Hematology: Development of T-lymphocytes. Selection (selection) of the lymphocyte set (repertoire); selection of lymphocytes that do not respond to their own (self) antennas

Subsequently, the surviving T-lymphocytes descend into the thymus medulla, where they undergo the stage of negative (negative) selection. At the same time, they interact with thymic dendritic cells, which express complexes of histocompatibility molecules with peptides obtained from various molecules of their own organism. As a result of such an interaction, only those T-lymphocytes survive, whose antigen-recognizing receptor is not able to recognize these complexes, and the rest die by induced apoptosis, which is achieved due to the production of glucocorticoids. Due to the mechanism of negative selection, prevention of autoimmune diseases is carried out.

In general, only about 2-5% of all cells that arrived in the thymus for differentiation survive, which indicates an extremely strict selection of T-lymphocytes and a high degree of reliability of the mechanism for the formation of central immune tolerance. However, not all available autoantigens are still present in the thymus, so it is necessary to implement mechanisms to maintain tolerance in the periphery.

The essence of the clonal selection theory of F. Burnet is that in the process of maturation of lymphocytes, a strict culling of cells occurs according to the following criteria:

Inability to recognize the MHC 1 and MHC 2 receptors of the cells of one's own body;

The ability to recognize self antigens presented on MHC 1 and MHC 2.

Cells that have the above characteristics are to be destroyed. The remaining lymphocytes continue to differentiate and become progenitors of clones - groups of lymphocytes that have an antigen-recognizing receptor of the same specificity.

Selection of T-lymphocytes

Immature T-lymphocytes migrate from the bone marrow to the thymus cortex and begin to rapidly divide. In the thymus cortex, in the process of contact with thymic epithelial cells that express both MHC I and MHC II molecules, positive selection is carried out. Lymphocytes capable of interacting with MHC molecules receive a positive stimulus - a signal to reproduce, and cells unable to interact with MHC receive a negative signal to self-destruction (apoptosis).

Further, the positively selected lymphocytes migrate to the thymus medulla, and a negative selection of T-lymphocytes occurs at the border of the cortex and the medulla. Negative selection is carried out in the process of their interaction with dendritic cells and macrophages, which present the body's own antigens.

Autoaggressive T-lymphocytes receive a signal for self-destruction (negative selection), autotolerant - continue to multiply and leave the thymus medulla, settle in peripheral organs immune system. It has been shown that the selection process fails and about 95% of T-lymphocytes die.

Lymphocytes located in the cortical layer of the thymus initially have both CD4 and CD8 receptors on the membrane. Further, cells that recognize MHC I lose CD4 and become CD8+, i.e. turn into CTLs, while cells that recognize MHC II, on the contrary, lose CD8 and turn into CD4+, i.e. in T-helpers.

T-lymphocytes that have undergone differentiation and selection in the thymus are called "naive" T-lymphocytes. After encountering the appropriate antigen, they become primed or effector by T-lymphocytes, ready to receive cytokine signals for activation.

B-lymphocyte selection

AT bone marrow immature B-lymphocytes undergo negative selection. Lymphocytes that are able to bind their own antigens with their surface antigen-recognizing IgM receptor receive a signal for self-destruction (apoptosis) and die. Negatively selected B-lymphocytes divide, and each of them forms a group of descendants, a clone, with the same specificity. Mature B-lymphocytes exit the bone marrow into the bloodstream and colonize the lymphoid organs.

Lecture 6. Immunity disorders

Immune disorders include:

Hypersensitivity reactions;

autoimmune reactions;

immunodeficiency states.

Hypersensitivity reactions. Classification of Gell and Coombs - 4 types of hypersensitivity reactions.

MIRV type 1.

Asthma, hay fever, eczema, hives, food allergies.

Allergens: medicinal substances, heterologous serum, plant pollen, feces of dust micromites, food products (eggs, milk, crabs, fish, etc.).

Factors contributing to the penetration of allergens into the mucous membrane are diesel exhaust particles (DEP) contained in the urban atmosphere.

hereditary predisposition to allergic reactions Type 1 is associated with the HLA-B8 and DR3 alleles.

Diagnosis: staging skin tests.

Treatment: desensitization - subcutaneous injection of increasing doses of the allergen, as a result, there is a switch to the predominant synthesis of IgG.

Prevention: exclusion of contact with the allergen; if necessary, the introduction of heterologous therapeutic serum - a fractional introduction according to Bezredka. Prescribing antihistamines.

HSR type 2 - cytotoxic reactions involving IgG and complement. They are observed if antibodies react with an antigen located on the cell membrane. In this case, complement is added to the resulting complex, the last fractions of which (C5-C9) are called perforins. The protein molecules of these fractions are embedded in the cell membrane, forming a large pore through which water enters the cell. The result is cell lysis. This type of hypersensitivity can develop with prolonged use of drugs that can be adsorbed on red blood cells; An example is the antiarrhythmic drug quinidine. An example of HSR type 2 is hemolytic disease of the newborn with Rh conflict (reticulocytosis). Another example is thrombocytopenic purpura.

