[The phage sensitivity and lysogeny of cultures of Streptococcus pyogenes group A isolated in different streptococcal infections]. / Fagochuvstvitel'nost' i lizogeniia kul'tur Streptococcus pyogenes gruppa A, vydelennykh pri razlichnykh streptokokkovykh infektsiiakh.

The collection of moderate phages of S. pyogenes, group A, had been created earlier. As shown in this work, group A streptococcal cultures isolated from patients with rheumatism, glomerulonephritis and tonsillitis exhibited different sensitivity to the phages of this collection: the cultures were lyzed by phages of groups II and III in rheumatism, group III in tonsillitis and group I in glomerulonephritis. The study revealed that lysogeny was widely spread among S. pyogenes strains isolated from patients with different diseases under study. Most frequently occurred among cultures isolated from tonsillitis patients. In this disease only phage-resistant streptococcal cultures proved to be lysogenic. Lysogeny was found among both phage-sensitive and phage-resistant cultures in rheumatism and especially in glomerulonephritis.

[Level of antibodies to different determinants of Streptococcus group A polysaccharide and autoantibodies to basal layer of the skin epithelium in rheumatism]. / Uroven' antitel k razlichnym determinantam polisakharida streptokokka gruppy A i autoantitela k bazal'nomu sloiu épiteliia kozhi pri revmatizme.

Direct dependence was established between the presence of autoantibodies reacting with the basal layer of the skin epithelium (BLSE) and the high level of antibodies to the streptococcal group A polysaccharide (APS). By the primary active rheumatic fever (PARF) autoantibodies to the BLSE are revealed. By the recurrent active rheumatic fever (RARF) and in the control sera, autoantibodies reacting with the BLES, apparently, are directed to the rhamnose determinants of APS. These data confirm: different level of antibodies to the GS and to the rhamnose determinants of APS by PARF, RARF and in the control sera; the experiments of the autoantibody inhibition, reacting with the BLSE by the APS or the polysaccharide of streptococci A-variant, containing only the rhamnose determinants.

[The enhancement of the immunogenicity of streptococcal group-A M protein by conjugation with a synthetic polyelectrolyte]. / Povyshenie immunogennosti M-belka streptokokkov gruppy A pri kon''iugatsii s sinteticheskim poliélektrolitom.

Immunization with the polypeptide fragment of group A streptococcal protein M conjugated with the copolymer of acrylic acid and N-vinylpyrrolidone in complete Freund's adjuvant has been found to lead to a sharp increase in the level of antibodies to the type-specific determinants of protein M, detected in the enzyme immunoassay (EIA). The possibility of the application of such sera to preliminary typing of streptococci in EIA with the use of whole microbial cells as antigens has been shown. The data on high activity of the sera thus obtained in the bactericidal test with streptococci of the homologous type are presented. Recommendations on the use of sera obtained by the above method for highly precise typing of the virulent cultures of group A streptococci in the bactericidal test are given.

[Comparison of the frequency of detection of autoantibodies to epidermal antigens with the level of antibodies to polysaccharide of group A Streptococcus and the number of T-suppressors in glomerulonephritis]. / Sopostavlenie chastoty obnaruzheniia autoantitel k antigenam épidermisa s urovnem antitel k polisakharidu streptokokka gruppy A i chislom T-supressorov pri glomerulonefrite.

By the acute glomerulonephritis (GN) of streptococcal etiology, autoantibodies (AA) reacting with the basal layer of skin epithelium (BLSE) are discovered. The presence of this AA's correlate with the high level of antibodies to the streptococcal group A polysaccharide (A-PS). In the control sera such AA's and the high level antibodies to A-PS are discovered very rarely. By the GN of non-streptococcal etiology, AA's to the BLSE apparently of other specificity are obtained in some cases, in spite of the absence of antibodies to A-PS. AA's reacting with the differentiated layers of skin epithelium are discovered in the high percent of cases by GN. The presence of these AA's do not correlate with the levels of antibodies to A-PS. The reduction of the number of T-lymphocyte suppressors is established in the blood by the presence of AA's to the BLSE by GN. This question is a subject of later investigations by the different autoimmune processes. Such data can apparently corroborate the previously expressed hypothesis, that AA's to BLSE, which as a rule react with endocrine thymus epithelium, are the cause of the beginning of immunoregulatory disorders, characteristic of autoimmune processes.

