Cytokine-secreting activity of blood eosinophils in pulmonary tuberculosis.

Modern immunological studies showed that eosinophilic granulocytes producing the key mediators of cellular and humoral immune response contribute to the common cytokine imbalance developing in tuberculous infection. A significant increase in BCG-induced secretion of IL-2, IL-5, and TNF-α by eosinophils in patients with pulmonary tuberculosis indicated high reserve reactivity of eosinophilic cells realizing their functional potential in regulation of the specific resistance reactions of the microorganism under conditions of M. tuberculosis infection.

[The immune stressor effects of T-regulatory cells under infiltrative tuberculosis of lungs].

The article deals with the characteristics of sup-population composition of T-regulator: cells with suppressor activity and production of immunoregulatory cytokines suppressing immune response (IL-10, TGF-beta) in patients with infiltrative tuberculosis of lungs. It is proved that the leading role in formation of immunodepression and tuberculin anergy under infiltrative tuberculosis of lungs is played by T-regulatory, cells with phenotype CD4+CD25+Foxp3+. It is demonstrated that the immunodepression mediated by cytokine production is connected with increasing of both basal and BCG-induced secretion of IL-10 on the background of decrease of level of production of TGF-beta by mononuclear leukocytes in vitro.

[Subpopulation structure of T-regulatory cells and proliferative response of blood lymphocytes in vitro under pulmonary tuberculosis].

Subpopulation structure of T-regulatory cells and proliferative activity of blood lymphocytes in vitro in patients with different clinical forms of pulmonary tuberculosis were studied in this work. It has been shown that Trn--natural T-regulatory lymphocytes (CD4+CD25+Foxp3+) play a leading role in formation of immune suppression under infiltrative, disseminated and fibrosis-cavernous pulmonary tuberculosis. Besides, their number is increased in blood of both tuberculin-positive and tuberculin-negative patients. Negative correlation between the number of Trn and proliferative activity of blood lymphocytes (basal, mitogen- and antigen-induced)has been established, which testifies about participation of Trn in suppression of lymphocyte proliferation and Th1- and Th2-immune response.

Psychoimmune interactions in women of reproductive age with endometriosis.

Psychoimmune interactions were studied in women of reproductive age with endometriosis. Pronounced immunological shifts manifested in a shift of the T-cellular immunity, resulting in imbalanced production of pro- (IL-1ß, IL-2, IFN-γ) and anti-inflammatory (IL-4) cytokines. Significant correlations between the severity of mental shifts and immunopathogenetic factors in the studied patient population demonstrated the psychoneuroimmune nature of endometriosis.

[Apoptosis-inducing action of antituberculosis drugs of the main group in vitro].

The influence of the main antituberculosis drugs (isoniazid, rifampicin, ethambutol) on in vitro apoptosis of peripheral blood lymphocytes from patients with pulmonary tuberculosis was researched. It was shown that all the investigated drugs induced apoptotic death of the lymphocytes in vitro, that could result in disturbance of antigen-specific response formation in pulmonary tuberculosis.

Allelic polymorphism of cytokine genes during pulmonary tuberculosis.

Modern immunological and molecular genetic studies showed that tuberculosis is accompanied by an imbalance in the production of immunoregulatory cytokines by mononuclear leukocytes. T allele and homozygous TT genotype of T-330G polymorphism in the IL2 gene, T allele and TT genotype of C-590T polymorphism in the IL4 gene, and CC genotype of A-1188C polymorphism in the IL12B gene are immunogenetic factors that have protective activity against susceptibility to pulmonary tuberculosis. Susceptibility to tuberculous infection is associated with A1A2 genotype of the polymorphic region +3953 A1/A2 in the IL1B gene; G allele and TG and GG genotypes of T-330G polymorphism in the IL2 gene; C allele and CC and CT genotypes of C-590T polymorphism in the IL4 gene; and AC genotype of the polymorphic region A-1188C in the IL12 gene.

[Allelic polymorphism of the IL-2and IL-4 genes in herpesvirus infection].

