Pre-treatment of t- and b-lymphocytes. T lymphocytes What is the biological significance of different types of T lymphocytes

In the process of evolution, humans have developed two immune systems - cellular and humoral. They arose as a means of combating substances that are perceived as foreign. These substances are called antigens. In response to the introduction of an antigen into the body, depending on the chemical composition, dose and form of administration, the immune reaction will be different: humoral or cellular. The division of immune functions into cellular and humoral is associated with the existence of T- and B-lymphocytes. Both lineages of lymphocytes develop from a lymphatic stem cell in the bone marrow.

T lymphocytes. Cellular immunity. Thanks to T-lymphocytes, the body's cellular immune system occurs. T lymphocytes are formed from hematopoietic stem cells that migrate from the bone marrow to the thymus gland.

The formation of T lymphocytes is divided into two periods: antigen-independent and antigen-dependent. The antigen-independent period ends with the formation of antigen-reactive T lymphocytes. During the antigen-dependent period, the cell prepares to encounter the antigen and multiplies under its influence, resulting in the formation of various types of T cells. Antigen recognition occurs due to the fact that on the membrane of these cells there are receptors that recognize antigens. As a result of recognition, cells multiply. These cells fight against antigen-carrying microorganisms or cause rejection of foreign tissue. T cells regularly move from lymphoid elements into the blood and interstitial environment, which increases the likelihood of them encountering antigens. There are different subpopulations of T lymphocytes: killer T cells (i.e. fighters), which destroy cells with antigen; T helper cells, which help T and B lymphocytes respond to antigens, etc.

T-lymphocytes, upon contact with an antigen, produce lymphokines, which are biologically active substances. With the help of lymphokines, T lymphocytes control the function of other leukocytes. Various groups of lymphokines have been identified. They can both stimulate and inhibit the migration of macrophagocytes, etc. Interferon produced by T lymphocytes inhibits the synthesis of nucleic acids and protects the cell from viral infections.

B lymphocytes. Humoral immunity. During the antigen-dependent period, B lymphocytes are stimulated by the antigen and settle in the spleen and lymph nodes, follicles and reproduction centers. Here they are converted to plasma cells. The synthesis of antibodies - immunoglobulins - occurs in plasma cells. Humans produce five classes of immunoglobulins. B lymphocytes take an active part in the immune processes of antigen recognition. Antibodies interact with antigens located on the surface of cells or with bacterial toxins and accelerate the uptake of antigens by phagocytes. The antigen-antibody reaction is the basis of humoral immunity.

During an immune response, both humoral and cellular immunity mechanisms are usually at work, but to varying degrees. Thus, with measles, humoral mechanisms predominate, and with contact allergies or rejection reactions, cellular immunity predominates.

Lymphocytes are special cells in the body of a living being. They are responsible for protecting it from external irritants, infections, and viruses. But the concept of “lymphocytes” itself is quite broad and general. Within themselves, these cells will be divided into several more groups. In this article we will take a closer look at one of them - T-lymphocytes. Functions, types of cells, their normal indicators, deviations from the norm in human blood - all these topics will be discussed further.

Origin of cells

Where are T-lymphocyte cells formed? Although their main place of “residence” is the bloodstream (lymphocytes also live in other tissues), they are not formed there. The place of their “birth” is the bone red marrow. It is known as the hematopoietic tissue of the body. That is, in addition to lymphocytes, erythrocytes and white blood cells (neutrophils, leukocytes, monocytes) will also be formed here.

The structure of lymphocytes

The "anatomical" features are as follows:

  • Large kernel of round or oval shape.
  • There will be no granularity in the cytoplasm (the contents of the cell itself).
  • If there is little cytoplasm in a cell, it is called narrow-plasma, if there is a lot - wide-plasma.

In terms of their structure, the lymphocytes that inhabit the blood will be slightly different from their counterparts that live in other tissues. And that's okay. Moreover, cells “living” in one place will also have some external differences among themselves.

Types of lymphocytes

In addition to the types of T lymphocytes, there are various groupings of these cells in general. Let's look at them.

The first classification is by size:

  • Small ones.
  • Big ones.

The second classification is based on the functions performed:

  • B lymphocytes. They can recognize foreign particles and produce deadly antibodies against them. In other words, they are responsible for humoral immunity.
  • T lymphocytes. The main function is responsibility for cellular immunity. They come into contact with foreign bodies and destroy them.
  • NK cells. Natural killers that can recognize cancerous, defective cells and destroy them. Responsible for maintaining the normal cellular composition of the entire body.

