Well-functioning immune system healthy person able to cope with most external and internal threats. Lymphocytes are blood cells that are the first to enter the battle for the purity of the body. Viruses, bacteria, fungus are the daily concern of the immune system. Moreover lymphocyte functions are not limited to detecting external enemies.

Any damaged or defective cells of one's own tissues must also be detected and destroyed.

Functions of lymphocytes in human blood

The main performers in the work of immunity in humans are colorless blood cells - leukocytes. Each variety fulfills its function, most important of which are allocated specifically to lymphocytes. Their number relative to other leukocytes in the blood sometimes exceeds 30% . Functions of lymphocytes are quite diverse and accompany the entire immune process from beginning to end.

In essence, lymphocytes detect any fragments that do not correspond to the body genetically, give a signal to start a battle with foreign objects, control its entire course, actively participate in the destruction of “enemies” and end the battle after victory. As conscientious guards, they remember each violator by sight, which gives the body the opportunity to act faster and more efficiently at the next meeting. This is how living beings manifest a property called immunity.

The most important lymphocyte functions:

1. Detection of viruses, bacteria, other harmful microorganisms, as well as any abnormal cells of one’s own body (old, damaged, infected, mutated).
2. A message to the immune system about the “invasion” and the type of antigen.
3. Direct destruction of pathogenic microbes, production of antibodies.
4. Management of the entire process using special “signal substances”.
5. Winding down the active phase of the “battle” and managing the cleanup after the battle.
6. Preservation of memory of each defeated microorganism for subsequent rapid recognition.

The production of such immune soldiers occurs in the red bone marrow, they have different structure and properties. It is most convenient to distinguish immune lymphocytes by their functions in defense mechanisms:

• B lymphocytes recognize harmful inclusions and synthesize antibodies;
• T-lymphocytes activate and inhibit immune processes, directly destroy antigens;
• NK lymphocytes perform a function control over the tissues of the native organism, are capable of killing mutated, old, degenerated cells.

Based on their size and structure, they are distinguished between large granular (NK) and small (T, B) lymphocytes. Each type of lymphocyte has its own characteristics and important functions, which are worth considering in more detail.

B lymphocytes

Distinctive features include the fact that normal operation the body requires not just young lymphocytes in large quantities, but hardened, mature soldiers.

Maturation and education of T cells take place in the intestines, appendix, and tonsils. In these "training camps" young bodies are trained to perform three important functions :

1. “Naive lymphocytes” are young, not activated blood cells that have no experience of encountering foreign substances, and therefore do not have strict specificity. They are able to show a limited reaction to several antigens. Activated after meeting an antigen, they are sent to the spleen or bone marrow for re-maturation and rapid cloning of their own kind. After ripening, plasma cells very quickly grow from them, producing antibodies exclusively to this type of pathogen.
2. Mature plasma cells, strictly speaking, are no longer lymphocytes, but factories for the production of specific soluble antibodies. They live only a few days, eliminating themselves as soon as the threat that caused the defensive reaction disappears. Some of them will later be “preserved” and will again become small lymphocytes with memory of the antigen.
3. Activated B-lymphocytes, with the assistance of T-lymphocytes, can become repositories of the memory of a defeated foreign agent; they live for decades, perform a function transmitting information to their “descendants”, providing long-term immunity, accelerating the body’s response to meeting the same type of aggressive influence.

B cells are very specific. Each of them is activated only when encountering a certain type of threat (a strain of a virus, a type of bacteria or protozoa, a protein, a chemical substance). The lymphocyte will not react to pathogens of a different nature. Thus, the main function of B lymphocytes is to provide humoral immunity and produce antibodies.

T lymphocytes

Young T-bodies are also produced by the bone marrow. This type of red blood cells undergoes the most stringent step-by-step selection, which rejects more than 90% of young cells. “Nurture” and selection occur in the thymus gland (thymus).

Pay attention!The thymus is an organ that enters the phase of greatest development between 10 and 15 years, when its mass can reach 40 g. After 20 years, it begins to decrease. In old people, the thymus weighs the same as in babies, no more than 13 g. The working tissues of the gland after 50 years are replaced by fatty and connective tissue. Accordingly, the number of T cells decreases and the body’s defenses weaken.

As a result of the selection occurring in the thymus gland, T-lymphocytes are eliminated that are not capable of binding any foreign agent, as well as those that have detected a reaction to proteins of the native organism. The remaining ripened bodies are considered suitable and are scattered throughout the body. A huge number of T cells (about 70% of all lymphocytes) circulate in the bloodstream; their concentration is high in the lymph nodes and spleen.

Three types of mature T lymphocytes leave the thymus:

• T-helpers. They help perform functions B lymphocytes, other immune agents. They guide their actions during direct contact or give orders by releasing cytokines (signal substances).
• Killer T cells. Cytotoxic lymphocytes that directly destroy defective, infected, tumor, and any modified cells. Killer T cells are also responsible for the rejection of foreign tissue upon implantation.
• T-suppressors. Execute important function supervision of the activity of B lymphocytes. Slow down or stop the immune response, if necessary. Their immediate responsibility is to prevent autoimmune reactions, when protective bodies mistake their cells for hostile ones and begin to attack them.

T-lymphocytes have the main properties: regulate the speed of the protective reaction, its duration, serve as an obligatory participant in certain transformations and provide cellular immunity.

NK lymphocytes

Unlike small forms, NK cells (null lymphocytes) are larger and contain granules consisting of substances that destroy the membrane of the infected cell or destroy it entirely. The principle of defeating hostile inclusions is similar to the corresponding mechanism in T-killers, but is more powerful and does not have pronounced specificity.

NK lymphocytes do not undergo the maturation procedure in lymphatic system, are able to react to any antigens and kill such formations that T-lymphocytes are powerless against. For such unique qualities they are called “natural killers.” NK lymphocytes are the main killers of cancer cells. Increasing their number and increasing activity is one of the promising directions for the development of oncology.

Interesting! Lymphocytes carry large molecules that transmit genetic information throughout the body. The important function of these blood cells is not limited to protection, but extends to the regulation of tissue repair, growth, and differentiation.

Often, after receiving the results of a blood test, we can read a doctor’s conclusion that there are elevated lymphocytes in the blood. What does this mean, is this disease dangerous, and can it be cured?

What are lymphocytes?

All white blood cells that perform immune function are called leukocytes. They are divided into several categories:

• Neutrophils,
• Eosinophils,
• Basophils,
• Monocytes,
• Lymphocytes.

Each of these groups performs strictly defined tasks. If we compare the immune forces of the body with an army, then eosinophils, basophils and monocytes are special branches of the military and heavy artillery, neutrophils are soldiers, and lymphocytes are officers and guards. In relation to the total number of leukocytes, the number of cells of this type in adults averages 30%. Unlike most other white blood cells, which usually die when confronted with an infectious agent, lymphocytes can act repeatedly. Thus, they provide long-term immunity, while the remaining leukocytes provide short-term immunity.

Lymphocytes, together with monocytes, belong to the category of agranulocytes - cells that do not have granular inclusions in the internal structure. They can survive longer than other blood cells - sometimes up to several years. Their destruction, as a rule, occurs in the spleen.

What are lymphocytes responsible for? They perform a wide variety of functions, depending on their specialization. They are responsible for both humoral immunity, associated with the production of antibodies, and cellular immunity, associated with interaction with target cells. Lymphocytes are divided into three main categories - T, B and NK.

T cells

They make up approximately 75% of all cells of this type. Their embryos are formed in the bone marrow, and then migrate to the thymus gland (thymus), where they turn into lymphocytes. Actually, their name speaks about this (T stands for thymus). Their greatest number is observed in children.

In the thymus, T cells “undergo training” and acquire various “specialties”, turning into the following types of lymphocytes:

• T cell receptors,
• T-killers,
• T helper cells
• T-suppressors.

B cells

Among other lymphocytes, their share is approximately 15%. Formed in the spleen and bone marrow, then migrate to lymph nodes and concentrate in them. Their main function is to provide humoral immunity. In the lymph nodes, type B cells become familiar with antigens presented to them by other cells of the immune system. After this, they begin the process of forming antibodies that react aggressively to the invasion of foreign substances or microorganisms. Some B cells have a “memory” for foreign objects and can retain it for many years. Thus, they ensure that the body is ready to meet the “enemy” fully armed if it reappears.

NK cells

The proportion of NK cells among other lymphocytes is approximately 10%. This variety performs functions much like those of killer T cells. However, their capabilities are much wider than those of the latter. The name of the group comes from the phrase Natural Killers. This is the real “anti-terrorist special forces” of the immune system. The purpose of the cells is to destroy degenerated cells of the body, primarily tumor cells, as well as those affected by viruses. At the same time, they are able to destroy cells that are inaccessible to killer T cells. Each NK cell is “armed” with special toxins that are lethal to target cells.

