Physiology of the thymus gland (thymus)

The thymus gland (timus) has long been thought of as an endocrine organ, although it has emerged from numerous observations that it is more an object of hormonal influences than a source of specific hormones. However, in recent years a number of active substances have been isolated from the thymus gland, which have an effect mainly on the immune processes in the body.

In humans, the thymus is located behind the sternum, reaching from below the arch of the aorta. It consists of two closely adjoining parts, covered with a connective tissue capsule, from which partitions divide the organ into separate lobules. In each of them, the cortex and the medulla are distinguished. At the time of birth, the mass of the thymus is 10-15 g. Later it increases, reaching a maximum at the onset of puberty (30-40 g), and then decreases (the age involution of the thymus). In a number of cases, with sudden death at autopsy, a thymus of large size was found. The combination of this with a loose ("lymphatic") physique for a long time already gave rise to talk about the existence of a special thymic-lymphatic status, supposedly causing an extremely high susceptibility of the organism to adverse effects. Currently, the thymic-lymphatic status is not given so much importance and even express doubts about its very existence. Indeed, in cases of violent death, the size of the thymus is usually as large as when it is expected to be a thymic-lymphatic status. On the other hand, the apparent thymus hyperplasia, which occurs, for example, in malignant myasthenia gravis, usually does not lead to sudden death. Physiological involution of the gland consists in the gradual disappearance of the characteristic cellular elements from it, replacing them with adipocytes and fibrous tissue. There is also an acute involution of the thymus gland, usually associated with stress.

The cortical substance of the thymus is represented by small lymphocytes and a small number of reticuloendothelial cells. The ratio of these elements is approximately 100: 1. In the brain substance there are so-called Hassala bodies - clusters of epithelial cells, surrounding lymphocytes and eosinophils. However, the first in the medullar layer is about 20 times smaller than the second. The latter have villi and contain a Schick-positive material resembling a thyroid gland colloid. Electron microscope studies reveal in these cells a rough endoplasmic reticulum, a well-developed lamellar complex (the Golgi apparatus), and granules, the contents of which may have hormonal activity. Regarding the structure of the walls of the vessels in the thymus gland (ie, the presence of a histohematomic barrier in this organ), there is no consensus. Arteries pass only in the cortical substance of the thymus, while the veins - in the brain. Mitoses are found practically only in lymphocytes of the cortical layer of the thymus gland.

Based on the structural features of this organ, it is believed that it serves as an important source of lymphocytes in the body, but, unlike other similar structures, does not directly participate in immune responses. The cystic formations present in the thymus, the cells of the walls of which possess secretory signs, can reflect the endocrine function of this organ.

In phylo- and ontogeny, a clear connection is observed between the appearance and development of the thymus, on the one hand, and the emergence of immunological reactivity of the organism, on the other. Therefore, the main role of the thymus is seen in the regulation of immunological processes. With this function, the lymphopoietic activity of this organ is also closely related. In the thymus, different subpopulations of T-lymphocytes, which exert helper, suppressor and killer action, are differentiated. In recent years, it has been shown that the immunoregulatory and lymphopoietic functions of the thymus are carried out due to the secretion of humoral factors. Secretory activity seems to have epithelial cells of the medulla. The role of the thymus in the body is clearly visible on the example of pathological conditions developing when its functions are insufficient or when it is absent.

The table shows some hypothetical dependencies of clinical syndromes on thymus gland activity, but there are no indications of a number of other proven functions. However, even in this form it gives an idea of the variety and importance of the physiological activity of the thymus.

Functions of the thymus gland and syndromes caused by their violation

Functions	Syndromes
Development of immunocompetence Restoration of immunocompetence Maintaining Immunocompetence Regulation of the peripheral lymphoid system Production of a factor stimulating the bone marrow Products of hypoglycemic factor Produce of permeability factor Producing of a factor inhibiting neuromuscular transmission	Immune Deficiency Syndrome Autoimmune diseases Neoplasia Lymphoid proliferation Timoma, agammaglobulinemia with erythrocyte aplasia Hypoglycemia in leukemia Hypersensitivity of delayed type Malignant myasthenia gravis

Neonatal thymectomy of animals (especially rodents) leads to the development of a so-called wasting syndrome (stagnation in the growth, depletion of lymphoid tissue, hypogammaglobulinemia, dystrophic changes in the skin with hair loss, atrophy of subcutaneous fat and, finally, early death. In addition to the purely immunological causes of the onset of this syndrome, the formation of a disturbance in the interaction of certain thymic factors with the somatotropic function of the pituitary gland may play a role in its genesis. Close changes develop in the outset GOVERNMENTAL uzkorodstvennogo by crossing mutant lines of rodents with congenital absence of the thymus gland (mutant Nye athymia). Such animals can completely lack T-lymphocytes, cell-mediated immunity does not appear, and they die much earlier than usual individuals of this species. Congenital hypoplasia and aplasia of the thymus in humans are characterized by generalized lymphoid depletion and hypertrophy of peripheral lymphoid structures. There is a depression of the synthesis of immunoglobulins and cellular immunity. Usually children with such pathology do not live up to 1 year. Treatment of patients with a normal thymus drug (thymosin) improves their condition, which is accompanied by an increase in the number of T-lymphocytes in the blood.

