T-helpers, what is it? Find out what it means T-helpers are increased or decreased. Pretreatment of T- and B-lymphocytes T lymphocytes respond

What is the norm of lymphocytes in the blood? Is there a difference in their number in men and women, children and adults? Now we'll tell you everything. The level of lymphocytes in the blood is determined during general clinical tests for the purpose of primary diagnosis of the presence of infectious diseases, allergic reactions, and, if necessary, an assessment side effects from medications and the effectiveness of the chosen treatment.

Determining the amount of activated lymphocytes is not a routine laboratory test and is carried out only when indicated.

This analysis is not performed separately from the general immunological examination of the patient or the determination of other leukocyte cells (eosinophils, monocytes, lymphocytes in the blood, etc.) since it has no diagnostic value in isolation.

lymphocytes- These are white blood cells (a type of leukocytes), through which the protective function of the human body from foreign infectious agents and its own mutant cells is realized.

Abs lymphocytes- this is the absolute number of this type of cells, determined by the formula:

Total white blood cell count * Lymphocyte count (%)/100

Activated lymphocytes are divided into 3 subpopulations:

• T-lymphocytes - mature in the thymus, are responsible for the implementation of the cellular type of the immune response (direct interaction immune cells with pathogens). They are divided into T-helpers (they take part in antigen presentation of cells, the severity of the immune response and in the synthesis of cytokines) and cytotoxic T-lymphocytes (recognize foreign antigens and destroy them due to the release of toxins or the introduction of perforins that damage the integrity of the cytoplasmic membrane);
• B-lymphocytes - provide humoral immunity through the production of specific protein molecules - antibodies;
• NK-lymphocytes (natural killers) - dissolve cells infected with viruses or undergone malignant transformation.

It is known that lymphocytes in the blood are capable of synthesizing a number of antigens on their surface, and each of them is unique for its subpopulation and stage of cell formation. The functional activity of such cells is different. In most cases, they are a target for other leukocytes at the stage of immunophenotyping.

Cluster of differentiation and its types

Cluster designation - an artificially created nomenclature with the assignment of a number of various antigens that are produced on the surface of lymphocytes in the blood. Synonyms for the term: CD, CD antigen or CD marker.

During laboratory diagnosis, the presence of labeled cells in the general subpopulation of white blood cells is determined using monoclonal (same) antibodies with labels (based on fluorochrome). When antibodies interact with strictly specific CD antigens, a stable antigen-antibody complex is formed, while it is possible to count the remaining free labeled antibodies and determine the number of lymphocytes in the blood.

There are 6 types of CD antigen clusters:

• 3 - characteristic of T-lymphocytes, takes part in the formation of the signal transduction complex along the membrane;
• 4 - is identified on several types of leukocytes, helps to facilitate the process of recognition of foreign antigens when interacting with MHC (major histocompatibility complex) class 2;
• 8 - presented on the surface of cytotoxic T-, NK-cells, the functionality is similar to the previous type of clusters, only antigens associated with MHC class 1 are recognized;
• 16 - present on various types white blood cells, is part of the receptors responsible for the activation of phagocytosis and cytotoxic response;
• 19 - component of B-lymphocytes, necessary for their proper differentiation and activation;
• 56 - is produced on the surface of NK- and some T-cells, it is necessary to ensure their attachment to tissues affected by malignant tumors.

Indications for research

Activated lymphocytes in the blood of a child and adults are determined when:

• diagnostics of autoimmune diseases, oncopathologies, allergic reactions and their severity;
• diagnostics and control of treatment of acute infectious pathologies;
• carrying out differential diagnosis viral and bacterial infections;
• assessment of the state of the immune system (including in the presence of immunodeficiencies);
• assessment of the intensity of the immune response in case of severe infections that have become chronic;
• comprehensive examination before and after major surgery;
• suspicion of suppression of the immune status caused by a genetic mutation;
• control of the degree of immunity tension against the background of taking immunosuppressants or immunostimulants.

The norm of lymphocytes in the blood

The number of lymphocytes in the blood is determined using flow cytometry, the study period is 2-3 days, excluding the day of taking the biomaterial. It is important to correctly interpret the results obtained, it is desirable to attach the opinion of an immunologist to the immunogram. The final diagnosis is established on the basis of a combination of data from laboratory and instrumental methods of examination, as well as clinical picture patient.

It is noted that the diagnostic value increases significantly when assessing the intensity of immunity in a person in dynamics with regular repeated analyzes.

Activated lymphocytes in a blood test in a child and an adult are different, therefore, when deciphering the results, normal (reference) values ​​should be selected, taking into account the age of the patient.

Table of normal range of lymphocytes by age

The table shows the values ​​​​of acceptable norms of lymphocytes (individual subpopulations) in the blood in children and adults.

Deviation from reference values

Patients ask themselves: what does it mean if the lymphocytes in the blood are higher or lower than normal? It should be noted that a slight deviation from the reference values ​​may be the result of improper preparation for analysis. In this case, it is recommended to repeat the study.

The presence of a large number of atypical lymphocytes in a blood test in a child or adult indicates a pathological process. It is important to determine which type of the general subpopulation of white blood cells deviates from the norm.