Type 3 HSR are associated with the formation of a large number of immune complexes when a large amount of a foreign protein enters the body without prior sensitization, for example, when therapeutic or prophylactic heterologous antisera are administered. As a result of a temporary complement deficiency, small immune complexes are deposited in the walls of blood vessels, joints, and renal glomeruli. After completing the complement deficiency, it is fixed on small immune complexes (MICs) located in the tissues. Macrophages migrate to the formed large immune complexes (LIC), which absorb the NIC and secrete cytokines that cause an inflammatory response. The result of type 3 HSR is the development of serum sickness, the manifestations of which are vasculitis, arthritis and glomerulonephritis.

Type 3 HSR can manifest itself in the form of the so-called Arthus phenomenon. Unlike serum sickness, the Arthus phenomenon is a violent local inflammatory reaction, which is accompanied by tissue necrosis at the site of antigen injection. A prerequisite for the development of the Arthus reaction is the preliminary sensitization of the body with this antigen (foreign protein) and the presence in the blood serum of a high concentration of antibodies to this antigen.

HSR type 4 occur with the participation of cytotoxic lymphocytes.

There are 3 types of HSR type 3: contact, tuberculin and granulomatous.

Contact hypersensitivity is characterized by an eczematous reaction at the site of exposure to the antigen. Sensitization organism occurs, as a rule, compounds of nickel, chromium, substances that are part of detergents, i.e. haptens. The main APCs in contact hypersensitivity are dendritic cells of the skin - Langerhans cells. The reaction of contact hypersensitivity proceeds in 2 stages: sensitization and manifestations. The sensitization period lasts about 2 weeks. Hapten, having penetrated the skin, combines with protein. This complex is taken up by dendritic cells, which subsequently present the hapten-protein complex to T-lymphocytes. In a sensitized organism, after repeated contact with the antigen within 48-72 hours, T-lymphocytes migrate to the site of contact with the antigen and a local inflammatory reaction develops.

Tuberculin type hypersensitivity. Tuberculin is a filtrate of a killed tubercle bacillus culture containing bacterial antigens. It was first obtained by R. Koch.

A hypersensitivity reaction to tuberculin occurs only in individuals in whose body live tuberculosis pathogens are present. After intradermal injection of tuberculin, monocytes and sensitized T-lymphocytes migrate to the injection site, which secrete cytokines (TNF-alpha and beta). Cytokines increase the permeability of the vascular wall and an inflammatory infiltrate is formed at the injection site of tuberculin, which reaches its maximum size after 48 hours.

Granulomatous hypersensitivity. Granulomatous reactions develop when the infectious agent remains viable in macrophages, such as in tuberculosis and leprosy. An activated macrophage, inside which live pathogens are located, is transformed into an epithelioid cell, which actively produces cytokines - TNF. Epithelioid cells fuse with each other to form giant Langgans cells. In the center of the granuloma are epithelioid cells, Langgans cells and macrophages. The center of the granuloma is surrounded by T-lymphocytes. Outside of T-lymphocytes there is a zone of proliferating fibroblasts, which delimit the zone of inflammation from healthy tissues.

CENTRAL ORGANS OF IMMUNE

Central organs of immunity: thymus

Cells of the cortex and medulla of the thymus

Thymus - biological clock: thymus mass

Thymus - biological clock

T-lymphocyte maturation in the thymus: stage 1

T-lymphocyte maturation in the thymus: stage 2

CENTRAL ORGANS OF IMMUNE: positive and negative selection (selection) of cells

Thymocyte selection intensity

The structure of T receptors

What cells come to the periphery from the thymus?

The structure of the T receptor complex (TCR / CD3)

The structure of co-receptors (CD 4 or CD8)

The process of maturation of thymocytes: stages of formation of coreceptors

Rearrangement of T-cell receptor genes

Rearrangement of genes encoding the -chain of the T receptor

Rearrangement of the T cell receptor (TCR) genes

Rearrangement of genes encoding the T receptor by somatic recombination

Rearrangement of genes encoding the α-chain of the T receptor, assembly of the T receptor

Costimulation (immune response); lack of costimulation (anergy, tolerance). immune response).

