Search

The present investigation indicate that homologous polyclonal anti-idiotypic antibodies induce both humoral and cell-mediated immune response. Experiments on the exhaustion of immune sera with vaccine have revealed that anti-idiotypic antibodies induce not only specific antibodies to influenza virus antigens, but also antibodies to other epitopes of the globulin molecule of the anti-idiotype. Anti-idiotypic antibodies, when reintroduced into animals, induce the production of anti-influenza antibodies of the anamnestic type, but do not induce the formation of antihemagglutinins. The injection of influenza vaccine to animals, previously immunized with anti-idiotypic antibodies, induces the production of antihemagglutinins; an increase in the level of immune complexes and antibodies to anti-idiotype, i.e. anti-idiotypic antibodies, induces the development of immunological memory with respect to influenza virus antigens, including antihemagglutinins.

The injection of inactivated and live influenza virus into rabbits induces the formation of anti-idiotypic antibodies, appearing after anti-influenza hemagglutinins, in the blood. The presence of immune complexes antibody--anti-idiotypic antibody in the blood of the animals has been established. The booster immunization of the animals with influenza virus antigens produces a rise in the levels of both idiotypic and anti-idiotypic antibodies. The injection of autologous anti-idiotypic globulin into the primed animals ensures the induction of idiotypic and anti-idiotypic revaccinal reactions.

In serum of some healthy women and patients with fibroadenomatosis of the mammary gland antibodies to the cell membranes of adipocytes were detected. Interconnections between these antibodies and corresponding antigens in blood, on the one hand, and hormonal-metabolic status of probands, on the other hand, were observed. Possible autoimmune origin of phenomenon detected and its relation to the normal and pathological processes in adipose tissue are discussed.

Altogether 35 children suffering from different forms of glomerulonephritis were examined. It has been shown that in the pathogenesis of glomerulonephritis in children, an appreciable role is played not only by the action of pathogenic immune complexes but also by the mechanism of antibody-dependent cytotoxicity due to K-cells and lymphocytotoxicity, influencing the regulatory subpopulations of immunocompetent cells and acting directly on the structures of renal tissue. The nephrotic syndrome is characterized by the enhancement of serum lymphocytotoxicity whereas the nephritic syndrome by a rise in the blood of circulating immune complexes. In view of the fact that the process may become chronic, the rise of the activity of K-cells, of the level of lymphocytotoxins and the absence from the serum of circulating immune complexes should be regarded as unfavourable prognostic criteria.

A comprehensive clinicoimmunological examination was made of 105 male patients aged 35-65 years who suffered from coronary heart disease. The authors identified a group of 33 patients whose unstable course of angina pectoris was associated with pronounced apolipoprotein B sensitization, as well as with the presence of the autoimmune lipoprotein-antibody complex and abnormalities in the cellular link of immunity. All 33 patients received antianginal agents. Out of them, 15 patients took additionally a course of T-activin therapy to modulate immunological shifts. The results of the examination demonstrated that the immunomodulator exerted a beneficial effect both on the course of CHD (reduction in the number of anginal episodes, improvement of left ventricular contractility) and the immune system (recovery of T-suppressor function, disappearance of lipoprotein sensitization, decrease in the patient's blood detection rates of the autoimmune lipoprotein-antibody complexes from 83 to 28%). The highest effect was reached by T-activin 1.5-2 months following termination of the course therapy. Immunomodulating therapy is regarded as an additional approach to the treatment of CHD patients with marked lipoprotein sensitization.

The effect of a purified acetic acid extract of thymus (“thymarin”) and of three of its fractions obtained by ion-exchange chromatography, and consisting of individual substances of polypeptide nature, on the immune response was studied in mice immunized with sheep's erythrocytes. Thymarin and one of its fractions with a molecular weight of about 5000 were shown to have a marked stimulating action on the thymus-dependent immune response (the formation of cells producing IgM and IgG antibodies and the circulating antibody level).

The comparative immunologic activity of native, aggregated, and deaggregated (tolerogenic) human γ-globulin was studied in experiments on mice and guinea pigs. Diminished activity of the deaggregated preparation was found in reactions of local and general hypersensitivity in sensitized animals, together with diminished ability to stimulate the secondary humoral immune response.

The cytotoxic activity of rabbit antisera against brain and spinal cord antigens for mouse and guinea pig lymphocytes was investigated. None of the sera tested had any cytotoxic action on bone marrow lymphocytes, whereas sera against mouse brain and spinal cord, guinea pig brain, and myelin isolated from it were most toxic for lymphocytes of other lymphoid organs; the maximal toxic effect was found against thymocytes, it was less marked against lymph gland lymphocytes, and still less against spleen cells. The cytotoxicity of antisera against bovine spinal cord, and the myelin or basic protein isolated from it, was least of all and was the same against all the cells mentioned above; antiserum against encephalitogenic polypeptide 2c had virtually no cytotoxic activity. In its encephalitogenic properties fraction 2c considerably surpassed myelin and basic protein prepared from bovine spinal cord. Experiments with absorption of brain antiserum suggested that a cross-reacting antigen is present in the cerebral cortex. Subcutaneous injection of a relatively large dose of thymocytes (224×106) in Freund's complete adjuvant did not lead to the development of allergic encephalomyelitis in guinea pigs.