T-lymphocytes

An increase in T-lymphocytes (CD3 + CD19-) is observed against the background of leukemia, acute or chronic stage of the infectious process, hormonal failure, long-term use of drugs and biological additives, as well as at high physical activity and pregnancy. If the criterion is lowered, an assumption is made about liver damage (cirrhosis, cancer), autoimmune pathologies, immunodeficiencies, or suppression of immunity by drugs.

T-helpers

The concentration of T-helpers (CD3 + CD4 + CD45 +) significantly increases with beryllium intoxication, a number of autoimmune diseases and some infectious infections. A decrease in value is the main laboratory sign of secondary immunodeficiency, and can also be observed when taking steroid drugs and cirrhosis of the liver.

Increase in T-cytotoxic lymphocytes

The reasons for the increase in T-cytotoxic lymphocytes (CD3 + CD8 + CD45 +) are:

• allergic reaction of immediate type;
• autoimmune pathologies;
• lymphosis;
• viral infection.

Deviation from the norm to a smaller side indicates the suppression of the natural immunity of a person.

B-lymphocytes (CD19 + CD3 -) increase with severe emotional or physical stress, lymphoma, autoimmune diseases, as well as in case of prolonged formaldehyde vapor intoxication. Reactive B lymphocytes are reduced if they migrate to the focus of the inflammatory process.

Two types of natural killers: CD3 - CD56 + CD45 + and CD3 - CD16 + CD45 + reach their maximum values ​​in the regeneration phase of the human body after hepatitis and pregnancy, as well as in some onco-, autoimmune and hepatic pathologies. Their reduction is facilitated by the abuse of tobacco smoking and steroid drugs, as well as some infections.

How to prepare for the analysis?

In order to obtain the most reliable results, it is necessary to strictly follow the rules of preparation before donating the biomaterial, since lymphocytes in the blood are sensitive to many external factors (stress, drugs). The biomaterial for the study is venous blood serum from the cubital vein.

1 day before donating blood, the patient should stop drinking alcohol and any alcohol-containing products, as well as all medications. If it is impossible to cancel vital drugs, you need to report their intake to honey. staff. In addition, physical and emotional stress is excluded, which can cause an increase in the studied criteria.

Blood is donated on an empty stomach, the minimum interval between the procedure for taking the biomaterial and the last meal is 12 hours. For half an hour you need to stop smoking.

conclusions

Summing up, it is necessary to highlight the important aspects:

• the study is the main component in the diagnosis of lesions of the immune system;
• normal values ​​are selected according to the age of the examined patient;
• the accuracy of the data obtained depends not only on the correct implementation of the analysis methodology, but also on compliance with all the rules for preparing the person himself;
• it is unacceptable to use an immunogram separately for making a final diagnosis, since the deviation from the norm of various subpopulations of cells of the immune system may indicate a number of similar pathologies. In this case, an additional examination is prescribed, including a set of tests: C3 and C4 complement components, circulating immune complexes, as well as total immunoglobulins of classes A, G and M.
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✪ B-lymphocytes and T-lymphocytes of CD4+ and CD8+ populations

✪ Cytotoxic T-lymphocytes

✪ T-lymphocytes

✪ Lymphocytes

✪ B-lymphocytes (B-cells)