Why is a change in lymphocytes in the blood bad?

From the above, it may seem that the more of these cells in the blood, the higher a person’s immunity should be, and the healthier he should be. And often the condition when lymphocytes are elevated is really positive symptom. But in practice, everything is not so simple.

First of all, a change in the number of lymphocytes always indicates that not everything is in order in the body. As a rule, they are produced by the body for a reason, but to combat some problem. And the doctor’s task is to find out what elevated blood cells indicate.

In addition, a change in the number of white blood cells may mean that the mechanism by which they appear in the blood has been disrupted. And from this it follows that the hematopoietic system is also susceptible to some kind of disease. An increased level of lymphocytes in the blood is called lymphocytosis. Lymphocytosis can be both relative and absolute. With relative lymphocytosis, the total number of leukocytes does not change, but the number of lymphocytes increases relative to other types of leukocytes. With absolute lymphocytosis, both leukocytes and lymphocytes increase, while the ratio of lymphocytes to other leukocytes may not change.

A condition in which there are low lymphocytes in the blood is called lymphopenia.

Norms of lymphocytes in the blood

This norm varies depending on age. In young children, as a rule, the relative number of these cells is higher than in adults. Over time, this parameter decreases. It can also deviate greatly from the average for different people.

Lymphocyte norms for different ages.

As a rule, lymphocytosis in adults is spoken of if the absolute number of lymphocytes exceeds 5x109/l, and of the total number of leukocytes, the number of these cells is 41%. The minimum acceptable value is 19% and 1x109/l.

How to determine the level of lymphocytes

To determine this parameter, it is enough to take a general clinical blood test. The test is taken on an empty stomach; before the test, you should not engage in physical activity during the day, do not eat fatty foods, and do not smoke for 2-3 hours. Blood for general analysis is usually taken from a finger, less often from a vein.

A complete blood count allows you to find out how different types of white blood cells relate to each other. This ratio is called leukocyte formula. Sometimes the number of lymphocytes is directly indicated in the analysis transcript, but often the transcript contains only English abbreviations. Therefore, it is sometimes difficult for an ignorant person to find the necessary data in a blood test. As a rule, required parameter reported as LYMPH on a blood test (sometimes also LYM or LY). On the contrary, the content of blood cells per unit volume of blood is usually indicated, as well as normal values. This parameter may also be referred to as “abs lymphocytes.” The percentage of lymphocytes from the total number of leukocytes may also be indicated. It should also be taken into account that in different laboratories Different analysis methods may be used, so the results of a general blood test may differ somewhat in different medical institutions.

Causes of lymphocytosis

Why does the white blood cell count increase? This symptom can have several causes. First of all, these are infectious diseases. Many infections, especially viral ones, cause the immune system to produce increased amount Killer T cells and NK cells. This type of lymphocytosis is called reactive.

Viral infections that can cause an increase in lymphocytes in the blood include:

• Flu,
• Infectious mononucleosis,
• Herpes,
• Chickenpox,
• Measles,
• Rubella,
• Adeno viral infection,
• Mumps.

Also, increased lymphocytes in the blood can be observed during bacterial and protozoal infections:

• Tuberculosis,
• Brucellosis,
• Toxoplasmosis.

However, not every bacterial infection is accompanied by lymphocytosis, since many bacteria are destroyed by other types of leukocytes.

An increase in the number of white blood cells can be observed not only during illness, but also some time after recovery. This phenomenon is called post-infectious lymphocytosis.

Another cause of lymphocytosis is diseases of the hematopoietic system (leukemia) and lymphatic tissue (lymphoma). Many of them are malignant. With these diseases, lymphocytosis is observed in the blood, but the immune cells are not complete and cannot perform their functions.

The main diseases of the lymphatic and circulatory systems that can cause lymphocytosis:

• Lymphoblastic leukemia (acute and chronic),
• Lymphogranulomatosis,
• Lymphoma,
• Lymphosarcoma,
• Multiple myeloma.

Other reasons that can cause an increase in the number of immune cells:

• Alcoholism;
• Frequent smoking of tobacco;
• Taking narcotic substances;
• Taking certain medications (levodopa, phenytoin, some analgesics and antibiotics);
• The period before menstruation;
• Prolonged fasting and diets;
• Long-term consumption of foods rich in carbohydrates;
• Hyperthyroidism;
• Allergic reactions;
• Poisoning with toxic substances (lead, arsenic, carbon disulfide);
• Immunity disorders;
• Endocrine disorders (myxedema, ovarian hypofunction, acromegaly);
• Early stages of some cancers;
• Neurasthenia;
• Stress;
• Vitamin B12 deficiency;
• Injuries and wounds;
• Splenectomy;
• Accommodation in high mountains;
• Radiation injuries;
• Taking certain vaccines;
• Excessive physical activity.

Many autoimmune diseases, that is, diseases in which the immune system attacks healthy cells of the body can also be accompanied by lymphocytosis:

• Rheumatoid arthritis,
• Systemic lupus erythematosus.

Lymphocytosis can also be temporary or permanent. The temporary type of disease is usually caused by infectious diseases, injuries, poisoning, and medications.

Spleen and lymphocytosis

Since the spleen is an organ where immune cells break down, it surgical removal for some reason it can cause temporary lymphocytosis. However, subsequently the hematopoietic system returns to normal and the number of these cells in the blood stabilizes.

Oncological diseases

However, the most dangerous causes of lymphocytosis are cancers that affect the hematopoietic system. This reason also cannot be discounted. And therefore, if it is impossible to associate a symptom with some external cause, then it is recommended to undergo a thorough examination.

The most common hemato-oncological diseases in which lymphocytosis is observed are acute and chronic lymphoblastic leukemia.

Acute lymphoblastic leukemia

Acute lymphoblastic leukemia is a serious disease of the hematopoietic system, in which immature immune cells are formed in the bone marrow that cannot perform their functions. The disease most often affects children. Along with the increase in lymphocytes, there is also a decrease in the number of red blood cells and platelets.

Diagnosis of this type of leukemia is made using a puncture bone marrow, after which the number of immature cells (lymphoblasts) is determined.

Chronic lymphocytic leukemia

This type of disease is more common in older people. With it, there is a significant increase in non-functional B-type cells. In most cases, the disease develops slowly, but is almost untreatable.

When diagnosing a disease, first of all, the total number of type B cells is taken into account. When examining a blood smear, tumor cells can be easily identified based on their characteristic features. To clarify the diagnosis, immunophenotyping of cells is also performed.

Lymphocytes in HIV

HIV (human immunodeficiency virus) is a virus that directly attacks the cells of the immune system and causes a serious disease - AIDS (acquired immunodeficiency syndrome). Therefore, the presence of this virus cannot but affect the number of lymphocytes in the blood. Usually on early stages lymphocytosis is observed. However, as the disease progresses, the immune system becomes weaker and lymphocytosis gives way to lymphopenia. Also with AIDS, there is a decrease in the number of other blood cells - platelets and neutrophils.

Lymphocytes in urine

Sometimes the presence of lymphocytes can be observed in the urine, which should not normally be the case. This sign indicates the presence of an inflammatory process in genitourinary system– for example, about urolithiasis, bacterial infections in the genitourinary tract. In kidney transplant patients, the presence of lymphocytes may indicate the process of organ rejection. These cells can also appear in the urine during acute viral diseases.

Decreased lymphocytes - causes

Sometimes a situation opposite to lymphocytosis can be observed - lymphopenia, when lymphocytes are low. For lymphocytes, a decrease is typical in the following cases:

• Severe infections that deplete lymphocytes;
• AIDS;
• Tumors of lymphoid tissue;
• Bone marrow diseases;
• Severe types of heart and kidney failure;
• Taking certain medications, for example, cytostatics, corticosteroids, antipsychotics;
• Radiation exposure;
• Immunodeficiency state;
• Pregnancy.

A situation where the number of immune cells is lower than normal may be a temporary phenomenon. So, if during an infectious disease a lack of lymphocytes is replaced by an excess, this may indicate that the body is close to recovery.

Changes in lymphocytes in the blood of women

For such a parameter as the content of lymphocytes, there are no gender differences. This means that both men and women should have approximately the same number of these cells in their blood.

