Abstract. Daily IgA production in human organism comprises 3 to 5 g, thus exceeding total synthesis of other Ig classes. IgA in human body is presented by 9 structural variants. Its molecules belong to two subclasses, IgA1 and IgA2, the latter represented by two allotypes. In human serum, IgA1 monomers predominate, that are produced by the bone marrow cells. Mucosa-associated lymphoid tissues produce dimeric IgA1 and IgA2 molecules containing an accessory polypeptide J-chain. When transported across epithelial layer to the mucosal surface, an extracellular segment of polymeric IgA receptor (pIgAR) is joining the dimeric IgA1, which becomes a ‘secretory’ component being a part cesretory IgA (sIgA) molecule. The main function of sIgA is to bind bacteria and viruses at the mucosal surfaces, thus preventing pathogens to invade the internal spaces of the organism (immune exclusion). If transferred across epithelium, IgA may neutralize the viruses penetrating the cells, like as bind and deliver proteins and other antigens to the mucosal surface. The leukocyte IgA receptor (FcαRI, CD89) is expressed on the neutrophils, eosinophiles, monocytes/macrophages, as well as dendritic and Kupffer cells. The cytoplasmic domain FcαRI is devoid of an activation ITAM motif. To transduce signal, an FcαRI-associated chain of Fcγ receptor is used. Due to this mechanism, IgA binding leads to activation of phagocytosis, endocytosis, antigen presentation, synthesis of proinflammatory mediator and other immune functions. Fcα/μR receptor is a structural homologue of pIgR, and it is able to bind IgA and IgM, being, however, expressed only at the surface of mature B lymphocytes and macrophages. Interaction of IgA with asialoglycoprotein and transferrin (CD71) receptors, like as with some other molecules, that have yet undetermined role in immune defense and development of pathological events.

Abstract. The aim of the present study was to determine the different profiles of the immune responsiveness of the patients with fibro-cavernous pulmonary tuberculosis to PPD from M.tuberculosis in comparison with their response to standart mitogen and IFNγ. A pronounced specific Th1 response was found, evidenced by the enhanced proliferation and IL-2 and IFNγ production after contact of their peripheral blood mononuclear cells (PBMCs) with PPD. At the same time a high frequency of PPD-anergy was shown: сonsiderable proportion of TB patients was characterized by low proliferative response to PPD coupled with the low levels of IL-2 and IFNγ. Most of the patients revealed failure of monocyte/macrophage oxidative burst in response to PPD. Additionally a positive correlation was found between the levels of their PBMC’s oxidative burst and IL-4 production.

Abstract. Local immune responses of mucous membranes of an organism are the first and most significant barriers preventing many virus infections, including influenza. The barrier against influenza infection is the mucosalassociated lymphoid tissue of the upper airways. It is considered, that nasopharyngeal-associated lymphoid tissue (NALT) in rodents is an equivalent of lymphoid tissue in human Waldeyer’s ring. Present work is the first attempt to analyze and compare the development of cellular and antibody immune responses in NALT in a mouse model of experimental influenza infection using a pathogenic influenza A (H1N1) virus and an attenuated reassorted (2/6 genetic formula) live influenza A (H1N1) vaccine.

It was shown, that the vaccine strain inherits the ability to induce high-grade local antibody responses like as the virulent parental strain. However, the vaccine strain is inferior to virulent parental strain in capacity to stimulate production of circulating antibodies. Both parental and Р 2/6 strains are equally able to induce lymphoproliferative immune response in NALT lymphocytes. The attenuated reassortant virus is able to stimulate proliferation of Th (CD4+), B-cells (CD19+) and CTL (CD8+) in NALT. As shown by the cytokine activity testing (IFN-γ, IL-6), the attenuated reassortant virus activates both Th1- and Th2-lymphocytes in NALT.

Abstract. The goal of this work was a multiplex single-step evaluation of the levels of stimulated cytokine production in the supernates of cultivated mononuclear cells from healthy Caucasian individuals. We compared the levels of cytokines for various groups. In Th1 cells, the production of INF-γ is typically greater than production of IL-2. Analysis of Th2-derived cytokines demonstrated predominance of IL-10 production over other cytokines. Furthermore, we observed in healthy donors a significantly stronger production of IL-13 as compared to IL-4. These cytokines function as co-stimulators of proliferation for pre-activated B-cells.