Types of T lymphocytes

This group of lymphocytes within itself will be divided into several more types:

  • Killer T cells.
  • T-helpers.
  • T-suppressors.
  • Memory T cells.
  • Amplicators-lymphocytes.

Killer T-cells: what type?

These are the most famous representatives of the group of T-lymphocytes. Their main task is the destruction of inferior, defective cells of the body. Another name for the group is cytotoxic T-lymphocytes. In other words, they are responsible for eliminating cells (“cyto”) that have a toxic effect on the entire body.

The main function of killer T cells is immune surveillance. Cells aggressively act on foreign protein. It is this useful function that can be harmful when organs are transplanted to a person. T-killers strive to quickly destroy the “stranger,” not realizing that it is he who is able to save the body. Therefore, the patient takes medications for some time after organ transplantation that suppress the immune system. The drugs reduce the percentage of killer T cells in the blood and disrupt their interaction. Thanks to this, the transplanted organ takes root, and the patient does not face complications or death.

The mechanism of action of this type of lymphocyte on a foreign element is very interesting. Phagocytes, for example, aggressively “attack” a “stranger” for its subsequent devouring and digestion. T-killers against their background are “noble killers”. They touch the object with their processes, then break contact and move away. Only after such a “kiss of death” does the foreign microorganism die. Why?

When touched, killer T cells leave a piece of their membrane on the surface of the body. It has properties that allow it to corrode the surface of the object of attack - up to the formation of through holes. Through these holes, potassium ions leave the microorganism, and water and sodium ions take their place. The cellular barrier is broken, there is no longer a boundary between the internal and external environment. The microorganism is inflated by the water entering it, the cytoplasmic proteins and organelles are destroyed. The remains of the “stranger” are then devoured by phagocytes.

Helpers

The main function of these T-lymphocyte cells is to help. Hence their name, which comes from an English word translated the same way.

But who or what do these T-lymphocytes come to the rescue of? They are designed to induce and stimulate an immune response. It is under the influence of T-helpers that the T-killers, with whom we have already become acquainted, will activate their work.

Helpers will begin to transmit data about the presence of a foreign protein in the body. And this is valuable information for B lymphocytes - they, in turn, begin to secrete certain protective antibodies against it.

T helper cells also stimulate the work of another type of “guard” cells - phagocytes. In particular, they interact closely with monocytes.

Suppressors

This term itself means "suppression". From here the function of T-suppressors becomes clear to us. Helpers in our body will activate the protective, immune function, and these T-lymphocytes, on the contrary, will suppress it.

Don't think that this has any negative impact on the system. Suppressor T cells are responsible for regulating the immune response. After all, somewhere you need to react to a certain stimulus with restraint and moderation, and somewhere you need to accumulate all available forces against it.

Amplifiers

Let us now turn to the functions of T-lymphocytes of this group. After one or another aggressor penetrates the body, the content of lymphocytes immediately increases in the blood and tissues of a living creature. For example, in just a few hours their volume can double!

What is the reason for such a rapid growth of the army of protective cells? Maybe the fact is that somewhere in the body they are “hidden” in reserve for the time being?

This is true. Some mass of mature, full-fledged lymphocytes lives in the thymus and spleen. Only up to a certain point these cells are not “defined” with their purpose and function. They will be called amplifiers. If necessary, these cells turn into one or another type of T-lymphocyte.

Memory cells

Experience, as you know, is the main weapon. Therefore, having coped with any threat, our T-lymphocytes remember it. In turn, the body produces special cells that will store this information until a new “battle” with this foreign element. These elements will be memory T cells.

A secondary aggressor (of the type that the immune system has already resisted) enters the body. The memory T cell recognizes it. Then this particle begins to actively multiply in order to give the foreign organism a secondary worthy immune response.

Normal indicators of T-lymphocytes in human blood

In this category it is impossible to provide any specific figure - normal values ​​​​will vary depending on the age of the person. This is due to the peculiarities of the development of his immune system. With age, the volume of the thymus gland will decrease. Therefore, if in childhood lymphocytes predominate in the blood, then with adulthood they transfer the leading position to neutrophils.

The level of T-lymphocytes in the blood helps determine a general clinical blood test. The normal indicators here are:

  • (50.4±3.14)*0.6-2.5 thousand.
  • 50-70%.
  • The “helper/suppressor” ratio is 1.5-2.

What do increased and decreased indicators indicate?

An increased level of T-lymphocytes in the blood may indicate the following:

  • Chronic or acute lymphocytic leukemia.
  • Hyperactive immunity.
  • Sézary's syndrome.

