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Substantiated in the paper is urgency of development of pathogenetically adequate immunotherapeutic approaches to the treatment of HIV-infection, that is supposed to have good prospects. Consideration is given to experimental and clinical-and-immunological findings concerning effects of different immunomoderivative drug preparations and of their synthetic analogues on the trigger mechanisms, with sequelae of their development in the cytokin-chemokin system outlined. A possibility is shown based on principle of our using with an immunotherapeutic purpose some cytokins, soluble receptors, antibodies to cytokins and receptors, those antibodies and ligands combined with toxins, chemical compounds affecting the synthesis of cytokin and other biologically active substances as well. Unspecific active immunotherapy is regarded as a good supplement to antiretroviral therapy preventing development of resistance to drugs.

Efficacy was studied of the use of the drug preparation "Immunal" (LEK, Slovenia [correction of Slovakia]) in a combined treatment of acute bronchitis in children in poor health. The main group of 39 children received conventional treatment supplemented with a course of the drug "Immunal", 10 drops on a three-times daily schedule over 30 days. The use of "Immunal" in a complex therapy of acute bronchitis in children made for a sooner disappearance of clinical manifestations of the illness, decline in ESR, rise in IgG. The immunological properties of "Immunal" are manifested mainly by normalization of the functional state of the phagocytosing cells.

Membrane structures of the mast cells are mainly of protein nature, since trypsin treatment causes almost complete loss of mast cell ability to form rosettes. Trypsin-sensitive proteins have no critical role in the formation of membrane thymocytes structures, which cause their affinity to the mast cells. Sialic acids play a role in organization of the membrane thymocyte structures.

It is established that incubation of the mast cells and lymphocytes in vitro in the medium 199 at 4 degrees C promotes spontaneous formationof mast cell-lymphocyte rosettes. While incubating in medium 199 at 37 degrees C a considerable part of mast cell-lymphocyte rosettes irreversibly dissociate in contrast to E-rosettes. Loss of ability to the formation of rosettes is due to the loss of the corresponding complementary structures mainly by the mast cells. The data are obtained which allow supposing participation in the process of dissociation of the shedding and capping phenomena induced by contact interaction of ++mast cells and lymphocytes.

Levels of thymic hormones in blood serum were found to decrease during the development of Guerin's carcinoma, methylcholanthrene- and DMBA-induced carcinogenesis, soft tissue sarcomas, mammary cancer, in children with tumors of the urinary-genital tract, that evidences for the suppression of the thymic endocrine function in neoplastic processes. A decrease in the level of substances, active in the test under study is not revealed in patients with different forms of leukemias. The tumour elimination normalizes the thymic endocrine function, while multiagent chemotherapy increases the insufficiency. The data obtained suggest the immunotherapy for malignant neoplasms with thymic hormones.

One of the fractions of the thymus extract of a calf obtained by the authors restored the synthesis of antibodies to sheep erythrocytes in neonatally thymectomized mice and rats. Fractions isolated anologously from the tonsils and the lymph nodes failed to influence the antibody genesis. The data obtained are in favor of the endocrine function of the thymus of significance in the establishment and regulation of the immunological reactivity.

Typhoid infection was reproduced by introducing the infective agent into the bone marrow of noninbred rabbits. After the injection of thymostimulin on the first day of infection the release of typhoid bacilli continued for 1-3 weeks; when thymostimulin was injected on day 20, the release of typhoid bacilli stopped in two weeks. In the control group the release of typhoid bacilli continued during the whole term of observation. The injection of thymostimulin at an early period after infection was thus found to prevent the development of chronic typhoid infection with the elimination of the infective agent from the body of rabbits.

The formation of mastolymphocyte rosettes was used to determine that in chronic lymphocytic leukemia and bovine leukemia, unlike healthy people and animals as well as patients with solid tumours of different localization and Hodgkin's disease, a large amount of cells appear among peripheral blood lymphocytes having membrane affinity for mast cells. This may be used as an additional criterion in laboratory diagnosis of these diseases.

Whole-body X-irradiation of rats caused inhibition of endocrine function of thymus. The effect was a function of radiation dose and time after irradiation. 72 h following irradiation with doses of 6 and 8 Gy the thymus hormone content of blood serum fell down the level registered in the thymectomized animals. Cellularity of the thymus and spleen concurrently decreased. The kinetics of spontaneous chemiluminescence of blood serum, thymus and spleen cells characterized the hypersecretion of glucocorticoids in response to radiation activation of lipid peroxidation in radiosensitive rat organs.