Herpesvirus infection is accompanied by imbalance of peripheral mononuclear production of cytokines, by polarizing an immune response by the Th2 pathway. The homozygous TT genotype of T330G polymorphism in the IL-2 gene is an immunogenetic factor that has a protective activity against susceptibility to herpesvirus infection. The risk of progression, the recurrent course of the infection and its poor outcome is positively associated with the heterozygous TG genotype in the IL-2 gene T-330G promoter region and with the homozygous CC type and C allele in the IL-4 gene C-590T promoter region.

[Effects of recurrent herpetic infection on functional activity of T-cells in patients with rheumatoid arthritis].

AIM: To evaluate effects of recurrent herpetic infection on functional activity of regulatory cell subpopulations in patients with rheumatoid arthritis. MATERIAL AND METHODS: We studied in vitro production of marker cytokines of type 1 T-helpers (IL-2), type 2 T-helpers (IL-4), type 3 T-helpers TGFbeta and type 1 T-regulators (IL-10) and counted CD4+CD25+ T-cells in the blood of patients with recurrent herpetic infection and having no clinical manifestations of Herpes virus reactivation. RESULTS: Patients with recurrent herpes had more active production of IL-10, but reduced count of CD4+CD25+ lymphocytes. CONCLUSION: IL-10 hyperproduction observed in recurrent herpetic infection may contribute to progression of rheumatoid arthritis.

[Modulatory effect of isoniazid and rifampicin in vitro on cytokine secretion in pulmonary tuberculosis].

The effects of isoniazid and rifampicin on the peripheral mononuclear production of IL-2, IL-12, IL-10, IFN-gamma, and TGF-beta were evaluated in patients with infiltrative pulmonary tuberculosis. Irrespective of the susceptibility of the causative agent to the essential antituberculous drugs, rifampicin was ascertained to initiate increased IL-2 secretion and to reduce the generation of IL-12, IFN-gamma and TGF-beta. Isoniazid suppressed the mononuclear leukocytic production of IFN-gamma in drug-sensitive pulmonary tuberculosis, and conversely, stimulated it in the drug-resistant type. Rifampicin showed a more significant negative effect on mononuclear cytokine-producing activity. In drug-resistant pulmonary tuberculosis, the imbalance of spontaneous, protein- and drug-induced mononuclear secretion of cytokines was established to be more pronounced than in drug-sensitive tuberculosis.

[The molecular-genetic aspects of tubercular infection forecasting and immunotherapy].

In article is presented, the analysis of the data of the literature and own researches, concerning molecular-genetic mechanisms of antimycobacterial immunity infringements. The role of the factors defining features of a current and an outcome of a tubercular infection, namely of immunity system condition, feature of infecting microbic Mycobacterium tuberculosis strain biological properties (a genotype, a spectrum of drag sensitivity/resistance), influence of combined antitubercular chemotherapy is disc issed. The opinion is expressed that the given factors are necessary for taking into consideration for working out methodology the personalised preventive maintenance and correction of immunity infringements during pulmonary tuberculosis.

[Role of cytokines in the modulation of lymphocytic subpopulational composition in patients with pulmonary tuberculosis].

The parameters of the lymphocytic CD-population composition and the production of cytokines in the cell cultures of peripheral blood mononuclear cells were studied in patients with infiltrative pulmonary tuberculosis. A marked reduction in the relative and absolute count of CD3+ and CD4+ lymphocytes and an increase in the level of CD8- and CD16-positive cells were established in both drug-sensitive and drug-resistant types of the disease. A significant increase in the production of IL-12 and a reduction in the spontaneous elaboration of interferon-gamma were observed in all the examinees. Addition of lipid and protein myobacterial antigens (Beijing strains) caused a notable decrease in the generation of the study cytokines as compared with the respective parameters in healthy donors and their basal secretion irrespective of the type of a tuberculous process.

Role of genetically determined production of immunoregulatory cytokines in immunopathogenesis of chronic viral hepatitides.

Immunopathogenesis of chronic viral hepatitides was studied by modern immunological, molecular, genetic methods. We revealed an imbalance in the production of immunoregulatory cytokines by mononuclear leukocytes (primarily of the Th2 type). The risk of progression and chronic course of viral hepatitides in Caucasian population was associated with alleles of promoter regions -330G and -592A in the IL-2 and IL-10 genes, respectively, as well as with the T/T genotype of the polymorphic region C590T in the IL-4 gene. The C/C genotype of the IL-10 gene promoter region C592A was shown to be a factor determining resistance to long-term persistence of hepatitis B and C viruses.