Subtitles

I have already talked about the main cells of the specific immune system, and now we will once again summarize what we have learned. Let's start with the B-lymphocyte, which I always draw in blue.. Here it is in front of you. Membrane immunoglobulins are present on the surface of B-lymphocytes, and each such lymphocyte has its own variant of the variable domain. I repeat: B-lymphocytes have membrane immunoglobulins on the surface, and each such lymphocyte has its own version of the variable domain. I'll draw the variable domains in pink. Another B-lymphocyte will have different variable domains. Therefore, they can respond to a variety of antigens that have entered the body. In this case, B-lymphocytes are activated. What is needed for this and what happens in this case? Let's talk about what happens when B-lymphocytes are activated. What do you need to start activation? This requires the pathogen to bind to the membrane immunoglobulin. We write that the pathogen binds. The pathogen binds to membrane immunoglobulin. But this is not enough. Normally, a B-lymphocyte needs stimulation from a T-lymphocyte. So we write: stimulation by a T-lymphocyte. In what situation is such stimulation necessary? B-lymphocyte is an antigen-presenting cell. It absorbs the antigen, cleaves it and shows it along with MHC class 2. We will also draw it now. This is class 2 MHC. Antigen fragments bind to it. This complex binds to an activated T helper, which has a receptor with a variable domain specific for that particular antigen. Yes, the receptor turned out to be crooked, but the essence is clear, at least I will hope so. After activation, differentiation follows: the cell divides, and its descendants can become effector cells. This is true for both T- and B-lymphocytes. Once activated, the lymphocyte produces effector and memory cells. Memory cells are stored for a long time, and as a result of division, a lot of them are obtained. When the same pathogen re-enters, it is more likely to stumble upon the memory cell, triggering a rapid immune response. Effector B-lymphocytes are factories for the production of immunoglobulins. So, effector B-lymphocytes - produce immunoglobulin. The logic is this: since the antibody approaches the antigen that has entered the body, more should be synthesized. All the production capacity of the cell is taken to synthesize antibodies. I'll tell you one fact that my wife suggested to me. Overhearing how I recorded the last video. She is a specialist in hematology and understands immunology, so I trust her in this: she is an expert in this matter. In the last video, I recklessly stated that antibodies are produced by activated effector B-lymphocytes. So it really is - antibodies are produced exclusively by B-lymphocytes. However, antibody-secreting cells have their own name. These effector B lymphocytes are commonly referred to as plasma cells. I'll write down the term. In the course of differentiation, the name changes. This is the name of the B-lymphocyte, which began to secrete antibodies. Thereafter, it is exclusively referred to as a plasma cell. So when asked which cells produce antibodies, do not answer that they are B-lymphocytes. The correct answer is: plasma cells. This is a common term used in immunology as well as rheumatology. Excuse me, did I say my wife is a hematologist? No, she's a rheumatologist. Sometimes I get confused about this. So, the essence of B-lymphocytes is the production of antibodies that will bind to the antigens of viruses or bacteria and make them visible to macrophages and other phagocytes. But that's all about them, now let's move on to T-lymphocytes. I will tell about them what was not in the previous videos. So, there are two types of T-lymphocytes. You already know about helpers and cytotoxic T-lymphocytes, but there is another classification of lymphocytes, and I will tell you about it. So there are two varieties. Both have a T-cell receptor. I'll draw it like this. T-cell receptor. In addition, there are a number of other proteins on their membranes. Some T-lymphocytes have a membrane protein called CD4. CD4. Other T-lymphocytes have another protein - this is CD8. We'll sign it too. CD8. The lymphocyte on the right is called a CD8-positive T-lymphocyte. It has CD8 on its membrane. And here is a CD4-positive T-lymphocyte. Here are two varieties. They are divided according to these proteins. The CD4 protein is a receptor that has an affinity for MHC class 2 proteins. Most CD4-positive cells are T helpers. In most cases, if CD4-positive cells are mentioned in a conversation, then out of habit they mean precisely helper T-lymphocytes. They usually talk about them. Perhaps I'll sign it - T-helper. The CD8 receptor has an affinity for MHC class 1. We indicate this in the figure. In cancer cells, MHC class 1 on the membrane is associated with cancer antigens. Therefore, CD8 is characteristic of cytotoxic lymphocytes. CD8 is characteristic of cytotoxic lymphocytes. Usually, before the cell is activated, it is called CD4- or CD8-positive, and the function of the lymphocyte is said after activation. Already after. These are terminological features. I hope you get the gist. Now let's remember what this lymphocyte does. It binds to MHC proteins that are found on the membrane along with antigens. Here is class 1 MHC. As I said in the last video, every cell with a nucleus has it. Let's say something bad happened in the cage. Something bad, maybe it's a virus. Maybe cancer. The affected cell must die, otherwise it will copy the virus or multiply if it is a tumor. So, CD8-positive T-lymphocytes kill cells affected by a virus or oncology. They kill affected cells that might otherwise threaten the entire body as a whole. T-helpers are a completely different matter. Let's take a dendritic cell, an antigen-presenting cell. She has MHC class 2, to which fragments of the digested antigen are connected. It activates helper T-lymphocytes, which divide and differentiate into effector and memory cells. The effector T-lymphocyte has several functions. Helper T-lymphocyte activates B-lymphocytes and releases cytokines. Releases cytokines. An activated lymphocyte releases many substances that serve as a signal to other cells, such as other lymphocytes, while raising the alarm. Some of these cytokines help cytotoxic lymphocytes in their activation. Cytokines raise the alarm and CD8-positive, that is, cytotoxic T-lymphocytes, effector lymphocytes, are taken to kill the cells. As for memory cells, these are copies of the original lymphocytes that are permanently stored in this place in case of a repeat of the threat, in order to provide a faster response. I hope that I didn’t confuse you too much with new terms, but it was necessary. And now you know that antibodies are synthesized not by B-lymphocytes, not by them, but by cells that have their own name. These are plasma cells or plasmocytes.

Types of T-lymphocytes

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

Differentiation in the thymus

All T cells originate from hematopoietic red bone marrow 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 (English Double Negative (DN)) (CD4-CD8-). At the next stage, thymocytes express both coreceptors and are called double positive (Eng. 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 DN1 substage (English 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 actively divide and finally lose the ability to transform into other cell types (for example, B-lymphocytes or myeloid cells). Going to the DN2 substage (eng. Double Negative 2 ), thymocytes express CD44 + CD25 + CD117 + and become early T-cell progenitors (eng. Early T-cell Progenitors (ETP)). During the DN3 substage (eng. Double Negative 3 ), ETP cells have a combination of CD44-CD25 + and enter into the process β-selection.