During pregnancy, moderate lymphopenia is usually observed. This is due to the fact that increased lymphocytes in the blood of women during pregnancy can harm the fetus, which has a different genotype compared to the mother’s body. However, in general, the number of these cells does not decrease below normal limits. However, if this happens, the immune system may be weakened and the woman’s body may be susceptible to various diseases. And if the number of lymphocytes turns out to be higher than normal, then this situation threatens early interruption pregnancy. Thus, it is very important for pregnant women to control the level of lymphocytes in the blood. To do this, it is necessary to undergo regular tests, both in the first and second trimesters of pregnancy.

In women, certain phases may also cause an increase in the number of immune cells menstrual cycle. In particular, during premenstrual syndrome, a slight increase in lymphocytes may be observed.

Lymphocytosis in children

When a baby is born, its lymphocyte level is relatively low. However, then the body begins to intensively produce white blood cells, and, starting from the first weeks of life, there are a lot of lymphocytes in the blood, much more than in adults. This is explained by natural reasons - after all, a child has a much weaker body than an adult. As the child grows older, the number of these cells in the blood decreases, and at a certain age there are fewer of them than neutrophils. Subsequently, the number of lymphocytes approaches adult levels.

However, if there are more lymphocytes than normal for a certain age, then this is a cause for concern. It is necessary to understand what causes lymphocytosis. Usually, the child’s body reacts very violently to every infection, such as ARVI, measles, rubella, releasing a huge amount of white blood cells. But when the infection subsides, their number returns to normal.

However, it should be remembered that lymphocytosis in children can also be caused by such a serious disease as acute lymphoblastic leukemia. Therefore, it is important to regularly check your baby's white blood cell count through blood tests.

Symptoms of lymphocytosis

Does lymphocytosis manifest itself in any other way besides changes in blood composition? If it is caused by an infectious disease, the patient will experience symptoms characteristic of this disease, for example, fever, chills, headaches, cough, rash, etc. But these symptoms are not symptoms of lymphocytosis itself. However, in some cases, with an increase in lymphocytes caused by non-infectious causes, an enlargement of the lymph nodes and spleen, the organs where most lymphocytes are located, may be observed.

Diagnosis of the causes of lymphocytosis

When the number of lymphocytes increases, the reasons for the increase are not always easy to detect. First of all, it is recommended to consult a general practitioner. Most likely, he will give directions for several additional tests - blood for HIV, hepatitis and syphilis. In addition, they may be assigned additional research– Ultrasound, computed tomography or magnetic tomography, radiography.

May be required additional analysis blood, which would eliminate the error. To clarify the diagnosis, an operation such as a lymph node or bone marrow puncture may be necessary.

Typical and atypical immune cells

When determining the cause of an increase in lymphocytes important role plays a role in determining the number of typical and atypical types of cells.

Atypical lymphocytes are blood cells that have different properties and sizes compared to normal ones.

Most often, atypical cells are observed in the blood in the following diseases:

• Lymphocytic leukemia,
• Toxoplasmosis,
• Pneumonia,
• Chicken pox,
• Hepatitis,
• Herpes,
• Infectious mononucleosis.

On the other hand, in many diseases a large number of atypical cells are not observed:

• Mumps,
• Rubella,
• Flu,
• AIDS,
• Adenoviral infection
• Malaria,
• Autoimmune diseases.

Use of other blood parameters in diagnosis

A factor such as (ESR) should also be taken into account. In many diseases this parameter increases. The dynamics of other blood components are also taken into account:

• Total white blood cell count (may remain unchanged, decrease or increase),
• Dynamics of platelet count (increase or decrease),
• Dynamics of the number of red blood cells (increase or decrease).

An increase in the total number of leukocytes with a simultaneous increase in lymphocytes may indicate lymphoproliferative diseases:

• Lymphocytic leukemia,
• Lyphogranulomatosis,
• Lymphoma.

This condition may also be characteristic of:

• acute viral infections
• hepatitis,
• endocrine diseases,
• tuberculosis,
• bronchial asthma,
• removal of the spleen,
• cytomegalovirus infection,
• whooping cough,
• toxoplasmosis,
• brucellosis.

Relative lymphocytosis (in which the total number of white blood cells remains approximately constant) is usually characteristic of severe bacterial infections such as typhoid fever.

In addition, it occurs in the case of:

• Rheumatic diseases,
• Hyperthyroidism,
• Addison's disease
• Splenomegaly (enlarged spleen).

A decrease in the total number of leukocytes against the background of an increase in the number of lymphocytes is possible after severe viral infections or against their background. This phenomenon is explained by the depletion of the reserve of rapid immunity cells, primarily neutrophils, and the increase in long-term immunity cells - lymphocytes. If this is the case, then, as a rule, this situation is temporary, and the number of white blood cells should soon return to normal. Also, a similar state of affairs is typical for taking certain medications and poisoning.

A decrease in the number of red blood cells due to lymphocytosis is usually characteristic of leukemia and bone marrow diseases. In addition, cancer of the bone marrow is usually accompanied by a very large increase in lymphocytes - approximately 5-6 times higher than normal.

A simultaneous increase in the number of red blood cells and lymphocytes can be observed in heavy smokers. The ratio of different types of lymphocytes can also be of diagnostic value. For example, with myeloma, first of all, the number of type B cells increases, with infectious mononucleosis - types T and B.

Treatment and prevention

Should lymphocytosis be treated? In the event that lymphocytes are increased due to some disease, for example, infectious, then treatment of the symptom itself is not required. You should pay attention to the treatment of the disease that caused it and lymphocytosis will go away on its own.

Infectious diseases are treated with either antiviral drugs or anti-inflammatory drugs. In many cases, it is enough just to provide the lymphocytes with comfortable conditions to fight the infection - give the body rest, eat right and drink plenty of fluids to remove toxins from the body. And then the lymphocytes, like soldiers of a victorious army, will “go home” and their level in the blood will decrease. Although this may not happen the next day after the end of the illness. Sometimes a trace from past infection in the form of lymphocytosis can be observed for several months.

A completely different matter is leukemia, lymphoma or myeloma. They will not go away “on their own,” and in order for the disease to recede, a lot of effort must be made. The treatment strategy is determined by the doctor - it can be chemotherapy or radiation radiotherapy. In the most severe cases, a bone marrow transplant is used.

Severe infectious diseases, such as mononucleosis, AIDS, also require careful treatment with antibiotics and antiviral agents.

Everything that has been said about the treatment of lymphocytosis is also true regarding the prevention of this condition. Specific prevention it does not require, it is important to strengthen the body in general and the immune system in particular, eat right, avoid bad habits, treat chronic infectious diseases in a timely manner.

MINISTRY OF EDUCATION AND SCIENCE OF UKRAINE

TAVRICHESKY NATIONAL UNIVERSITY

THEM. V.I. VERNADSKY

FACULTY OF BIOLOGY

DEPARTMENT OF BIOCHEMISTRY

Academic discipline: IMMUNOLOGY

Topic: “B-lymphocytes. Receptors and markers. Participation in the immune response"

Abstract prepared by:

Student: Levchenko Natalya Nikolaevna

Checked:

Zalevskaya Irina Nikolaevna

Simferopol, 2013

Introduction

2 B-lymphocyte markers

Introduction

lymphocyte receptor antigen

The cells of the immune system, which are entrusted with key functions in the implementation of acquired immunity, belong to lymphocytes, which are a subtype of leukocytes.

Lymphocytes are the only cells in the body that can specifically recognize self and foreign antigens and respond with activation to contact with a specific antigen. With very similar morphology, small lymphocytes are divided into two populations that have different functions and produce different proteins.

One of the populations was called B lymphocytes, from the name of the organ “bursa of Fabricius”, where the maturation of these cells in birds was first discovered. In humans, B lymphocytes mature in the red bone marrow.

B lymphocytes recognize antigens with specific immunoglobulin receptors, which appear on their membranes as B lymphocytes mature. The interaction of an antigen with such receptors is a signal for the activation of B lymphocytes and their differentiation into plasma cells that produce and secrete antibodies specific to a given antigen - immunoglobulins.

The main function of B lymphocytes is also specific antigen recognition, which leads to their activation, proliferation and differentiation into plasma cells - producers of specific antibodies - immunoglobulins, i.e. to a humoral immune response. Most often, B lymphocytes require the help of T lymphocytes in the form of the production of activating cytokines to develop a humoral immune response.

Chapter 1. General characteristics B lymphocytes

Specific immunological recognition pathogenic organisms- this is entirely a function of lymphocytes, so they are the ones who initiate the reactions of acquired immunity. All lymphocytes originate from bone marrow stem cells, but T lymphocytes then develop in the thymus, while B lymphocytes continue their development in the red bone marrow (in adult mammals). The term B-lymphocytes is derived from the first letter of the English name of the organs in which these cells are formed: bursa of Fabricius (bursa of Fabricius in birds) and bone marrow (bone marrow in mammals).

