Thymus (thymus gland) is an organ of lymphopoiesis (lymphocyte formation), in which maturation, differentiation and immunological training of T-lymphocytes (T-cells) of the human immune system and many other animal species occur.

The involution of the thymus occurs with age, and leads to changes in its structure and a decrease in its tissue mass.

The process of gland involution is a conserved sequence in almost all vertebrates, birds, bony fish, amphibians, and reptiles.

The thymus is a secretory gland in the prepubertal (before puberty) period of development of the human reproductive system and plays an important role in the functioning of the immune system.

The thymus is a soft organ located between the human lungs.

It is a bilobed structure located almost at the top of the heart and located along the trachea.

The gland has a triangular shape, and is divided into two lobes enclosed in a fibrous environment. Thymus petals have a pink, opaque color.

According to the structural structure, the thymus gland consists of two main parts - the cortex and the medulla. The surface layer of the thymus petals is called the cortex.

• Genes that control thymus size and the subsequent rate of its involution also differ between individuals, which explains the different susceptibility of an individual to pathogens.
• Genetic disorders, such as Down syndrome and DiGeorge, can significantly affect early immune programming by impairing thymus growth.
• Environmental factors in the process of human development have a significant impact on the function of the thymus gland. For example, zinc deficiency can lead to organ atrophy, leading to an increased risk of bacteria and viruses infecting the body.
• Malnutrition during human development, negatively affects the structure and function of the thymus. Even the amount of breastfeeding a baby receives, and the length of each feeding, affects its function.
• Differences between male and female development, contribute to gender dependence in disease susceptibility. Compared to men, women experience a lower risk of bacterial, viral, and fungal infections, but have an increased chance of developing autoimmune diseases, including multiple sclerosis.
• Steroids, such as estrogen and testosterone, also affect thymus size and function, especially during puberty.

What is thymus involution?

Despite the essential role of the thymus in immune health, the thymus is weakly active or inactive for most of a person's life.

The organ is most active in childhood and reaches its maximum weight of about 30 grams during puberty.

After reaching the maximum weight, the activity of the thymus constantly decreases.

The decrease in the activity of the thymus corresponds to a decrease in its size, as well as a gradual and almost complete replacement of its tissue - adipose.

Physiological atrophy, or age-related involution of the thymus, is closely related to the natural decline in the functions of the human immune system over time. Reducing the size of the thymus leads to a decrease in lymphopoiesis. As a result, antigen recognition is impaired and the body's rejection of the primary immune response increases.

According to statistics, about 80 percent of people over the age of 60 suffer from chronic diseases, partly caused by the involution of the thymus.

Age changes

Although the involution of the thymus is associated with, it is not induced by age-related changes and begins from the first year of a person's life.

The thymus microenvironment, or stroma (reticular tissue), is vital for the growth and development of T-lymphocytes.

The deterioration of the stroma in the elderly is caused by the loss of thymus epithelial cells. The activity of epithelial cells is regulated by the FOXN1 gene, the expression of which decreases with age.

The epithelial space of the thymus begins to decrease from the first year of life in the amount of 3% until the onset of the average age of 35-45 years, after which it is reduced to 1% by the time of death.

Involution of the thymus leads to a decrease in the output of T cells. In adults, simple T cells are maintained through homeostatic proliferation (cell division). The ability of the immune system to mount a strong protective response also depends on the diversity of T cell receptors.

Although homeostatic proliferation helps maintain simple T cells even with almost no thymic activity, it does not result in an increase in their receptor diversity.

For as yet unknown reasons, the diversity of simple T cells drops sharply around the age of 65 years.

Loss of thymus function and simple T-cell diversity is believed to contribute to immunosuppression in the elderly, including an increase in cancers, autoimmune reactions, and opportunistic infections caused by opportunistic pathogens.

Under certain circumstances, the thymus can also undergo an acute involution (the so-called transitional). It is caused by stress, infections, pregnancy, and malnutrition.

There is growing evidence that thymic involutions are plastic and can be therapeutically inhibited or reversed to enhance immune system functions in adults.

Thymus involution studies can help develop treatment options, especially when it is difficult to restore immune function after chemotherapy, ionizing radiation, or infections involving human immunodeficiency virus.

Related video

How is it that children and the elderly are more susceptible to disease? It's all about age, which greatly affects immunity. In children, immunity is just beginning to form, and in the elderly, protective mechanisms are significantly weakened, so the elderly get sick more often.

What to do if the child is often sick?

It often happens that a child often begins to get sick immediately after birth. Such children are prone to colds, allergies and diathesis from the first six months of their lives onwards. Parents of sick children should urgently consult an immunologist, receive regular consultations and analyze the activity of the immune system by conducting appropriate tests. These tests will determine the number of T- and B-lymphocytes, immunoglobulins, monocytes, basophils, nitrophils and exenophiles, and will also help to find out how effectively the complement system is functioning.

A sick child is grief for the family:

All this data can be obtained after a blood test, which allows you to find out if an immune response develops to the vaccination that is given to children in the first days of life, whether they have antibodies and what type they belong to. In most cases, other studies will be needed, appointed by the immunologist, who, based on the results obtained, makes his conclusion.

Ultrasound allows you to find out the size of the thymus, the mass of the spleen and lymph nodes. The more parents study the structure, capabilities and state of the immune system, the easier it is to correctly correct the life and development of the child.

Of course, vaccination is extremely important. If certain defects are found in the work of the immune system, it is necessary to limit some contacts of the child with the external environment, in particular, with sick people. This is important, because any contact with an infectious agent can cause a serious blow to the body. And even if no problems are found, the work of the immune system should not be endangered.

Of course, we are all interested in when the degree of immune protection begins to decrease. Such changes, which can be attributed to the aging process, can begin in some people as early as 35-40 years. Aging primarily affects the central organs, such as the bone marrow and thymus, in which T-lymphocytes are differentiated and trained. These organs decrease with age, because connective tissue appears instead of glandular tissue, as a result of which the capabilities and potential of the thymus decrease.

In older people, the B-system of immunity functions quite reliably, but the T-system of lymphocytes is constantly weakening, especially its control function. This applies, first of all, to the prompt detection of atypical tumor cells and their destruction. Because the immune system is weakened, it misses these cells and does not detect them in time. Tumor cells have such a feature: if the cell has already formed and was not detected in time (such cells are created all the time, and the immune system constantly hunts and controls them), then the cell can begin to divide and create a colony. But this colony eventually develops into a tumor.

Cell of the immune system:

When the immune system is strong enough, it keeps the tumor under control and prevents it from developing. However, a tumor is an extremely vile and insidious formation. As soon as she sees a gap in the protection of the immune system, the tumor immediately begins to develop and increase in size by leaps and bounds. Further complicating the task is the fact that tumor cells can independently migrate to other areas of the body, metastasize and gradually destroy the body. As you can see, the better the state of the immune system, the better the body's defense against malignant tumors.

Of course, medicine is a complicated matter, who would argue. Such articles perform a purely educational function, but are not able to replace an experienced doctor. But in our world there is also an opportunity to help oneself, for example, to find worthy medical offers on a specialized bulletin board. There are interesting options on which you can choose the right doctor or the right medical service.