On the contrary, a reduced content of T-elements indicates the following pathologies and diseases:

  • Chronic infections - purulent processes, HIV, tuberculosis.
  • Reduced production of lymphocytes.
  • Genetic diseases causing immunodeficiency.
  • Tumors of lymphoid tissue.
  • Renal and heart failure observed at the last stage.
  • T-cell lymphoma.
  • The patient is taking medications that destroy lymphocytes.
  • Consequence of radiation therapy.

We got acquainted with T-lymphocytes - the protective cells of our body. Each type performs its own special function.

The total number of T-lymphocytes in the blood of adults is normal - 58-76%, absolute number - 1.1-1.7-10"/l.

Mature T-lymphocytes are “responsible” for cellular immune reactions and carry out immunological surveillance of antigenic homeostasis in the body. They are formed in the bone marrow and undergo differentiation in the thymus gland, where they are divided into effector (killer T-lymphocytes, delayed-type hypersensitivity T-lymphocytes) and regulatory (helper T-lymphocytes, suppressor T-lymphocytes). In accordance with this, T-lymphocytes perform two important functions in the body: effector and regulatory. The effector function of T lymphocytes is specific cytotoxicity towards foreign cells. The regulatory function (T-helper - T-suppressor system) is to control the intensity of the development of a specific reaction of the immune system to foreign antigens. A decrease in the absolute number of T-lymphocytes in the blood indicates a lack of cellular immunity, an increase indicates immune hyperactivity and the presence of immunoproliferative diseases.

The development of any inflammatory process is accompanied almost throughout its entire duration by a decrease in the content of T-lymphocytes. This is observed in inflammation of a wide variety of etiologies: various infections, nonspecific inflammatory processes, destruction of damaged tissues and cells after surgery, trauma, burns, heart attack, destruction of malignant tumor cells, trophic destruction, etc. The decrease in the number of T-lymphocytes is determined by the intensity of the inflammatory process, but this pattern is not always observed. T-lymphocytes react most quickly of all immunocompetent cells to the onset of the inflammatory process. This reaction manifests itself even before the development of the clinical picture of the disease. An increase in the number of T-lymphocytes during the inflammatory process is a favorable sign, and a high level of T-lymphocytes with pronounced clinical manifestations of such a process, on the contrary, is an unfavorable sign, indicating a sluggish course of the inflammatory process with a tendency to become chronic. The complete completion of the inflammatory process is accompanied by normalization of the number of T-lymphocytes. An increase in the relative number of T-lymphocytes is not of great clinical significance. However, an increase in the absolute number of T-lymphocytes in the blood is very important for the diagnosis of leukemia. Diseases and conditions leading to changes in the number of T-lymphocytes in the blood are presented in table. 7.19.



Table 7.19. Diseases and conditions leading to changes in the amount

T lymphocytes (CD3) in the blood


Continuation of Table 7.19

Helper T lymphocytes (CD4) in the blood

The number of T-helper lymphocytes in the blood of adults is normal - 36-55%, absolute

Quantity - 0.4-1.110"/l-

T-lymphocytes are helpers (inducers) of the immune response, cells that regulate the strength of the body’s immune response to a foreign antigen, control the constancy of the body’s internal environment (antigenic homeostasis) and cause increased production of antibodies. An increase in the number of helper T-lymphocytes indicates immune hyperactivity, while a decrease indicates immunological deficiency.

The ratio of T-helpers and T-suppressors in the peripheral blood is of key importance in assessing the state of the immune system, since the intensity of the immune response depends on this. Normally, cytotoxic cells and antibodies should be produced as much as they are necessary to remove a particular antigen. Insufficient activity of T-suppressors leads to the predominance of the influence of T-helpers, which contributes to a stronger immune response (pronounced antibody production and/or prolonged activation of T-effectors). Excessive activity of T-suppressors, on the contrary, leads to rapid suppression and abortive course of the immune response and even phenomena of immunological tolerance (an immunological response to the antigen does not develop). With a strong immune response, the development of autoimmune and allergic processes is possible. The high functional activity of T-suppressors in such a response does not allow the development of an adequate immune response, and therefore the clinical picture of immunodeficiency is dominated by infections and a predisposition to malignant growth. The CD4/CD8 index of 1.5-2.5 corresponds to a normergic state, more than 2.5 - hyperactivity, less than 1.0 - immunodeficiency. In severe cases of the inflammatory process, the CD4/CD8 ratio may be less than 1. This ratio is of fundamental importance when assessing the immune system in patients with AIDS. In this disease, the human immunodeficiency virus selectively infects and destroys CO4 lymphocytes, as a result of which the CD4/CD8 ratio decreases before values ​​significantly less than 1.