β selection

The T-cell receptor genes consist of repeating segments belonging to three classes: V (eng. variable), D (eng. diversity) and J (eng. joining). During somatic recombination, gene segments, one from each class, are linked together (V(D)J recombination). Random combination of sequences of V(D)J segments leads to the appearance of unique sequences of variable domains of each of the chains of the receptor. The random nature of the formation of sequences of variable domains allows the generation of T cells that can recognize a large number of different 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 β-subunit of the receptor are the first to undergo recombination in DN3 cells. To exclude the possibility of the formation of a non-functional peptide, the β-subunit forms a complex with the invariable α-subunit of the pre-T-cell receptor, forming the so-called. pre-T cell receptor (pre-TCR). Cells unable to form functional pre-TCR die by apoptosis. Thymocytes that have successfully passed β-selection move to the DN4 substage (CD44 -CD25 -) and undergo the process positive selection.

positive selection

Cells that express pre-TCR on their surface are still not immunocompetent, since they are not able to bind to molecules of the major histocompatibility complex. Recognition of MHC molecules by the T-cell receptor requires the presence of CD4 and CD8 co-receptors on the surface of thymocytes. The formation of a complex between pre-TCR and the CD3 coreceptor 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 proteins of both classes of MHC (MHC-I and MHC-II). Cells that are unable to interact with MHC proteins of the cortical epithelium undergo apoptosis, while cells that successfully carry out such an 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 in combination with MHC proteins on medullary thymic epithelial cells (mTECs). Thymocytes actively interacting with their own antigens undergo apoptosis. Negative selection prevents the emergence of self-activating T cells capable of causing autoimmune diseases of the clone. Some of the cells in this clone turn into effector T cells, which perform functions specific to this type of lymphocyte (for example, they secrete cytokines in the case of T-helpers or lyse the affected cells in the case of T-killers). Another part of the activated cells is transformed into T-cells memory. 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 provide a secondary immune response that is carried out in a shorter time than the primary one.

The interaction of the T-cell receptor and co-receptors (CD4, CD8) with the major histocompatibility complex is important for the successful activation of naive T-cells, but it is not sufficient by itself 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 human body includes many components that are in constant relationship with each other. The main mechanisms include: respiratory, digestive, cardiovascular, genitourinary, endocrine and nervous systems. In order to protect each of these components, there are special defenses of the body. The mechanism that protects us from the harmful effects of the environment is immunity. It, like other body systems, has connections with the central nervous system and endocrine apparatus.

The role of immunity in the body

The main function of immunity is protection from foreign substances penetrating from the environment or formed endogenously during pathological processes. It carries out its action thanks to special blood cells - lymphocytes. Lymphocytes are a type of leukocytes and are constantly present in the human body. Their increase indicates that the system is fighting a foreign agent, and a decrease indicates a lack of protective forces - immunodeficiency. Another function is the fight against neoplasms, which is carried out through the tumor necrosis factor. The immune system includes a collection of organs that serve as a barrier to harmful factors. These include:

• skin;
• thymus;
• spleen;
• The lymph nodes;
• red bone marrow;
• blood.

There are 2 types of mechanisms that are inextricably linked. Cellular immunity fights harmful particles through T-lymphocytes. These structures, in turn, are divided into T-helpers, T-suppressors, T-killers.

The work of cellular immunity

Cellular immunity operates at the level of the smallest structures of the body. This level of protection includes several different lymphocytes, each of which performs a specific function. All of them come from whites and occupy the bulk of them. T-lymphocytes got their name due to the place of their origin - the thymus. begins to produce these immune structures during the period embryonic development human, ends their differentiation in childhood. Gradually, this organ ceases to perform its functions, and by the age of 15-18 it consists only of adipose tissue. The thymus produces only elements of cellular immunity - T-lymphocytes: helpers, killers and suppressors.

When a foreign agent enters, the body activates its defense systems, that is, immunity. First of all, macrophages begin to fight the harmful factor, their function is to absorb the antigen. If they cannot cope with their task, then the next level of protection is connected - cellular immunity. The first to recognize the antigen are T-killers - killers of foreign agents. The activity of T-helpers is to help the immune system. They control the division and differentiation of all body cells. Another of their functions is the formation of a relationship between the two, that is, helping B-lymphocytes to secrete antibodies, activating other structures (monocytes, T-killers, mast cells). T-suppressors are needed in order to reduce the excessive activity of helpers, if necessary.

Types of T-helpers

Depending on the function performed, T-helpers are divided into 2 types: the first and second. The former carry out the production of tumor necrosis factor (fight against neoplasms), gamma-interferon (fight against viral agents), interleukin-2 (participation in inflammatory reactions). All these functions are aimed at the destruction of antigens that are inside the cell.

The second type of T-helpers is needed to communicate with these T-lymphocytes produce interleukins 4, 5, 10 and 13, which provide this relationship. In addition, type 2 T-helpers are responsible for products that are directly related to allergic reactions organism.

Increase and decrease of T-helpers in the body

There are special norms for all lymphocytes in the body, their study is called an immunogram. Any deviation, regardless of whether it is an increase or a decrease in cells, is considered abnormal, that is, some kind of pathological condition. If T-helpers are lowered, then the body's defense system is not able to fully carry out its action. This condition is an immunodeficiency and is observed during pregnancy and lactation, after illness, with chronic infections. An extreme manifestation is HIV infection - a complete violation of the activity of cellular immunity. If T-helpers are elevated, then an excessive reaction to antigens is observed in the body, that is, the fight against them passes from a normal process into a pathological reaction. This condition is observed in allergies.