[Antibodies to the rhamnose determinants of the polysaccharide of streptococci group A in the sera of rheumatism patients and donors]. / Antitela k ramnoznym determinantam polisakharida streptokokkov gruppy A v syvorotkakh bol'nykh revmatizmom i donorov.

In the sera of patients with recurrent rheumocarditis, and especially in cases of primary rheumatism, the level of antibodies to group A streptococcal polysaccharide (A-PS) has been found, according to the results of the enzyme immunoassay, to be considerably higher than in the sera of healthy donors. The level of antibodies to rhamnose determinants (RD) of A-PS has been determined by the inhibition of the immunoenzyme reaction with A-PS under the influence of a variant of group A streptococcus and rhamnose disaccharides with the bonds alpha 1-2 and alpha 1-3. In patients with recurrent rheumocarditis the level of antibodies to A-PS has been shown to be considerably higher than in healthy donors having these antibodies. In acute primary rheumatism a high level of antibodies to A-PS has been detected only in a few cases, and at the same time the prevalence of antibodies to the specific RD of A-PS, bound with beta-N-acetylglucosamine, is observed. In the sera of patients with recurrent rheumocarditis and donors having a high content of antibodies to the rhamnose site of A-PS antibodies, seemingly active against at least two RD, have been detected. In acute primary rheumatism an insignificant amount of antibodies to the rhamnose site of A-PS may probably cause the autoimmune process accompanying rheumatism. This suggestion is substantiated by the previously established capacity of these antibodies for inducing the suppression of cytotoxic cell reactions to microbial antigens.

[Autoantibodies against the basement membrane layer of the skin epithelium as an indicator of the activity of the autoimmune process in children with chronic hepatitis B]. / Autoantitela k bazal'nomu sloiu épiteliia kozhi kak pokazatel' aktivnosti autoimmunnogo protsessa pri khronicheskom gepatite B u detei.

In different forms of chronic hepatitis B, autoantibodies reacting with the epithelium of the basal skin layer (EBSL) and with the epithelium of the cortical and medullary areas of the thymus can be detected by indirect immunofluorescence. The rate of demonstration and the level of these antibodies were established to depend directly on the activity of chronic hepatitis. The data obtained indicate that autoantibodies to EBSL are typical not only for the beginning of the autoimmune process but may also serve as an indicator of the activity of chronic autoimmune disease. The highest titers of the autoantibodies were demonstrated in aggressive hepatitis B associated with liver cirrhosis (in 100% of cases). The data obtained were compared to the liver biopsy findings. Therefore, demonstration of the high titers of autoantibodies can be used without liver biopsy for the diagnosis of liver cirrhosis in hepatitis B.

[Secondary immunopathology in patients with an acute streptococcal infection]. / Vtorichnaia immunopatologiia u bol'nykh s ostroi streptokokkovoi infektsiei.

The authors studied the activity of complement, nonspecific adaptive reactions of the body, the presence of antibodies to cross-reacting antigens of Streptococcus, the concentration of circulating immune complexes, some cellular characteristics of the immunogram in patients with different forms of streptococcal infection. The changes revealed allow a conclusion about the presence of autoimmune processes, most pronounced in chronic and recurrent forms of diseases. In the formation of streptococcal infection relapses, of the role is pathology of the complement system in combination with disorders in other components of nonspecific anti-infection resistance.

[The suppression of delayed hypersensitivity to BCG antigens in BALB/c mice during the production of antibodies to the rhamnose determinants of Streptococcus group A polysaccharide]. / Supressiia giperchuvstvitel'nosti zamedlennogo tipa k antigenam BTsZh u myshei linii BALB/c pri produktsii antitel k ramnoznym determinantam polisakharida streptokokka gruppy A.

The data obtained for the first time in our studies indicate that the production of antibodies to group A streptococcal polysaccharide (A-PS), one of the cross-reacting streptococcal antigens, may suppress delayed hypersensitivity (DH) to microbial antigens. The existence of sharply pronounced correlation between the suppression of DH and the presence of antibodies to the rhamnose area of A-PS in the blood of BALB/c mice immunized with the pepsin-treated culture of group A streptococci has been shown. The suppression of DH is absent in the immunized animals of the same group whose blood contains antibodies to the determinant, specific for A-PS. As revealed in this study, the effect of the suppression of antigen-specific cytotoxicity linked with DH to BCG antigens can be reproduced by mixing lymph node cells taken from these two groups of the animals. The data thus obtained are possibly linked with the activation of nonspecific T suppressors in the production of antibodies to the rhamnose determinants of A-PS in the animals immunized with streptococci. The mechanism of the newly discovered phenomenon is discussed.