An increase in the CD4/CD8 ratio (up to 3) is often observed in the acute phase of various inflammatory diseases due to an increase in the level of T helper cells and a decrease in T suppressor cells. In the middle of an inflammatory disease, there is a slow decrease in T-helper cells and an increase in T-suppressor cells. When the inflammatory process subsides, these indicators and their ratio are normalized. An increase in the CD4/CD8 ratio is characteristic of almost all autoimmune diseases: hemolytic anemia, immune thrombocytopenia, Hashimoto's thyroiditis, pernicious anemia, Goodpasture's syndrome, systemic lupus erythematosus, rheumatoid arthritis. An increase in the CD4/CD8 ratio due to a decrease in the level of CD8 in the listed diseases is usually detected at the height of an exacerbation with high activity of the process. A decrease in the CD4/CD8 ratio due to an increase in CD8 levels is characteristic of a number of tumors, in particular Kaposi's sarcoma. Diseases and conditions leading to changes in the number of CD4 in the blood are presented in table. 7.20.

Table 7.20. Diseases and conditions leading to changes in the number of CD4 in the blood


Continuation of the table. 7.20

Their main function is to ensure the body’s protective response to irritants (pathogenic microorganisms, histamines, parasites, etc.). Lymphocytes are also responsible for the “immune memory” of the body. Unlike other types of leukocytes, they no longer fight with external agents, but with internal ones, for example, with their own affected cells (mutating, cancerous, viral, etc.).

Types of lymphocytes and their function

Once in the blood, lymphocytes live in their “basic” form for a couple of days, then the body’s glands distribute them into various functional subtypes, which allows lymphocytes to more accurately respond to pathogenic microorganisms.

T lymphocytes

The thymus gland (thymus) is responsible for the creation of T-lymphocytes from 80% of the basic ones. After “training,” T-lymphocytes, in turn, are divided into subtypes:

  • T-helpers (helpers);
  • T-killers (killers);
  • T-suppressors (limiters).

Assassins are naturally trained to attack foreign agents and eliminate them. Helpers produce special components that support and improve the function of killer cells. Suppressors literally limit the immune response to invasion to prevent the active breakdown of healthy cells in the body.

B lymphocytes

From the basic set, up to 15% of white cells become B lymphocytes. They are considered one of the most important immune cells. It is enough for them to encounter a foreign agent (bacterium, histamine, fungus, virus, etc.) once in order to forever remember it and the way to fight it, which makes the immune response in the future faster and more accurate. Thanks to the adaptation function of B lymphocytes, immune resistance appears for life and also increases the effectiveness of vaccination.

NK lymphocytes

Naturalkiller (NK) is translated from English as “natural killers,” which most accurately corresponds to the purpose of these agents. Only 5% of basic lymphocytes degenerate into NK lymphocytes. This subspecies is entirely responsible for eliminating its own cells if they form markers of viral or cancer damage.

Indications for analysis

Lymphocyte analysis is carried out as part of a clinical (general) blood test with a leukocyte formula. It is prescribed for the diagnosis of the following pathologies:

  • general inflammatory processes in acute and chronic form;
  • autoimmune diseases;
  • infectious, viral or fungal infections;
  • suppuration and sepsis;
  • internal bleeding;
  • oncology;
  • allergic reaction;
  • pathological course of pregnancy;
  • diseases of the hematopoietic and circulatory system;
  • pathologies of the lymphatic system;
  • radiation sickness;
  • monitoring the effectiveness of treatment.

Norm of lymphocytes

White cells are assessed in the same way as leukocytes, based on absolute (LYM#) and relative (LYM%) indicators.

If abnormal values ​​are detected, additional tests are prescribed that make it possible to accurately determine the number of lymphocyte subtypes. Typically, such a need arises to assess the activity of the immune process, response and memory.

Lymphocytes are increased (lymphocytosis)

As a result of the analysis, an excess of the norm of lymphocytes established by age and individual physiological indicators may be revealed. This deviation is called lymphocytosis and indicates the following:

  • there are inflammatory or infectious processes, viral, bacterial pathologies in the body;
  • in the pathogenesis of the disease there is a peak or transition to the early stage of recovery;
  • the presence of a disease that, as a rule, occurs once in a lifetime and develops lasting immunity (chickenpox, mononucleosis, rubella, measles and others);
  • poisoning of the body with heavy metals (lead), chemical components (arsenic, tetrachloroethane), and some medications. The level of lymphocytes in this case will allow us to assess the size and danger of the dose taken;
  • oncological processes.