The physiological processes of age-related restructuring of the human immune system affect several levels. Among them, the most significant are:
change in the functional properties of the elements of the stroma (cellular microenvironment) of immune organs, in which the development and differentiation of immunocompetent cells occur;
decrease in the potential properties of early precursors, primarily lymphoid cells;
limiting the formation of anti-antigenic diversity (repertoire) of the main molecules of the immune system (antigen-recognizing T-cell receptors and antibodies) as a key functional characteristic of acquired immunity with a predominance of molecules with an auto-aggressive orientation;
decrease in the proliferative activity of immunocompetent cells, dependent on internal (gene changes) and external (cytokines and other mediators) factors;
narrowing of the clone of immunocompetent cells, mainly in the immune response to primary immunization;
imbalance of immunoregulatory mechanisms with a predominance of immunosuppressive or autoaggressive components;
change in the molecular prerequisites for programmed cell death (apoptosis).

Cellular immune response
Numerous experimental and clinical observations suggest that the earliest age-related changes occur in thymus-dependent immune functions that follow thymus involution, followed by a change in B-cell function.

There is a connection between thymus involution and age-related changes in the immune system as a whole.

Age-related involution of the thymus is a physiological process and differs from accidental involution, which usually occurs acutely under the influence of various factors (radiation, glucocorticoids, etc.). The use of glucocorticoids for therapeutic purposes can accelerate the natural involution of the thymus.

In the process of aging, the thymus, the central organ of the immune system, undergoes profound degenerative changes. The formation of the thymus, as is known, is completed by the end of the first half of intrauterine development. Then no new structures are formed in the thymus. The mass of the organ increases, which is regulated by the age of the person and reaches 30-40 g by the period of puberty. In the future, the thymus gland gradually decreases to 10-13 g by the age of 70-90. Adipose tissue replaces specific components of the thymus.

Thymic tissue, including functioning lymphocytes, does not completely disappear.

The rapid exit of mature T-lymphocytes from the thymus, which is characteristic of the neonatal period and early childhood, is then inhibited and extremely slowed down in the elderly. Quantitative and qualitative changes in T cells (disturbances in proliferative activity, activation signal transduction, sensitivity to cytokines) and disturbances in the ratio of their immunoregulatory subpopulations are largely a consequence of thymus involution.

The inability of the thymus microenvironment to ensure the full differentiation of T-cell precursors is considered as one of the key mechanisms of age-related immunopathology. Numerous experiments with the transfer of thymus cells and bone marrow stem cells from young to old mice and vice versa have shown that the impairment of immune functions in bone marrow chimeras that received a thymus transplant from old animals depends on the inability of the thymic microenvironment to support the development of T cells.

A reflection of age-related changes occurring in the thymus and indicating a gradual loss of the hormone-synthesizing function of thymic epithelial cells is a decrease in the concentration of thymic hormones in serum.

The level of thymosin, thymulin and other hormones in the circulation reaches a maximum at an early age and then gradually decreases. After 40 years, the normal content of hormones drops sharply, and in pathological conditions this process accelerates. There is a relationship between the level of thymus hormones in serum, human age and the development of immunopathology, mainly of the immunodeficient type.

As the thymus ages, the relative abundance of cells entering the cell cycle changes. It has been shown that in mice at the age of 1 month, about 50% of thymocytes are in the cell cycle, and by 2 years (old animals), the number of such cells is about 30%. In the thymus of adult mice remains about 2% of the maximum number of thymocytes.

The number of committed precursors of T-lymphocytes in the bone marrow gradually decreases. The emphasis on the role of the thymus in the involution of the immune system as a whole is not accidental. In the thymus, there are processes that are of fundamental importance for the formation of a full-fledged immune system. The thymus creates a diverse repertoire of antigen-recognizing T-cell receptors based on an initially limited set of so-called germline genes. As a result of random rearrangement (rearrangement) of the products V, D, J, C of the T-cell receptor genes, a set of T-cells is formed that can recognize any antigen that exists in nature, including its own body. To remove T cells with the potential to react against "self" antigens, another important mechanism is activated - negative and positive selection.

As a result of the interaction of "autoaggressive" T-cells with peptides of "their" antigens, fixed through molecules of the major histocompatibility complex class II (HLA-DR) on the surface of antigen-presenting thymus cells, elimination of such T-lymphocytes occurs (negative selection ). The recognition by T cells of an antigenic peptide presented by an antigen presenting cell is referred to as the "double recognition phenomenon". T cells that have passed the stage of negative selection continue their further development (positive selection), migrate from the thymus to the periphery, where they perform the function of double recognition.

CD4 and CD8 T-lymphocytes with the main functions of helper and cytotoxic cells, respectively, arrive from the thymus to the periphery. These cells are referred to as "naive", or untrained, as they have not yet interacted with foreign antigens. The phenotypic characteristic of such cells is the CD45A molecule. After interaction with a foreign antigen, a pool of memory cells with the CD45R0 phenotype is formed.

In the peripheral blood of newborns, CD45RA T cells predominate. In the course of ontogenesis, their level decreases, and in old age, CD45R0 T-lymphocytes with the characteristics of memory cells predominate. An increase in the pool of memory T cells can lead to immune dysfunctions with increased production of certain immunoregulatory cytokines.

As the thymus ages, this function is gradually lost. At the same time, the process of extrathymic differentiation of T-lymphocytes is largely preserved. The development of T cells occurs in a number of structures, in particular those associated with mucous membranes, such as in the intestine. However, T-lymphocytes of non-thymic localization are limited in their ability to create a variety of T-cell receptors and to reject cells with an autoaggressive orientation. The proliferative activity of T cells in old people is reduced, which leads to limited clonal expansion and effective response to antigen challenge in vivo. There is a connection between increased mortality and the lack of an adequate response of lymphocytes to mitogens (phytohemagglutinin) in healthy elderly people. The proliferative response to the mitogen is suppressed to a greater extent.

It is known that mainly naive CD4+ CD45RA+ T-lymphocytes react to mitogens. A decrease in the number of naïve CD4 T cells in old people correlates with a decrease in mitogen proliferation and the production of interleukin-2 (lymphocyte growth factor), which is necessary for an optimal proliferative response. The addition of exogenous interleukin-2 does not restore the reduced proliferative response of naïve CD4 T cells in old people. The proliferative response to mitogens of lymphocytes of centenarians does not differ in amplitude from proliferation in 20-30-year-old people. However, reaching the peak of proliferation is delayed by several days.

The clinical manifestation of the defectiveness of the proliferative ability of T-cells is immune deficiency with its inherent set of infections. In humans, the number of T-cells in the peripheral blood begins to decrease from the age of 30, relatively stabilizes by the age of 70, and decreases again after 80 years. The absolute values ​​of T-lymphocytes change more than the relative values. The ratio of immunoregulatory subpopulations of CD4/CD8 T cells in peripheral blood increases with aging. Also, the level of type 1 helper T-lymphocytes (Th1; the main source of interleukin-2) decreases and the level of type 2 helper T-lymphocytes (Th2), which regulates antibody formation, including those with an autoimmune focus, increases. An increase in the number of immunoglobulin-producing cells in tissues and IgG, IgE, IgA in serum is associated with an increase in T cells. Intensive apoptosis of mature T-lymphocytes is considered as one of the most important characteristics of the aging of the human immune system.