In experiments on thymectomized adult CBA mice the effect of a homogeneous factor of polypeptide nature from the thymus, with mol. wt. about 5000 (thymarin-III) on the cellular and humoral indices of immunity was studied in animals. Thymectomy in animals was shown to sharply reduce the number of T-cells in the spleen. Correspondingly, the ability of the mice to produce both IgM- and IgG-antibody-forming cells and humoral antibodies against a thymus-dependent antigen (sheep's red blood cells) was sharply inhibited in the mice. Subcutaneous injection of thymarin-III in a dose of 1 μg/kg into the animals daily for 7 days completely restored the T-cell population of the spleen and restored the normal immunologic reactivity of the animals.

The effect of acetic acid extracts of the bovine thymus and pineal glands and hypothalamus, purified by gel filtration, on the content of circulating antibodies and the number of antibody-forming cells was investigated in experiments on mice. Extracts of the thymus and pineal glands, injected for 10 days, stimulated immunogenesis induced by injection of sheep's red cells, whereas the hypothalamic extract had an inhibitory action.

Rabbit antisera against antigens of whole mouse, rabbit, guinea pig, and human brain were found to have a cross cytotoxic action on lymphocytes of the thymus, lymph nodes, and spleen of the animals of these species. Mouse thymus cells were the most sensitive (index of cytotoxicity 63–100%); the cells of other mouse lymphoid organs and lymphocytes of the other species of animals and man were more resistant. Bone marrow cells were not injured by any serum. Antigens responsible for the cytotoxic properties of the sera were found to be located in the human cerebral cortex and to be absent from the white matter and the brain stem.

Experiments on mice (296 animals) were made to study the capability of native and deaggregated preparations of human globulin to fix complement as well as the relationship of this indicator to tolerogenic properties of the preparations in question. Ultracentrifuged preparations were discovered to have the decreased capability to activate complement. As anticomplementary properties of the preparations become more demonstrable their tolerogenicity declines. The decreased capability to activate complement can be used as criterion in screening tolerogenic preparations.

A total of 48 patients with chronic renal failure, 42 of them after allotransplantation of cadaveric kidney, were studied for leukocyte spontaneous migration and corresponding alterations in migration activity in the presence of renal antigens reflecting recipient sensitivity towards organospecific renal antigens. High levels of leukocyte spontaneous migrations and renal antigen sensitization were recorded in patients with acute course of renal transplant rejection versus those with no evidence of rejection or the persons with slowly progressing chronic rejection. It was stated that alterations in leukocyte migratory activity, both spontaneous and challenged by presence of renal antigen, could demonstrate the activity of immune processes in a recipient of renal transplant. The findings are of help in answering the question of how long the transplant could exist. Moreover, organospecific renal antigens are considered as possible participants, in line with transplantation antigens, in the mechanism of kidney rejection.

The role of T and B cells in the immunological memory and prolonged antibody production in mice was studied; for this purpose CBA mice were immunized with SRBC in doses of 1 X 10(6) or 1 X 10(9) cells, decapitated 21--25 days later, and their spleen cells were treated with T or B antiserum and transferred in a dose 7 x 10(7) cells to syngeneic recipients treated with cyclophosphamide for suppressing their immunity. The treatment of the donor spleen cells with T or B antiserum resulted in a considerable decrease in the hemagglutinin level, as well as in the number of IgM- and IgG-forming cells. The transfer of T and B cells, mixed in equal amounts, to syngeneic recipients restored the immunological memory of the animals; in those cases when the mixture had the prevalence of T cells the restoration of the immunological memory was even more pronounced. The donor spleen cells treated with T or B antiserum, when tested for their ability to produce IgM- and IgG-forming cells in vitro (prior to their transfer to the recipient), showed a decrease in the production of IgM-forming cells (68%) and IgG-forming cells (74%) only under the action of B antiserum, whereas T antiserum had no influence on the production of IgM- and IgG-forming cells in vitro.

Effect of homogeneous polypeptide thymus factor of mol weight about 5000 (thymarin-III) on cellular and humoral immune responses of thymectomized adult CBA mice was studied. Thymectomy proved to greatly decrease the number of T-cells in the spleen. Accordingly, the capability of these mice to produce both IgM and IgG antibody-forming cells in response to the thymus-dependent antigen (sheep red blood cells) was significantly depressed. Subcutaneous injections of thymarin-III (1 microgram per g of body weight) for 7 days completely restored the T-cell spleen population and normalized the animals' immune response.

Deaggregation of human globulin by the treatment with urea solution has been studied. Urea treatment resulted in dose-dependent lowering of complement fixing globulin capacity. The optimal urea dose was 0.12 M for 10 mg/ml of protein. Deaggregated globulin was stable and tolerogenic in the experiments on mice.