Relationship between cellular and humoral immunity

As you know, the immune system exercises its protective properties at two levels. One of them acts exclusively on cellular structures, that is, when viruses enter or abnormal gene rearrangements, the action of T-lymphocytes is activated. The second level is humoral regulation, which is carried out by affecting the entire body with the help of immunoglobulins. These protection systems in some cases can work separately from each other, but most often they interact with each other. The connection between cellular and humoral immunity is carried out by T-helpers, that is, “helpers”. This population of T-lymphocytes produces specific interleukins, these include: IL-4, 5, 10, 13. Without these structures, the development and functioning of humoral defense is impossible.

Importance of T-helpers in the immune system

Thanks to the release of interleukins, the immune system develops and protects us from harmful influences. prevents oncological processes, which is one of the most important functions of the body. All this is carried out by T-helpers. Despite the fact that they act indirectly (through other cells), their importance in the immune system is very important, as they help organize the protective properties of the body.

Designation T-lymphocytes comes from the first letter of the name thymus - thymus, or thymus gland. The share of T-lymphocytes in peripheral blood accounts for 40-70% of all lymphocytes. While in the thymus, T cells acquire surface receptors for various antigens, after which they enter the bloodstream and populate peripheral lymphoid organs. Here, these still immature cells can respond to antigens for which they already have receptors by proliferation followed by differentiation into T-lymphocytes.

Among T-lymphocytes, the following classes are distinguished.

1. T-killers , or killers (from English to kill - to kill). These cells, possessing cytotoxicity, directly or through the cytokines (lymphokines) secreted by them, destroy foreign cells. They participate in the rejection of foreign tissues during transplantation, carry out the lysis of their own pathologically altered (virus-infected, mutant or tumor) cells, as well as microbes, fungi, mycobacteria. Cytotoxic activity of T-killers- important mechanism of cellular immunity.

2. Antigen-reactive T-lymphocytes . They have receptors for the antigen to recognize it. Having recognized “its” antigen, the T-lymphocyte turns into an immunoblast and begins to produce a mediator, under the influence of which T-helpers are activated and multiply, i.e. the course of subsequent immune reactions is stimulated. After the end of the reaction, the blast again turns into a small lymphocyte.

3. T-helpers, or assistants (from English to help - to help). There are two types of these cells:

T-T-helpers that enhance the activity of T-killers (i.e. cellular immunity), and T-V helpers facilitating the course of humoral immunity. T-lymphocytes do not have the ability to synthesize and secrete antibodies, but, interacting with B-lymphocytes, they contribute to their transformation into plasma cells - the actual antibody-formers.

The helper effect of T-lymphocytes is carried out either by direct intercellular contact, or indirectly by humoral agents (IL-2, B-cell germ and differentiation factors).

T-helpers have morphogenetic activity, which consists in their ability to accumulate and stimulate cell proliferation in regenerating tissues, for example, hepatocytes during liver resection, renal epithelial cells of an intact kidney after unilateral nephrectomy. Therefore, the number of T-helpers in the blood increases with the strengthening of regenerative processes in various tissues of the body.

4. T-amplifiers enhance the functions of both T- and B-lymphocytes, but to a greater extent the former.

5. T-helper inductors activate T-suppressors.

6. T-suppressors , or oppressors (from English to suppress - to oppress). Among these lymphocytes, there are also 2 types of cells: T-T suppressors, suppressing the differentiation and proliferation of T-lymphocytes, and T-V suppressors depressing humoral immunity. There are specific (in relation to the immune response to one specific antigen) and non-specific (in relation to the immune response to a number of antigens) suppressor effects.

7. T-countersuppressors interfere with the action of T-suppressors and, therefore, enhance the immune response.

8. immune memory T cells . They account for about 10% of all T-lymphocytes. They circulate in the body without division for up to 10 years. These cells store information about previously active antigens and regulate the secondary immune response, which manifests itself in a shorter time, as it bypasses the main stages of this process.

9. T-differentiating lymphocytes (Td-lymphocytes) involved in the regulation of hematopoiesis. They produce IL-2, IL-4, colony-stimulating factor, etc., which have a modulating effect on the differentiation and proliferation of progenitor cells. different levels maturation in the granulocytic-macrophage-erythroid series of hematopoiesis.

Thus, the main functions of T-lymphocytes are:

1 – providing cellular immunity;

2 – participation in the regulation of humoral immunity;

3 – participation in the regulation of hematopoiesis;

4 – secretory, due to the production and release of many cytokines - hematopoietic hormones, including interleukins (2,3, 4,5,6,9,10) and other factors (they are also called mediators of cellular immunity). Cytokines affect various functions of lymphocytes and other blood cells, and are also involved in many physiological and pathological reactions.

It has now been established that other blood cells, as well as endotheliocytes, fibroblasts, hepatocytes, etc., are also involved in the production and secretion of cytokines.

Classification and functions of B-lymphocytes

B-lymphocytes are those lymphocytes that differentiate from stem cells in the fetal liver and then in the bone marrow or Peyer's patches. In birds, they are formed in the bursa (bag) of Fabricius, hence their name - B-lymphocytes.