Antibody formation
Significant age-related quantitative and qualitative changes occur in humoral immune processes. Deviations in the B-cell link of the immune system of old people are associated both with a violation of the thymus-dependent stages of immune processes, and with the internal failure of B-lymphocytes. The number of immunoglobulins and B cells secreting antigen-specific antibodies changes. The function of antibody-forming cells that produce antibodies of the IgG class is more impaired compared to IgM antibodies, which reflects a violation of the ability of T cells to switch the isotype of antibody molecules. The absolute parameters of total immunoglobulins tend to increase with age. Contrary to popular belief that B-lymphocyte levels do not change with aging, studies conducted in apparently healthy people have found a significant decrease in CD19+ B-cells with age. The age-related dynamics of the number of B-cells can be associated with a change in the mechanisms that determine the distribution of lymphocytes between blood and tissues, and an increase in the lifespan of B-lymphocytes and plasma cells in the spleen follicles.

It is known that with age not only the mass of lymphoid tissue of the thymus decreases, but also changes occur in the cellular composition of the spleen and lymph nodes, such as a decrease in the number of follicles, an increase in the number of plasma cells and macrophages. Violation of the expression of adhesion molecules with age can affect the ability of B-lymphocytes to recirculate. Changes in B-cell lifespan are shown in a model of lymphocytes in old people. It is known that expression of the Fas (CD95) receptor, through which this process is triggered, decreases with aging.

Qualitative deviations are characterized by rearrangement of the antibody repertoire in terms of specificity, isotype, affinity, and idiotype. These changes may play a role in more severe infections in older people and especially in reducing the effectiveness of vaccination.

Antibody formation for all practically important vaccines (anti-influenza, anti-tetanus, against salmonella, pneumococci, etc.) decreases with age. Suppression of the production of antibodies of the IgG class (secondary immune response) and high-affinity antibodies with protective properties against bacterial and a number of viral antigens is essential for the insufficiency of the immune response. One of the features of the humoral immune response of old people is an increase in the concentration of autoantibodies specific to autoantigens, DNA, thyroglobulin, immunoglobulins (rheumatoid factor), which is characteristic of many typical autoimmune diseases. As we age, the level of autoantiidiotypic antibodies increases.

Antibody formation in the elderly is accompanied by a violation of the clone-specific characteristics of antibodies and an increase in the concentration of polyclonal autoantibodies, which manifests itself in an increase in the frequency of monoclonal immunoglobulins (benign paraproteinemia).

As the body ages, the level of so-called natural antibodies decreases, for example against staphylococci, salmonella and other pathogens. B-lymphocytes can undergo unregulated polyclonal activation with a loss of optimal response to a specific antigenic stimulus.

In the serum of elderly people, a wide range of autoantibodies directed against individual proteins, cell surface components, and nuclear structures is detected. About 50% of older people have these autoantibodies. It is believed that the main subpopulation of B cells that produce monoclonal autoantibodies are CD5+ type 1 B cells, which differ from typical type 2 B cells. CD5+ B cells, which are credited with the production of autoantibodies, constitute the main repertoire of antibody-producing cells in the embryonic period. Their circulating levels increase in many adult autoimmune diseases and during the aging of the immune system. In the peripheral blood of healthy adults, they make up less than 5% of all B-lymphocytes.

A cloud of macrophage cells are capable of producing pro-inflammatory cytokines (interleukins-1, -6, -8, tumor necrosis factor a in large quantities and thus maintaining an inadequate inflammatory process in tissues. Defective interaction of antigen-presenting cells in relation to triggering "antibody formation is especially reflected in the effectiveness of vaccination of old people. In such situations, complex vaccines, consisting of pathogen antigens and an immunomodulator, give a positive effect. An example is the domestic influenza influenza vaccine developed at the Institute of Immunology of the Ministry of Health of the Russian Federation, which includes influenza virus antigens and the polyoxidonium immunostimulator. This vaccine is well proven itself in the vaccination of the elderly against influenza.

The population of natural killer cells that lyse target cells modified by the virus, tumor, mutant cells by a mechanism not limited by the major histocompatibility complex, changes ambiguously with age. With an increase in the number of natural killer cells expressing activation markers (CD95-Fas and HLA-DR), their cytotoxicity may correspond to the activity of natural killer cells in young people. At the same time, activity in response to stimulation with interleukin 2 decreases and the lytic potential of individual cells is suppressed, possibly due to a decrease in the production of inositol (1,4,5) triphosphate in response to stimulation (impaired generation of second messengers and deregulated activation). Increased activity of individual subpopulations of natural killer cells (CD16+CD57) may serve as a compensatory defense mechanism in T-cell deficiency.

The lack of certain trace elements (zinc, magnesium, selenium, etc.) and vitamins (E, C), which are important for T-cell immune reactions and phagocytosis, leads to increased sensitivity of old people to bacterial infections. Protein deficiency is associated with a decrease in the proliferative activity of lymphocytes, the production of cytokines, and the antibody response to some vaccines.

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Federal State Budgetary Educational Institution of Higher Education

Amur State Medical Academy of the Ministry of Health of the Russian Federation

Department of Physiology and Pathophysiology

Subject:" Immunity and blood functions during aging"

Work completed: Sechkareva Maria

Checked by: Andreevskaya I.A.

Blagoveshchensk 2016

Introduction

Life and death of an organism. Between them gradual aging. Aging - in biology, the process of gradual impairment and loss of important functions of the body or its parts, in particular the ability to reproduce and regenerate. Due to aging, the body becomes less adapted to environmental conditions, reduces and loses its ability to resist disease and injury.

Population aging is the most characteristic demographic phenomenon of the modern era and is due to a complex set of factors, including the characteristics of population reproduction, the intensity and direction of population migration, and the sanitary and demographic consequences of wars. Approximately from the end of the 19th century, a trend towards an increase in life expectancy at birth was identified, developed and now has a stable character. This trend is especially pronounced in the developed countries of Europe, the USA, Japan and China. Thus, for example, according to the UN, the European average for the period from 1950 to 2005 life expectancy increased by more than eight years: from 65.6 to 73.7 years. In this regard, as well as in connection with a decrease in the birth rate in developed countries, in recent decades, many states have faced a situation of "aging" of the population: an increase in the proportion of older people (from 65 years and above) and related problems.

Indeed, the average age of the population Japan in 2000 it was already 41.3, in Switzerland? 38.7, in Italy- 40.3. At the same time, in the same countries in 1960, this indicator was, respectively: Japan- 25.5, in Switzerland - 32.5, in Italy- 31.3. And these numbers continue to grow.

Every day on Earth, 100,000 people die from diseases caused by aging. Old age is to blame for the development of terrible ailments, with which people have not yet learned how to deal effectively.

The problem of human aging is one of the most acute in modern science. After all, its solution will not only lead to such a desirable and at the same time utopian dream of eternal life, immortality, but will also deliver.

The first attempts at a scientific explanation of aging began at the end of the 19th century. In one of the first works, Weisman proposed the theory of the origin of aging as a property that arose as a result of evolution. According to Weisman, "non-aging organisms are not only not useful, they are harmful because they take the place of the young," which, according to Weisman, should have led evolution to the appearance of aging.

An important step in the study of aging was a paper by Professor Peter Medawar before the Royal Society of London in 1951 entitled "An Unsolved Problem in Biology". In this lecture, he emphasized that animals in nature rarely live to an age when aging becomes noticeable, thus evolution could not have influenced the development of aging. This work marked the beginning of a series of new studies.