A single intravenous injection of dimethyl sulfoxide disturbed permeability of the blood-brain barrier (BBB) and caused passage of rhodamin from the blood into the brain in guinea pigs. Brain microinjury, injection of Freund's complete adjuvant or dimethyl sulfoxide increased BBB permeability to brain antigens detected in the animals' blood as early as the first 24 hours after the procedure. Antibodies appeared in the serum and/or delayed type hypersensitivity cell reactions formed in some of the animals later. Daily intraperitoneal dimethyl sulfoxide injections led to increase of the morbidity and mortality indices among animals with experimental allergic encephalomyelitis induced by sensitization with myelin basic protein and Freud's complete adjuvant. The results of the experiment show the important role of BBB permeability in the pathogenesis of experimental allergic encephalomyelitis.

Serum immunoglobulins G, A, M were studied along with a parallel investigation of the laboratory indicators of the destructive-inflammatory process and other indices of organism reactivity in 378 patients with acute and chronic pyo-inflammatory diseases and a critical mechanical trauma. Such an approach allowed an objective substantiation of the dynamics of serum immunoglobulins to be given. They may be recommended as prognostic criteria for the selection of curative tactics and assessment of quality of the surgical and conservative treatment.

The work demonstrates that after the injection of a heterogenous antigen into rabbits the appearance of antibodies is followed by the "spontaneous" formation of anti-idiotypic antibodies. These anti-antibodies, detected by means of several serological reactions, are specific and have an idiotypic character. Circulating antibody--anti-idiotypic antibody complexes have been detected in the blood of the animals. The injection of autologous anti-idiotypic antibodies into the immunized animals ensures the stimulation of the formation of antibodies and anti-idiotypic antibodies. Immunological memory with respect to anti-idiotypic antibodies develops in the body of the immunized animals.

The influence of purified acetic acid thymus extract (thymarin) and its three fractions isolated by ion-exchange chromatography upon immune response to SRBC in mice was studied. Each fraction was identified as homogeneous individual material of polypeptide nature. Crude thymus extract and one of its fractions with an approximate molecular weight of 5000 exerted a strong stimulating effect on the thymus-dependent response: formation of IgM- and IgG-antibody producing cells and on the circulating antibody level.

An attempt was made to further characterize some conditions determining the decrease of immunological responsiveness in patients with mammary gland cancer. To reveal the delayed-type cell hypersensitivity, the antigens of Mycobacterium tuberculosis, staphylococcus, fungi Candida were employed as well as a contact allergen--dinitrochlorobenzene. Tests were made prior to the treatment and in different terms after it. To determine T-lymphocytes the rosette-formation test with sheep erythrocytes was used. Also, the degree of lymphoplasmocytic infiltration of the tumor and the amount of peripheral blood lymphocytes were estimated. Under examination were 126-patients with mammary gland cancer, 56--with benign tumors and 73--practically healthy subjects. The frequency of positive skin tests for any of the antigens under study was lower in breast cancer patients than in the group with benign tumors and healthy subjects. There was no manifest inhibition of the immune response in the initial stages of mammary gland cancer.

Rabbit antisera against antigens of mouse, rabbit, guinea pig and human whole brain cross-reacted in the cytotoxic test with the lymphocytes of the thymus, lymph nodes and the spleen of these animal species. Mouse thymocytes were most sensitive to the antibrain sera (cytotoxic index -- 63--100 per cent); cells from other mouse lymphoid organs and lymphocytes of rabbit, guinea pig and man were more resistant. Bone marrow lymphocytes were not damaged by any of these sera. The antigens which induced the cytotoxic properties of the sera were found only in the human cerebral cortex, but not in the white matter of the brain stem.

The authors studied the influence of the cells of normal lymphoid organs on the level of immunological response in the recipients of splenic cells from the suppressed animals. The organ cells were mixed with the suppressed ones and were administered to the recipients together with the reimmunizing dose of the antigen. Cells of the spleen, of the lymph nodes, the thymus or of the bone marrow suppressed the capacity of the memory cells to the realization of the immunological response to sheep red blood cells and egg albumin. The spleen cells of one and a half month old mice were more active than the cells of young or old animals. The suppressor activity persisted after the administration to donors of various doses of cortisone or heating of the cells transferred at 56 degrees C. Treatment with T-antiserum or heating at 80 degrees C led to reduction of the suppressor action of normal cells.

Extracts from bovine tissue were prepared by the acetic acid treatement and purified by gel filtration. All the preparations were injected into CBA mice for 10 days. Extracts from the thymus and the epiphysis proved to increase the number of antibody-forming cells generated in the spleen and the level of serum hemagglutinins in response to the immunization with sheep red cells. As to the hypothalamic extract, it depressed the immune response.

Immunological properties of native, aggregated, and disaggregated (tolerogenic) human gamma-globulin were compared in experiments on mice and guinea pigs. Disaggregated preparation was shown to give diminished local and general hypersensitivity reaction in sensitized animals and had decreased ability to induce secondary humoral immune response.