The bursa of Fabricius is one of the central organs of immunogenesis in birds, located in the cloaca and controls the humoral immune response. Removal of this organ leads to the abolition of antibody synthesis. The analogue of the bursa of Fabricius in mammals is the red bone marrow.

Main function B-lymphocytes (or rather the plasma cells into which they differentiate) are the production of antibodies. Exposure to an antigen stimulates the formation of a clone of B-lymphocytes specific to this antigen. The newly formed B lymphocytes then differentiate into plasma cells that produce antibodies. These processes take place in the lymphoid organs regional to the site where the foreign antigen enters the body. lymphocytes make up about 15-18% of all lymphocytes found in the peripheral blood. After recognizing a specific antigen, these cells multiply and differentiate, transforming into plasma cells. Plasma cells produce large amounts of antibodies (immunoglobulins Ig), which are the own receptors of B-lymphocytes in dissolved form. Lymphocytes produce and secrete into the bloodstream antibody molecules, which are modified forms of the antigen-recognition receptors of these lymphocytes. The appearance of antibodies in the blood after the appearance of any foreign protein - antigen - regardless of whether it is harmful or harmless to the body, and constitutes an immune response. The emergence of antibodies is not easy defensive reaction body against infectious diseases, but a phenomenon of broad biological significance: this general mechanism recognition of "stranger". For example, the immune reaction will recognize as foreign and will try to remove from the body any abnormal and, therefore, potentially dangerous variant of the cell in which, as a result of a mutation in the chromosomal DNA, a mutant protein molecule is formed. Mammalian lymphocytes (B cells) differentiate first in the fetal liver and, after birth, in the red bone marrow. The cytoplasm of resting B cells lacks granules but contains scattered ribosomes and rough endoplasmic reticulum tubules. Each B cell is genetically programmed to synthesize immunoglobulin molecules embedded in the cytoplasmic membrane. Immunoglobulins function as antigen recognition receptors specific for a particular antigen. About one hundred thousand receptor molecules are expressed on the surface of each lymphocyte. Having encountered and recognized an antigen corresponding to the structure of the antigen recognition receptor, B cells multiply and differentiate into plasma cells, which form and secrete in soluble form large quantities of such receptor molecules - antibodies. Antibodies are large glycoproteins found in blood and tissue fluid. Because they are identical to the original receptor molecules, they interact with the antigen that originally activated the B cells, thus exhibiting strict specificity.

Once the antigen binds to the B cell's receptors, the cell becomes activated. B cell activation consists of two phases: proliferation and differentiation; all processes are induced by contact with antigen and T-helpers. As a result of proliferation, the number of cells capable of reacting with the antigen introduced into the body increases. The importance of proliferation is great because in a non-immunized organism there are very few B cells specific for certain antigens. Some of the cells proliferating under the influence of antigen mature and differentiate sequentially into antibody-forming cells of several morphological types, including plasma cells. Intermediate stages of B cell differentiation are marked by the changing expression of a variety of cell surface proteins required for B cell interactions with other cells.

Each B-lymphocyte that differentiates in the bone marrow is programmed to produce antibodies of only one specificity.

Antibody molecules are not synthesized by any other cells of the body, and all their diversity is due to the formation of several million clones of B cells. They (antibody molecules) are expressed on the surface membrane of the lymphocyte and function as receptors. At the same time, about one hundred thousand antibody molecules are expressed on the surface of each lymphocyte. In addition, B lymphocytes secrete into the bloodstream the antibody molecules they produce, which are modified forms of the surface receptors of these lymphocytes.

Antibodies are formed before the antigen appears, and the antigen itself selects antibodies for itself. As soon as an antigen enters the human body, it literally encounters an army of lymphocytes carrying various antibodies, each with its own individual recognition site. The antigen binds only to those receptors that exactly match it. Lymphocytes that have bound the antigen receive a trigger signal and differentiate into plasma cells that produce antibodies. Since the lymphocyte is programmed to synthesize antibodies of only one specificity, the antibodies secreted by the plasma cell will be identical to their original, i.e. surface receptor of the lymphocyte and, therefore, will bind well to the antigen. So the antigen itself selects antibodies that recognize it with high efficiency.

The entire development path of B lymphocytes from a hematopoietic stem cell to a plasma cell includes several stages, each of which is characterized by its own cell type.

A total of 7 types are identified:

) stem hematopoietic (hematopoietic) cell - a common precursor for all germs of differentiation of lymphomyelopoiesis;

) common lymphoid precursor of B-cells and T-cells for the B- and T-cell path of development - the earliest lymphoid cell for which one of the two directions of development has not yet been determined;

A) early pro-B cell - the closest descendant of the previous cell type and the predecessor of subsequent, advanced in differentiation cell types (the prefix “pro” from the English progenitor);

B) late pro-B cell;

) pre-B cell - a cell type that has finally entered the B-cell path of development (the prefix “pre” from the English precursor);

) immature B cell - a cellular form that completes bone marrow development, which actively expresses surface immunoglobulin and is at the stage of selection for the ability to interact with its own antigens;

) mature B cell - a cell type of the periphery, capable of interacting only with foreign antigens;

) plasma cell (plasmocyte) - an effector, antibody-producing cellular form that is formed from a mature B cell after its contact with an antigen.

Chapter 2. Receptors and markers of B lymphocytes

1 Antigen recognition receptors of B cells: general characteristics

Antigen recognition receptors of B lymphocytes are immunoglobulin molecules. Circulating antibodies are structurally similar to the bulk of B-cell receptors, but lack their transmembrane and cytoplasmic segments. The main classes of membrane-bound immunoglobulins (mIg) found on the surface of mature, unstimulated B lymphocytes are IgM and IgD. Both types of molecules can be present simultaneously on the same B cell, and they have the same specificity, and it is possible that these antigen receptors can interact with each other to control lymphocyte activation and lymphocyte suppression.

The receptor for B lymphocytes that recognizes antigen is IgM. Membrane-bound IgM (mIgM) is typically a monomeric immunoglobulin, i.e. a single unit of four polypeptide chains. This molecule has a hydrophobic sequence located at the C-terminal region of the heavy chain and is designed to fix the molecule to cell membrane. The number of receptor molecules reaches 10 - 100 thousand. per cell. M is encoded by the same set of genes as its serum counterparts. Their only structural difference is an additional fragment at the C-terminus of the molecule, which plays the role of a membrane anchor.

In ontogenesis, the first membrane forms of IgM appear at the final stage of B-cell differentiation in the bone marrow. Mature B cells express a fairly large amount of this protein: 2 * 105 molecules per cell. Such a receptor immunoglobulin interacts either with a protein or corpuscular antigen (Fig. 3.1), or with antigenic determinants on the surface of antigen-presenting cells (macrophages, dendritic cells, etc.).

Figure 1. Structure of the B-cell receptor

Antigen recognition receptors of B cells have been detected quite easily, mainly using anti-immunoglobulin antibodies, either radiolabeled or chemical elements, or fluorescein. When an antigen binds to the corresponding receptor and under the influence of cytokines produced by monocytes, macrophages and T-lymphocytes, B-lymphocytes are activated, which begin to divide and differentiate into plasma cells. Some activated B lymphocytes turn into memory cells, which provide a faster and more effective immune response upon repeated contact with the antigen. Additional components (Ig-alpha (CB79a) and Ig-beta (CD79b)) are directly associated with the main part of the receptor, connecting it to intracellular signal transduction pathways.

The cytoplasmic region of mIg is small and not suitable for interaction with C-proteins or tyrosine kinases. The role of CD3 in the case of mIgM appears to be played by the heterodimer associated with mIgM, consisting of two glycoproteins connected by a disulfide bond with molecular masses of 32-34 kDa (IgM-alpha) and 37-39 kDa (IgM-beta, IgM-gamma). The beta and gamma chains are products of the same gene and are produced by alternative splicing. Both chains are representatives of the immunoglobulin superfamily and contain one domain each in the extracellular part. The cytoplasmic regions of these polypeptides have a conserved sequence, including six amino acids located in a certain way relative to each other. The same sequence is found in the gamma, delta, and zeta chains of CD3, suggesting similar functions of CD3 and IgM alpha-IgM beta. Cytoplasmic fragments contain potential phosphorylation sites.

2 B-lymphocyte markers

In the periphery (outside the bone marrow), B lymphocytes acquire their characteristic cell surface markers.