[Suppression of cytotoxic cellular reactions by the production of antibodies to rhamnose determinants of streptococcal group A polysaccharide cross-reacting with antigens of the skin epithelium]. / Supressiia tsitotoksicheskikh kletochnykh reaktsii pri produktsii antitel k ramnoznym determinantam polisakharida streptokokka gruppy A, perekrestno-reagiruiushchikh s antigenami épiteliia kozhi.

By the BALB/c mice after different periods of immunization with the streptococci group A, treated with pepsin, antibodies belonging to autoantibodies to the determinants (DT) of polysaccharide (A-PS), cross-reactive (CR) with the epithelial skin cells, were investigated. In one of the mice groups, in the autologous system, on the target cells--macrophages of lymph nodes, the suppression of cytotoxic (CT) reactions was obtained. The CR are bound with the delayed type hypersensitivity appearing after the sensibilization with BCG. The suppression effect correlate (z-0.95) with the presence in the sera antibodies to the rhamnose DT'S of A-PS, which cross-react with the cells of basal and superbasal layers of skin epithelium. Antibodies to the group specific of the A-PS, cross-react only with the basal skin layer and not produce the suppression of CT reactions. It is possible that they also prevent the suppression of CT reactions, bound with the CR antibodies to the rhamnose DT-S of A-PS. The obtained data corroborate the earlier supposition that the autoantibodies to the CR DT'S of A-PS reacting with the skin epithelial cells as a rule common the thymus epithelial cells. It is possible that different IRD'S can prevent or stimulate the development of autoimmune processes by the infections with the streptococci group A.

[Group A streptococcal polysaccharide--stimulator of nonspecific cytotoxic reaction in autologous system of spleen cells]. / Polisakharid streptokokka gruppy A--stimuliator nespetsificheskikh tsitotoksicheskikh reaktsii v autologicheskoi sisteme kletok selezenki.

p4 was shown the ability of group A streptococcal polysaccharide (A-PS) to stimulate nonspecific cytotoxic effect of spleen cells on autologous adherent cells (macrophages). The stimulating effect can be observed in vivo under the treatment of spleen cells with A-PS and any antigen (BSA, PPD, M-protein of group A streptococci). In the presence of antigen A-PS can induce nonspecific cytotoxic effect of normal spleen cells (mice CBA, BaLB/c) and of the mice with DHT and therefore these two immunologic phenomena do not depend on each other. Because A-PS has cross-reactive (CR) determinant with thymus epithelial antigen (factor), it can be assumed that via the CR determinant A-PS links with T-cells receptor for this thymus factor and thus realized the stimulating effect as it's functional analogue.

[The effect of immunization with Streptococcus group A on the development of delayed hypersensitivity to BCG antigens in mice of different strains]. / Vliianie immunizatsii streptokokkom gruppy A na razvitie giperchuvstvitel'nosti zamedlennogo tipa k antigenam BTsG u myshei raznykh linii.

Antibodies to group A streptococcal polysaccharide (A-PS) have been shown to appear within three weeks after the injection of group A streptococcus culture, heat-killed and treated with pepsin (A-STP), in the blood of not only BALB/c mice, but also CBA mice. As revealed in this study, in BALB/c mice antibodies are mainly active against the group-specific antigenic determinant (AD) of A-PS and in CBA mice, against the rhamnose AD of A-PS, common for streptococci of different groups. This study has revealed that the appearance of antibodies to the rhamnose AD of A-PS in the blood of CBA mice inhibits antigen-specific cytotoxicity, appearing with the development of delayed hypersensitivity to BCG antigens. This effect is not linked with the immunization of the animals with high doses of streptococci. Experiments have shown that the in vitro transfer of the inhibition of antigen-specific cytotoxicity to lymph node cells of normal BCG-sensitized animals may be carried out with lymph node cells of CBA mice, immunized with A-STP and having antibodies to the rhamnose AD of A-PS, but not with the serum containing these antibodies. The mechanisms of this effect are discussed.