Lymphocytes are low (lymphopenia)

The number of lymphocytes can decrease in three cases:

    The body released lymphocytes to eliminate the foreign agent, the white cells died, and the analysis was carried out precisely at this moment (even before the maturation of the new “defenders”). This could happen early in the disease process (before the peak). Sometimes low lymphocytes also cause “long-term” pathologies, such as AIDS, HIV and tuberculosis.

    Treatment with certain groups of drugs, for example, corticosteroids, cytostatics, etc.

  • The organs and systems responsible for hematopoiesis and specifically for the formation of lymphocytes were affected. In this case, the cause of low lymphocyte levels may be:

    • all types of anemia (iron deficiency, folate deficiency, aplastic);
    • blood diseases (leukemia);
    • lymphosarcoma, lymphogranulomatosis;
    • cancer tumors and methods of their treatment (chemo- and radiation therapy);
    • Itsenko-Cushing's disease.

A low level of lymphocytes often indicates serious and even incurable pathologies.

The analysis is deciphered by a hematologist, in consultation with a diagnostician, infectious disease specialist and oncologist. The sooner the analysis is carried out, the greater the likelihood of identifying the disease at an early stage and providing effective treatment for the patient.

Preparation for the procedure

Preparation for analysis involves the following steps:

  • Before donating blood, you should not eat food for 10-12 hours. Therefore, the analysis is prescribed in the morning (usually before 12 o’clock), except in cases where the level of lymphocytes needs to be monitored regularly. In infants, the procedure is carried out 1.5-2 hours after feeding.
  • You can drink water only without gas, and abstain from it 1-2 hours before the procedure. Juices, hot drinks, soda, etc. prohibited.
  • 24 hours before the procedure, you must avoid alcohol, spicy and heavy foods, and 2 hours before you stop smoking or using nicotine substitutes.
  • Before donating blood, you need to inform your doctor about taking medications and undergoing physiotherapeutic or other treatment courses. It is advisable to do the analysis before or 2 weeks after treatment.
  • It is recommended to take a test (including a repeat test) in the laboratory of the hospital where further examination and treatment will take place.

For standard microscopic examination, capillary blood is taken from a finger or a vein. In newborns, blood can be collected from the heel.

If the laboratory uses modern counter-cytometers, then at least 5 ml of material is needed for the study. In this case, blood is drawn from a vein.

What can affect the result

  • A nurse’s mistake during blood sampling, as well as violation of the rules for storing and transporting biomaterial;
  • Laboratory assistant’s mistake when studying the material;
  • Dishonesty of a patient who violated the rules for preparing for analysis;
  • Any, even minor, stress or physical activity immediately before the test;
  • Medical procedures performed on the eve of the procedure (radiography, physiotherapy, puncture, MRI, CT, massage, etc.);
  • A sudden change in body position before donating blood can also give a false positive result;
  • Menstruation in women. Doctors advise carrying out the test no earlier than 4 days after the end of menstrual bleeding;
  • Pregnancy. The patient should warn the doctor about the early stages of pregnancy before taking blood.

    agammaglobulinemia(agammaglobulinaemia; a- + gammaglobulins + Greek. haima

    blood; synonym: hypogammaglobulinemia, antibody deficiency syndrome) is the general name for a group of diseases characterized by the absence or sharp decrease in the level of immunoglobulins in the blood serum; autoantigens

    (auto-+ antigens) - the body’s own normal antigens, as well as antigens that arise under the influence of various biological and physicochemical factors, in relation to which autoantibodies are formed; autoimmune reaction

    -- the body's immune response to autoantigens; (allergy allergy ; Greek allos other, different +

    ergon action) - a state of altered reactivity of the body in the form of increased sensitivity to repeated exposure to any substances or to components of its own tissues; Allergy is based on an immune response that causes tissue damage;

    active immunity

  • immunity resulting from the body's immune response to the introduction of an antigen;

    • The main cells that carry out immune reactions are T- and B-lymphocytes (and their derivatives - plasmacytes), macrophages, as well as a number of cells interacting with them (mast cells, eosinophils, etc.). T lymphocytes, B lymphocytes Lymphocytes The lymphocyte population is functionally heterogeneous. lymphocytes (0-cells). Lymphocytes develop from undifferentiated lymphoid bone marrow precursors and, upon differentiation, receive functional and morphological characteristics (presence of markers, surface receptors), detected by immunological methods.