The main markers of B lymphocytes are membrane Ig, while cells of one clone (rapidly formed as a result of a series of successive divisions of the offspring of one B cell) express Ig molecules that specifically bind only one Ag epitope. Such cells synthesize monoclonal ATs that are capable of recognizing and binding only one Ag. The Ag-binding site of the membrane Ig B-lymphocyte plays the role of a cellular Ag-recognition receptor. In addition to membrane Ig, the B lymphocyte carries other markers; receptors of the Fc fragment of Ig, CD10 (on immature B cells), CD19, CD20, CD21, CD22, CD23 (probably involved in cellular activation), receptors for C3b and C3d, MHC class I and I molecules.

Membrane immunoglobulin is a specific marker of B cells because it is expressed on all mature B lymphocytes and is absent on other cells. The predominant class of membrane immunoglobulins on native (not exposed to antigen) B cells is IgM. It is present on the surface of all native B lymphocytes, starting from the immature B cell stage (see section 3.3.1.2) (Table 3.2). On mature natives

In B cells, along with IgM, IgD is present. The number of immunoglobulin molecules on the surface of a naïve B cell is about 150,000. During the immune response, immunoglobulin classes switch to IgG, IgA and IgE. B cells of the blood and secondary lymphoid organs carry predominantly IgG on their surface, and B cells of the mucous membranes carry IgA.

In addition to immunoglobulin, the BCR contains several other molecules. Two of them - CD79a and CD79b - form an integral part of the BCR, three more - CD19, CD21 and CD81 - are functionally associated with it and form a physical connection with the BCR only upon cell activation. The variants of CD79 molecules - a and b - are also called Ig? and Ig?. Using non-covalent bonds, they form heterodimers associated with membrane immunoglobulin. These molecules have similar sizes and molecular weights (about 40 kDa). Involvement of Ig? and Ig? in signal transmission is based on the connection of their cytoplasmic part with intracellular tyrosine kinases.

The CD19 molecule belongs to the immunoglobulin superfamily. CD19 plays an important signaling function because this molecule is associated with PI3K kinase. CD21 is a receptor for complement components (CR2), involved in enhancing the antigenic signal, as well as in regulating the activity of B lymphocytes. CD81 is classified as a tetraspanin (permeates the membrane 4 times); the function of this molecule is not precisely determined.

The tyrosine kinase Fyn is associated with the cytoplasmic regions of the membrane immunoglobulin, and the tyrosine kinases Blk, Lyn, Lck, as well as Syk, which are involved in the transmission of the activation signal, are associated with the molecules CD79, CD19 and CD81. In addition, the lipid kinase PI3K is located near the cytoplasmic part of the CD19 molecule. This abundance of signaling enzymes associated with BCR components ensures the initiation and transmission of activation signals upon antigen binding.

Chapter 3. Subpopulations of B lymphocytes

All B lymphocytes have a number of general properties: They produce antibodies and immunoglobulin (Ig), express the antigen recognition Ig receptor (B-Cell Receptor - BCR) and the surface markers CD 19 and CD45 (B220). At the same time, several subpopulations of B cells can be distinguished, differing in origin, differentiation, phenotype and functional properties.

There are 3 main subpopulations of B cells (Table 1). One of them is discussed above - B2 cells (sometimes called ordinary B cells), localized mainly in the spleen, bone marrow, lymph nodes, Peyer's patches and individual follicles of the intestinal lymphoid tissue. The histological unit that is the site of concentration of B2 cells is the lymphoid follicle. These cells make up the vast majority of circulating B lymphocytes and play a major role in the humoral immune response. The other two subpopulations are B1 and marginal zone B cells (MZB cells). Most of the data on the various subsets of B lymphocytes have been obtained in mice. Information about subpopulations of human B cells is extremely scarce.

B1 cells are localized mainly in serous cavities -

abdominal and pleural. A small number of B1 lymphocytes, predominantly antibody-secreting cells, are found in the spleen, where they account for 1-5% of the number of B cells. Some B1 cells migrate (through the omentum) to the intestinal mucosa and mesenteric lymph nodes (up to 50% of IgA producers in the intestinal lymphoid tissue are B1 cells). They are absent in mouse lymph nodes. There are 2 subpopulations of B1 cells. Basic differential feature at the same time - the expression of the membrane molecule CD5 (known as one of the markers of T cells). B1a cells simultaneously carry IgM and CD5 molecules on their surface. CD5 is absent from all other B lymphocytes, including B1b cells, which are otherwise very similar to B1a cells. B1 cells are characterized by an “activated phenotype,” which is manifested in the expression of costimulatory molecules CD80 and CD86 on their surface. This property ensures the ability of B1 lymphocytes to perform the functions of APC.a and B1b cells express BCR containing the membrane form of IgM. There are known exceptions: a switch from IgM to IgA in the lamina propria of the intestine has been described. The rearranged V genes of membrane IgM B1a cells do not contain N-inserts (i.e., the TdT enzyme does not participate in their rearrangement). The diversity of V genes of B1 cells is significantly lower than that of B2 cells. This is due to differences in developmental conditions: B1a cells in ontogenesis appear earlier than other subpopulations - even before birth. They develop in the fetal liver with the participation of IL-5 and IL-10 from progenitor cells different from those of ordinary B cells. Even in the embryonic period, B1 cells migrate to the serous cavities, where they exist throughout the life of the organism.

B1 cells are capable of self-maintenance through very slow proliferation, replenishing the loss of cells dying by the mechanism of apoptosis.

B1b cells also develop in the liver of embryos and, after birth, in the bone marrow from other progenitor cells. B1b lymphocytes settle in the periphery somewhat later than B1a cells - immediately before and immediately after birth. When V genes are rearranged in B1b cells, a certain number of N inserts are formed. B1b cells also migrate to the serous cavities and remain there by self-renewal.

Both types of B1 cells can differentiate into antibody-producing cells without antigen stimulation. At the same time, they secrete predominantly IgM antibodies (in the intestine - also IgA). Most of these antibodies are specific to the body's own proteins (DNA, histones, collagen, cytoskeletal components, blood group antigens, etc.); many of them are polyspecific, i.e. capable of interacting with several antigens, including autologous ones. These antibodies have low affinity (affinity) for antigens, including self-antigens, and are not capable of causing tissue damage. Approximately half of serum IgM is secreted by B1 cells. Natural antibodies produced by B1a lymphocytes are often specific to microbial antigens and opsonize pathogens, playing an important role in innate immune responses.

These cells can take part in the adaptive immune response, which is more characteristic of B1b cells. The B1 cell response is predominantly thymus independent. B1 cells constantly circulate between the spleen and the abdominal cavity, but do not enter the follicles because they do not express the BLC chemokine receptor CXCR5 (CXCL13). Related to this is the fact that processes?improvement? humoral immune response in the form of switching isotypes and increasing affinity for antigens does not affect or minimally affects B1 cells.

Another type of B lymphocyte is the marginal zone B cell (MZB). They are localized almost exclusively in marginal zone spleen, separating the white pulp from the red. Phenotypically, these cells are more similar to B2 cells than to B1 cells. They come from the same bone marrow progenitor cells. The main membrane immunoglobulin of MZB cells is IgM, which is expressed more strongly than on B2 cells. At the same time, IgD is present on the membrane in very small quantities. These cells are similar in phenotype to activated B lymphocytes. They contain molecules CD69, CD25, CD38, and a small amount of CD23. Noteworthy is the presence of the CD1d molecule, which is involved in the presentation of lipid antigens.

The separation of the MZB cell line from the general B2 cell line occurs at the transitional stage of transition cells (T3), when future MZB cells weaken the expression of IgD rather than IgM (like B2 cells), and lose the CD23 molecule. MZB lymphocytes do not express the chemokine receptor CXCR5, which allows cells to migrate into follicles. Key factor differentiation of MZB cells - Notch-2. Under the influence of sphingosine-1-phosphate and with the participation of adhesion molecules LFA-1 and VLA-4, they migrate to the marginal zones of the spleen. MZB cells do not participate in recycling, but perform shuttle operations. migration to lymphoid follicles and back, receiving information about antigens entering the spleen with blood. The lifespan of MZB lymphocytes is comparable to the lifespan of the body. The decrease in the number of MZB cells caused by damaging factors is quickly eliminated. The cells participate in the humoral immune response to pathogens entering the bloodstream. They carry out a thymus-independent immune response to encapsulated pathogens. Due to the strong expression of MHC-II molecules and co-stimulatory molecules, MZB cells have a strong ability to interact with T-helper cells, but their participation in the thymus-dependent immune response is poorly understood. When responding to antigens, MZB cells differentiate into short-lived antibody-producing cells. The V genes of MZB cells are rarely affected by mutations, which is typical for the development of plasma cells outside the germinal centers. In these cells, there is no switching of immunoglobulin classes, and even MZB memory cells carry IgM rather than IgG on their surface. IgM+ memory cells predominate in the marginal zone of the human spleen.