Much less demonstrative are the consequences of thymus removal in adult individuals, and such effects are manifested after a fairly long time. In the operated mice, the "graft versus host" reaction is reduced. Immune deficiency under such conditions can be observed only by slowing the recovery of a population of long-lived immunocompetent cells, reduced by exposure to, for example, X-ray irradiation.

With the factors produced by thymus, a number of autoimmune diseases are associated, in which antibodies to the antigens of the body's own tissues appear in the blood. The most attention among such diseases attracts malignant myasthenia gravis, accompanied by pronounced changes in the thymus gland (autoimmune thymitis). From the normal thymus, a factor (thymine) is released, which slows the transfer of the nerve impulse to the muscle cells. Its hypersecretion can underlie the development of a malignant myasthenia gravis. In addition, thymic factors (or their deficiency), acting on immunocompetent cells, can promote the production of "clone-inhibited" lymphocytes of antibodies directed against acetylcholine receptors and other muscle cell antigens.

There are other data indicating the hormonal activity of the thymus gland. Age dynamics of the size of the thymus has long allowed to suggest its participation in the regulation of body growth. However, although substances that influence growth have been isolated from the thymus tissue, but their presence has been found in other tissues. Nevertheless, it is shown that, after thymectomy, the growth effects of the growth hormone are significantly weakened. Direct evidence of systemic production of thymic factors gave experiments with transplantation of the thymus gland enclosed in finely porous diffuse chambers. This operation contributed to the elimination or alleviation of symptoms of thymectomy.

At present, many (more than 20) substances with a biological effect in various test systems have been isolated from the thymus tissue. Most of them are still poorly understood. In a number of cases, it is not even known whether they really are different compounds or differ only in the extraction method. The substances produced in the thymus include polypeptides (thymosin fraction-5, thymopoietin, thymic blood factor, thymic active factor - AFT-6, thymarin) with a molecular weight of 900-14000 daltons and other factors exhibiting different activity with respect to expression markers of T cells, cancellation of wasting syndrome, restoration of the T-lymphocyte population in athymic mice, stimulation of DNA synthesis, growth of tumors and other phenomena. In a number of cases, the amino acid sequence of such factors (for example, the thymic blood factor) is established, the localization of the active part of the molecule and even the mechanism of their action (via cAMP and prostaglandins). Thus, thymopoietin is a single-chain peptide consisting of 49 amino acid residues. It induces the differentiation of prolimocytes into immunologically competent T cells with complete expression of surface antigens. The effect of the native thymopoietin molecule is reproduced by a synthetic pentapeptide containing the amino acid sequence from the 32nd to the 36th residue. With its intravenous administration, manifestations of rheumatoid arthritis can be mitigated.

Alpha-1-thymosin isolated from the bull's thymus extract contains 28 amino acid residues. It is now obtained by methods of genetic engineering. When it is injected with athymic dwarf mice, proliferation of lymphocytes is observed, the rate of body growth increases and the ability to reject allografts is restored. Clinical interest is presented by the data on the favorable effect of thymosin injection on children with hereditary forms of immunodeficient conditions, as well as patients with lymphocytopenia after irradiation or chemotherapy for malignant tumors.

A more detailed description of the relevant factors is given in the guidelines on immunology, since they control mainly immunological reactions. At the same time, there are data that allow us to include the thymus gland in a more traditional system of endocrine regulation in the body. These data indicate the relationship of the thymus with the activity of other endocrine glands. Thus, antiserum to the pituitary tissue causes atrophy of the thymus in newborn mice. On the contrary, the antilymphocyte serum determines the degranulation of acidophilic cells in the anterior pituitary gland in which growth hormone is synthesized. To similar changes in the pituitary gland results in neonatal thymectomy. In adult rats, removal of the gland leads to an increase in the level of growth hormone in the blood. Increases and the content of TSH. Thymectomy causes an increase in the weight of the adrenal glands with a drop in the content of ascorbic acid and cholesterol in them, which is a sign of an increase in the secretory activity of the adrenal cortex. There was also an increase in the level of corticosteroids (especially aldosterone) in the blood of thymectomized animals. Data on the effect of these substances (as well as sex hormones) on the condition of the thymus gland are well known. With regard to the effect of thymic factors on the function of other endocrine glands, the results of experimental studies are less definite; The clinic also does not provide clear indications of the presence of appropriate interactions.

Among the metabolic effects of thymectomy and thymosin, an increase in triglycerides in the serum of thymectomized animals and its normalization under the influence of thymosin should be noted.

[1], [2], [3], [4], [5], [6], [7], [8]