    T lymphocytes 0-lymphocytes (null) are devoid of surface markers and are considered as a reserve population of undifferentiated lymphocytes. - the most numerous population of lymphocytes, making up 70-90% of blood lymphocytes. They differentiate in the thymus gland - the thymus (hence their name), enter the blood and lymph and populate T-zones in the peripheral organs of the immune system - lymph nodes (deep part of the cortex), spleen (periarterial sheaths of lymphoid nodules), in single and multiple follicles of various organs, in which, under the influence of antigens, T-immunocytes (effector) and memory T-cells are formed. T-lymphocytes are characterized by the presence of special receptors on the plasmalemma that are capable of specifically recognizing and binding antigens. These receptors are products of immune response genes. T lymphocytes provide cellular

    immunity, participate in the regulation of humoral immunity, produce cytokines under the influence of antigens. In the population of T-lymphocytes, several functional groups of cells are distinguished: cytotoxic lymphocytes (TC), or Killer T cells (Tk), T helper cells (Tx), T-suppressors (Tch). Tcs participate in cellular immunity reactions, ensuring the destruction (lysis) of foreign cells and their own altered cells (for example, tumor cells). Receptors allow them to recognize proteins of viruses and tumor cells on their surface. In this case, the activation of TC (killers) occurs under the influence

    histocompatibility antigens

    on the surface of foreign cells.

    A decrease in the number of Tx in the blood leads to a weakening of the body’s defense reactions (these individuals are more susceptible to infections). A sharp decrease in the number of Tx in individuals infected with the AIDS virus was noted.

    Tc are capable of inhibiting the activity of Tx, B-lymphocytes and plasma cells. They are involved in allergic reactions and hypersensitivity reactions. Tc suppress the differentiation of B lymphocytes.

    One of the main functions of T lymphocytes is the production cytokines, which have a stimulating or inhibitory effect on cells involved in the immune response (chemotactic factors, macrophage inhibitory factor - MIF, nonspecific cytotoxic substances, etc.).

    Natural killers. Among the lymphocytes in the blood, in addition to the TCs described above, which perform the function of killers, there are so-called natural killers (NK, N.K.

  • ), which are also involved in cellular immunity. They form the first line of defense against foreign cells and act immediately, quickly destroying cells. NKs in their own body destroy tumor cells and cells infected with a virus. TCs form a second line of defense, since their development from inactive T lymphocytes takes time, so they come into action later than NKs. NK are large lymphocytes with a diameter of 12-15 microns, have a lobulated nucleus and azurophilic granules (lysosomes) in the cytoplasm.

    • Development of T- and B-lymphocytes

  • The ancestor of all cells of the immune system is the hematopoietic stem cell (HSC). HSCs are localized in the embryonic period in the yolk sac, liver, and spleen. In the later period of embryogenesis, they appear in the bone marrow and continue to proliferate in postnatal life. From the BMSC, a lymphopoiesis progenitor cell (lymphoid multipotent progenitor cell) is formed in the bone marrow, which generates two types of cells: pre-T cells (precursor T cells) and pre-B cells (precursor B cells).

    • Pre-T cells migrate from the bone marrow through the blood to the central organ of the immune system - the thymus gland.

    Even during embryonic development, a microenvironment is created in the thymus that is important for the differentiation of T lymphocytes. In the formation of the microenvironment, a special role is given to the reticuloepithelial cells of this gland, capable of producing a number of biologically active substances. Pre-T cells migrating into the thymus acquire the ability to respond to microenvironmental stimuli. Pre-T cells in the thymus proliferate and transform into T lymphocytes carrying characteristic membrane antigens (CD4+, CD8+). T-lymphocytes generate and “deliver” into the blood circulation and thymus-dependent zones of peripheral lymphoid organs 3 types of lymphocytes: Tc, Tx and Tc. “Virgin” T-lymphocytes migrating from the thymus gland (virgin T-lymphocytes) are short-lived. Specific interaction with the antigen in peripheral lymphoid organs serves as the beginning of the processes of their proliferation and differentiation into mature and long-lived cells (T-effector and memory T-cells), which make up the majority of recirculating T-lymphocytes.

    Not all cells migrate from the thymus gland. Some T-lymphocytes die. There is an opinion that the cause of their death is the attachment of an antigen to an antigen-specific receptor. There are no foreign antigens in the thymus gland, so this mechanism can serve to remove T-lymphocytes that can react with the body’s own structures, i.e. perform the function of protection against autoimmune reactions. The death of some lymphocytes is genetically programmed (apoptosis). - cluster of differentiation- differentiation cluster) is based on groups of monoclonal antibodies that react with the same differentiation antigens.

    Multiclonal antibodies to a number of differentiation antigens of human T-lymphocytes have been obtained. When determining the total population of T cells, monoclonal antibodies of CD specificities (CD2, CD3, CDS, CD6, CD7) can be used.