List of used literature

1.A. Royt, J. Brustoff, D. Meil. Immunology - M.: Mir, 2000

.Lebedev K.A. - Immunology in clinical practice, 1996

.Immunology (in 3 volumes) / Under. ed. U. Paul. - M.: Mir, 1988

.Yarilin A.A - Immunology, 2010

.Khaitov R.M., Ignatieva G.A., Sidorovich I.G., Immunology: Textbook. - M.: Medicine, 2000. 432 p.: ill. (Text. lit. For students of medical universities).

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B-lymphocytes play an important role in the implementation of immune mechanisms in the fluid environment of the body: their effect on humoral defense and properties, features of the primary and secondary response.

Students studying the basics of immunology or people interested in health issues are familiar with a type of cell called B lymphocytes, which provide protection against the introduction of foreign microorganisms into the human internal environment.

This type of lymphocyte is formed at the stage of embryonic development in humans and other mammals in the liver and bone marrow tissue from stem cells. In adults, B lymphocytes are produced exclusively in the most important organ of the hematopoietic system - the bone marrow - the spongy contents of large bones and the superficial cerebral cortex.

Properties of b-lymphocytes and their primary response

Lymphocytes and plasma cells circulating in the blood have long been known to science, but it is a fact that B lymphocytes (which make up 15-30 percent of the total white blood cell population) differentiate plasma cells. The next stage of development (or proliferation) of b-lymphocytes is the production of antibodies that recognize any foreign microorganism (viruses, bacteria, chemicals). This process becomes possible due to the production of more than one thousand immunoglobulin molecules of various types by B lymphocytes.

The immune response occurs due to the synthesis of antibodies that react to the appearance of any protein compound - antigen - in the body.

Diagnosis of “foreign” components occurs, regardless of how harmful or harmless they are to humans, with the help of immunogen-recognizing receptors (immunoglobulins) that B-lymphocytes are equipped with. B-lymphocytes synthesized by the bone marrow are sent to the lymphoid tissues of the body and settle in them, being activated at the first contact with the antigen protein, being human protectors from any pathologies.

There are three types of mature b-lymphocytes:

1. "Naive", or unactivated b-cells that have not come into contact with the antigen. As a rule, they react poorly to the appearance of any stimulus. In this case, young b-cells accumulate in the spleen, and more mature ones - in the lymph nodes.
2. b memory lymphocytes are the longest-living and most efficient immunodefenders, providing the fastest immune response, since they are the descendants of cells that have already encountered a certain antigen protein. They produce a “mega quantity” of immunoglobulins when the type of antigen is recognized (its reappearance).
3. Plasmocytes. They are the final stage of the development of b-lymphocytes and active participants in the humoral immune response. These cells contain few membrane antibodies, but they are capable of producing mega quantities of various soluble analogues. Plasmocytes in the blood do not live long: no more than two to four days, and in the absence of antigens they are eliminated, while plasma cells localized in the bone marrow can exist for several decades.

Thus, not only pathogens of infectious diseases are determined, but also mutant protein molecules that have changes in chromosomal DNA.

Secondary response

After cleansing the body of foreign particles, many b lymphocytes return to the lymphoid tissues in the form of non-activated cells. Unlike short-lived b-lymphocytes located in the peripheral blood system, they can wait a long time for a certain immunogen (virus, bacteria or toxic component), being descendants of cells activated by this type of antigen before.

This type of lymphocyte is capable of proliferating, maintaining or increasing its population. Therefore, when an immunogen enters the body again, these b-cells react instantly and intensively, producing several thousand corresponding receptors, the role of which is played by immunoglobulins.

This reaction is called a secondary humoral response. Unlike the first, it begins much faster and proceeds more intensely, since the immunogen is already known, and the body produces a much larger volume of B-lymphocytes to respond to it.

There are two subgroups of such cells: B1 and B2. The difference between them is that they produce different types of antibodies:

1. The first subgroup includes antibodies designed to combat “fresh” immunogen that has just entered the body. Such immunoglobulins are marked with the letter M. They are localized in the border cavities to eliminate microbes that have overcome the protective barriers.
2. Another subgroup includes antibodies, the activity of which is aimed at infections that have settled inside the body. They can be identified by their marking with the letter G.

The most numerous order of B-lymphocytes is the first subgroup, which is responsible for the immune response to external stimuli.

Features of B-lymphocytes

Natural antibodies produced by B-lymphocytes are capable of performing functions that are essential for overall human health:

• “initial defensive cordon” that protects against pathogens;
• removal of catabolic products and dead cells;
• presentation of the type and nature of immunogens to T lymphocytes;
• maintaining the dynamic constancy of autoimmune processes;
• anti-inflammatory effect;
• opposition pathological processes in case of tissue integrity violation.

All functions of B-lymphocytes are closely related to the properties of the immunoglobulins they produce. Today, science knows five types of such receptors: M, G, A, E and D.

Immunoglobulins G have the following qualities:

1. They are leaders in the fight against humoral immunity against infections.
2. The ability to penetrate the placenta and form its own protection against infections in the fetus.
3. The ability to neutralize bacterial exotoxins, bind protein compounds and precipitate antigens in the form of cloudiness (precipitation).

Immunoglobulins labeled M:

• They develop in the fetus itself, without penetrating the placental barrier, and actively fight infections.

• They are formed at the initial stage of the introduction of foreign objects and have high activity against gram-negative bacteria.
• They stimulate agglutination (precipitation) from bacteria and other foreign cells, participate in the activation of complement (a whole cascade of reactions of a biochemical nature) and neutralization of viruses.
• They perform the most important work of eliminating (identifying and destroying) the pathogen in the bloodstream, stimulating the processes of phagocytosis (digestion) of the antigen.

Immunoglobulins A:

1. They are active in local (local) immunity.
2. They prevent damage to the mucous membrane by bacteria, preventing their attachment to it.
3. Participate in the processes of complement activation and phagocytosis, neutralize enterotoxins.

Immunoglobulins D are secreted by plasma cells localized in the adenoids and tonsils. Specializes this type as membrane receptors for immunogens.

Their functions are:

1. Development of local immune defense.
2. Antiviral activity.
3. Participation in complement activation (but rarely), as well as in autoimmune reactions.
4. Promote B-lymphocyte differentiation and promote an anti-idiotypic response.

The introduction of any foreign antigen provokes the human body to produce immunoglobulins of all types. Subsequently, when the structure of the “foreigner” is identified, regulatory systems begin to operate, which will force B-lymphocytes to produce a priority type of immunoglobulins.

Plasmocytes derived from B cells inhibit the work of subsequent parent lymphocytes until the initial death of antibody-producing cells begins in the active lymph nodes.

In this way, a sufficient amount of immunoglobulins is controlled certain type for complete destruction of foreign microorganisms.

Each B-lymphocyte formed in human bone marrow produces antibodies of only one type. The diversity of such molecules is due to the programming of the body for effective immune protection and the creation of many millions of cloneable B cells.

In addition, the surface of each of these lymphocytes is covered with 100-150 thousand immunoglobulins, aimed at recognizing antigens of the same type. This is how the ability of the cells that protect the body to identify the “enemy” with high accuracy is manifested.

Having come into contact with the pathogen once, B lymphocytes remember it and adapt to produce antibodies that can eliminate the problem. Thanks to this quality of essential cells, the body receives immunity to the disease throughout their entire life. The benefits of vaccination are based on this principle.

Update: October 2018

Lymphocytes are small blood cells from the group of leukocytes that perform a very important function. They are responsible for human resistance to infectious diseases and are the first obstacle to cancer cells. Therefore, any significant change in the number of lymphocytes is a signal from the body that needs to be heeded.

How are lymphocytes formed?

The main organs that form lymphocytes are the thymus (before puberty) and the bone marrow. In them, cells divide and remain until they encounter a foreign agent (virus, bacteria, etc.). There are also secondary lymphoid organs: lymph nodes, spleen and formations in digestive tract. This is where most lymphocytes migrate. The spleen is also the depot and place of their death.

There are several types of lymphocytes: T, B and NK cells. But they are all formed from a single precursor: a stem cell. It undergoes changes, eventually differentiating into the right type lymphocytes.

Why are lymphocytes necessary?

How to determine the number of lymphocytes?

The number of lymphocytes is reflected in the general blood test. Previously, all cell counts were carried out manually using a microscope. Nowadays, automatic analyzers are more often used to determine the number of all blood cells, their shape, degree of maturity and other parameters. The standards for these indicators for manual and automatic determination differ. Therefore, confusion still often arises if the analyzer results are close to manual standards.