Over the years, scientists have proposed many different theories of aging. This is the theory of accumulation of mutations, and the theory of one-time soma, and the mitochondrial theory, and many others.

One of the modern directions in the study of this issue is the study of the aging of the immune system. It is known that cases of various infectious diseases, autoimmune processes and tumors become more frequent with age. Perhaps this is partly due to age-related defects in the immune system. The association of such a wide range of age-related pathologies with defects in the immune system has led to the suggestion that immune system aging may limit lifespan.

Despite the fact that a lot of experimental and clinical studies have been performed, indicating age-related depletion of the immune system, the available data are still insufficient to explain all the manifestations of aging. Many cellular and humoral components involved in immune responses, and a large number of modulating non-immune factors, which can also change in old age, do not allow drawing a comprehensive picture of immunoaging even today. However, some evidence in favor of the theory of immunological aging no longer leaves any doubt that the aging of the immune system is inextricably linked with the aging of the whole organism.

Immunity- the ability of the body to immunity and resistance to foreign substances of various origins. This complex defense system was created and changed simultaneously with the development of evolution. These changes continue even now, as environmental conditions are constantly changing, and hence the living conditions of existing organisms. Thanks to immunity, our body is capable of recognizing and destroying disease-causing organisms, foreign bodies, poisons and internal degenerated cells of the body.

Antibodies that neutralize microbial poisons (toxins) are called antitoxins. All antibodies are specific: they are active only against certain microbes or their toxins. If the human body has specific antibodies, it becomes immune to these infectious diseases.

Discoveries and ideas of I.I. Mechnikov about phagocytosis and the significant role of leukocytes in this process (in 1863 he delivered his famous speech on the healing powers of the body, in which the phagocytic theory of immunity was first presented) formed the basis of the modern doctrine of immunity (from Latin "immunis" - freed) . These discoveries have made it possible to achieve great success in the fight against infectious diseases, which for centuries have been a true scourge of mankind.

A great role in the prevention of contagious diseases is preventive and therapeutic vaccinations - immunization with the help of vaccines and sera, which create artificial active or passive immunity in the body.

Types of immunity

innate immunity is a hereditary trait and provides immunity to a particular infectious disease from the moment of birth and is inherited from parents. Moreover, immune bodies can penetrate the placenta from the vessels of the mother's body into the vessels of the embryo, or newborns receive them with mother's milk. immunity aging phagocytosis

acquired immunity divided into natural and artificial, and each of them is divided into active and passive.

natural active immunity produced in humans during transmission of an infectious disease. So, people who have had measles or whooping cough in childhood no longer get sick with them again, since protective substances - antibodies - have formed in their blood.

Natural passive immunity due to the transition of protective antibodies from the mother's blood, in whose body they are formed, through the placenta into the blood of the fetus. Passively and through mother's milk, children receive immunity against measles, scarlet fever, diphtheria, etc. After 1-2 years, when the antibodies received from the mother are destroyed or partially removed from the child's body, his susceptibility to these infections increases dramatically.

artificial active immunity occurs after inoculation of healthy people and animals with killed or weakened pathogenic poisons - toxins. The introduction into the body of these drugs - vaccines - causes a mild disease and activates the body's defenses, causing the formation of appropriate antibodies in it.

To this end, systematic vaccination of children against measles, whooping cough, diphtheria, poliomyelitis, tuberculosis, tetanus and others is carried out in the country, thanks to which a significant reduction in the number of cases of these serious diseases has been achieved.

artificial passive immunity is created by administering to a person serum (blood plasma without fibrin protein) containing antibodies and antitoxins against microbes and their toxin poisons. Sera are obtained mainly from horses that have been immunized with the appropriate toxin. Passively acquired immunity usually lasts no more than a month, but it manifests itself immediately after the introduction of therapeutic serum. Timely administered therapeutic serum containing ready-made antibodies often provides a successful fight against a serious infection (for example, diphtheria), which develops so quickly that the body does not have time to produce enough antibodies and the patient may die.

The mechanism of aging of the immune system

Immunity by phagocytosis and the production of antibodies protects the body from infectious diseases, frees it from dead, degenerate and become foreign cells, causes rejection of transplanted foreign organs and tissues.

After some infectious diseases, immunity is not developed, for example, against a sore throat, which can be ill many times.

Modern immunological studies have shown that the causes of aging and the development of age-related diseases can be controlled by immunological factors.

An important role in the etiology and pathogenesis of aging is assigned to various immunological mechanisms: thymic involution and dysfunction of cellular immunity; genetically programmed system of immunological surveillance; viral infection.

With age, in the imbalance of immunity, thymus involution and a decrease in the level of thymic hormones are of the greatest importance. This leads to a change in the function of T cells and a violation of their immunoregulatory properties. Reduced reactivity of T-lymphocytes manifests itself:

III in a decrease in the ability of proliferation and blast transformation under the influence of PHA;

III in increasing the survival of allogeneic skin grafts and engraftment of induced tumors.

At 50-65 years, the number of T-lymphocytes decreases, and B-lymphocytes - increases, T-killers are not formed, the response to T-dependent antigens sharply decreases and remains on T-independent ones.

Quantitative and functional defectiveness of T-cells leads to a decrease in the response of DTH to exogenous antigens and enhances them in relation to endogenous ones. The mortality of such persons is high and is caused by bronchopneumonia, vascular and heart diseases.

A natural consequence of the aging of the body are disorders of immune processes associated with a weakening of autotolerance and an increase in the content of autoantibodies. Autoantibodies appear in low titers in 50% of healthy elderly people, especially women. With age, the amount of IgG and IgA in the blood serum increases against the background of a decrease in IgM.

The mortality of people with high titers of autoantibodies in the blood serum is higher than those without autoantibodies. These individuals are more likely to develop cardiovascular disease and cancer.

A paradoxical fact is that the increased formation of autoantibodies in old age is proportional to the decrease in immunoreactivity. It is believed that this is due to the loss of function of T-suppressors and T-helpers.

The appearance of autoantibodies in tissues is possible as a result of changes in the chemical structure of macromolecules, genetic errors and mutations due to the formation of forbidden clones.

There is a point of view (G.A. Gatti, R.A. Good, 1970) that the attenuation of the immunological activity of the body with age, first of all, reflects the genetically programmed biological clock, in accordance with which the reproduction of T-lymphocytes is limited through the CNS and the endocrine system. All other immunological aspects of aging can be considered as secondary to hereditary thymus deficiency: the manifestation of autoimmune and immunodeficiency processes, the development of malignant tumors and severe infections caused by weakly virulent pathogens.

A number of researchers (J.E. Hotchin, J.A. Levy, R.C. Mellors et al., 1971-1974) suggested a possible role of viruses in the pathogenesis of aging and diseases such as autoimmune and cancer. An association has been shown between persistent slow viral infection and a variety of autoimmune disorders.

There are various theoretical approaches to assessing the immunological foundations of the aging process. R.V. Petrov believes that age-related declines in immunoreactivity are the result of aging of the entire immune system.

According to F.M. Burnet, aging is a loss of tolerance to one's own structures and the appearance of clones of immunocompetent cells capable of reacting against one's own antigens. In the development of these complementary theories, it is assumed that in the process of aging the ability to recognize "one's own" decreases and autoimmune reactions occur. This is accompanied by a decrease in lymphoid tissue and the number of plasma cells, hypoplasmia of lymphoid organs, fibrosis, hyalinization and atrophy of the kidneys, weight loss, etc.