On studying the surface of intact and cryogenic masto- and lymphocytes by the scanning electron microscopy the formation of close membrane contacts was detected between thymocytes and mast cells looking in vitro as mastolymphocyte rosettes (ML-rosettes). During ML-rosette formation changes in cell surface organization were observed. Availability of viable thymocytes is necessary for ML-rosette formation. The surface topography of cells constituting the ML-rosettes is seen changing during rosette formation. It is proposed that the mastocyte may function as an acceptor acquiring immunological specificity through the contact with lymphocytes whose membrane responds actively towards the antigen by changing its surface. Reorganization of the lymphocyte plasma membrane may be perceived by mastocytes as a signal of granule secretion.

The content of thymic serum factor in mice during the early postnatal ontogenesis is at the level characteristic of immunologically mature animals. Their spleen rosette-forming cells are, however, much less sensitive to antilymphocytic serum than those of adult animals. The sensitivity to the latter did not increase after incubation of splenocytes with thymosin or upon its multiple introduction to the neonatal mice. The results obtained suggest the refractoriness of the spleen rosette-forming cells to the thymic hormones during early postnatal ontogenesis.

The adenosine deaminase, 5'-nucleotidase, AMP-aminohydrolase and adenylate kinase activities and thymostimulin influence on these indices in vivo were studied in rat thymus and spleen lymphocytes in the latent period of DMBA-induced mammary carcinogenesis. The adenosine deaminase activity was established to increase while 5'-nucleotidase and AMF-aminohydrolase activity to decrease in the thymocytes of intact animals treated with thymostimulin; the adenylae kinase activity of spleen lymphocytes decreased as compared with that in the rats not treated with the preparation. The dynamics of changes in the investigated enzymes in activities in lymphocytes was of wave-like pattern in the latent period. The treatment of animals with thymostimulin in this period normalized adenosine deaminase activity and decreased the activity of the other enzymes in these cells.

The contents of thymic hormones and endogenous substances with thymosin-like activity (TLA) was studied under conditions of administering thymostimulin and splenin during DMBA-induced carcinogenesis in rat mammary glands. It has been established that during latent carcinogenesis there is an inhibition of thymic endocrine function which persists in tumour-bearing animals. Injections of thymostimulin and splenin induce synthesis of substances with TLA, accompanied by an inhibition of blastoma development.

Cytochemical studies were performed to reveal activities of phosphatase, chloracetate esterase, neutral alpha-naphtyl acetate esterase and non-specific esterase, and their results enabled us to ascertain the nature of cells forming mastolymphocyte rosettes. Rosette-forming cells were shown to be mast cells to which non-mature cells of T-lymphocyte origin are joined.

It is shown that prodigiosan is an inductor of synthesis of the substances with the thymosin-like activity. The suggestion about inhibition of 3-methylcholanthrene-induced blastomogenesis by prodigiosan which is mediated by the substances with the thymosin-like activity and interferon is discussed. We present the hypothetical diagram of the development of the above mentioned mechanism. The significance of the obtained findings for elaboration of the immunotherapy is discussed.

No production of interferon was observed in ten-day mice in response to the injection of the Newcastle disease virus. Single injection of the calf thymus extract fraction obtained by the method of Gujlling et al. to newborn mice induced the capacity of interferon genesis in the animals at the age of ten days. Adult rats produced interferon in response to Newcastle disease virus. The intensity of interferon synthesis was unaltered 2 to 3 months after thymectomy.

It was shown in experiments of CC57W mice that cocarcinogenic activity of influenza A/PR8/34 virus correlates with acute or chronic pattern of infection. Prolonged persistence of the virus resulted in significant stimulation of the lung tumor incidence in infected mice. The prevention with thymosin of chronic influenza infection development in CC57W mice lead to a decrease in the incidence of lung tumors to the control level.

A fraction stimulating the antibody synthesis to sheep erythrocytes in administration during the neonatal period to mice and partially restoring the antibodygenesis in neonatally thymectomized rats was isolated from a calf thymus extract. Morpho-histochemical studies demonstrated a marked plasmocytic reaction in the spleen of neonatally thymectomized rats under the effect of the thymus extract fraction in response to immunization with sheep erythrocytes; however, there occurred no normalization of morphotopographic peculiarities of the splenic tissue, including the thymus-dependent regions. Administration of the extract was also not accompanied by any weight gain of the lymphoid organs, or increase in lymphocyte count in the peripheral blood and the count of splenic cells transforming into blasts under the effect of phytohemagglutinin.