    Differentiation antigens of T cells are known, which are characteristic either of certain stages of ontogenesis, or of subpopulations differing in functional activity.

    Thus, CD1 is a marker of the early phase of T-cell maturation in the thymus. During the process of thymocyte differentiation, CD4 and CD8 markers are simultaneously expressed on their surface. However, subsequently the CD4 marker disappears from some cells and remains only on a subpopulation that has ceased to express the CD8 antigen. Mature CD4+ cells are Tx. CD8 antigen is expressed on approximately ⅓ of peripheral T cells that mature from CD4+/CD8+ T lymphocytes.

    The CD8+ T cell subset includes cytotoxic and suppressor T lymphocytes. Antibodies to the CD4 and CD8 glycoproteins are widely used to distinguish and separate T cells into Tx and Tx, respectively.

    In addition to differentiation antigens, specific markers of T lymphocytes are known.

    T-cell antigen receptors are antibody-like heterodimers consisting of α- and β-chains of polypeptides. Each chain is 280 amino acids long, and the large extracellular portion of each chain is folded into two Ig-like domains: one variable (V) and one constant (C). The antibody-like heterodimer is encoded by genes that assemble from multiple gene segments during T cell development in the thymus.

    There are antigen-independent and antigen-dependent differentiation and specialization of B and T lymphocytes. proliferation and differentiation of T- and B-lymphocytes occur when they encounter antigens in peripheral lymphoid organs, and effector cells and memory cells (retaining information about the active antigen) are formed.

    The resulting T-lymphocytes form a pool long-lived, recirculating lymphocytes, and B lymphocytes - short-lived cells.

66. Characteristics of B-lymphocytes.

B lymphocytes are the main cells involved in humoral immunity. In humans, they are formed from red bone marrow HSCs, then enter the blood and further populate the B-zones of peripheral lymphoid organs - the spleen, lymph nodes, and lymphoid follicles of many internal organs. Their blood contains 10-30% of the entire population of lymphocytes.

B lymphocytes are characterized by the presence of surface immunoglobulin receptors (SIg or MIg) for antigens on the plasmalemma. Each B cell contains 50,000...150,000 antigen-specific SIg molecules. In the population of B lymphocytes there are cells with different SIgs: the majority (⅔) contain IgM, a smaller number (⅓) - IgG and about 1-5% - IgA, IgD, IgE. The plasmalemma of B lymphocytes also contains complement receptors (C3) and Fc receptors.

When exposed to an antigen, B lymphocytes in peripheral lymphoid organs are activated, proliferate, and differentiate into plasma cells that actively synthesize antibodies of various classes that enter the blood, lymph, and tissue fluid.

B cell differentiation

Precursors of B cells (pre-B cells) further develop in birds in the bursa of Fabricius (bursa), where the name B lymphocytes comes from, and in humans and mammals - in the bone marrow.

The bursa of Fabricius (bursa Fabricii) is the central organ of immunopoiesis in birds, where the development of B lymphocytes occurs, located in the cloaca. Its microscopic structure is characterized by the presence of numerous folds covered with epithelium, in which lymphoid nodules are located, bounded by a membrane. The nodules contain epithelial cells and lymphocytes at various stages of differentiation. During embryogenesis, a medullary zone is formed in the center of the follicle, and a cortical zone is formed at the periphery (outside the membrane), into which lymphocytes from the medullary zone probably migrate. Due to the fact that only B-lymphocytes are formed in the bursa of Fabricius in birds, it is a convenient object for studying the structure and immunological characteristics of this type of lymphocyte. The ultramicroscopic structure of B lymphocytes is characterized by the presence of groups of ribosomes in the form of rosettes in the cytoplasm. These cells have larger nuclei and less dense chromatin than T lymphocytes due to increased euchromatin content.

B lymphocytes differ from other cell types in their ability to synthesize immunoglobulins. Mature B lymphocytes express Ig on the cell membrane. Such membrane immunoglobulins (MIg) function as antigen-specific receptors.

Pre-B cells synthesize intracellular cytoplasmic IgM but do not have surface immunoglobulin receptors. Bone marrow virgin B lymphocytes have IgM receptors on their surface. Mature B lymphocytes carry immunoglobulin receptors of various classes on their surface - IgM, IgG, etc.

Differentiated B-lymphocytes enter the peripheral lymphoid organs, where, under the influence of antigens, proliferation and further specialization of B-lymphocytes occur with the formation of plasmacytes and memory B-cells (MB).