An increase in lytic enzymes is important, which leads to the release of self-antigens, including altered transplantation histocompatibility antigens. They are species-specific membrane glycoproteins found in connective tissue as part of soluble and polymeric collagen and elastin. Free (soluble) glycoproteins enter the bloodstream and induce immune responses against soluble, polymeric connective tissue and elastin antigens.

It has been established that glycoproteins are phylogenetically characteristic of all species, from bacteria to higher animals. In humans, they are found in significant quantities in embryonic tissues, in the thymus, spleen - organs rich in reticular tissue and glycoproteins, are involved in the selection and suppression of clones of immunocompetent cells. In old age, immunocompetent cells appear - mutants that react with structural glycoproteins and thereby involve connective tissue in age-related pathology. With age, tissue regeneration decreases and the frequency of cell recognition errors increases. At the same time, glycoproteins are precursors of recognition structures.

It has not been finally established what (etiological or pathogenetic) role is played by disorders of the immune system in the aging process. Many diseases of the elderly are of an immunological nature, therefore, by targeting the immune system, it is possible to slow down the aging process.

The influence of immunity on the aging process

"If in the body of an adult it was possible to reproduce the immunological processes characteristic of a 10-year-old child (the healthiest period of human life), life expectancy would increase by 3, 4 or even 5 times." So says the American scientist Donner Denkl.

In 1975, immunologists succeeded in transplanting the thymus gland and bone marrow from young mice into old ones. The experiment confirmed the possibility of maintaining health and prolonging the life of experimental animals: the immune system of 19-month-old mice was rejuvenated to the level of 4-month-old ones. In terms of our century, this would mean the transformation of a 60-year-old person into a 20-year-old, i.e., threefold rejuvenation. A few more years passed, and bone marrow and thymus transplantation stepped into clinics, saving people from premature aging.

Composition and functions of blood

Blood, continuously circulating in a closed system of blood vessels, performs the most important functions in the body: transport, respiratory, regulatory and protective. It ensures the relative constancy of the internal environment of the body.

Blood is a type of connective tissue consisting of a liquid intercellular substance of complex composition - plasma and cells suspended in it - blood cells: erythrocytes (red blood cells), leukocytes (white blood cells) and platelets (platelets). 1 mm 3 of blood contains 4.5-5 million erythrocytes, 5-8 thousand leukocytes, 200-400 thousand platelets.

In the human body, the amount of blood is on average 4.5-5 liters or 1/13 of its body weight. Blood plasma by volume is 55-60%, and formed elements 40-45%. Blood plasma is a yellowish translucent liquid. It consists of water (90-92%), mineral and organic substances (8-10%), 7% proteins. 0.7% fat, 0.1% - glucose, the rest of the dense plasma residue - hormones, vitamins, amino acids, metabolic products.

Formed elements of blood

red blood cells - non-nuclear red blood cells, having the shape of biconcave discs. This form increases the cell surface by 1.5 times. The cytoplasm of erythrocytes contains the hemoglobin protein, a complex organic compound consisting of the globin protein and the blood pigment heme, which contains iron.

The main function of red blood cells - transportation of oxygen and carbon dioxide. Red blood cells develop from nucleated cells in the red bone marrow of cancellous bone. In the process of maturation, they lose the nucleus and enter the bloodstream. 1 mm 3 of blood contains from 4 to 5 million red blood cells.

The life span of erythrocytes is 120-130 days, then they are destroyed in the liver and spleen, and bile pigment is formed from hemoglobin.

Leukocytes - white blood cells containing nuclei and not having a permanent shape. 1 mm 3 of human blood contains 6-8 thousand of them.

Leukocytes are formed in the red bone marrow, spleen, lymph nodes; their life expectancy is 2-4 days. They are also destroyed in the spleen.

The main function of leukocytes - protection of organisms from bacteria, foreign proteins, foreign bodies. Making amoeboid movements, leukocytes penetrate through the walls of capillaries into the intercellular space. They are sensitive to the chemical composition of substances secreted by microbes or decayed cells of the body, and move towards these substances or decayed cells. Having come into contact with them, leukocytes envelop them with their pseudopods and draw them into the cell, where they are split with the participation of enzymes.

Leukocytes are capable of intracellular digestion. In the process of interaction with foreign bodies, many cells die. At the same time, decomposition products accumulate around the foreign body, and pus forms. Leukocytes that capture various microorganisms and digest them, I.I. Mechnikov called phagocytes, and the very phenomenon of absorption and digestion - phagocytosis (absorbing). Phagocytosis - defensive reaction of the body.

platelets (platelets) - colorless, non-nuclear round-shaped cells that play an important role in blood clotting. In 1 liter of blood there are from 180 to 400 thousand platelets. They are easily destroyed when blood vessels are damaged. Platelets are produced in the red bone marrow.

Formed elements of blood, in addition to the above, play a very important role in the human body: in blood transfusion, coagulation, as well as in the production of antibodies and phagocytosis.

Blood functions

1. The respiratory function is to bind and transfer 02 from the lungs to the tissues and C 02 from the tissues to the lungs.

2. The trophic function of blood is associated with the provision of all cells of the body with nutrients coming from the digestive organs and other organs.

3. Excretory function: blood transports metabolic end products from tissues to excretory organs.

4. Thermoregulatory function: blood carries heat from energy-intensive organs and warms the organs, losing it.

5. Ensuring water and electrolyte metabolism: in the arterial part of most capillaries, fluid and electrolytes enter the tissues, in the venous part they return to the blood.

6. Protective function: blood protects the body from bacteria, viruses and genetically alien cells and substances.

7. Humoral regulation: blood carries hormones and other biologically active compounds from the cells where they are formed, other organs and tissues.

Changes in the cellular composition of the blood

The number of nucleated cells in the bone marrow decreases with age. and it increases the volume occupied by fat cells. So, in people under the age of 65, about half of the bone marrow is occupied by adipose tissue, and later 2/3 of it is replaced by fat. It is likely that this loss of hematopoietic cells exacerbates osteoporosis.

Most pronounced with aging quantitative changesinindicators of erythron. So, if in 20-year-old men the average content of erythrocytes in the blood is 5.3-1012 / l, then in 60-year-old men it is less - 5.05 * 1012 / l; the content of hemoglobin in men and women younger than 60 years is 156 and 135 g/l, respectively, and in 96 and 106-year-olds - 124 g/l.

Decreased oxygen capacity of the blood put in a causal relationship with an age-related decrease in basal metabolism, with a deficiency of iron, folic acid and vitamin B 12 often found in the elderly. Thus, in almost 30% of older people, the content of vitamin B 12 in the blood serum is reduced. atrophic gastritis, detected in 81% of people over 60 years of age.

With age, the average erythrocyte volume increases. For example, in 20-year-old men it is 89 μm 3, in 60-year-old men it is 93 μm 3. The reasons causing an increase in the average volume of erythrocytes in the elderly include increased peroxidation in cell membranes, smoking and alcohol consumption that affect the cytoskeleton erythrocytes. Indeed, in smokers, the average volume of erythrocytes is 1.5 μm 3 higher than in non-smokers. A moderate amount of alcohol has the same effect. Thus, macrocytosis is found in 85% of persons suffering from alcoholism or consuming more than 80 g of ethanol per day (the amount of ethanol contained in 4 mugs of beer).