[Monoclonal antibodies cross-reacting with fibroblasts of interstitial connective tissue of the myocardium and cell wall protein antigens of group A Streptococcus]. / Monoklonal'nye antitela, perekrestno reagiruiushchie s fibroblastami interstitsial'noi soedinitel'noi tkani miokarda i belkovymi antigenami kletochnoi stenki streptokokka gruppy A.

Monoclonal antibodies (MCA) B6/5 and C5/3 were obtained after immunization of BALB/c mice with the protein non-type-specific antigens (NTSA) of streptococcal group A cell wall. MCA B6/5 in the indirect immunofluorescence react with human and animal interstitial connective tissue (ICT) of the myocardium and human fibroblast culture cells. MCA C5/3 react with the bands of muscle fibers of the myocardium. MCA B6/5 and C5/3 are autoantibodies. It was revealed that these MCA are directed to two streptococcal cross-reacting antigens (CRA). Production of B6/5 and C5/3, apparently, does not depend on the possibility of some streptococcal antigens to bind fibrinogen. Bound immunoglobulins were not revealed in the ICT and in the muscle fibres by the cultivation of the C5/3 monoclone. Firstly it was stated that, MCA B6/5, reacting with fibroblasts and with streptococcal CRA, are capable to fix in the ICT of myocardium, what is typical for the phenomenon described in rheumatic fever.

[Monoclonal autoantibodies to different epithelial structures of the thymus gland obtained by the immunization with streptococcal group A antigens]. / Monoklonal'nye autoantitela k razlichnym épitelial'nym strukturam timusa, poluchennye pri immunizatsii antigenami streptokokka gruppy A.

By the indirect immunofluorescence method it was shown to which epithelial thymus structures monoclonal antibodies (mAT) reacting with the different epidermal structures are directed. These mAT related to the autoantibodies were obtained earlier, as a result of lymphoid cells polyclonal activation, by the immunization of BALB/c mice with streptococcal group A nonspecific protein antigens of the cell wall. It was shown that mAT A6/1, reacting with the basal layer of the skin epithelium are directed to the epithelium of the cortical and medullar thymus zones, which is regarded as the so called endocrinal epithelium. These mAT, by the study with immunoblotting method, react with the protein of mV SOkD, B5/1 mAT to the skin epithelium, on the thymus sections react with the single cells around the Hassel bodies.

[Monoclonal antibodies to polysaccharides of group A streptococci cross reacting with mammalian connective tissue]. / Monoklonal'nye antitela k polisakharidu streptokokka gruppy A, perekrestno reagiruiushchie s soedinitel'noi tkan'iu mlekopitaiushchikh.

Monoclonal antibodies (MCA) D 4/1 were obtained by immunization of BALB/c mice with group A streptococci treated with pepsin. MCA D 4/1 react in ELISA test with streptococcal group A, C, L, and A-variant (V) polysaccharides (PS). D 4/1 are autoantibodies, cross-reacting in immunofluorescent test with all the epithelial layers and fibroblast-like structures of human and BALB/c mouse skin. The MCA react also with the interstitial connective tissue of human, mouse and bovine myocardium and with the fibroblast cultures explanted from the skin of donors and rheumatic patients. Tissue reactions partially inhibited purified streptococcal group A, C and L PS, however, complete inhibition was obtained only with V PS. It is suggested that MCA D 4/1 are directed to CR-antigen, common for fibroblasts, all the layers of skin epithelium and one of the rhamnose determinants of group A polysaccharide.

[Production of monoclonal antibodies to tissue-specific antigens of human skin epithelium]. / Poluchenie monoklonal'nykh antitel k tkanespetsificheskim antigenam épiteliia kozhi cheloveka.

Immunization of BALB/c mice with non-type-specific protein antigens of the cellular wall of group A streptococcus and formalin-treated streptococcal culture resulted in stimulating production of polyclonal autoantibodies to antigens of the epithelium of human and murine skin. As a result of hybridoma technique using splenic cells of immunized animals, monoclonal antibodies to different antigens of epidermal cell cytoplasm, i.e. antigen of basal cells, antigen of differentiated cell layers (spinous and granular) and antigen common to cells of all epidermal layers, were obtained. The immunofluorescence tests on monoclonal antibodies to epidermal basal cell antigen showed them to engage cells only of tumors histogenetically associated with the epidermal tegumental epithelium.