During their development, many B cells switch from producing antibodies of one class to producing antibodies of other classes. This process is called class switching. All B cells begin their antibody synthesis activities by producing IgM molecules, which are embedded in the plasma membrane and serve as receptors for the antigen. Then, even before interacting with the antigen, most B cells proceed to the simultaneous synthesis of IgM and IgD molecules. When a virgin B cell switches from producing membrane-bound IgM alone to simultaneously producing membrane-bound IgM and IgD, the switch probably occurs due to a change in RNA processing.

When stimulated by antigen, some of these cells become activated and begin to secrete IgM antibodies, which predominate in the primary humoral response.

Other antigen-stimulated cells switch to producing IgG, IgE, or IgA antibodies; Memory B cells carry these antibodies on their surface, and active B cells secrete them. IgG, IgE, and IgA molecules are collectively called secondary class antibodies because they appear to be formed only after antigenic stimulation and predominate in secondary humoral responses.

With the help of monoclonal antibodies, it was possible to identify certain differentiation antigens, which, even before the appearance of cytoplasmic µ-chains, make it possible to classify the lymphocyte carrying them as a B-cell line. Thus, the CD19 antigen is the earliest marker that allows a lymphocyte to be classified as a B-cell. It is present on pre-B cells in the bone marrow and on all peripheral B cells.

The antigen detected by monoclonal antibodies of the CD20 group is specific for B lymphocytes and characterizes later stages of differentiation.

On histological sections, the CD20 antigen is detected on B cells of the germinal centers of lymphoid nodules and in the cortex of the lymph nodes. B lymphocytes also carry a number of other (eg, CD24, CD37) markers.

67. Macrophages play an important role in both natural and acquired immunity of the body. The participation of macrophages in natural immunity is manifested in their ability to phagocytose and in the synthesis of a number of active substances - digestive enzymes, components of the complement system, phagocytin, lysozyme, interferon, endogenous pyrogen, etc., which are the main factors of natural immunity. Their role in acquired immunity is the passive transfer of antigen to immunocompetent cells (T and B lymphocytes) and the induction of a specific response to antigens. Macrophages are also involved in ensuring immune homeostasis by controlling the proliferation of cells characterized by a number of abnormalities (tumor cells).

For the optimal development of immune reactions under the influence of most antigens, the participation of macrophages is necessary both in the first inductive phase of immunity, when they stimulate lymphocytes, and in its final phase (productive), when they participate in the production of antibodies and the destruction of antigen. Antigens phagocytosed by macrophages induce a stronger immune response compared to those that are not phagocytosed by them. Blockade of macrophages by introducing a suspension of inert particles (for example, carcass) into the animal's body significantly weakens the immune response. Macrophages are able to phagocytose both soluble (for example, proteins) and corpuscular antigens. Corpuscular antigens cause a stronger immune response.

Some types of antigens, for example pneumococci, containing a carbohydrate component on the surface, can be phagocytosed only after preliminary opsonization. Phagocytosis is greatly facilitated if the antigenic determinants of foreign cells are opsonized, i.e. connected to an antibody or a complex of antibody and complement. The opsonization process is ensured by the presence of receptors on the macrophage membrane that bind part of the antibody molecule (Fc fragment) or part of complement (C3). Only IgG class antibodies can directly bind to the macrophage membrane in humans when they are in combination with the corresponding antigen. IgM can bind to the macrophage membrane in the presence of complement. Macrophages are able to “recognize” soluble antigens, such as hemoglobin.

There are two stages in the antigen recognition mechanism that are closely related to each other. The first stage involves phagocytosis and digestion of the antigen. In the second stage, polypeptides, soluble antigens (serum albumins) and corpuscular bacterial antigens accumulate in the phagolysosomes of the macrophage. Several introduced antigens can be found in the same phagolysosomes. The study of the immunogenicity of various subcellular fractions revealed that the most active antibody formation is caused by the introduction of lysosomes into the body. The antigen is also found in cell membranes. Most of the processed antigen material released by macrophages has a stimulating effect on the proliferation and differentiation of T- and B-lymphocyte clones. A small amount of antigenic material can persist for a long time in macrophages in the form of chemical compounds consisting of at least 5 peptides (possibly in connection with RNA).

In the B-zones of the lymph nodes and spleen there are specialized macrophages (dendritic cells), on the surface of their numerous processes many antigens are stored that enter the body and are transmitted to the corresponding clones of B-lymphocytes. In the T-zones of lymphatic follicles there are interdigitating cells that influence the differentiation of T-lymphocyte clones.

Thus, macrophages take a direct active part in the cooperative interaction of cells (T- and B-lymphocytes) in the body’s immune reactions.