When performing pairwise comparisons of the growth factor concentrations, we have shown higher levels of G-CSF production than that of GM-CSF, thus reflecting predominance of differentiation stimuli for granulocytopoiesis over monocytopoiesis in bone marrow of healthy humans.

Among pro-inflammatory cytokines tested, the significantly higher TNF-α production is prevalent. Low levels of ConA stimulated IL-7 production from the bone marrow stromal cells, which activates complete differentiation of T- and B-lymphocyte progenitors, might be due to low mitogen activity for the non-lymphoid cells.

Abstract. Vascular endothelial cells (VECs) are able to induce HIV1 replication in СD4+ Tcells, thus determining their resistance for apoptosis. The revealed facts are specific to EC/Tcell culture and are stipulated by the cellcell interactions between the VECs and HIV1 producing cells, thus being a consequence of activation of ‘productively infected’ T cells.

Abstract. Forty-two patients with progressive vulgar psoriasis (PASI = 19.7 ± 1.5) and 40 healthy volunteers were under investigation. Psoriatic patients were characterized by increased number of CD4+ CD95+ peripheral blood T lymphocytes, which correlates with clinical psoriatic score, and by increased levels of soluble Fas (sFas) in serum, as compared to controls (resp., 1868.1 ± 186.8 pg/ml vs. 1281.4 ± 142.5 pg/ml, PLSD = 0.019). The levels of spontaneous lymphocyte apoptosis and anti-Fas (Mab)-induced apoptosis in psoriatic patients did not differ from the controls. However, apoptosis induced by “oxidative stress” (50 M Н202, 4 hrs) was depressed in the patients. Moreover, a simultaneous assessment of cell cycle structure (metachromatic staining with Acridine Orange), apoptosis and Fas receptor expression (AnnV-FITC/antiFas mAbs-PE staining) following a short-term mitogenic stimulation (PHA-P, 5 µg/ml, 24 hrs) were performed. We found no marked differences in mitogenic reactivity, activation-induced apoptosis, and activation-induced Fas receptor expression when studying lymphocytes from healthy donors and psoriatic patients. However, PHA-activated lymphocytes from psoriatic patients displayed a significantly decreased ratio of AnnV+CD95+ to the total AnnV+ subpopulation, thus suggesting a decreased role of Fas-dependent mechanisms of apoptosis during the cell activation. The data obtained confirm a view, that an abnormal lymphocyte “apoptotic reactivity”, which plays a crucial role in the mechanisms of autoimmunity, may also of importance in the pathogenesis of psoriasis.

Abstract. In present study, a comparative analysis of spontaneous and LPS-stimulated production of Th1/ Th2 (IFN-γ/IL-4, IL-13), and monocyte-derived pro- and anti-inflammatory cytokines (TNF-α/IL-10) was carried out in blood cell cultures of healthy donors and the patients with chronic viral hepatitis complicated with liver fibrosis and cirrhosis. The patients’ cells exhibited an increased production of both Th1/proinflammatory and Th2/anti-inflammatory cytokines. Meanwhile, hepatitis-induced cirrhotic transformation correlates with enhancement of spontaneous IL-4 and IL-13 production (not observed in fibrosis patients), and progressive increase of spontaneous IFN-γ, TNF-α and IL-10 secretion. In turn, the progression of cirrhosis is connected with increase of pro-inflammatory blood activity and reduction of anti-inflammatory potential. E.g., the patients with grade C cirrhosis have significantly higher index of TNF-α/IL-10 and IFN-γ/IL-10 ratio, as compared to the grade A patients. Moreover, we revealed a positive correlation of TNF-α/IL-10 ratio with cytolysis and severity of cirrhosis (Child-Pugh score), and a reverse correlation between the grade of liver cirrhosis and LPS-induced stimulation index of IL-10. Predominance of pro-inflammatory cytokines, displayed as increased IFN-γ/IL-10 ratio, was also associated with presence of anemia. Hence, the profile of cytokines produced by peripheral blood cells reflects some clinical features in the patients with chronic virus hepatitis complicated with fibrosis and cirrhosis.