After acquiring antigenic specificity, which is associated with the appearance of receptors on the membrane in the form of immunoglobulins, these still immature cells settle mainly in the lymph nodes, spleen, Peyer's patches. Here, under the action of antigens and cytokines, most B-lymphocytes proliferate and differentiate into plasma cells that secrete antibodies. By binding to antigens, antibodies destroy foreign cells and neutralize their waste products. Antibodies are carried by a liquid medium (blood). This speaks of providing them with humoral immunity.

Among circulating blood lymphocytes, B-lymphocytes account for 20-30%. They, like T-lymphocytes, constantly recirculate, but at a slower pace.

Among B-lymphocytes, several types are also distinguished.

B-killers, as well as T-killers, provide cytotoxic and cytolytic effects. The cytotoxic reaction of lymphocytes does not require the participation of complement, but requires sensitization of the target cell.

B-helpers present an antigen, enhance the action of Td-lymphocytes and T-suppressors, and also participate in other reactions of cellular and humoral immunity.

B-suppressors inhibit the proliferation of antibody producers (i.e. most B-lymphocytes).

B-lymphocytes of immunological memory are formed during antigenic stimulation of B-lymphocytes and “remember” this antigen.

Other types of lymphocytes

In addition to the two types of lymphocytes (T- and B-), there are other lymphocytes.

The third group of lymphocytes - neither T- nor B-lymphocytes, or O-lymphocytes. These are the precursors of T and B cells and constitute their reserve. Their proportion among peripheral blood lymphocytes is 10-20%.

To O-lymphocytes, most researchers include natural (natural) killers, or NK lymphocytes. Like other killer lymphocytes, NK lymphocytes secrete perforins, proteins that can “drill” holes (pores) in the membrane of foreign cells. NK-lymphocytes also contain proteolytic enzymes (cytolysins), which penetrate into a foreign cell through the resulting pores and destroy it.

Other varieties of O-lymphocytes (according to most authors) are L- and K-lymphocytes. They are able to carry out antibody-dependent lysis of target cells: L-lymphocytes - autologous and allogeneic monocytes; K-lymphocytes - allogeneic and xenogenic tumor cells, modified by viruses of T- and B-lymphocytes, monocytes, fibroblasts, erythrocytes.

The fourth group of lymphocytes - D-lymphocytes, or "double lymphocytes", which carry on their surface markers of T- and B-lymphocytes and they are able to replace both those and others.

Plasma cells

Plasma cells are normally absent in human blood. They are in the bone marrow lymph nodes, spleen, as well as among the connective tissue elements of various organs.

A plasma cell is a spherical or oval formation with a diameter of 8-20 microns. It contains many ribosomes and large mitochondria. Plasma cells live from 2 days to 6 months. The main function of plasma cells is the production of antibodies. In a mature cell, 1×10 13 - 7×10 13 antibody molecules are found.

REGULATION OF LYMPHOPOIESIS

Lymphocyte production is regulated at 3 different levels.

Intercellular level regulation is carried out by various mediators - lymphokines (cytokines). Thus, IL-9 (T-cell growth factor) stimulates the proliferation of T-cells, IL-7 stimulates B-cells.

tissue level regulation is carried out by keylons - specific inhibitors cell division. Thymus kalon is an inhibitor of T-lymphocytes, spleen kalon is an inhibitor of B-lymphocyte division.

Regulation at the level of the whole organism mainly carried out by the neuro-endocrine system. Humoral stimulators of various stages of lymphocyte differentiation are lymphopoietins isolated from bone marrow and leukocytes. Histamine, catecholamines, prostaglandins E increase the production of cAMP, which enhances the proliferative potential of cells. Glucocorticoids, a-globulins and C-reactive blood protein inhibit lymphopoiesis.

The number of lymphocytes in the blood decreases with stress, with radiation sickness. Lymphocytosis develops with chronic tuberculous intoxication, as well as with insufficient production of hormones of the adrenal cortex.

The cells of the immune system are lymphocytes, macrophages and other antigen-presenting cells(A-cells, from the English accessory-auxiliary), as well as the so-called third cell population(i.e. cells that do not have the main surface markers of T- and B-lymphocytes, A-cells).

According to functional properties, all immunocompetent cells are divided into effector and regulatory. The interaction of cells in the immune response is carried out with the help of humoral mediators - cytokines. The main cells of the immune system are T- and B-lymphocytes.

Lymphocytes.

In the body, lymphocytes constantly recirculate between areas of accumulation of lymphoid tissue. The location of lymphocytes in the lymphoid organs and their migration along the blood and lymphatic channels are strictly ordered and associated with the functions of various subpopulations.

Lymphocytes have a common morphological characteristic, but their functions, surface CD (from clasterdifference) markers, individual (clonal) origin, are different.

By the presence of surface CD markers, lymphocytes are divided into functionally different populations and subpopulations, primarily T- (thymus-dependent that have undergone primary differentiation in the thymus) lymphocytes and B - (bursa-dependent, matured in the bag of Fabricius in birds or its analogues in mammals) lymphocytes.

T-lymphocytes.

Localization.

They are usually localized in the so-called T-dependent zones of peripheral lymphoid organs (periarticularly in the white pulp of the spleen and paracortical zones of the lymph nodes).

Functions.

T-lymphocytes recognize the antigen processed and presented on the surface of antigen-presenting (A) cells. They are responsible for cellular immunity, cell-type immune reactions. Separate subpopulations help B-lymphocytes respond to T-dependent antigens the production of antibodies.