[Cytokines and antiviral immuniy].

In the review of modern literature and results of own research about role of immunoregulation cytokines imbalance system in pathogen of deep-rooted virus infections are analyzed. The question on molecular mechanisms of cytokine chain deregulation at persistent virus infections is discussed.

[Immunopathogenetic features of tick-borne encephalitis under long-term viral antigenemia].

The occurrence of chronic tick-borne encephalitis viral antigenemia characterized by the asymptomatic course or minimal clinical manifestations is caused by the virus-immune cell interaction. Cellular immunity was studied in 183 patients with chronic (more than 6-month) tick-borne encephalitis viral antigenemia, by evaluating the immunophenotypic and cytogenetic statuses, structural and functional features, cytokine profile, and peripheral lymphocytic apoptosis. The findings suggest impairments in the cooperation of immunocompetent cells and in the classical scheme of antiviral immunity regulation in tick-borne encephalitis viral persistence due to the changes in lymphocytic structural and functional properties.

[Dysregulation of cytokine production by mononuclear cells of peripheral blood in persistent infection with a virus of tick-borne encephalitis].

Tick-borne encephalitis is accompanied by dysregulation of cytokine production of mononuclear leucocytes of peripheral blood. The changes of production of IFN-r by mononuclear leucocytes of peripheral blood positively correlated with a degree of activity of pathological process and intensity of clinical symptoms of neuroninfection. On the contrary, secretion of IL-12 mononuclears directly correlated with virus persistence in the organism and does not depend on clinical presentation of the disease.

[Immunoregulatory cytokines and chronization of type C hepatitis: matching of clinical and immunological manifestations].

The study demonstrates significant changes of cytokine-producing ability of mononuclear blood leucocytes in type 'hepatitis, correlating with the degree of hepatic lesion. The results showed that various morphologic types of chronic virus type C hepatitis were associated with disbalance in production of pro- and antiinflammatory cytokines, i.e. decrease of tumor necrosis factor (TNF)-alpha concentration and a significant rise of interleukin (IL)-4 and IL-10 concentations, which were the most prominent in cases of severe hepatic fibrosis and high histologic activity of hepatitis. The study established a direct correlation between increase of the ability of mononuclear blood leucocytes to synthesize IL-4, and the progress of the pathologic process.

Molecular mechanisms of changes in TNF-alpha production by blood mononuclears in chronic viral hepatitis C.

Chronic viral hepatitis C is associated with decreased production of TNF-alpha by the peripheral blood mononuclear leukocytes irrespective of virus genotype and degree of the morphological activity of the process in the liver. This process positively correlates with the increase in the content of TNF-alpha soluble receptor (molecular weight 55 kDa), which can play a role in the mechanisms of immunopathogenesis of long persistence of hepatitis C virus in the body.

Chronic tick-borne encephalitis virus antigenemia: possible pathogenesis pathways.

Study of the proliferative potential and immunophenotype of lymphocytes and cytokine-producing capacity of mononuclear cells in patients with chronic tick-borne encephalitis virus antigenemia showed changes in T cell lymphoproliferative response, relative content of T cells and T helper inductors, immunoregulatory index, and imbalance in the production of immunoregulatory Th1 and Th2 cytokines.

[Typical changes of lymphocyte surface architectonics in chronic viral infection].

With the use of scanning electron microscopy, lymphocyte surface architectonics has been described in cases of chronic viral persistence at tick-borne (vernal) encephalitis, hepatitis types A and B, and Herpes simplex. In lymphocytic population smooth and plicate cells in addition to cells with vesicles and outgrowths on the surface prevailed. The appearance of lymphocytes with a combined type of superficial microrelief was registered. It is supposed that despite the variety of types of lymphocyte surface architectonics and possible causes promoting their polymorphism, changes in superficial ultrastructure of immunocompetent cells for chronic viral infection have a nonspecific character.