibody. Idiotypes are regions of the variable part of the immunoglobulin molecule, which themselves are antigenic determinants. Antibodies raised against such antigenic determinants (anti-idiotypic antibodies) are capable of distinguishing between antibodies of different specificities. Using anti-idiotypic sera, the same variable region can be detected on different heavy chains and in different cells.

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

IgG - the main class of immunoglobulins found in blood serum (80% of all immunoglobulins) and tissue fluids. It has a monomeric structure. 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 during 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 receipt of colostrum containing large quantities of this immunoglobulin. The content of IgG in the blood depends on antigenic stimulation: its level is extremely low in animals kept under sterile conditions. It increases rapidly when the animal is placed in normal conditions.

IgM constitutes approximately 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 first appear in membrane-bound monomeric form on the surface of B lymphocytes. It is believed that IgM appeared earlier in the phylogenesis of the immune response of vertebrates than IgG. Antibodies of this class are released into the blood in the early stages of the primary immune response. The binding of antigen to IgM causes the attachment of the Clq component of complement and its activation, which leads to the death of microorganisms. Antibodies of this class play a leading role in eliminating microorganisms from the bloodstream. If a high level of IgM is detected in the blood of newborns, 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, no significant differences were revealed in the amino acid composition of the constant regions of the light and heavy chains of IgM of different classes of vertebrates.

IgA exists in two forms: in blood serum and in the secretions of exocrine glands. Serum IgA accounts for approximately 13% of the total immunoglobulin content in the blood. Dimeric (predominant), as well as tri- and tetrameric forms are represented. 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 - a secretory component. The latter is produced by glandular epithelial cells and ensures the binding and transport of IgA into 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 act as 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 secretions, it turned out that the maximum level of slgA was found in tears, and the highest concentrations of the secretory component were in the lacrimal glands.

IgD constitutes less than 1% of the total content of immunoglobulins in 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 half-life in blood plasma (about 2.8 days). The latter may be due to the large extent 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 antigen.

IgD-secreting plasma cells 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 for lymphocytes and may be involved in the induction of immunological tolerance.

IgE is present in the blood in trace amounts, making up only 0.002% of all immunoglobulins in the blood serum. Like IgG and IgD, it has a monomeric structure. Produced primarily by plasma cells in the mucous membranes of the digestive tract and respiratory tract. The carbohydrate content of the IgE molecule is 12%. When injected subcutaneously, this immunoglobulin remains in the skin for a long time, binding to mast cells. Subsequently, the 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 obviously the protection of the mucous membranes of the body through local activation of blood plasma factors and effector cells due to the induction of an acute inflammatory response. 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 IgG, complement, and neutrophils circulating in the blood 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 and fibrinolysis, form cascade systems for effectively protecting 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. In this case, the product of one reaction serves as a catalyst for the next one. The first evidence of the existence of the complement system was obtained at the end of the 19th century. when studying the mechanisms of the body’s defense against 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 by producing antibodies that can agglutinate these cells without causing their death. The addition of fresh serum to this mixture caused death (cytolysis) of the immunized objects. This observation provided the impetus for intensive research aimed at elucidating the mechanisms of lysis of foreign cells.

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

without the participation of antibodies - alternative

with the participation of antibodies - classic

Alternative way to activate the computerelements

The first pathway of complement activation, caused by foreign cells, is more ancient from a phylogenetic point of view. A key role in activating 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 S3 is slowly activated by interaction with water and trace amounts of proteolytic enzymes in blood plasma, leading to the formation of C3b and C3a (S3 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 enzymes in the blood plasma - factor D. The resulting complex C3bBb is a C3-convertase - an enzyme that breaks down C3 into C3a and C3b.

Some microorganisms can activate C3Bb convertase with the formation of a large number 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 thioester bond is activated and the reactive C3b derivative is covalently bound to the microbial membrane. One active center of C3bBb allows a large number of C3b molecules to contact 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 into C3bI, the latter, under the influence of proteolytic enzymes, is cleaved to the final inactive peptides C3c and C3d. The next activated component, C5, interacts with membrane-bound C3b, becomes a substrate for C3bBb and is cleaved to form a short peptide C5a, with the C5b fragment remaining fixed on the membrane. Then C5b sequentially attaches C6, C7 and C8 to form a complex that promotes the orientation of the molecules of the last component C9 on the membrane. This leads to the unfolding 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 of receptors for S3b and S33 on the surface of phagocytic cells, the adhesion of microorganisms is facilitated;

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

stimulate the chemotaxis of neutrophils to the site 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 expansion of blood capillaries and increase their permeability;

c) proteinases that appear during complement activation, despite their substrate specificity, are capable of activating 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.

Classic pathway of complement activation

Initiation of the classical pathway occurs when an antibody associated with a microbe or other cell carrying foreign information binds and activates the first component of the Clq cascade. This molecule is polyvalent for antibody binding. It consists of a central collagen-like core that branches into six peptide chains, each of which ends in an antibody-binding subunit. According to electron microscopy, the entire molecule resembles a tulip. Its six lobes are formed by the C-terminal globular regions of the polypeptide chains; the collagen-like regions are twisted into a three-helical structure in each subunit. Together they form a stem-like structure due to the association of disulfide bonds in the N-terminal region. 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 the three subunits into a single complex, Ca 2+ ions are required. 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 reactions. A minority of complement in the body is activated via an alternative pathway, which can occur in absence of antibodies. This nonspecific pathway of complement activation is important when phagocytes destroy aging or damaged body cells, 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 predominant.

Cytokines

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

The following mechanisms of action of cytokines are distinguished:

Intracrine mechanism - the action of cytokines inside the producing 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.