In addition, the forms sometimes do not indicate the rate of lymphocytes in the child’s blood. Therefore, it is necessary to clarify the standards for each age group.

Norms of lymphocytes in the blood

What do elevated lymphocytes in the blood mean?

Lymphocytosis is an increase in the number of lymphocytes. It can be relative and absolute

• Absolute lymphocytosis– a condition in which the number of lymphocytes exceeds age norms. That is, in adults - more than 4 * 10 9 cells per liter.
• Relative lymphocytosis– change in the percentage of white cells in favor of lymphocytes. This happens when the total number of leukocytes decreases due to the neutrophil group. As a result, the percentage of lymphocytes becomes larger, although their absolute value remains normal. A similar blood picture is considered not as lymphocytosis, but as leukopenia with neutropenia.

It is important to remember that if neutrophils are reduced and lymphocytes are increased only as a percentage, this may not reflect the true picture. Therefore, most often in blood tests they focus specifically on the absolute number of lymphocytes (in cells per liter).

Causes of elevated lymphocytes in the blood

• Chronic lymphocytic leukemia
• Acute lymphoblastic leukemia

• Autoimmune processes (thyrotoxicosis)
• Lead, arsenic, carbon disulfide poisoning
• Taking certain medications (levodopa, phenytoin, valproic acid, narcotic and non-narcotic analgesics)
• Splenectomy

Stress and hormonal fluctuations

Changes in the neutrophil/lymphocyte ratio can occur in stressful situations. Including when entering the doctor's office. Excessive physical activity has the same effect. In such cases, lymphocytosis is insignificant (no more than 5 * 10 9 cells per liter) and is temporary. Increased lymphocytes in the blood of women also occur during menstruation.

Smoking

A general blood test for an experienced smoker may differ significantly from the results of a person without bad habits. In addition to general blood thickening and an increase in the number of red blood cells, there is always an increase in the level of lymphocytes.

Infectious diseases

The entry of an infectious agent into the body leads to the activation of all protective forces. During bacterial infections, a large number of neutrophils are produced, which destroy microbes. And when viruses penetrate, lymphocytes come into play. They mark cells affected by viral particles, produce antibodies against them and then destroy them.

Therefore, with almost any viral infection, relative lymphocytosis occurs, and often absolute lymphocytosis. This indicates the beginning of the formation of immunity to the disease. Saved increased level lymphocytes throughout the entire recovery period and sometimes a little longer. Blood tests are especially affected by infectious mononucleosis. Some chronic bacterial infections also cause the growth of lymphocytes (tuberculosis and syphilis, for example).

Mononucleosis

This is an infection caused by the Epstein-Barr virus. This virus affects almost all people sooner or later. But only in some people does it lead to symptoms collectively called infectious mononucleosis. The virus is transmitted through saliva during close household contacts, as well as through kissing. The latent period of the disease can last more than a month. The main target of viral particles is lymphocytes. Symptoms of the disease:

• temperature increase
• sore throat
• enlarged lymph nodes
• weakness
• night sweats

The disease is more easily tolerated by children younger age. Teenagers and adults may feel the signs of infection much more strongly. To diagnose mononucleosis, complaints, examination and test analysis are usually sufficient: lymphocytes in the child’s blood are elevated, abnormal mononuclear cells are present. Sometimes an immunoglobulin test is used. Treatment for a viral infection is usually symptomatic. Requires rest, drinking enough fluids, and for fever, antipyretic drugs (paracetamol,). In addition, it is better to avoid playing sports during illness. Mononucleosis causes an enlargement of the spleen, which processes blood cells. This increase, combined with trauma, can lead to organ rupture, bleeding, and even death.

Whooping cough

This is a severe infectious disease of the respiratory tract. It most often affects children, although there is high vaccination coverage in recent years dramatically reduced the incidence of infection.

Whooping cough begins as a typical cold, but after 1-2 weeks a paroxysmal cough occurs. Each attack can end in severe vomiting. After 3-4 weeks, the cough becomes calmer, but persists for a long time. I used to have whooping cough common cause death and disability of children. But even now children are at risk of cerebral hemorrhage and convulsive syndrome during an attack.

Diagnosis is based on symptoms, PCR results And enzyme immunoassay. In this case, in a general blood test, significant leukocytosis almost always occurs (15-50 * 10 9), mainly due to an increase in the number of lymphocytes.

Antibiotics are used to treat whooping cough. However, they rarely shorten the duration of the disease, but can reduce the incidence of complications. The main defense against this serious illness is DTP vaccination, Pentaxim or Infanrix.

Blood tumors

Unfortunately, lymphocytosis is not always reactive in response to infection. Sometimes it is caused by a malignant process that causes cells to divide uncontrollably.

Acute lymphoblastic leukemia (ALL)

A tumor disease of the blood in which immature lymphoblasts are formed in the bone marrow that have lost the ability to turn into lymphocytes is called ALL. Such mutated cells cannot protect the body from infections. They divide uncontrollably and inhibit the growth of all other blood cells.

ALL is the most common type of blood tumors in children (85% of all childhood hemoblastoses). It is less common in adults. Risk factors for the disease include genetic abnormalities (Down syndrome, for example), radiation therapy and intense ionizing radiation. There is information about the effect of pesticides in the first three years of a child’s life on the risk of developing ALL.

Signs of ALL:

• Symptoms of anemia: pallor, weakness, shortness of breath
• Symptoms of thrombocytopenia: unreasonable bruises and nosebleeds
• Symptoms of neutropenia: fever, frequent severe infectious diseases, sepsis
• Enlarged lymph nodes and spleen
• Bone pain
• Neoplasms in the testicles, ovaries, mediastinal area (thymus)

To diagnose acute lymphoblastic leukemia, a complete blood count is required. It most often has a reduced number of platelets and red blood cells. The white blood cell count may be normal, low, or high. At the same time, the level of neutrophils is reduced, and the level of lymphocytes is relatively increased, often there are lymphoblasts. If there is any suspicion of a tumor, a bone marrow puncture is performed, with the help of which a final diagnosis is made. The criterion for a tumor is a large number of blasts in the bone marrow (more than 20%). Additionally, cytochemical and immunological studies are carried out.

Treatment of ALL

The main principles of treatment of blood tumors are the introduction of remission, its consolidation and maintenance therapy. This is achieved with the help of cytostatic drugs. Chemotherapy is difficult for many, but it is the only treatment that gives a chance for recovery. If the disease does return (relapse), then more aggressive cytostatic therapy regimens are used or bone marrow is transplanted. Bone marrow transplantation is performed from a relative (if suitable) or from another suitable donor.

Prognosis for ALL

Advances in oncohematology make it possible to cure a large number of patients with acute lymphoblastic leukemia. Positive prognosis factors include young age, leukocyte count less than 30,000, absence of genetic damage, and entry into remission within 4 weeks of treatment. In this situation, more than 75% of patients survive. Each relapse of the disease reduces the chances of full recovery. If there have been no relapses for 5 years or more, the disease is considered defeated.

Chronic lymphocytic leukemia (CLL)

A blood tumor in which the level of mature lymphocytes in the bone marrow increases is called CLL. Although tumor cells differentiate into their final forms, they are unable to perform the functions of lymphocytes. While ALL most often affects children and young adults, CLL usually occurs after 60 years of age and is not such a rare cause increased lymphocytes in the blood of an adult. This type of leukemia is the only one for which risk factors have not been established.

Symptoms of CLL:

• Enlarged lymph nodes (painless, mobile, dense)
• Weakness, pallor
• Frequent infections
• Increased bleeding
• If the condition worsens: fever, night sweats, weight loss, enlarged liver and spleen

Quite often, CLL is an incidental finding during a routine blood test, since this disease is asymptomatic for a long time. Results are considered suspicious if the number of leukocytes exceeds 20*10 9 /l in adults, and the number of platelets and red blood cells is sharply reduced.

A feature of the treatment of CLL is its resistance to chemotherapy. Therefore, therapy is often delayed until obvious symptoms appear. In this condition, a person can live without treatment for several years. If the condition worsens (or leukocytes double in six months), cytostatics can slightly increase life expectancy, but more often they do not affect it.

Thyrotoxicosis

One of the important functions of lymphocytes is the formation of delayed allergic reactions. That is why an increase in such cells may indicate an autoimmune process. A striking example is diffuse toxic goiter (Graves-Bazedow disease). For unknown reasons, the body begins to attack its own receptor cells, as a result of which the thyroid gland is in constant activity. Such patients are fussy, restless, and find it difficult to concentrate. There are often complaints of irregular heart function, shortness of breath, elevated temperature, hand trembling. Eyes of the sick toxic goiter wide open and sometimes seem to be coming out of their sockets.