Plasma iron exchange per day slightly higher in persons from 61 to 80 years old than in 19-50-year-olds, respectively, 125±47 µmol/l of blood and 112±27 µmol/l. At the same time, in older people, compared with young people, the use of iron by non-erythroid tissue is increased.

Conclusion

Based on the highlighted aspects of the functioning of the innate system, we can conclude that it plays an important role in the aging process of the human body. Disturbances that occur during the aging process in the innate immune system can lead to serious diseases such as Parkinson's disease and autoimmune diseases, tumors. In addition, there is a general decrease in the body's resistance to external infections. The reason for this is the violation of the phagocytic activity of macrophages, and the violation of the usual cytokine secretion, which provides a stable microclimate for the functioning of all parts of the immune response. Negative disturbances in the innate immune response also have a negative impact on the adaptive link of human immunity, further weakening its protection.

Changes in the cells of the innate immune system often consist not so much in their quantitative expression, but in the inhibition of their activity, the weakening of the functional processes necessary for normal life, and even the acquisition and strengthening of qualities that negatively affect the body.

And if we talk about changes in blood functions during aging, then it should be noted that, in the elderly, pronounced shifts in the structure and regulatory mechanisms of hemostasis. After 40 years, there is a shift in the balance of hemostasis towards an increase in the procoagulant activity of the blood and an increase in the intensity of intravascular thrombosis. This is evidenced by an increase in the concentration of fibrin breakdown products, fibrinogen, factor XIII activity, and an increase in plasma tolerance to heparin. In response to this restructuring, the anticoagulant link, fibrinolysis, is activated in the procoagulant hemostasis system. However, the increase in fibrinolytic activity of the blood lags behind the increase in its procoagulant activity. As a result, the coagulant properties of blood increase with aging. This is also facilitated by a more pronounced increase in the activity of the procoagulant link in the elderly, compared with the young, in response to the activation of the sympathetic-adrenal system during stress (the action of catecholamines) against the background of little changing fibrinolytic activity.

On the other hand, with age in the endothelium of arteries the production of plasminogen activators gradually decreases, the production of prostaglandins decreases, which reduces the antiaggregation activity of the vascular wall and creates a predisposition to intravascular thrombus formation. Hypercholesterolemia developing in the elderly, an increase in thromboglobulin concentration also increase the sensitivity of platelets to aggregants (substances that stimulate platelet aggregation). The foregoing makes clear a sharp increase with age in the risk of thrombosis and embolism.

Withlist of used literature

1. Butenko G.M. In: Actual problems of molecular, cellular and clinical immunology. M.: Ed. VINITI. 1983; 12:84-100.

2. Immunology of aging. Under. ed. T. Macinodan and E. Younis. M.: Mir; 1980

3. Prokhorov A.M. - B.E. S. Volume 1. Moscow: "Sov. Encyclopedia", 1991, 863 p.

4. Human anatomy M.G. Weight gain, N.K. Lysenkov St. Petersburg, publishing house "Hippocrates", 1999; 704s.

5. http://www.dendrit.ru/page/show/mnemonick/obschie-svoystva-i-funkcii-krovi/

6. http://doctor-v.ru/med/funkcii-krovi-pri-styarenii/

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Anatomical and physiological features, reserve capabilities

An increase in the frequency and severity of infectious diseases, the frequency of tumors and autoimmune diseases with age indicates significant changes in the body's immune system, which are characterized as “aging of the immune system”. With age, non-specific and specific protection decreases, which is associated with an increase in the sensitivity of old people to infections and tumors. The T-cell link of the immune system suffers mainly as a result of the age-related involution of the thymus.

Different populations of immunocompetent cells that perform different functions differ in their lifespan. Along with long-lived cells (macrophages, dendritic cells, memory lymphocytes), there are short-lived cells whose life span is measured in days or hours, and therefore their constant renewal is required throughout life (granulocytes, T- and B-lymphocytes, etc.). With age, the ability to regenerate tissues and cells decreases, which affects the maintenance of the number of short-lived populations of immunocompetent cells.

It should be taken into account that immune-mediated processes of destruction of body tissues can make a significant contribution to the aging process. Mutations that change the structure of proteins lead to the appearance of chemically altered macromolecules that accumulate in the body with age and are recognized by lymphocytes as foreign, which leads to autoaggression. Therefore, a decrease in the effector functions of the immune system in old age has its advantages: this ensures less severity of immunologically mediated damage to one's own tissues.

To the greatest extent, the aging of the immune system is reflected in the mechanisms of immunoregulation: the ratios of regulatory subpopulations of lymphocytes and their ability to produce immunoregulatory molecules - cytokines change.

The aging of the immune system depends on many individual characteristics: genetic predetermination, acute and chronic infectious diseases suffered during the life, medication intake, dietary patterns, and the severity of age-related changes in other systems. In this regard, it is important to distinguish secondary immunodeficiencies from age-related physiological features of the immune system in senile people.

For many body systems (immune, endocrine, cardiovascular), the critical age is approximately the same: the most dangerous age is considered to be 70-79 years. Higher indicators of the state of health of people after 80 years of age are associated with the selection of older people who are most resistant to the action of various risk factors.

The results of studying the immune system of healthy people who have reached the age of 100 can serve as a source of optimism. In such people, an amazing preservation of all immunological mechanisms was revealed. Despite the long past involution of the thymus, they have only a slightly reduced number of T lymphocytes while maintaining the diversity of their functional repertoire, with a normal proportion of T memory cells. In such people, the bulk of T lymphocytes are Th0, producing both gamma-interferon and interleukin-4. These people have a slightly reduced number, but the functions of B lymphocytes are preserved. Their cytokines retain sufficient immunoregulatory activity. The number of natural killers they have increased. The number of surface molecules on lymphocytes is increased, and their tendency to apoptosis is reduced. Such old people did not have tissue-specific autoantibodies characteristic of the aging of the immune system. The results obtained indicate the possibility of age-related restructuring of the immune system without the formation of a characteristic senile immunodeficiency. The necessary conditions for such “successful aging” are genetic predetermination, combined with an appropriate lifestyle. The individuals described above represent an exception to the general rule that most protective functions decline in the aging organism.

Unlike young and middle-aged people, in whom neuroimmune connections are clearly traced at the level of limbicoreticular structures, with aging, the influence of limbicoreticular structures on immune structures decreases or is completely lost. With age, the hormonal regulation of the immune system is also disturbed, in the elderly, the steroid hormones of the adrenal cortex react differently to stimulation: the secretion of cortisol increases, and the secretion of dehydroepiandrosterone (DHEA) decreases. DHEA deficiency in the senile body is associated with many manifestations of the aging of the immune system (Fig. 3-13).

All barrier functions of the body are sharply weakened. In the composition of the skin of the elderly, the number of antigen-presenting Langerhans cells is reduced, which is associated with a reduced ability to allergize. A parallel decrease in the functions of T- and B-lymphocytes and the production of cytokines is manifested by a pronounced decrease in the adaptive capabilities of the skin's immune system. In people older than 60 years, the density of Langerhans cells is also reduced in the conjunctival epithelium of the eye, which may indicate a weakened protection of the conjunctiva of the eye. In old age, mucus secretion decreases, which makes it easier for bacteria to colonize mucous membranes. Dysfunctions of the ciliary epithelium, loss of elasticity of lung tissues, weakened cough reflex predispose to bacterial invasion in the respiratory tract. Reduced bladder contractility leads to stagnation of urine and an increased incidence of urinary tract infections. In the elderly, the process of wound healing is impaired, however, the response of fibroblasts to activation by cytokine - transforming growth factor-beta is completely preserved.

