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The paper provides the results of examining about 3,000 industrial workers exposed to various xenobiotics. Various phases of immune responses were noted in 40-60% of persons with nonspecific chronic pulmonary, gastrointestinal, gynecological diseases at remission. 10-20% of the industrial workers under study were diagnosed as having secondary immunodeficiency whose criteria were the presence of one of clinical syndromes, a sharply significant reduction in immunoglobulins, normal levels of circulating immune complexes and normal values of the lymphocytic enzymes alpha-glycerophosphate dehydrogenase, succinate dehydrogenase, lactate dehydrogenase. The stimulation of the immune system in clinically healthy individuals who have a service length of 3 year or more should be regarded as development of an immune response to a xenobiotic or its metabolites.

The paper provides the authors' own data and the data available in the literature concerning diurnal rhythms of immunological parameters in the development of experimental immunopathological conditions. Desynchronizing these rhythms, a change in the light regime is shown to accelerate the time course of the development of an autoimmune process in mice. The potentialities of chronotherapy of experimental immunodeficiencies with thymic preparations have been studied. It is emphasized that chronobiological studies are particularly essential in solving the biomedical problems of the Far North with its extreme conditions and a great deal of desynchronizing factors.

The reported and original research data on immune regulation of cellular proliferation and differentiation in diverse tissues are summarized. Such regulative function is considered to be the expression of the proposed role of the immune system in the realization of genetic information at the integral bodily level. It is postulated that in addition to the information flow: DNA--RNA--protein (in each cell), another information flow may exist: the central organs of the lymphoid system--lymphocytes migrating to different organs and tissues--organs and tissues characterized by specific organ, tissue and differentiation antigens.

A study was made of the level of corticosterone in mouse blood plasma after 4-time daily administration of thymopthin (a drug containing 1% of thymosin-alpha 1, synthesized in the All-Union Research Institute of Technology of Blood Substitution and Hormonal Drugs) at a doze of 0.05 mg per mouse in the morning and evening. The object of investigation was blood plasma of CBA male mice aged 12-16 weeks. The investigation was experimental. The purpose was to elucidate a possible role of thymic hormones in the regulation of circadian rhythm of glucocorticoid function of the adrenal cortex. Plasma concentration of corticosterone was determined by concurrent protein binding of hormones. Thymopthin administration was shown to result in change of circadian rhythm of the level of corticosteroids in mouse plasma. Drug administration in the morning elevated daily concentration of corticosterone, that also evening reduced it as compared to the control group that in the received the same volume of physiological salt solution. A curve of the daily time course was obtained as a result of smoothing by a method of the least squares. These results should be taken into account when using thymic drugs for therapeutic and experimental purposes.

By means of the radioautographic method the state of cellular restoration of the gastric epithelium has been estimated after administration of syngenic lymphocytes to mice. Under conditions of physiological regeneration T-lymphocytes are able to inhibit proliferation of the epithelial cells and to limit the size of the proliferation zone in crypts. The inhibition degree of the proliferative activity depends on the doze of the T-cells administered. In order to demonstrate their activity, T-cells do not need DNA and RNA synthesis de novo. At the same time, protein synthesis is necessary; it occurs on long-living mRNA lymphocytes. The T-lymphocyte action is reversible at the tissue, but not at the cellular level. The mechanism of decreasing cell reproduction under effect of T-lymphocytes is described. In the process of lymphoid regulation of the cellular restoration in the intestinal epithelium changes in the size of the proliferative pool play the main role.

The pattern of lactate dehydrogenase isoenzyme spectrum changes on different stages of T-lymphocyte differentiation was studied An enriched population of stem cells has LDH-5, 4 and 3 isoenzymes, and much less LDH-2 activity. The isoenzyme pattern of thymic cell precursors consists of LDH-5, 4, 3 and 2. All the five LDH isoenzymes were found in cortical thymocytes. Medullary thymocytes reveal LDH-5, 4 and 3 isoenzymes. T-lymphocytes of peripheral lymphoid organs contain mainly LDH-5 and in a lesser degree LDH-4 activity.

