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IgA is an important component of the mucosal system of the body. It limits penetration of pathogens into the bloodstream. Inflammatory diseases such as Crohn disease and colitis may be associated with disorders of IgA synthesis. Both B1 and B2 cells are a source of IgA in the intestines. Special attention is paid to B1 cells, which are able to respond to T-independent type 2 antigens and produce natural antibodies. B1 cells produce about 50% of the intestinal IgA including specific antibodies to the components of microorganisms contained in the gastrointestinal tract. The mechanism of IgA formation in the T-independent way is not investigated in details. It was suggested that the γδТ-cells promote switching to IgA synthesis by B1 cells. This assumption may be supported by their co-localization with B1 lymphocytes in the intestinal mucosa, as well as participation, along with B1 cells, in formation of the first-line defense against the pathogens. In addition, the both lymphocyte subpopulations evolve during initial ontogenesis, earlier than “classic” В2 and αβT cells. Therefore, it was suggested that γδT lymphocytes may be involved into the processes of induction and/or regulation of IgM and IgA production by B1 cells in response to TH2 antigens.In the present study, we have shown the effect of γδT cells upon generation of IgM- and IgA-forming B1 cells in response to α-1,3-dextran in vitro. We also studied the dynamics of the mRNA expression for IgM- and IgA-heavy chains by the B1 cells at different terms of in vitro culture.It was found that, during co-cultivation of B1 cells with 20% γδT lymphocytes, there is no increase in the number of dextran-specific IgM-producing cells. The B1 cells exhibited an increase of IgM heavy chain mRNA expression in response to dextran but not in co-cultures. Expression of mRNA for IgM heavy chains in co-cultures was decreased compared to non-treated B-cell cultures. Contrary to the earlier assumption, a presence of γδT lymphocytes in culture did not enhance the formation of IgA producents. The obtained data suggest regulatory properties of the γδТ lymphocytes during the B1 cells response to T-independent antigens.

Currently actively discussed the role of innate immunity receptors, in particular TLRs in the immunopathogenesis of bronchial asthma (BA). The aim of our work was to study the expression of ТLR2 and TLR4 on the nasal mucosal cells and peripheral blood leukocytes of patients with BA of different severity. The study included 40 children with asthma (3-12 years) and 10 healthy children. Methods: real-time PCR, flow cytometry and multiplex immunofluorescence analysis evaluated the levels of pro and anti-inflammatory cytokines (IL-1β, IL-1ra, IL-6, IL-8, IL-10, TNFα) in nasal swabs. The result of the study hyperactivation of the factors of innate immunity at the level of the mucosal of the nasal cavity in patients with asthma, manifested by increased gene expression of TLR2, TLR4, and production of proinflammatory as well as anti-inflammatory cytokines. Correlation between cytokine levels and the severity of asthma. In the peripheral blood identified a significant increase in the expression of TLR2 and TLR4 on circulating CD14 + monocytes in children with BA. Thus, the increase of gene expression of TLRs mucosa of the nasal cavity, increase surface expression of TLR2 and TLR4 on circulating monocytes of patients with bronchial asthma compared to healthy children. The revealed changes indicate the involvement of the system of TLRs in the immunopathogenesis of bronchial asthma. In the future, TLRs can be used as markers to predict the course of ad and possible therapeutic targets.

Specific perinatal infections make about 30% in causal structure of infant mortality. Among the respiratory diseases of perinatal period, pneumonias take a special place, due to higher frequency, severity, complications and adverse outcomes. The aim of this work was to study microflora and factors of innate immunity (TLR2, TLR4, HBD-1, HBD-2, TNFα and NF-kB) at the level of the mucous membranes of the upper respiratory tract during intrauterine infection of fetus and perinatal pneumonia. Causal structure of ventilator-associated pneumonias at the intensive care unit represents a broad spectrum of pathogens with high resistance to antibiotics. Changes of immunological parameters (recognizing structures, i.e., TLR2, TLR4, HBD-1; HBD-2 defensins; proinflammatory TNFα cytokine and NF-kB transcription factor) in patients with intrauterine infections and pneumonia are ambiguous. Decreased expression of TLR2, TLR4 genes, along with increased of TNFα and NF-kB gene expression. These changes correlate with type of infectious pathogen, thus allowing us to assume that the pathogen, due to pathogenicity factors, may directly affect innate immunity mechanisms.

Toll-like receptors (TLR) are involved into innate immune recognition of microorganisms, including pathogenic bacteria. The aim of this work is to assess relative levels of TLR2 and TLR9 expression in cervical epithelial cells of women with inflammatory diseases of pelvic organs. The total group of patients consisted of 47 persons, including 20 women with urogenital infections, and 27 women comprised a control group. Using real-time PCR, we identified the opportunistic pathogens and gene expression levels of TLR2, TLR9 in the cervix epithelial cells. It was shown that expression of TLR9 in the group with urogenital infections was 13.7-fold higher than in control group. We have revealed that a significant increase of TLR9 expression in the mucosal epithelium from cervical canal correlated with detection of infectious pathogens in the samples.

Treatment of malignant tumors is among challenging issues of clinical medicine. Dissemination and matestasis of tumor cells plays a major role in oncology, being immediately dependent on chemotaxis of tumor cells. Hence, the aim of our study is to evaluate migration of tumor cells, in terms of ligand-mediated chemotaxis of a human U 937 lymphoma cell line. Synthetic TLR ligands (DNA_lig, RNA_lig) were used as chemoattractants. Assessment of time-dependent TLR expression by the migrating cells (including TLR2, TLR3, TLR7, TLR9) was carried out by means of real-time PCR, using Boyden’s chamber system for the migration assays. We have revealed an increased cell migration towards DNA_ lig and TNFα gradient. Expression of TLR2, TLR7 and TLR9 was found to be increased under the influence of TNFα (respectively 1.5-, 4- and 19-fold). Under the influence of DNA_lig, TLR9 expression was 105-fold increased, whereas TLR3 expression was 2-fold higher, along with decrease of TLR2 expression. Expression of TLR 3 was shown to be 3-times higher under the influence of RNA_lig. The effects observed could be potentially applied for suppression of tumor cell chemotaxis by means of these ligands and by influencing different pathways of chemotaxis regulation.