O. I. Urazova

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.

Functional activity of Th-17 lymphocytes in pulmonary tuberculosis.

Increased content of CD4+CD161+IL-17A+ Th17 lymphocytes in the peripheral blood was found in patients with pulmonary tuberculosis irrespective of the clinical form (infiltrative, disseminated) and variant of the disease (drug-sensitive, drug-resistant). The elevated content of Th17 cells in pulmonary tuberculosis is associated with hypersecretion of Th17-associated cytokines IL-17A and IL-22 in vitro that was most pronounced (in case of IL-17A) in patients with disseminated pulmonary tuberculosis.

Regulation of antibacterial (antitubercular) immunity mediated by T-helper type-17 lymphocytes

An analysis of the current views on the functional and immunoregulatory role of T-helper type-17 lymphocytes (Thl7) in the anti-infectious immune response, in particular in the development of the protective immune reactions to intracellular pathogens is presented. Special attention is paid to the participation of these lymphocytes and the cytokines produced by them in immune response to the invasion of Mycobacterium tuberculosis. The molecular mechanisms, underlying the predominant development of Th17 lymphocytes and/or regulatory T cells (Treg) with the evaluation of the interconnection of these cell subpopulations in the formation of an immune imbalance in infectious pathology are studied.

Cytogenetic impairments of peripheral blood lymphocytes during infectious mononucleosis.

We performed chromosomal analysis and micronucleus test of peripheral blood lymphocytes during infectious mononucleosis. The content of lymphocytes with structural chromosome aberrations and micronuclei increased in patients with pronounced clinical and hematological signs of infectious mononucleosis (acute stage). There were cells with changed number of chromosomes. These cytogenetic abnormalities persisted both during convalescence and in the delayed period after recovery.

Factors of Th17 and Treg Lymphocyte Differentiation in Pulmonary Tuberculosis

In patients with infiltrative pulmonary tuberculosis, the increase in IL-6 secretion, the decrease in TGFβ production (in case of drug resistance of the causative agent), and unchanged level of IL-1β secretion by mononuclear leukocytes in vitro were associated with increased number of CD4+CD161+IL-17A+ Th17 lymphocytes in the peripheral blood. In patients with disseminated drug-resistant pulmonary tuberculosis, TGFβ hyperproduction promoted differentiation of CD4+CD25+FoxP3+ Treg lymphocytes with immunosuppressive activity.

LPO and apoptosis during pulmonary tuberculosis.

LPO and apoptosis in blood mononuclear cells were studied in patients with pulmonary tuberculosis before and during treatment with standard chemotherapeutics. Pulmonary tuberculosis was accompanied by LPO activation and intensification of apoptosis in lymphocytes and monocytes. These changes were observed before and after the course of intensive care. The intensity of lipid peroxidation retuned to normal, while activity of apoptosis remained high after therapy.

Subpopulation composition of peripheral blood lymphocytes in children with infectious mononucleosis.

In patients with viral and bacterial infectious mononucleosis during the acute period of disease and clinical convalescence blood content of CD72+ and CD16+ lymphocytes increased compared to normal. The count of CD8+ cells increased in viral mononucleosis during convalescence and these changes persist in delayed periods after convalescence. In bacterial mononucleosis the content of CD72+ lymphocytes return normal 18 months after convalescence.

Особенности экспрессии CCL11/эотаксина, рецептора CCR3 и эозинофильной пероксидазы в опухолевой ткани при раке желудка и толстого кишечника

The purpose of the study was to analyze the expression of CCL11/eotaxin, CCR3 receptor to eotaxin and eosinophil peroxidase (EXP) in tumor tissue and its relation to tissue eosinophilia in gastric and colon cancers. Materials and methods . 52 patients with gastric cancer and 55 patients with colon cancer were examined. The material of the study was samples of malignant tumors of the stomach and large intestine obtained during a surgery. The expression of CCL11/eotaxin, CCR3 and EXP in the tumor tissue was evaluated by immunohistochemical method. For statistical processing of the results, one-factor dispersion and correlationregression (by Spearman) methods of analysis were used. Results. High expression of CCL11/eotaxin by tumor cells is typical of stomach and colon cancers with eosinophilic infiltration of the tumor tissue. The CCR3 receptor to eotaxin on the cell membrane of infiltration of the tumor tissue in gastric and colon cancers is found in 100% of cases. Expression of CCR3 (at stomach cancer) and EXP (at stomach and colon cancers) by cells of the tumor microenvironment with eosinophilic granulocytes infiltration is significantly higher than in the cells of the tumor microenvironment without eosinophilic infiltration. Conclusion. Tissue eosinophilia in gastric and colon cancers develops due to the ability of transformed malignant cells to produce CCL11/eotaxin that mediates the attraction of CCR3-expressing eosinophil granulocytes in the tumor tissue. High level of EPX (marker enzyme of eosinophils) expression by cells of tumor microenvironment in the gastric and colon cancers with tissue eosinophilia suggests the expressed cytotoxic potential of eosinophilic granulocytes, which can be directed against tumor cells.

Expression of Galectins-1 and Galectin-3 in Stomach and Colorectal Cancer with Tissue Eosinophilia

We analyzed the expression of galectin-1 and galectin-3 in tumor tissue in stomach and colorectal cancer with and without tissue eosinophilia. Low expression of galectin-3 was detected in all patients with malignant gastrointestinal tumors irrespective of the presence of eosinophilia. Low expression of galectin-1 was detected only in patients with gastrointestinal cancer associated with eosinophilia. Association of galectin-1 expression with eosinophilic infiltration of the tumor tissue in stomach and colorectal cancer was detected.

Subpopulation Structure of IFNγ-Producing T Lymphocytes in Patients with Pulmonary Tuberculosis

The study of subpopulation structure of IFNγ-producing T cells in patients with pulmonary tuberculosis revealed a decrease in the number of CD3+ IFNγ+ cells against the background of significantly increased IFNγ secretion in vitro irrespective of the clinical form of the disease and drug sensitivity of M. tuberculosis, most strongly expressed in case of the disseminated tuberculosis. In patients with infiltrative drug-sensitive and drug-resistant pulmonary tuberculosis, increased number of Th1/Th17 lymphocytes (CD4+ IFNγ+IL-17A+) and, conversely, decreased number of blood γδT cells was detected.