The paracrine mechanism is the action of cytokines on nearby cells and tissues. For example, IL-1, -6, -12, -18, TNFα, produced by a macrophage, activate T-helper cells (Th0), recognizing 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 producer 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 multi-organ damage in toxic-septic conditions.

Interleukins

Currently, the structure and functions of 16 interleukins have been isolated and 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-helper cells, plays a key role in the development of inflammation, stimulates myelopoiesis and the early stages of erythropoiesis (later suppresses it, being an antagonist of erythropoietin), and is a mediator of the interaction between the immune and nervous systems. Inhibitors of IL-1 synthesis are prostaglandin E2 and glucocorticoids.

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

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

Interleukin-4. Stimulates the proliferation of B-lymphocytes activated by antibodies to IgM. Produced by T-helper cells of the Th2 type, on which it has a differentiation-stimulating 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. Produced by lymphocytes, monocytes/macrophages, fibroblasts, hepatocytes, keratinocytes, mesangial, endothelial and hematopoietic cells. The spectrum of biological action is similar to IL-1 and TNFα, participates in the development of inflammatory and 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 preT cells, causes antigen-dependent proliferation of T lymphocytes outside the thymus. Removal of the IL-7 gene in animals leads to 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 Th2 type T helper cells. Supports the proliferation of activated T-helper cells, affects erythropoiesis and mast cell activity.

Interleukin-10. Produced by T-helper cells of the Th2 type, 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, and the production of acute phase proteins.

Responsible for the safety and normal functioning of organs and systems, protecting them from dangerous agents.

Photo 1. Immunity is responsible for the body’s ability to resist threats. Source: Flickr (Danielle Scruggs)

What is humoral immunity

The humoral immune response involves molecules that are found in the blood. B-lymphocytes play a critical role in its functioning. This differs from cellular immunity, which depends on T lymphocytes.

Note! Humoral immunity is aimed at destroying pathogens that are in the blood and in the extracellular space.

B lymphocytes- these are cells of the immune system that are produced by the liver of the fetus in the womb, and after birth - in the red bone marrow contained in the tubular bones.

Each B lymphocyte has an antigen recognition receptor on its surface. Antigens are any substances that the body views as potentially dangerous. In particular, they are part of pathogenic viruses and bacteria. After contact with antigen B lymphocytes can transform into plasma cells capable of producing immunoglobulins.

Immunoglobulins (antibodies, Ig) are protein compounds that prevent the proliferation of pathogenic microorganisms and neutralize the toxins they secrete.

There are 5 classes of immunoglobulins:

They differ in composition, structure and functions.

How does humoral immunity work?

B lymphocytes are formed from stem cells in the bone marrow. After maturation, they enter the bloodstream. On their surface there are cells that can be separated from lymphocytes and circulate in the blood independently of them.

When an antigen enters the body, immunoglobulin M binds to it and inactivates it. Antibodies trigger a pattern of activation of complement (a complex of complex proteins in the blood, protein enzymes that protect against foreign agents), which leads to the destruction of the pathogen.

Once this happens, the B lymphocytes turn into plasma cells. They begin to produce immunoglobulins of different classes, designed to fight similar antigens.

Antibodies bind pathogens and prevent them from damaging body tissues.

Humoral immune response

The immune reaction, which consists of the activation of B lymphocytes and their production of immunoglobulins, is called the humoral immune response.

Note! The formation of specific antibodies designed to fight specific antigens is the main goal of the immune response. After entering the blood, immunoglobulins provide reliable protection against pathogenic substances and microorganisms.

There are two stages of the humoral immune response:

inductive - at this stage antigen recognition occurs;
productive - at this stage, B-lymphocytes turn into plasma cells and secrete antibodies, then immune reactions slow down until they stop completely.

In the productive phase of the humoral immune response, memory cells are formed, which are activated if a repeated encounter with the antigen occurs.

Photo 2. Antibodies produced in the blood are able to resist pathogenic microflora. Source: Flickr (NavySoul).

In this case, a secondary immune reaction occurs. It develops in the same way as the primary one, but proceeds much faster.

Cellular immunity

When this type of immunity works, cells of the immune system are activated. The main ones are T-killer cells, natural killer cells and macrophages.

T-killers- these are cells that fight viruses, intracellular bacteria and cancer cells. They are a type of lymphocyte. Natural killer cells are another type of lymphocyte. They are responsible for fighting viruses and cancer cells.
Macrophages- These are cells of the immune system that are capable of absorbing and digesting bacteria, the remains of dead cells and other pathogenic particles. This process is called phagocytosis, and the cells that are capable of carrying it out are called phagocytes. Macrophages are a type of phagocyte.
Cytokines- these are protein molecules that ensure the transfer of information from one immune cell to another. In this way, their activities are coordinated. These molecules are also responsible for coordinating the work of the immune system with the activities of the nervous and endocrine systems. In addition, cytokines can independently suppress viruses.

Note! Cellular immunity is responsible for the destruction of intracellular bacteria, pathogenic fungi, foreign cells and tissues, as well as cancer cells. It fights pathogens that are inaccessible to the humoral immune response.

How does cellular immunity work?

There are nonspecific and specific cellular immunity.

The first involves the capture, engulfment and digestion of pathogens by phagocytes. They gradually envelop the foreign agent, and then destroy it with the help of special enzymes.

T-killer cells, natural killer cells and other lymphocytes are responsible for specific cellular immunity.

The first to come into action are T-helper cells, which trigger the immune response. During the immune response, killer T cells interact with cells infected with viruses and intracellular bacteria, as well as cancer cells, and destroy them.

Natural killer cells, in turn, fight cells that are inaccessible to the action of killer T cells.

After the pathogens are destroyed, T-suppressor cells come into play, suppressing the immune response.