Origin and maturation.

The ancestor of all blood cells, including lymphocytes, is a single bone marrow stem cell. It generates two types of precursor cells, the lymphoid stem cell and the red blood cell precursor, from which both leukocyte and macrophage precursor cells are derived.

The formation and maturation of immunocompetent cells is carried out in the central organs of immunity (for T-lymphocytes - in the thymus). Progenitor cells of T-lymphocytes enter the thymus, where pre-T-cells (thymocytes) mature, proliferate and differentiate into separate subclasses as a result of interaction with stromal epithelial and dendritic cells and exposure to hormone-like polypeptide factors secreted by thymic epithelial cells (alpha1- thymosin, thymopoietin, thymulin, etc.).

During differentiation, T-lymphocytes acquire a specific set of membrane CD markers. T cells are divided into subpopulations according to their function and CD marker profile.

T-lymphocytes recognize antigens with the help of two types of membrane glycoproteins - T-cell receptors(family of Ig-like molecules) and CD3, non-covalently bonded to each other. Their receptors, unlike antibodies and B-lymphocyte receptors, do not recognize freely circulating antigens. They recognize peptide fragments presented to them by A-cells through a complex of foreign substances with the corresponding protein of the main histocompatibility system of classes 1 and 2.

There are three main groups of T-lymphocytes- helpers (activators), effectors, regulators.

The first group of helpers activators) , which include T-helpers1, T-helpers2, inductors of T-helpers, inductors of T-suppressors.

1. T-helpers1 carry CD4 receptors (as well as T-helpers2) and CD44, are responsible for maturation T-cytotoxic lymphocytes (T-killers), activate T-helpers2 and cytotoxic function of macrophages, secrete IL-2, IL-3 and other cytokines.

2. T-helpers2 have common for helper CD4 and specific CD28 receptors, provide proliferation and differentiation of B-lymphocytes into antibody-producing (plasma) cells, antibody synthesis, inhibit the function of T-helpers1, secrete IL-4, IL-5 and IL-6.

3. T-helper inductors carry CD29, are responsible for the expression of HLA class 2 antigens on macrophages and other A-cells.

4. Inductors of T-suppressors carry the CD45 specific receptor, are responsible for the secretion of IL-1 by macrophages, and the activation of the differentiation of T-suppressor precursors.

The second group is T-effectors. It includes only one subpopulation.

5. T-cytotoxic lymphocytes (T-killers). They have a specific CD8 receptor, lyse target cells carrying foreign antigens or altered autoantigens (graft, tumor, virus, etc.). CTLs recognize a foreign epitope of a viral or tumor antigen in complex with an HLA class 1 molecule in the plasma membrane of the target cell.

The third group is T-cells-regulators. Represented by two main subpopulations.

6. T-suppressors are important in the regulation of immunity, providing suppression of the functions of T-helpers 1 and 2, B-lymphocytes. They have CD11 and CD8 receptors. The group is functionally heterogeneous. Their activation occurs as a result of direct stimulation by an antigen without significant involvement of the major histocompatibility system.

7. T-consuppressors. Do not have CD4, CD8, have a receptor for a special leukin. Contribute to the suppression of the functions of T-suppressors, develop resistance of T-helpers to the effect of T-suppressors.

B lymphocytes.

There are several subtypes of B-lymphocytes. The main function of B cells is the effector participation in humoral immune reactions, differentiation as a result of antigenic stimulation into plasma cells that produce antibodies.

The formation of B-cells in the fetus occurs in the liver, later in the bone marrow. The process of maturation of B-cells is carried out in two stages - antigen - independent and antigen - dependent.

The antigen is an independent phase. B-lymphocyte in the process of maturation goes through the stage pre-B-lymphocyte- an actively proliferating cell having cytoplasmic mu-type C H chains (i.e., IgM). Next stage- immature B-lymphocyte characterized by the appearance of membrane (receptor) IgM on the surface. The final stage of antigen-independent differentiation is the formation mature B-lymphocyte, which can have two membrane receptors with the same antigenic specificity (isotype) - IgM and IgD. Mature B-lymphocytes leave the bone marrow and colonize the spleen, lymph nodes and other accumulations of lymphoid tissue, where their development is delayed until they encounter their “own” antigen, i.e. prior to antigen-dependent differentiation.

Antigen dependent differentiation includes activation, proliferation and differentiation of B cells into plasma cells and memory B cells. Activation is carried out in various ways, depending on the properties of antigens and the participation of other cells (macrophages, T-helpers). Most of the antigens that induce the synthesis of antibodies require the participation of T-cells to induce an immune response. thymus-dependent pntigens. Thymus-independent antigens(LPS, high molecular weight synthetic polymers) are able to stimulate the synthesis of antibodies without the help of T-lymphocytes.

B-lymphocyte recognizes and binds antigen with the help of its immunoglobulin receptors. Simultaneously with the B-cell, the antigen is recognized by the T-helper (T-helper 2) as presented by the macrophage, which is activated and begins to synthesize growth and differentiation factors. The B-lymphocyte activated by these factors undergoes a series of divisions and simultaneously differentiates into plasma cells producing antibodies.