Costimulatory molecular interactions on APC and T-lymphocyte: CD40-CD 40L and complex B7-CD 28

Mature T-lymphocytes: a life path in the periphery

Effector T cell emigration into tissue during viral infection

Mature T-lymphocytes: recirculating and resident

Stages of development of B lymphocyte

Developmental stages of B cells

Developmental stages of B cells

Development of B cells in the bone marrow

Postulates of the theory of clonal selection

Genes of immunoglobulin (Ig) molecules

Rearrangement of genes encoding light chains of the Ig molecule

Positive and negative selection of B lymphocytes in the bone marrow

Genes of Ig molecules

Further stages in the development of B-lymphocytes

Release of mature B cells to the periphery

Scheme of B-lymphocyte response to antigen

Subpopulations of B lymphocytes: B1 and B2

Subpopulation of B1 lymphocytes

Questions for lesson number 3a

Test tasks for lesson No. 3

Test tasks for lesson No. 3

Test tasks for lesson number 3

TCR) and various co-receptors (surface markers). They play an important role in the acquired immune response. They provide recognition and destruction of cells carrying foreign antigens, enhance the action of monocytes, NK cells, and also take part in switching immunoglobulin isotypes (at the beginning of the immune response, B cells synthesize IgM, later switch to the production of IgG, IgE, IgA).

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

T-helpers

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

T-killers

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

γδ T-lymphocytes

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

T-lymphocytes that provide central regulation of the immune response.

All T cells originate from red bone marrow hematopoietic stem cells that migrate to the thymus and differentiate into immature thymocytes. The thymus creates the microenvironment necessary for the development of a fully functional T cell repertoire that is MHC-limited and self-tolerant.

Thymocyte differentiation is divided into different stages depending on the expression of various surface markers (antigens). On the very early stage, thymocytes do not express CD4 and CD8 co-receptors and are therefore classified as double negative (eng. Double Negative (DN)) (CD4-CD8-). In the next step, thymocytes express both co-receptors and are called double positive. Double Positive (DP)) (CD4+CD8+). Finally, at the final stage, cells are selected that express only one of the co-receptors (eng. Single Positive (SP)): either (CD4+) or (CD8+).

The early stage can be divided into several sub-stages. So, at the substage DN1 (eng. Double Negative 1), thymocytes have the following combination of markers: CD44+CD25-CD117+. Cells with this combination of markers are also called early lymphoid progenitors. Early Lymphoid Progenitors (ELP)). Progressing in their differentiation, ELP cells actively divide and finally lose the ability to transform into other cell types (for example, B-lymphocytes or myeloid cells). Moving on to the DN2 substage (eng. Double Negative 2), thymocytes express CD44+CD25+CD117+ and become early T cell progenitors. Early T-cell Progenitors (ETP)). During the DN3 substage Double Negative 3), ETP cells have a combination of CD44-CD25+ and enter the process of β-selection.

β selection

The T-cell receptor genes consist of repeating segments belonging to three classes: V (eng. variables), D (English) diversity) and J (eng. joining). In the process of somatic recombination, gene segments, one from each class, are joined together (V(D)J recombination). The combined sequence of V(D)J segments results in unique sequences for the variable domains of each of the receptor chains. The random nature of the formation of sequences of variable domains makes it possible to generate T cells capable of recognizing a large number of various antigens, and, as a result, provide more effective protection against rapidly evolving pathogens. However, this same mechanism often leads to the formation of non-functional subunits of the T-cell receptor. The genes encoding the TCR-β receptor subunit are the first to undergo recombination in DN3 cells. To exclude the possibility of formation of a non-functional peptide, the TCR-β subunit forms a complex with the invariable pre-TCR-α subunit, forming the so-called. pre-TCR receptor. Cells unable to form a functional pre-TCR receptor die by apoptosis. Thymocytes that successfully pass β-selection move to the DN4 substage (CD44-CD25-) and undergo a positive selection process.

positive selection

Cells that express the pre-TCR receptor on their surface are still not immunocompetent, as they are unable to bind to major histocompatibility complex (MHC) molecules. Recognition of MHC molecules by the TCR receptor requires the presence of CD4 and CD8 coreceptors on the surface of thymocytes. The formation of a complex between the pre-TCR receptor and the CD3 co-receptor leads to inhibition of rearrangements of the β subunit genes and, at the same time, causes activation of the expression of the CD4 and CD8 genes. Thus thymocytes become double positive (DP) (CD4+CD8+). DP thymocytes actively migrate to the thymus cortex where they interact with cortical epithelial cells expressing both MHC complexes (MHC-I and MHC-II). Cells that are unable to interact with the MHC complexes of the cortical epithelium undergo apoptosis, while cells that have successfully completed this interaction begin to actively divide.

negative selection

Thymocytes that have undergone positive selection begin to migrate to the cortico-medullary border of the thymus. Once in the medulla, thymocytes interact with the body's own antigens presented on the MHC complexes of the medullary thymic epithelial cells(mTEK). Thymocytes actively interacting with their own antigens undergo apoptosis. Negative selection prevents the emergence of self-activating T cells capable of causing autoimmune diseases, being an important element of the body's immunological tolerance.