In old age, the functions of phagocytic cells are impaired. With infections in the elderly, leukocytosis is less pronounced, cell mobilization to foci of inflammation and infection is weakened, the response to the action of inflammatory mediators is reduced, and the ability to kill bacteria captured during phagocytosis is reduced. In granulocytes with aging, the sensitivity to apoptosis sharply increases in the presence of interleukin-2 or LPS. In people over 65 years of age, the cytotoxic activity of blood monocytes against tumor cells is partially lost. Their monocytes secrete interleukin-1 less, produce oxygen radicals less (Fig. 3-13).

The defective production of pro-inflammatory cytokines by macrophages is indirectly evidenced by a less pronounced rise in temperature in the elderly in response to the development of infection. With age, the ability of macrophages to respond with activation to appropriate inducers, including activating cytokines, such as interferon gamma, decreases. These age-related macrophage defects can be corrected under the influence of pituitary hormones (prolactin and growth hormone), which may indicate the importance of neuro-endocrine-immune interactions in the aging process.

The decrease in antiviral and antitumor protection in the elderly is associated with the quantitative and functional defectiveness of natural killers. Old people have a reduced number of circulating natural killer cells. These cells in the elderly are characterized by reduced lytic activity and are more difficult to activate.

The involution of the thymus ends in adulthood, and by old age only a small fibrous remnant is left, constituting 10% of the initial volume. The gradual loss of the thymus is easily tolerated. Obviously, by the end of thymus involution, a sufficient population of long-lived memory T-lymphocytes has already accumulated in the body. The output of mature T-lymphocytes decreases dramatically with age, although the number of bone marrow progenitors does not decrease. Defective lymphokine-controlled thymocyte proliferation processes and defects in the thymus microenvironment are limiting in aging. Against the background of thymus involution, its microenvironment does not sufficiently initiate the early stages of T-cell differentiation. Interleukin-7, a product of stromal cells, is considered critical for lymphocyte differentiation. It is possible that a defect in the production or reception of interleukin-7 accompanies aging and limits the processes of proliferation and differentiation of T-lymphocytes.

In connection with the age-related involution of the thymus, the possibility of extrathymic generation of T-cells is of particular importance. The intestinal-associated lymphoid tissue is the most important site for extrathymic differentiation of T-lymphocytes, which increases compensatory in the course of age-related restructuring.

The absence of the thymus after 50-60 years is manifested by an increase in the proportion of immature T-lymphocytes and a decrease in the levels of thymic hormones in the peripheral blood. The functional inferiority of T-lymphocytes in old people is partly due to the absence of thymic hormones and can be corrected with the introduction of exogenous thymic hormones. Thymus involution apparently also affects the selection of T-cell precursors, which leads to the maturation of autoreactive clones of T-lymphocytes and increased production of autoantibodies in old age.

The total number of cellular elements of the immune system does not change with age. Sometimes there is mild lymphopenia. However, the ratio of individual populations and subpopulations of lymphocytes and their functional activity in the elderly undergo significant changes. It has been suggested that lymphocytes with various defects accumulate with age. Another assumption comes from the fact that functioning cells retain their normal activity, and after their death they are replaced by weakened cells. The balance of regulatory subpopulations of T-lymphocytes is disturbed with the greatest constancy in old people. Data on changes in the CD4 + /CD8 + ratio are very contradictory: according to some data, it decreases, according to others, it increases. With age, the proportion of memory T cells increases. However, in very old people, the number of memory cells becomes lower than in the elderly. This also applies to CD4 + and CD8 + cells.

T-lymphocytes of the elderly are characterized by a reduced response to the action of antigens. The proportion of blood mononuclear cells that respond by proliferation to standard antigens is reduced by 50-80% compared to the cells of young people. The proliferative response declines more sharply with age in men than in women. In T-lymphocytes of people over 65 years of age, the proliferative response to tetanus toxoid is reduced both before and after immunization with the appropriate vaccine preparation. After immunization with the influenza vaccine in the elderly, the cellular response is short-term, a large number of specific cytotoxic T-lymphocytes do not accumulate, it is not possible to detect increased production of interleukin-2, and there is no increase in antibody titers.

Age-related DNA damage and mutations in the DNA of lymphocytes in old people are combined with a decrease in the ability to repair DNA, which is a consequence of a decrease in the activity of the DNA-protein kinase complex. All this leads to impaired lymphoproliferation and clonal expansion of T-lymphocytes in old age. Another limitation of the clonal expansion of T-lymphocytes in the elderly may be the loss of telomeres and the ability to increase telomerase activity, which increases with age.

In people over 65 years of age, in response to antigenic stimulation of T-lymphocytes, instead of activation, their apoptosis occurs, which leads to the development of T-deficiency. The increase in apoptosis of T lymphocytes and other immunocompetent cells in the elderly is associated with dysregulation of programmed death.

In old age, weakening or absence of skin-allergic reactions to the introduction of widespread infectious allergens is often detected: viral and bacterial. The likelihood of complete anergy increases with age: thus, anergy to tuberculin is detected in only 1 out of 10 people under 55 years old, and in people over the age of 55 years - in 1 out of 3. The development of a cell-mediated skin allergic reaction to a standard inducer (DNHB) occurs in 5% of people under 70 years of age and in 35% of people over 70 years of age. Insufficiency of skin-allergic reactions is associated not only with defects in lymphocytes, but also with defects in antigen-presenting cells (macrophages, dendritic cells). Thus, in the skin of the elderly, the number of antigen-presenting Langerhans cells is halved, and the remaining cells are distinguished by less branched processes and reduced production of cytokines. Monocytes, dendritic cells of the elderly, are characterized by a reduced ability to present antigens.

T-lymphocytes of the elderly are characterized by reduced production of interleukin-2 and a reduced number of high-affinity interleukin-2 receptors, while at the same time, the production of interleukin-4 is increased. The low proliferative activity of T-lymphocytes of the elderly is corrected in cultures with the addition of interleukin-2. T-lymphocytes of the elderly are also characterized by reduced production of interleukin-3, gamma-interferon, granulocyte-monocyte colony-stimulating factor. The normal aging process is accompanied by an increase in the production of multifunctional cytokines interleukins-4, -5, -6 and -10, which begin to be produced constitutively and uncontrollably and have the ability to predominantly inhibit the functions of T-lymphocytes and macrophages. The production of interleukin-6 increases with age, in contrast to other pro-inflammatory cytokines. An increase in the level of this cytokine, out of connection with the development of inflammation, indicates a violation of the regulation of its production. With age, the level of estrogens, inhibitors of the interleukin-6 gene, decreases. The regulation of the production of this and other cytokines is a function of the steroid hormone - androsterone, the level of which decreases with age. Dysregulation of the synthesis of interleukin-10 is associated with a drop in the level of intracellular glutathione, the regulator of oxidative processes, the concentration of which decreases with age due to a decrease in the level of androsterone (Fig. 3-13).