The pathways of B cell activation and cell cooperation in the immune response to different antigens and involving populations with and without antigen Lyb5 B cell populations differ. Activation of B-lymphocytes can be carried out:

T-dependent antigen with the participation of proteins MHC class 2 T-helper;

T-independent antigen containing mitogenic components;

Polyclonal activator (LPS);

Anti-mu immunoglobulins;

T-independent antigen that does not have a mitogenic component.

Cooperation of cells in the immune response.

All links of the immune system are involved in the formation of the immune response. systems - systems macrophages, T- and B-lymphocytes, complement, interferons and the major histocompatibility system.

Briefly, the following steps can be distinguished.

1. Uptake and processing of antigen by macrophage.

2. Presentation of the processed antigen by a macrophage with the help of a protein of the main histocompatibility system class 2 to T-helpers.

3. Recognition of the antigen by T-helpers and their activation.

4. Antigen recognition and activation of B-lymphocytes.

5. Differentiation of B-lymphocytes into plasma cells, synthesis of antibodies.

6. Interaction of antibodies with antigen, activation of complement systems and macrophages, interferons.

7. Presentation with the participation of MHC class 1 proteins of foreign antigens to T-killers, destruction of cells infected with foreign antigens by T-killers.

8. Induction of T- and B-cells of immune memory capable of specifically recognizing an antigen and participating in a secondary immune response (antigen-stimulated lymphocytes).

immune memory cells. Maintenance of long-lived and metabolically inactive memory cells recirculating in the body is the basis for the long-term preservation of acquired immunity. The state of immune memory is determined not only by the longevity of T- and B-memory cells, but also by their antigenic stimulation. Long-term preservation of antigens in the body is provided by dendritic cells (depot of antigens), which store them on their surface.

Dendritic cells- populations of outgrowth cells of lymphoid tissue of bone marrow (monocytic) genesis, presenting antigenic peptides to T-lymphocytes and retaining antigens on their surface. These include follicular process cells of the lymph nodes and spleen, Langerhans cells of the skin and respiratory tract, M - cells of the lymphatic follicles of the digestive tract, dendritic epithelial cells of the thymus.

CD antigens.

Cluster differentiation of surface molecules (antigens) of cells, primarily leukocytes, is making strides forward. To date, CD antigens are not abstract markers, but receptors, domains, and determinants that are functionally significant for the cell, including those that are not initially specific for leukocytes.

The most important differentiation antigens of T-lymphocytes human are the following.

1. CD2 - an antigen characteristic of T-lymphocytes, thymocytes, NK cells. It is identical to the sheep erythrocyte receptor and provides the formation of rosettes with them (method for determining T-cells).

2. CD3 - necessary for the functioning of any T-cell receptors (TCR). CD3 molecules have all subclasses of T-lymphocytes. The interaction of TKR-CD3 (it consists of 5 subunits) with the antigen-presenting MHC class 1 or 2 molecule determines the nature and implementation of the immune response.

3. CD4. These receptors have T-helpers 1 and 2 and T-inducers. They are a co-receptor (binding site) for the determinants of MHC class 2 protein molecules. It is a specific receptor for the envelope proteins of the human immunodeficiency virus HIV-1 (gp120) and HIV-2.

4.CD8. The CD8+ T-lymphocyte population includes cytotoxic and suppressor cells. Upon contact with the target cell, CD8 acts as a co-receptor for HLA class 1 proteins.

Differentiation receptors of B-lymphocytes.

On the surface of B-lymphocytes there can be up to 150 thousand receptors, among which more than 40 types with different functions have been described. Among them are receptors for the Fc component of immunoglobulins, for the C3 component of complement, antigen-specific Ig receptors, receptors for various growth and differentiation factors.

Brief description of methods for assessing T- and B-lymphocytes.

To detect B-lymphocytes, the method of rosette formation with erythrocytes treated with antibodies and complement (EAC-ROK), spontaneous rosette formation with mouse erythrocytes, the method of fluorescent antibodies with monoclonal antibodies (MAB) to B-cell receptors (CD78, CD79a,b, membrane Ig ).

To quantify T-lymphocytes, the method of spontaneous rosette formation with ram erythrocytes (E-ROK) is used, to identify subpopulations (for example, T-helpers and T-suppressors) - an immunofluorescence method with MCA to CD receptors, to determine T-killers - cytotoxicity tests .

The functional activity of T- and B-cells can be assessed in the reaction of blast-transformation of lymphocytes (RBTL) to various T- and B-mitogens.

Sensitized T-lymphocytes involved in delayed-type hypersensitivity reactions (DTH) can be determined by the release of one of the cytokines - MIF (migration inhibitory factor) in the reaction of inhibition of migration of leukocytes (lymphocytes) - RTML. For more information on methods for assessing the immune system, see lectures on clinical immunology.

One of the features of immunocompetent cells, especially T-lymphocytes, is the ability to produce a large amount of soluble substances - cytokines (interleukins) that perform regulatory functions. They ensure the coordinated work of all systems and factors of the immune system, thanks to direct and feedback between different systems and subpopulations of cells provide stable self-regulation of the immune system. Their definition gives additional insight into the state of the immune system.