Abstract. Uterine leiomyoma (UL) is a hormone-dependent benign tumor of uterus. Social significance of UL is stipulated by its high rate among fertile females. Scarce data exist about the impact of cytokines in UL progression. Th1/Th2 paradigm is one of crucial points in modern immunology. Evaluation of cytokines involved into either type of immune response is of special significance for studying the diseases accompanied by the changes of extracellular matrix, e.g., leiomyomas. In present study, we analyzed peritoneal fluids from UL patients, with multiplex detection of IL-2, IL-4, IL-5, IL-10, IL-12, IL-13, GM-CSF, IFN-γ and TNF-α (Th1/Th2 panel), by means of a Bio-Plex® instrument (Bio-Rad, USA). Twenty-seven patients were observed in our study (20 patients with UL, and 7 myoma-free women (a group of comparison). The mean age of the patients was 43.5±0.6 years. The duration of UL ranged from 0 to 18 years. As a result, the levels of IL-10, GM-CSF, IFN-γ and TNF-α in patients with long-existing UL (over 5 years) were significantly higher (p<0,05) than in group with a disease story of <5 years. IFN-γ values in peritoneal fluid patients with UL did inversely correlate with uterine size. Moreover, the levels of IFN-γ in patients with smaller uterine volume (<8 weeks of pregnancy) were increased in relation to the group with larger tumor size. IL-10 contents were increased in the patients with adenomyosis, rapid and slow growth of UL, and in both types of tumor (simple and proliferative). Increased IL-5 levels were observed in the patients with single tumor nodules (as related to the patients bearing multiple nodes, and comparison group). Furthermore, intramural and subserosal location of nodes was characterized by increased levels of IL-5. In the patients free of adenomyosis, IL-5 value was increased against the comparison group. The changes in IL-2, IL-4, IL-12 and IL-13 levels in patients with UL were not statistically significant.

Abstract. The aim of present work was to study spontaneous proliferative activity of B-lymphocytes (SP-ABL) in the patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and non-specific ulcerative colitis (NSUC). In total, 128 patients with RA, 52 patients with SLE, and 29 patients with NSUC were observed. Thirty-four patients with osteoarthrosis (OA), 27 patients with reactive arthritis (ReA), 28 patients with chronic hepatitis (CH), 19 patients with chronic colitis (ChC), and 30 healthy donors comprised the control group. Significantly higher mean levels of SPABL have been revealed in the patients with RA, SLE, and NSUC, as compared to the control group. The SPABL values proved to exceed normal limits in 90.3 % of SLE patients, 82.8 % patients with RA, in 79.3 % patients with NSUC, and in 88.9 % of RA group with liver affection. Determination of SPABL may be used for assessment of immunologic activity in autoimmune inflammatory diseases.

Abstract. The effect of cytokine preparations (Interleukin-2/IL-2/Proleukin and interferon-alpha/IFN-α 2b/ Intron A) on immune cell subpopulations has been studied in the children suffering with advanced malignancies during intensive chemotherapy cycles combined with whole body hyperthermia (thermochemotherapy). It was shown that IFN-α 2b promotes recovery of peripheral lymphocyte counts in the patients. However, no sufficient changes were observed for the lymphocyte subpopulations. Furthermore, more profound lymphopenia along with increased contents of activated (CD25+, HLA-DR+) T cells occurs in a group of children treated with IL-2, as compared to the patients who received IFN-α 2b. Besides that, some differential effects upon the CD4+/CD8+ T-cell ratios were observed in the patients treated with Proleukin or Intron A, with a tendency to increase in CD4+ T-cells for the patients treated with IL-2. It was concluded that differential immunomodulatory mechanisms mediate the effects of IL-2 and IFN-α 2b in the patients with malignancies undergoing combined chemobiotherapy with whole-body hyperthermia.

Abstract. The aim of this study was to compare the efficiency of different methods applied for the diagnostics of brucellosis. Huddlson and Wright reactions, RoseBengal test, ELISA-based test system (IgG determination), and a test for antigen-binding lymphocytes (ABL) were used. There was shown that the specificity of tests was identical for either reactions based on detection of antibodies with commercial immune reagents and ELISA IgG. The sensitivity of ABL test is, however, superior to all the reactions based on antibody determination. The ABL test has advantages when compared with antibody detection techniques. This method permits early monitoring of brucellosis treatment/its efficiency since early terms, as well as differentiation between positive and false positive results of antibody determination in pregnant womеn.