In AKR/J mice lymphocytes of thymus, spleen and lymph nodes can be classified according to their morphology as revealed by the Stockinger and Kellner staining: I--basophilic cytoplasm, 1--3 large basophilic nucleoli (blast cells), II--basophilic cytoplasm, 1--4 small clearly visible nucleoli (T-lymphocytes), III-weakly basophilic cytoplasm, 1-4 small fairly visible nucleoli (B-lymphocytes). The number of cells of types I and II increases with the progressing of leucaemia. After the administration of somatotrophic hormone the number of cells of types I and II increases only in the lymphoid organs of 5 months old AKR/J mice.

A single administration of 1 X 10(9) heated erythrocytes to C57BL and BALB/c mice caused on the 13th day the appearance of antierythrocytic autoantibodies, an increase in the weight of the lymphoid organs, and lymphoreticular hyperplasia. These changes were more pronounced in BALB/c mice. During the development of autoimmune reactions the changes in the number of E- and EAC-rosette-forming cells in the thymus and spleen and in the immune response to the sheep erythrocyte immunization and E. coli endotoxin were revealed; distinct strain differences were observed. Daily somatotropic hormone administration (5 mg/kg of body weight) for 10 days decreased the degree of the autoimmune reactions development in mice of both strains. Its action was more expressed in BALB/c mice.

The pattern of lactate dehydrogenase isoenzyme has been examined for different murine lymphoid cell populations and for T and B lymphocyte populations. LDH-1, LDH-2, LDH-3, LDH-4 and LDH-5 were found in the thymus, LDH-3, LDH-4 and LDH-5 in the spleen, and LDH-4 and LDH-5 in lymph nodes. Enrichment of lymphocytes with T and B cells resulted in the appearance of LDH-4 and LDH-5 in T cell population, and of LDH-5 in B cell population. With the appearance of the autoimmune reaction, activity of LDH-5 in the thymus was seen to decrease. After the thymosin injection (4 fraction), activities of LDH-1, LDH-2 and LDH-3 diminished. A possible application of the LDH isoenzyme distribution pattern as a marker of T cell differentiation is discussed.

The activity of adenylcyclase in T and B cells of lymph nodes and spleen has been investigated in intact and autoimmune mice Balb/c and C57B1. Strain differences in the enzyme activity of intact and autoimmune mice were observed. It is concluded that the determination of adenylcyclase activity in lymphoid cells makes it possible to reveal the peculiarities of cell maturation in normal and pathological mice of different strains.

Following 1.5 month period after thymectomy of adult mice the crypt 3H-thymidine labelling index is decreased and the proliferative zone is reduced. Analysis of labeled cell distributions in the crypt revealed that thymectomy resulted in the initiation of enterocyte entering a maturation phase in the site shifted to the crypt base. Syngeneic T-lymphocytes injected intravenously to thymectomized mice increased the labeling index, but exerted no effect on the size of proliferative zone. The proliferative changes described were not due to changes in the number of divisions of rapidly proliferating enterocytes. The role of T-lymphocytes in modulation of intestinal epithelium proliferation and steady state maintenance is discussed.

Direct PFC to SRBC were enumerated simultaneously by the LHL and LHG in the spleens of partially tolerant and control rats. The sensitivity of LHL was higher than that of LHG, but the factor by which the number of PFC was higher in LHL than in LHG was in the two groups similar (1.44 in tolerant and 1.47 in control group). When the plaque size distribution was studied in the LHL, a significant increase in small size plaques was observed in tolerant rats. The findings are discussed and the conclusion is reached that the decrease in AFC number and not in antibody production by individual PFC is the main factor responsible for partial tolerance.