Functional defects of T-lymphocytes in old age may be associated with disturbances in the dynamic properties and fluidity of cell membranes. Lymphocytes of the elderly were found to have disturbances in calcium (Ca) metabolism. The influx of Ca ions is necessary for entry into the cell cycle after activation. Violation of the proliferative response of lymphocytes of the elderly is associated with a violation of Ca influx. Artificial enhancement of Ca influx under the action of the Ca ionophore restored the disturbed proliferative response of T-lymphocytes in old people. Violations of calcium transport were also found in the granulocytes of the elderly. It is likely that this age-associated cellular defect affects many body systems. Among lymphocytes, CD8 cells are the most affected by impaired Ca transport (Fig. 3-13).

The number of circulating B-lymphocytes does not change with age, but the number of germinal centers gradually increases in the lymph nodes, and the number of plasma cells in the bone marrow increases as a result of B-lymphocyte differentiation. There were no age-related changes in the ratios of immunoglobulin classes. The general trend of age-related changes is that the production of antibodies against exogenous antigens decreases with age, while the production of autoantibodies increases. The decrease in the antibody response of old people to exogenous antigens is associated with the defectiveness of T-helpers, and not with the weakening of the functions of B-lymphocytes.

When immunized with various vaccines (against tetanus, influenza, pneumococci), the elderly showed a weakened antibody response compared to young people, in addition, the antibodies formed in the elderly were distinguished by a reduced affinity for the antigen. In parallel with the decrease in the specific antimicrobial humoral immune response, the number of autoantibodies increases with age. Among them, polyspecific antibodies related to class M immunoglobulins predominate. The number of organ-specific autoantibodies also increases with age: to thyroglobulin, to DNA. More than 2/3 of people over the age of 60 have autoantibodies of different specificity in serum. Autoantibodies in old age may be the result, rather than the cause, of the development of pathology. Age-associated tissue degeneration, which occurs independently of immune mechanisms, leads to the release of large amounts of its own components, which were previously isolated from contact with the immune system. These autoantigens develop legitimate synthesis of autoantibodies.

The above-described senile physiological immunodeficiency is relatively mild: it rarely presents with severe opportunistic infections. Most often, senile immunodeficiency leads to the reactivation of tuberculosis or chronic viral infections such as herpes zoster. Cell-mediated immunity is impaired earlier and to a greater extent than humoral immunity with age. The most severe consequences of senile immunodeficiency are autoimmune diseases and malignant tumors. The possibility of getting sick with monoclonal gammopathy increases 20 times with increasing age from 50 to 70 years. The incidence of cancer increases 240 times between 15 and 90 years of age. People over the age of 65 make up half of all patients with malignant neoplasms. However, in older people, tumors tend to progress more slowly due to reduced production of cytokines that promote tumor growth.

Separate observations indicate the conjugation of a decrease in the life expectancy of the elderly with the degree of weakening of the functions of T-lymphocytes (decrease in the number of T-lymphocytes, the number of CD4 + cells, the proliferative activity of T-lymphocytes, and the production of interleukin-2). Older people with T-cell deficiency are considered a high-risk group with reduced survival compared to older people without evidence of immunodeficiency. In individuals over 85 years of age, decreased CD4+ T-lymphocytes and natural killer cells correlated with increased mortality in the subsequent two years. In persons aged 97-100 years, the activity of life, nutritional parameters correlated with the number of natural killers. Thus, the quality and duration of life of the elderly largely depend on the severity of immunological changes characteristic of physiological age-related immunodeficiency.

Risk factors.

Any adverse effects of the external environment are risk factors for the elderly, tk. their immune system loses its ability to adapt, which is quite pronounced at a young and mature age.

Infections are serious risk factors for the elderly due to the defectiveness of many protective mechanisms. Among them, viral infections are especially dangerous due to the defectiveness of cellular defense mechanisms.

Bad habits (smoking, alcoholism) become more and more significant risk factors with age, since the compensatory capabilities of the immune system are exhausted in old age.

Malnutrition is an important risk factor for the elderly. Anorexia and weight loss often accompany aging. Initially, people reduce their food intake as they age to counterbalance the decline in physical activity. Later, the development of pathological anarexia can be facilitated by: mental depression, other psychological and social conditions. In this case, a sharp weight loss is cytokine-dependent. Old people often have malnutrition, the causes of which may be: socio-economic insecurity, physical infirmity, isolation, dental problems. Nutritional deficiencies in the elderly cause defects in phagocytosis, cellular immunity, and a reduced immune response. Old people with protein malnutrition have a reduced response with fever and the production of acute phase reactants during infections, however, the production of pro-inflammatory cytokines by blood mononuclear cells of these old people was not reduced (Table 3-7)

Among the approaches to the correction of immunological disorders in the elderly deserve special attention: correction with the help of a balanced diet (diet), the use of physical exercises and hormone replacement therapy.

The accumulation of free radicals with age can be prevented by caloric restriction of the diet (calorie reduction by about 25%). Such a diet helps to reduce the production of interleukin-6 and prolong life.

Table 3-7.

Risk factors affecting the immune system of elderly and senile people and recommendations for preventing immune system disorders

RISK FACTORS	PREVENTION MEASURES
infections	Hormone replacement therapy with DHEA. Vaccination and seroprophylaxis of infections during epidemics. Careful personal hygiene. Low intensity exercise.
Malnutrition	Organization of rational nutrition. The use of nutritional supplements rich in vitamins and minerals.
Environmental problems, stress	Rational nutrition enriched with vitamins and microelements.
Smoking, alcoholism	Conducting explanatory work on the dangers of smoking and alcohol using examples of suppression of the immune system.

The earliest possible detection of signs of anorexia, an artificial increase in calorie intake, and, if necessary, parenteral nutrition, are recommended. When correcting nutritional deficiencies in groups of elderly people under constant supervision, an increase in the effectiveness of vaccination and a decrease in the risk of developing tumors were noted.

For older people, diets enriched with vitamins D, E, B6 and trace elements: zinc, calcium, magnesium are recommended. The use of fish oil as a dietary supplement has a very beneficial effect on the secretory functions of the phagocytic cells of the elderly, while the total fat content in the diet of the elderly should be minimal. Correction and increase of non-specific anti-infective protection can be achieved by long-term systematic addition of lactic acid bacteria to the diet of the elderly in the composition of fermented milk products. Food for the elderly should be tasty and attractive, given their reduced appetite.

To correct immunological defects in the elderly and the elderly, it is recommended to use physical exercises with low or moderate intensity for a short duration. In groups of old people systematically engaged in such exercises, an increase in the number of natural killers and T-lymphocyte activity was noted. Very moderate exercise programs caused even more pronounced stimulation of immunological functions in the elderly than in younger people.

Due to the fact that the decrease in immunological functions in the elderly correlates with a decrease in the production of the steroid hormone of the adrenal cortex DHEA, it was proposed to use this drug for immunocorrection in the elderly. A preliminary study in the experiment showed the possibility of restoring some of the immunological functions lost with age. The use of DHEA made it possible to significantly increase the effectiveness of vaccination. With the introduction of DHEA, people have been shown the absence of toxicity of the doses used, making it possible to restore the normal level of the hormone in the blood serum of the elderly. The use of the drug when vaccinating the elderly with an influenza vaccine made it possible to increase the production of specific antibodies. However, the results of hormonal immunocorrection are evaluated ambiguously.