The main laboratory sign of DTZ is high values hormones T3 and T4 with low TSH. There is often relative and sometimes absolute lymphocytosis in the blood. The reason for the increase in lymphocytes is the excessive activity of the immune system.

Treatment of DTG is carried out with thyreostatics, followed by surgery or radioactive iodine therapy.

Other autoimmune diseases (rheumatoid arthritis, Crohn's disease, etc.) are also combined with lymphocytosis.

Metal poisoning and medication use

Some heavy metals (lead) and medicines(chloramphenicol, analgesics, levodopa, phenytoin, valproic acid) can cause leukopenia due to a decrease in neutrophils. As a result, relative lymphocytosis is formed, which does not have clinical significance. It is more important to monitor the absolute number of neutrophils in order to prevent a severe condition (agranulocytosis) of complete defenselessness against bacteria.

Splenectomy

Splenectomy (removal of the spleen) is performed according to certain indications. Since this organ is the site of lymphocyte breakdown, its absence will cause temporary lymphocytosis. Eventually, the hematopoietic system itself will adapt to the new circumstances, and the cell level will return to normal.

What do low lymphocytes in the blood indicate?

Lymphopenia is a decrease in the number of lymphocytes less than 1.5 * 10 9 cells per liter. Causes of lymphopenia:

• Severe viral infection (hepatitis, influenza)
• Bone marrow depletion
• Drug influence (corticosteroids, cytostatics)
• Heart and renal failure final stage
• Tumors of lymphoid tissue (lymphogranulomatosis)
• Immunodeficiencies, including AIDS

Severe infection

A long-term, “exhausting” infectious disease depletes not only a person’s strength, but also reserves of immune cells. Therefore, after temporary lymphocytosis, a deficiency of lymphocytes occurs. As the infection is defeated, cell reserves are restored and tests return to normal.

Diseases of bone marrow with its depletion

Some diseases cause pancytopenia - the depletion of all blood cells in the bone marrow. In such cases, not only the number of lymphocytes is reduced, but also other types of leukocytes, red blood cells and platelets.

Fanconi anemia

Congenital Fanconi anemia is named after its most striking syndrome: anemic. But the basis of the disease is depletion of the bone marrow and inhibition of all hematopoiesis. In the analysis of patients, a decrease in the number of red blood cells, platelets and all types of white cells (including lymphocytes) is observed. Congenital pancytopenia is often accompanied by developmental anomalies (lack of thumbs, short stature, hearing loss). The main danger and the main cause of death is a decrease in the number of neutrophils and platelets, resulting in severe infections and massive bleeding. In addition, such patients have an increased risk of cancer.

Treatment of congenital pancytopenia is carried out hormonal agents. They can delay complications for some time. The only chance for a complete cure is a bone marrow transplant. But due to frequent cancer diseases, the average life expectancy of such people is 30 years.

Exposure to radiation

Exposure to various types of radiation (accidental or for treatment purposes) can lead to bone marrow dysfunction. As a result, it is replaced by connective tissue, and the supply of cells in it becomes poor. In blood tests in such cases, all indicators decrease: red blood cells, white blood cells and platelets. Lymphocytes are also usually low.

Drug influence

Some drugs (cytostatics, neuroleptics) used for vital signs, may have side effects. One of these effects is inhibition of hematopoiesis. The result is pancytopenia (a decrease in the number of all blood cells). Taking corticosteroids causes absolute neutrophilia and relative lymphopenia. Most often, the bone marrow will recover after stopping these medications.

Hodgkin's lymphoma (lymphogranulomatosis)

The main difference between lymphoma and lymphocytic leukemia is the initial site of its occurrence. Tumor cells in lymphomas are located locally, most often in the lymph nodes. In leukemia, the same malignant cells are formed in the bone marrow and are immediately carried into the general bloodstream.

Symptoms of Hodgkin's lymphoma:

• Enlargement of one or more lymph nodes
• Anemia, increased bleeding and susceptibility to infections (if the process is advanced)
• Intoxication (fever, night sweats, weight loss)
• Symptoms of compression of organs by a tumor: suffocation, vomiting, irregular heartbeat, pain

The main diagnostic method is a biopsy of the affected lymph node or organ. In this case, a piece of fabric is sent to histological examination, based on the results of which a diagnosis is made. To determine the stage of the disease, a bone marrow puncture is taken and a computed tomography scan of the main groups of lymph nodes is performed. Blood tests may be normal in the early stages of lymphoma. Deviations, including lymphopenia, occur as the disease progresses.

Treatment of the disease is carried out with cytostatic drugs followed by irradiation of the lymph nodes. For relapses, more aggressive chemotherapy and bone marrow transplantation are used.

The prognosis for such a tumor is usually favorable, with a 5-year survival rate of 85% or higher. There are several factors that worsen the prognosis: age over 45 years, stage 4, lymphopenia less than 0.6 * 10 9 .

Immunodeficiencies

Immune deficiency is divided into congenital and acquired. In both cases, the level of lymphocytes in the general blood test may change due to a deficiency of T cells. If the B-link is affected, then a routine blood test often does not reveal abnormalities, so additional research methods are required.

DiGeorge syndrome

This variant of immunodeficiency is also called hypoplasia (underdevelopment) of the thymus. The chromosome defect in this syndrome also causes heart defects, facial abnormalities, cleft palate and low level calcium in the blood.

If a child has an incomplete syndrome, when part of the thymus is still preserved, then he may not suffer too much from this disease. The main symptom is a slightly higher frequency of infectious lesions and a slight decrease in lymphocytes in the blood.

The full syndrome is much more dangerous, manifested by severe viral and fungal infections in the very early childhood, therefore requiring a thymus or bone marrow transplant for treatment.

Severe combined immunodeficiency (SCID)

Mutations of certain genes can lead to severe damage to cellular and humoral immunity - SCID (severe combined immunodeficiency). The disease manifests itself already in the first months after birth. Diarrhea, pneumonia, skin and ear infections, sepsis are the main manifestations of the disease. The causative agents of fatal diseases are microorganisms that are harmless to most people (adenovirus, CMV, Epstein-Barr, herpes zoster).

A general blood test reveals an extremely low content of lymphocytes (less than 2*10 9 cells per liter), the thymus and lymph nodes are extremely small.

Only possible treatment SCID – donor bone marrow transplant. If it is carried out in the first three months of the baby’s life, then there is a chance of a complete cure. Without therapy, children with combined immunodeficiency do not survive beyond 2 years of age. Therefore, if a child has low lymphocytes in his blood, he constantly suffers from severe infectious diseases, then it is urgently necessary to carry out additional examination and start treatment.

AIDS

Acquired immunodeficiency syndrome is associated with the damaging effects of HIV on T lymphocytes. This virus can enter through biological fluids: mainly blood and sperm, and also from mother to child. A significant decrease in lymphocytes does not occur immediately. Sometimes several years pass between infection and the onset of AIDS. As the disease progresses and lymphopenia increases, a person loses the ability to resist infections, which can lead to sepsis and death. The risk of tumors increases for the same reason: the disappearance of T cells. Treatment of HIV infection with special antiretroviral drugs helps control the disease and preserves required level immunity and prolongs life.

Features of lymphocytosis in children

• Immediately after birth, neutrophils predominate among all leukocytes in children. But by the 10th day of life, the number of lymphocytes increases, occupying 60% of all white cells. This picture persists up to 5-7 years, after which the ratio of lymphocytes and neutrophils reaches adult norms. Therefore, lymphocytosis in young children is normal physiological phenomenon, if it is not accompanied additional symptoms and changes in analyses.

• The body of young children often responds to infections very violently, producing a leukemoid reaction. It got its name because of its resemblance to blood tumors - leukemia. With such a reaction, the number of leukocytes significantly exceeds the norm and even the level of normal inflammation. Sometimes immature forms (blasts) appear in the blood in an amount of 1-2%. Other hematopoietic germs (platelets, erythrocytes) remain within normal limits. Therefore, extremely high values ​​of white blood (including lymphocytes) do not always mean cancer. Often the cause is common mononucleosis, chickenpox, measles or rubella.

The conclusion from the above is this: lymphocytes are extremely important cells in the human body. Their meaning can be a marker of very dangerous conditions, or it can indicate a common runny nose. The level of these cells should be assessed only in conjunction with other blood elements, taking into account complaints and symptoms. Therefore, it is better to entrust the assessment of the test results to your attending physician.