T-lymphocytes that successfully passed positive and negative selection in the thymus, got to the periphery of the body, but did not have contact with the antigen, are called naive T-cells (eng. Naive T cells). The main function of naive T cells is to respond to pathogens previously unknown to the body's immune system. After naive T cells recognize the antigen, they become activated. Activated cells begin to actively divide, forming many clones. Some of these clones develop into effector T cells that perform functions specific to that type of lymphocyte (eg, release cytokines in the case of T helpers or lyse diseased cells in the case of T killers). The other half of the activated cells transform into memory T cells. Memory cells remain in an inactive form after initial contact with an antigen until repeated interaction with the same antigen occurs. Thus, memory T cells store information about previously acting antigens and form a secondary immune response, which is carried out in a shorter time than the primary one.

Interactions of the T-cell receptor and co-receptors (CD4, CD8) with the major histocompatibility complex are important for successful activation of naive T cells, but are not sufficient by themselves for differentiation into effector cells. For the subsequent proliferation of activated cells, the interaction of the so-called. costimulatory molecules. For T helpers, these molecules are the CD28 receptor on the surface of the T cell and immunoglobulin B7 on the surface of the antigen presenting cell.

The function of T-lymphocytes in the human body

Lymphocytes are cells of the leukocyte link of the blood, performing a number of important functions. A decrease or increase in the level of these cells may indicate the development of a pathological process in the body.

The process of formation and function of lymphocytes

Lymphocytes are produced in the bone marrow, after which they migrate to the thymus gland, where, under the influence of hormones and epithelial cells, they undergo changes and differentiate into subgroups with different functions. In the human body there are also secondary lymphoid organs, these include the lymph nodes, the spleen. The spleen is also the site of lymphocyte death.

Distinguish between T and B lymphocytes. 10-15% of all lymphocytes in the lymph nodes are transformed into B-lymphocytes. Thanks to these cells, the human body acquires lifelong immunity to past diseases - at the first contact with a foreign agent (virus, bacterium, chemical compound), B-lymphocytes produce antibodies to it, remember the pathogenic element and, upon repeated interaction, mobilize immunity to destroy it. Also, due to the presence of B-lymphocytes in the blood plasma, the effect of vaccination is achieved.

In the thymus gland, about 80% of lymphocytes are converted into T-lymphocytes (CD3 is a common cell marker). T cell receptors detect and bind antigens. T-cells, in turn, are divided into three subspecies: T-killers, T-helpers, T-suppressors. Each of the types of T-lymphocytes is directly involved in the elimination of a foreign agent.

T-killers destroy and break down cells affected by bacteria and viruses, cancer cells. T-killers are the main element of antiviral immunity. The function of T-helpers is to enhance the adaptive immune response, such T-cells secrete special substances that activate the response of T-killers.

T-killers and T-helpers are effector T-lymphocytes, the function of which is to provide an immune response. There are also T-suppressors - regulatory T-lymphocytes that regulate the activity of effector T-cells. By controlling the intensity of the immune response, regulatory T-lymphocytes prevent the destruction of healthy body cells and prevent the occurrence of autoimmune processes.

Normal lymphocyte counts

Normal values ​​of lymphocytes are different for each age - this is due to the peculiarities of the development of the immune system.

Volume decreases with age thymus where most of the lymphocytes mature. Until the age of 6, it is lymphocytes that predominate in the blood, as a person grows older, neutrophils become leading.

• newborn children - 12-36% of the total number of leukocytes;
• 1 month of life - 40-76%;
• at 6 months - 42-74%;
• at 12 months - 38-72%;
• up to 6 years - 26-60%;
• up to 12 years - 24-54%;
• 13-15 years old - 22-50%;
• adult - 19-37%.

To determine the number of lymphocytes, a general (clinical) blood test is performed. With the help of such a study, it is possible to determine the total number of lymphocytes in the blood ( this indicator usually expressed as a percentage). To obtain absolute values, the calculation must take into account the total content of leukocytes.

A detailed determination of the concentration of lymphocytes is carried out during the implementation of an immunological study. The immunogram reflects the indicators of B and T lymphocytes. The norm of T-lymphocytes is 50-70%, (50.4 ± 3.14) * 0.6-2.5 thousand. Normal B-lymphocytes - 6-20%, 0.1-0.9 thousand. The ratio between T-helpers and T-suppressors is normally 1.5-2.0.

Increase and decrease in the level of T-lymphocytes

An increase in T-lymphocytes in the immunogram indicates an overactive immune system and the presence of immunoproliferative disorders. A decrease in the level of T-lymphocytes indicates a lack of cellular immunity.

With any inflammatory process, the level of T-lymphocytes is reduced. The degree of decrease in the concentration of T-cells is influenced by the intensity of inflammation, however, this pattern is not observed in all cases. If T-lymphocytes are elevated in the dynamics of the inflammatory process, this is a favorable sign. However elevated level T-cells against the background of severe clinical symptoms, on the contrary, is an unfavorable sign that indicates the transition of the disease to chronic form. After complete elimination of inflammation, the level of T-lymphocytes reaches normal values.

