Abstract. This article presents results of apoptosis detection among blood lymphocytes from the patients with autoimmune thyroid disorders, i.e., autoimmune thyroiditis (AIT) at euthyroid and hypothyroid stages, and in diffuse toxic goiter (DTG). Contents of CD95+, annexin V presenting (apoptotic) cells and TNFα in blood were analyzed. It was shown, that altered regulation of programmed lymphocyte death in autoimmune thyroid disorders is demonstrated by increased content of TNFα and CD95+ lymphocytes, being accompanied by decreased numbers of apoptotic cells in blood. Meanwhile, this pathology is expressed mostly in DTG, while being less significant in AIT at euthyroid stage, than in thyroid hypofunction. Possible mechanisms of the revealed disturbances are discussed. (Med. Immunol., 2008, vol. 10, N 2-3, pp 187-192).
Abstract. The article deals with results of studying combined effects of ethambutol and protein antigen of Мycobacterium tuberculosis upon proliferative response and cytokine-producing ability of peripheral blood mononuclear cells in patients with infiltrative lung tuberculosis prior to beginning of specific antibacterial therapy. The mononuclear blood cells were cultivated with complex protein antigen of Мycobacterium tuberculosis and ethambutol. In the patients with lung tuberculosis, a decrease in proliferative reserve of lymphocytes was detected, in absence of increased IL-2 and IL-10 secretion. The combined effect of ethambutol and protein antigen of Мycobacterium tuberculosis upon peripheral blood mononuclear cells in the patients with pulmonary tuberculosis and healthy donors was similar, and it was expressed as antiproliferative effect and selective suppression of IFNγ production.
Evaluation of proliferative and IL-2-producing activity of peripheral blood lymphocytes wasperformed, using cultural methods, in patients with drug-sensitive and drug-resistant infiltrative pulmonary tuberculosis. The cell testing was performed at basal level and following in vitro stimulation with recombinant IL-2 and M. tuberculosis antigens. It was established that clinical course of infiltrative pulmonary tuberculosis, independently on drug sensitivity/resistance of the infectious pathogen, is accompanied by suppression of spontaneous lymphoproliferation. The levels of induced IL-2 production in drug-sensitive tuberculosis proved to be increased, whereas a reserve of IL-2-secreting reactivity of blood lymphocytes was lower than in drugresistant infection. Also, it was revealed that the level of lymphoproliferative response induced by IL-2, does not depend on clinical variant of tuberculosis, whereas stimulation of IL-2 production in blood lymphocytes is attained only in cases of drug-resistant tuberculosis variant.
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.
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.
В статье представлен анализ данных литературы и собственных исследований, касающихся молекулярно-генетических механизмов нарушений антимикобактериального иммунитета. Обсуждается роль факторов, определяющих особенности течения и исход туберкулезной инфекции, а именно состояние системы иммунитета, особенности биологических свойств инфицирующего микробного штамма Mycobacterium tuberculosis (генотип, спектр лекарственной чувствительности/резистентности), влияние комбинированной противотуберкулезной химиотерапиии. Высказывается мнение, что данные факторы необходимо принимать во внимание для разработки методологии персонализированной профилактики и коррекции нарушений иммунитета при туберкулезе легких.
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.
In this article results of research of lipid peroxidation activity and enzymes of antioxidants protection parameters in lymphocytes of blood in 25 girls teenagers with autoimmune thyropathies are presented. It is shown, that in teenagers with autoimmune thyroiditis and diffusive toxic struma lipid peroxidation activity does not undergo the expressed rejections while the contents of restored giutathione, activity of catalase and enzymes of giutathione cycle in lymphocytes of peripheral blood change. Thus disbalance of antioxidants systems in lymphocytes in teenagers with autoimmune thyroiditis in a stage of euthyroidism is more expressed, than at diffusive toxic struma.