[The role of non-type-specific protein antigens of the cell wall in Streptococcus group A in developing delayed hypersensitivity]. / Rol' netipospetsificheskikh belkovykh antigenov kletochnoi stenki streptokokka gruppy A v razvitii giperchuvstvitel'nosti zamedlennogo tipa.

The role of the type-nonspecific (TNS) cell-wall antigens of group A streptococci has been determined. The study has been made on guinea pigs sensitized with whole microbial cells or HCl extracts containing TNS antigens. To determine delayed hypersensitivity, the in vitro cytotoxic test on adhering lymph-node cells in the autologous system has been used. The study has shown that sensitization with group A streptococci of different types or with TNS antigens induces the development of delayed hypersensitivity to TNS antigens (or antigen), common for different types of group A streptococci, but specific for this group. HCl extracts containing TNS antigens can be recommended as the preparation for testing delayed hypersensitivity to antigens, specific for group A streptococci.

[Preparation of monoclonal antibodies to nuclear DNA of mammalian cells by immunization with group A streptococcal polysaccharide conjugated with synthetic polyelectrolytes]. / Poluchenie monoklonal'nykh antitel k iadernoi DNK kletok mlekopitaiushchikh pri immunizatsii polisakharidom streptokokka gruppy A, kon"iugirovannym s sinteticheskimi poliélektrolitami.

Monoclonal antibodies (MAb) were obtained by hybridization of spleen cells from BALB/c mice immunized with streptococcal group A polysaccharide (A-PS) conjugated with synthetic polyelectrolytes (PEL). These MAb reacted with nuclei from human and mouse cells. MAb reacting with nuclei were obtained after prolonged immunization with conjugates and were not formed by hybridization of spleen cells from non-immunized mice or by the immunization with PEL. The investigation of Mab (B1/2 and A5/2) reacting with nuclei has shown that these Mab are directed against DNA and do not react with other tissue substances. No cross-reactions of Mab with A-PS used for immunization have been revealed. Mab B1/2 and A5/2 belong to autoantibodies.

[Antibodies reacting with thymus and skin epithelium and antibodies to cell nuclei in immunization with streptococcal group A polysaccharide conjugated with synthetic polyelectrolytes]. / Antitela, reagiruiushchie s épiteliem timusa i kozhi, i antitela k iadram kletok pri immunizatsii polisakharidom streptokokka gruppy A, kon''iugirovannymi s sinteticheskimi poliélektrolitami.

The antibodies to streptococcal group A polysaccharide (A-PS) have been obtained upon immunization of BALB/c mice with A-PS conjugated with synthetic polyelectrolytes (PEL). Prolonged immunization in the majority of cases revealed antibodies to cross-reactive determinant of A-PS reacting with human and mouse epithelium of the thymus and basal skin layer. These antibodies belong to autoantibodies. Later on, after the beginning of immunization some animals produced antibodies reacting with cellular nuclei. The formation of autoantibodies to nuclei is not related to crossreactions with A-PS, because A-PS do not inhibit these reactions. No antibodies reacting with the epithelial cells or with cellular nuclei have been observed upon immunization with A-PS in Freund adjuvant or with PEL alone. The production of autoantibodies to cellular nuclei is probably a result of immunoregulatory disorders associated with the damage of thymus epithelium by autoantibodies during immunization with A-PS conjugated with PEL.

[Autoantibodies to the thymus and skin epithelium in NZB/N mice and (NZBxNZW)F1 hybrids]. / Autoantitela k épitelial'noi tkani timusa i kozhi u myshei linii NZB/N i u gibridov (NZBxNZW)F1.

Antibodies reacting with thymus and skin epithelial cells were revealed by indirect immunofluorescence in sera of NZB/N mice and (NZB X NZW)F1 hybrids (B/W) 1-2 and 4-5 months of age. Similar antibodies were not found in sera of BALB/c mice. The inhibition experiments with DNA have shown that antibodies reacting with the thymus and skin epithelium differ from those reacting with the cellular nucleus. Positive reactions with the epithelium were obtained in all thymus and skin tissue samples of humans, guinea-pigs and NZB/N, B/W and BALB/c mice, including autologous tissues of NZB/N and B/W mice. Thus, antibodies reacting with thymus and skin epithelial tissues belong to autoantibodies. These autoantibodies are revealed during the first month of life before the onset of autoimmune processes. The role of these autoantibodies in the damage of thymus epithelium and the development of immunoregulatory disturbances, typical of autoimmune processes, needs further study.