The reason for the increase in the level of T-lymphocytes may be such disorders as:

• lymphocytic leukemia (acute, chronic);
• Cesari's syndrome;
• immune hyperactivity.

T-lymphocytes can be lowered in the following pathologies:

• chronic infectious diseases(HIV, tuberculosis, purulent processes);
• decreased production of lymphocytes;
• genetic disorders that cause immunodeficiency;
• tumors of lymphoid tissue (lymphosarcoma, lymphogranulomatosis);
• renal and heart failure of the last stage;
• destruction of lymphocytes under the influence of certain medications (corticosteroids, cytostatics) or radiation therapy;
• T-cell lymphoma.

The level of T-lymphocytes must be assessed in combination with other blood elements, taking into account the symptoms and complaints of the patient. Therefore, only a qualified specialist should interpret the results of a blood test.

What to do if the allergy does not go away?

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In addition, allergies lead to diseases such as asthma, urticaria, dermatitis. And the recommended medicines for some reason are not effective in your case and do not fight the cause in any way ...

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Lymphocytes: types and functions, norm and pathology in children and adults

Each "family" of cells of the leukocyte link is interesting in its own way, however, it is difficult not to notice and ignore lymphocytes. These cells are heterogeneous within their species. Receiving specialization through “learning” in the thymus gland (thymus, T-lymphocytes), they acquire high specificity for certain antigens, turn into killers who kill the enemy at the first stage, or assistants (helpers) who command other populations of lymphocytes at all stages accelerating or suppressing the immune response. T-lymphocytes remind B-cells, also lymphocytes, concentrated in lymphoid tissue and waiting for a command that it is time to start antibody formation, because the body cannot cope. Later, they themselves will participate in the suppression of this reaction, if the need for antibodies disappears.

Basic properties and functions, varieties of lymphocytes

Lymphocytes (LYM) are rightfully called the main figure of the human immune system. They, maintaining the genetic constancy of homeostasis (internal environment), are able to recognize "their own" and "alien" by the signs known to them. AT human body they solve a number of important tasks:

• Synthesize antibodies.
• Lyse foreign cells.
• They play a major role in transplant rejection, however, this role can hardly be called positive.
• Carry out immune memory.
• They are engaged in the destruction of their own defective mutant cells.
• Provide sensitization ( hypersensitivity, which is also not very useful for the body).

The lymphocyte community has two populations: T cells that provide cellular immunity and B-cells, which are entrusted with the function of providing humoral immunity, they realize the immune response through the synthesis of immunoglobulins. Each of the populations, depending on its purpose, is divided into varieties. All T-lymphocytes within a species are morphologically uniform, but differ in the properties of surface receptors.

The T cell population includes:

1. T-helpers (helpers) - they are ubiquitous.
2. T-suppressors (suppress the reaction).
3. T-killers (killer lymphocytes).
4. T-effectors (accelerators, amplifiers).
5. Immunological memory cells from T-lymphocytes, if the process ended at the level of cellular immunity.

In the B-population, the following types are distinguished:

• Plasma cells that enter the peripheral blood only in an extreme situation (irritation of the lymphoid tissue).
• V-killers.
• V-helpers.
• B-suppressors.
• Memory cells from B-lymphocytes, if the process has gone through the stage of antibody formation.

In addition, in parallel there is an interesting population of lymphocytes, which are called null (neither T nor B). It is believed that they turn into T- or B-lymphocytes and become natural killers (NK, N-killers). These cells are produced by proteins that have the unique ability to “drill” pores located in the membranes of “enemy” cells, for which NK was called perforins. Natural killers, meanwhile, should not be confused with killer T cells, they have different markers (receptors). NKs, unlike T-killers, recognize and destroy foreign proteins without developing a specific immune response.

You can talk about them for a long time and a lot

The rate of lymphocytes in the blood is 18 - 40% of all cells of the leukocyte link, which corresponds to absolute values ​​​​in the range of 1.2 - 3.5 x 10 9 / l.

As for the norm in women, they have more of these cells physiologically, therefore, an increased content of lymphocytes in the blood (up to 50 - 55%) associated with menstruation or pregnancy is not considered a pathology. In addition to gender and age, the number of lymphocytes depends on the psycho-emotional state of a person, nutrition, temperature. environment, in a word, these cells react to many external and internal factors, however, a level change of more than 15% is clinically significant.

The norm in children has a wider range of values ​​- 30-70%, this is due to the fact that the child's body only gets acquainted with the outside world and forms its own immunity. The thymus gland, spleen, lymphatic system and other organs involved in the immune response function much more actively in children than in an adult (the thymus generally disappears in old age, and other organs consisting of lymphoid tissue take over its function).

Table: norms in children of lymphocytes and other leukocytes by age

It should be noted that the number of cells contained in the peripheral blood is a small fraction of the circulating fund, and most of them are represented by T-lymphocytes, which, like all "relatives", originated from a stem cell, separated from the community in the bone brain and went to the thymus for training, in order to then carry out cellular immunity.