The effect of syngeneic thymocytes on the proliferative compartment of the small intestinal epithelium was studied in CBA mice. In mice that intravenously received thymus cells, the proliferative enterocyte activity was depressed, the proliferative zone reduced and the maturation zone enlarged. The data obtained indicate that medullary thymocytes are responsible for this effect. The regulatory role of the immune system with regard to cell proliferation is discussed.

Changes of the circadian rhythm of the general numbers of nucleus-containing cells and leucograms of peripheral blood in NZB mice with autoimmune spontaneous hemolytic anemia and in C57BL mice without visible disturbances in the system of immunostructural homeostasis were the most obvious in the white blood in NZB mice: a) disappearance of the circadian rhythm of the general number of nucleus-containing cells in peripheral blood owing to the inversion of circadian rhythm of the absolute number of neutrophiles; b) changes of circadian fluctuations of lymphocytes-neutrophiles ratio. The observed differences in circadian rhythms of hematological indices in NZB and C57BL mice seem to stem from insufficiency of adrenal cortex function and/or changes in functional state of hemopoietic tissue which can occur during the development of autoimmune processes.

With the aid of Till and McCulloch's method, 5 times 10(-6) thymic cells were found to cause an increase in the number of hemopoietic endogenous spleen colonies in syngeneic donor-recipient combination. Thymic cells of C57BL mice had no effect on the number of endogenous colonies in the spleen. 40 times 10(-6) thymic cells administered 24 hr after sublethal irradiation caused an increase in the number of colony forming units in the spleen within 14 days. Possible ways of the thymus effect on hemopoiesis are discussed.

The possibilities of inducing immunocompetent tissue-dependent changes were studied with the help of the intestinal epithelium model. It was found that thymectomy of adult mice or transplantation of syngeneic thymocytes to recipients with normal intestine function did not lead to changes in the intestinal epithelium whereas the injection of antilymphocyte serum or thymocytes to fasting mice resulted in the diminution of the size of the stem department, inhibition of the mitotic activity, and appearance of dystrophic changes in the intestinal epithelium. It is suggested that population changes in the lymphoid tissue may lead to alterations in the intestinal epithelial cells with different degree of maturity.

The amount of plasma cells is connected with intensity of humoral immunological reactions. In people died an accidental death, the amount of immature plasma cells is the least in the axillary and the greatest--in the mesenteric nodes, especially in the thymus-independent zone. The amount of lymphoblasts and large lymphocytes, reflecting intensity of the humoral and cellular immune reactions, is also the greatest in the mesenteric lymph nodes, both in the thymus-dependent and in the thymus-independent zone. In all probability, the intensity of the immunological processes is minimal in the axillary, it is middle in the iliac and cervical and it is maximal in the mesenteric lymph nodes. In each case it is probably connected with peculiarities of antigenic composition of the lymph inflow. The mesenteric lymph nodes are on the way of the foreign protein getting into the intestine. This is evidently reflected by the highest content of immature plasma cells, lymphoblasts and large lymphocytes in them.

Digitized images of Feulgen-stained normal murine T and B lymphocytes were analyzed by the computer and microphotometry. Differences between these cells were revealed. The entropy of optical density was found to show highly significant differences between T and B cells. The application of the automatic classification of T and B lymphocytes is discussed.

The correlative analysis of diurnal rhythms of cell number and adenylate cyclase cellular activity was performed in the thymus, spleen and peripheral blood of Swiss mice, intact or thymectomized at the age of 3 months. The existence of somehow synchronized diurnal rhythms of cAMP exchange and cell recirculation was found in the peripheral lymphocyte pool and in the thymus. Diurnal rhythm of cAMP synthesis in peripheral lymphocytes was regulated by the thymus. Thymectomy led to desynchronization of recirculating processes and cyclic nucleotide metabolism in immunocompetent cells.

Cortical matter increased in the thymus after ten-day dosage of Coombs-positive NZB mice with somatotropin and thyroxine; cortical matter predominated over medullar matter. Secondary lymphoid follicles disappeared and the number of mast and plasma cells decreased. With administration of the hormone, rosette-forming cells began to appear in the thymus.