The level of thymus serum factor (TSF) was studied in the circulation of adrenalectomized rats and in the administration of corticosteroids. The effect of adrenocortical hormones on the receptor properties of thymocytes by the ability of mast cells to form mastolymphocytic rosettes (MLR) with thymocytes was also studied. The TSF content was shown to decrease to the level observed in thymectomized animals 40 h after administration of 125 mg/kg hydrocortisone. The MLR amount formed by thymocytes decreased significantly either. Adrenalectomy mas accompanied by an increase in the TSF content early after operation and at later time the MLR amount rose. Sham adrenalectomy resulted in a decrease in the TSF amount early after operation.

A single injection of thymostimulin into mice in a dose of 45 micrograms/kg b.w. enhances the functional activity of macrophages, reaching it maximum on day 10, which prevents the formation of an infectious process in mice challenged with S. typhimurium (LD50). The irradiation of the animals in a sublethal dose leads to the complete abolition of the stimulating effect of thymostimulin on macrophages. The presence of an inducer mechanism of the activation of macrophages by thymostimulin, realized in the production of lymphokines, is suggested.

In experiments on C57BL and CC57W mice the acute or chronic course of experimental influenza infection has been shown to correlate with the activity of immune cytolysis. At a low level of the cytolytic activity of T-lymphocytes the prolonged persistence of influenza virus develops. The stimulation of cell-mediated immunity with thymosin prevents the development of chronic influenza infection.

Data on the possible participation of mast cells in the immunological surveillance are presented. Results of the investigations are adduced testifying to participation of mast cells as regulatory ones in the rejection of tumours by means of the development of the delayed hypersensitivity and as effector killer cells with cytolytic activity.

An examination of 16 children suffering from malignancies established marked chemotherapy--induced suppression of endocrine function of the thymus. These findings were in correlation with variations in peripheral blood lymphocytes level in spontaneous rosette-formation test with ovine red blood cells and autoerythrocytes. The levels of E- and A-rosette-forming cells returned to normal following in vitro incubation of peripheral blood lymphocytes with thymostimuline. It is suggested that immunocorrection by means of thymal hormones should be carried out in the course of chemotherapy.

A fraction stimulating antibody formation in neonatal animals was obtained in separation of the calf thymus extract (1A) prepared by the method of Goldstein et al. on a column with Sephadex G-25 (fine). Testing of the activity of analogous fractions of the extracts of calf tonsils, spleen, lymph nodes and the liver led to a supposition that the thymus was the only source of specific humoral factor stimulating antibody formation, which could accumulate in the peripheral lymphoid formations. Low activity of tonsillar extracts failed to confirm the hypothesis on the role played by the tonsils as the central immunity organ similar to the bursa Fabricii.

A decrease in proliferative rate of blood-circulating lymphocytes in response to LPS and PHA was registered in patients with fibroadenomatosis and cancer of the breast and stomach cancer. The said cells preincubated with Concanavalin A showed a weak inhibitory action on B-cells. The inhibition of T-cell proliferation by lymphocytes either remained unchanged or became less apparent in stage II breast cancer and slightly increased in stage III gastric cancer. Since no correlation was established between proliferative levels of T- and B-lymphocytes, two separate subpopulations of non-specific lymphocytes (T-T and T-B) were suggested.

A study was made of the effect of thymostimulin, a medicine of thymus principles, on immature cells including also mastocyte-affined lymphocytes possessing membranous affinity to mast cells--the influence which may result in contact interaction of the above cell types with the formation of mastocyte-lymphocyte rosettes. The results obtained indicated that under certain conditions thymus principles influenced lymphocyte ability for contact interaction with mast cells.

Mastocytes of newborn rats as well as those of adult ones are capable of rosette-formation, whereas the ability of lymphocytes to from rosettes increases with age. The thymocytes of 3-month-old mice lose the ability to mastolymphocytic rosette-formation (MLR) after priming for one hour at 45 degrees C. The ability of thymocytes and splenocytes to MLR-formation is closely related to the time course of immunization of the animals and the method of immunization. The thymocytes and splenocytes of mice with leukemia show a decreased and increased ability to MLR-formation, respectively.