B cells also go a long way from stem cells, through immature forms. Some of them die (apoptosis), and some of the immature forms, called "naive", migrate to the lymphatic organs for differentiation, turning into plasma cells and mature full-fledged B-lymphocytes, which will permanently move through the bone marrow, lymphatic system, spleen, and only a tiny fraction of them will go into the peripheral blood. Lymphocytes enter the lymphoid tissue through capillary venules, and they enter the blood through the lymphatic pathways.

There are few B-lymphocytes in the peripheral blood, they are antibody-formers, therefore, in most cases, they are waiting for the command to start humoral immunity from those populations that are everywhere and everyone knows - lymphocytes, called helpers or helpers.

Lymphocytes live in different ways: some for about a month, others for about a year, and still others remain for a very long time or even for life, along with information received from a meeting with a foreign agent (memory cell). Memory cells are located in different places, they are widespread, very mobile and long-lived, which provides long-term immunization or lifelong immunity.

All the complex relationships within a species, interaction with antigens that have entered the body, the participation of other components of immunity, without which the destruction of a foreign substance would become impossible, is a complex multi-stage process that is practically incomprehensible to an ordinary person, so we will simply omit it.

Don't panic

An increase in lymphocytes in the blood is called lymphocytosis. An increase in the number of cells above the norm in percentage terms implies relative lymphocytosis, in absolute terms, respectively, absolute. In this way:

Elevated lymphocytes in an adult are said to be if their content steps over the upper limit of the norm (4.00 x 10 9 / l). In children, there is a certain (not very strict) gradation by age: in infants and preschoolers, a value from 9.00 x 10 9 / l and above is taken as “a lot of lymphocytes”, and in older children the upper limit decreases to 8.00 x 10 9 / l.

Discovered in general analysis some increase in lymphocytes in an adult healthy person should not scare you with your numbers if:

1. This was preceded by hard physical labor, active sports, relaxing on the beach to get a "chocolate" tan, a wedding or a friend's name day.
2. The analyzes belong to the young healthy woman. Perhaps she has a period before, during or immediately after her period. In this phase of the cycle, aseptic inflammation develops in the endometrium with necrosis, edema, and leukocyte infiltration, which, however, is not considered as a real inflammatory process, this is a period of desquamation - a completely physiological phenomenon.
3. A pregnant woman donated blood. It is known that immunity decreases during pregnancy. This happens because the body, trying to prevent the reaction between the fetus and the mother (after all, the fetus carries 50% of someone else's information), adjusts and reduces its own defense force, while increasing the level of circulating lymphocytes.

Reaction or sign of a new pathology?

Lymphocytes are full diagnostic indicators in the general blood test, so their increase can also tell the doctor something, for example, the number of lymphocytes above the norm is detected when inflammatory processes, and this does not happen at the initial stage of the disease and, moreover, not during the incubation period. Lymphocytes are elevated during the transition phase of an acute process to subacute or chronic, and also when inflammation subsides and the process begins to subside, which is somewhat of an encouraging sign.

In the analyzes of some people, sometimes such phenomena can be observed when lymphocytes are increased and neutrophils are lowered. Such changes are typical for:

• Connective tissue diseases ( rheumatoid arthritis, systemic lupus erythematosus);
• Some viral (ARVI, hepatitis, HIV), bacterial and fungal infections;
• Endocrine disorders (myxedema, thyrotoxicosis, Addison's disease, etc.);
• Diseases of the central nervous system;
• Side effect of drugs.

Very high values ​​​​(pronounced lymphocytosis) are observed in fairly serious diseases:

1. Chronic lymphocytic leukemia;
2. Hyperplastic processes lymphatic system(Waldenström's macroglobulinemia)

Obviously, many of these diseases are childhood infections that lymphocytes must remember. A similar situation occurs during vaccination, memory cells will store information about someone else's antigenic structure for many years, in order to give a decisive rebuff in the event of a second meeting.

Unfortunately, not all infections provide stable lifelong immunity and not all diseases can be defeated by vaccination, for example, vaccines have not yet been found against syphilis and malaria, but the prevention of tuberculosis and diphtheria begins literally from birth, due to which these diseases are becoming less common and less often.

Low lymphocytes are more dangerous

This happens in the following pathological conditions:

1. Severe infectious diseases;
2. Secondary immunodeficiency;
3. Pancytopenia (decrease in all blood cells);
4. aplastic anemia;
5. Lymphogranulomatosis;
6. Severe pathological processes of viral genesis;
7. Separate chronic diseases liver;
8. Radioactive exposure for a long time;
9. The use of corticosteroid drugs;
10. Terminal stage of malignant tumors;
11. Kidney disease with insufficiency of function;
12. Insufficiency and circulatory disorders.

Obviously, if the lymphocytes are lowered, then suspicion will fall on a serious pathology faster.

Especially a lot of concern and questions are caused by low lymphocytes in a child. However, in such cases, the doctor will first of all think about the high allergic status of a small organism or a congenital form of immunodeficiency, and then he will search for the listed pathology if the first options are not confirmed.

The body's immune response to an antigenic stimulus, in addition to lymphocytes, is realized by other factors: various populations of cellular elements (macrophages, monocytes, eosinophils, and even representatives of the erythrocyte link - the erythrocytes themselves), bone marrow mediators, and the complement system. The relationship between them is very complex and not fully understood, for example, some “silent” population helps lymphocytes produce antibodies, which for the time being is blocked by the synthesis of their own antibodies, and only a special signal at the peak of the immune response forces the cells to start working ... All this makes the extra Just remember that we sometimes do not even know about our abilities. Perhaps the presence of hidden potential sometimes allows you to survive, it would seem, in incredible conditions. And in an attempt to defeat some kind of infection (at least the flu, at least something worse), we hardly think about some kind of lymphocytes and about the role that these small ones do not visible to the eye, cells will play for a big win.

Types of T-lymphocytes

This group of cells consists of several types, also called lymphocyte subpopulations. For a long time, only three of their types were distinguished: these are T-lymphocytes - helpers, killers and suppressors. However, in last years, starting from the th, the idea of ​​their existing varieties has undergone another transformation. In addition to known cells, experts have identified the existence of other types: memory T-cells and amplifier cells. Consider everything existing species lymphocytes in more detail.

T-killers:

T-killers are the best known subpopulation of lymphocytes. They have the ability to destroy defective cells of the body, coming into direct contact with them. They are also called cytotoxic lymphocytes: "cyto" in translation means "cell", the meaning of the word "toxic" does not need to be explained.

T-killers, strictly exercising immune surveillance, react aggressively to a foreign protein. They cause the reaction of rejection of the transplant during organ transplantation. For this reason, when a person is transplanted with any organ, he is given special medicines for some time that depress the immune system: they reduce the increased content of lymphocytes and disrupt their interaction. Otherwise, any such operation would end in the rejection of a new organ or tissue, and perhaps even the death of the patient who undergoes such an intervention.

The mechanism of work of these cells is interesting. Unlike phagocytes, which actively attack, devour, and digest foreign particles, T-killers behave, at first glance, rather restrainedly. With their processes, they touch the object, and then break the contact and "go about their business." The cell touched by the lymphocyte dies after some time... Why?

The fact is that during their “death kiss”, T-killers leave particles of their membrane on the surface of the cell they destroy. At the points of contact, the particles "corrode" the surface of the object of attack. As a result, a through hole is actually formed in a cell doomed to death. It loses potassium ions, sodium ions and water enter it - since the cell barrier is broken, its internal environment begins to communicate directly with the external one ... As a result, the cell swells with water that has penetrated inside it, cytoplasmic proteins come out of it, organelles are destroyed ... It dies, and further phagocytes approach it and devour its remnants. This is such a terrible punishment that the body prepares for all cells that have been recognized by the immune system as “wrong” or alien.

T-helpers:

The task of helpers at first glance is also quite obvious. These are helper cells (“help” means “help”). Who or what do they help? They induce, stimulate the immune response: under their influence, cytotoxic lymphocytes intensify their work. Also, helpers transmit information about the presence of a foreign protein in the body to B-lymphocytes, which secrete protective antibodies against them. Finally, helpers have a stimulating effect on the work of phagocytes, mainly monocytes.

T-suppressors:

"Suppression" means "suppression". If T-lymphocytes helpers enhance the immune response, then suppressors, on the contrary, suppress it. Moreover, these cells do not sabotage immune processes at all and do not harm our health. They simply regulate the strength of the immune response, which allows the immune system to respond with restraint and moderate force to stimuli.

Lymphocytes-amplifiers:

After the aggressor has entered the body, an increased content of lymphocytes is noted in the blood and tissues. Their number increases literally within a few hours and can increase more than 2 times. Why does the increase in the number of cells occur so quickly? It's just that the body has a certain supply of them.

Mature, full-fledged lymphocytes live in the spleen and thymus. Their difference from the rest lies only in the fact that they "have not decided" which type of lymphocytes they belong to. These are amplifier cells; if necessary, they are involved in increasing the number of other T-lymphocytes.

Memory T cells:

Having coped with the next threat, lymphocytes remember it. In the human body, a special clone of cells is formed, which store these “memories”. Each clone carries information about a certain type of threat. If some aggressor, with which the immune system has already met, enters the body, then the corresponding clone multiplies and quickly forms a secondary immune response.

The conversation about the types of lymphocytes and their functions is quite long. Here this topic was presented in the most acceptable and simple form, without loading with specific terms and incomprehensible names. Let's hope that any reader, even without medical education, roughly figured out how they function in his body different types T-lymphocytes.

From all this, one can draw an obvious conclusion: in order to live a full healthy life you need to have a strong immune system. It is necessary that the processes that many do not think about, and even more people do not even know, take place as they should.

If nature has not endowed you with stable immunity, you should think about how to independently take on its strengthening. To do this, you can start taking the drug Transfer Factor. It contains information molecules, with the help of which lymphocytes normally communicate with each other, control various processes and coordinate them. Compensating for the lack of natural information molecules, the tool is one of the most recommended and effective drugs to normalize the functioning of the immune system, improve health and prevent diseases.

Immune cells have memory

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The stage of cell differentiation described above is characterized by the fact that a large number of T- and B-lymphocytes appear in the body, which, with the help of their antigen-recognizing receptors (TAGRR and VAGRR), have the ability to recognize both their own (self, auto) and others (non-self , allo) antigens. This is potentially dangerous, since auto-reactive T- and B-lymphocytes, under certain circumstances, can cause a breakdown in tolerance and the development of autoimmune diseases. Therefore, the next stage in the development of the immune system is to select (select) among a large pool of T- and B-lymphocytes those that would not react with their own antigens, but at the same time retain the ability to distinguish between foreign antigens. So, the third stage of antigen-independent differentiation of lymphoid cells is the development (induction) of tolerance (reactivity, tolerance) towards autoantigens.

The primary function of TAGRR on thymocytes and VAGRR on precursors of B-lymphocytes is that they transmit a signal that leads to the selection (selection) of lymphoid cells that respond to auto-AG.

The secondary function of TAGRR and VAGRR is participation in the immune response at the stage of recognition of foreign antigens.

There are three ways of selection (selection) of lymphoid cells.

1. Destruction (deletion) of autoreactive T- and B-lymphocytes with high avidity (affinity) for auto-AG - negative selection; occurs in the central organs of the immune system.

2. Induction (establishment) of anergy of autoreactive lymphoid cells. This selection pathway is implemented on the periphery, while lymphocytes do not die due to their low avidity in relation to auto-AG. This form of negative selection reserves T- and B-cells in a state of immunological tolerance (non-response), but very often they retain autoreactive receptors on their surface.

Since the embryonic period is a period of formation of tolerance of the immune system, it is possible to achieve tolerance to foreign antigens if they are artificially introduced into the body during this period.

3.Positive selection; is that in the thymus and bone marrow, the contact of immature lymphocytes and pre-B-lymphocytes with auto-AG induces the maturation of T- and B-lymphocytes, but since the cell signal is insufficient due to low avidity, cell proliferation does not occur, which means there is no immune response.

We also consider one more - the fourth mechanism of tolerance due to the formation of active suppression on the periphery as a result of the function of T-regulatory cells or an imbalance of T-helpers of the 1st and 2nd types, which will be discussed below.

As already mentioned, autoreactive T- and B-lymphocytes remaining in the body under certain circumstances can cause a breakdown in tolerance and the development of an autoimmune disease.

At the stage of tolerance induction in the thymus, from thymocytes that carry two differentiation antigens CD4 and CD8 and are the so-called CD4+CD8+ cells, subpopulations of T-lymphocytes are formed: T-helpers (CD4+CD8-cells) and T-killers/suppressors ( CD4-CD8+ cells).

This ends the period of antigen-independent differentiation of T- and B-lymphocytes, they leave the thymus gland and bone marrow and settle in the T- and B-zones (respectively) of the peripheral organs of the immune system. The spreading lymphocytes are called mature resting cells, ready for an immune response. All of them are in the G(0) phase of the cell cycle.

It should be remembered that T- and B-cells express antigen-recognizing receptors on their surface, which are able to recognize only one antigen (more precisely, one determinant (epitope)).

Thus, the special organs where the differentiation of hematopoietic stem cells occurs are: for T-lymphocytes - the thymus, for B-lymphocytes - in the embryonic period - the liver, in the adult organism - the bone marrow.

There are the followingthe main stages of development and differentiation of T- and B-lymphocytes.

The first stage is the production of a large number of T- and B-lymphocytes with specificity for various antigens (including the antigens of one's own body). This step has two important steps:

1. The early precursor stage, when a surrogate immunoglobulin L-chain appears on the surface of the future B-lymphocyte. and on the surface of the future T-lymphocyte - GP-33 (one of the elements of TAGRR);

2. The stage of an immature precursor, when an immunoglobulin molecule or VGRAR appears on B-lymphocytes, and TAGRR with alpha-, beta- or gamma-, delta-chains appears on the surface of the T-lymphocyte.

The second stage is the elimination from a huge number of mature precursors of those cells that are reactive with respect to their own antigens. As a result of this “training” of the immune system, a state of tolerance develops.

The third stage is the maturation of the remaining lymphoid cells and their transformation into mature resting T- and B-lymphocytes capable of responding to foreign antigens.