The review examines in a comparative perspective the key moments of formation of innate and adaptive immune responses to different types of current flavivirus vaccines: live attenuated against yellow fever virus and inactivated whole virus against tick-borne encephalitis virus. Particular attention is paid to the ability of these different vaccines, containing exogenous pathogen-associated molecular structures, to stimulate innate immunity. Live attenuated vaccine by infecting several subtypes of dendritic cells activates them through various pattern-recognition receptors, such as Tolland RIG-I-like receptors, which leads to significant production of proinflammatory cytokines, including interferon-α primary mediator of innate antiviral immunity. By simulating natural viral infection, this vaccine quickly spreads over the vascular network, and the dendritic cells, activated by it, migrate to the draining lymph nodes and trigger multiple foci of Tand B-cell activation. Inactivated vaccine stimulates the innate immunity predominantly at the injection site, and for the sufficient activation requires the presence in its composition of an adjuvant (aluminum hydroxide), which effects the formation and activation of inflammasomes, ensuring the formation and secretion of IL-1β and IL-18 that, in turn, trigger a cascade of cellular and humoral innate immune responses. We demonstrated the possibility of involvement in the induction of innate immunity, mediated by the inactivated vaccine, endogenous pathogenassociated molecular patterns (uric acid and host cell DNA), forming at the vaccine injection site. We discuss the triggering of Band T-cell responses by flavivirus vaccines that determine various duration of protection against various pathogens. A single injection of the live vaccine against yellow fever virus induces polyvalent adaptive immune response, including the production of cytotoxic T-lymphocytes, Th1and Th2-cells and neutralizing antibodies, which may persist for up to 40 years after the vaccination. To induce and maintain protective immunity, mediated by the inactivated vaccine against tick-borne encephalitis virus, it is required: triple immunization, which results in the production primarily of neutralizing antibodies, and subsequent booster injections every 3 years. We considered the potential use of the data on immunological mechanisms of action of current vaccines to generate new highly efficient vaccines.

Pathogenesis of inflammatory bowel disease is complicated and multifactorial. T helper cells represent components of adaptive immune response, whereas Toll-like receptors, NOD-likereceptors, RIG-I-like receptors are involved in maintenance of mucosal, as well as commensal homeostasis. Aim of study was to evaluate the ability of Simvastatin and IL-1 receptor antagonist to modify the course of experimental ileitis in rats, with a focus on expression of TLR2, TLR4, NOD2, RIG-I, like as T-bet, GATA-3, RORγt, and FoxP3 transcription factors by resident lymphocytes in the small intestine. 

Experiments were carried out with male Wistar rats (5 to 7 months old). The immunopositive lymphocytes were determined by means of direct and indirect immunofluorescence technique, using monoclonal rat antibodies. 

Development of acute and chronic ileitis was associated with unidirectional tendency for increase of TLR2+ lymphocyte numbers, and decrease in total TLR4+ and FoxP3+ lymphocyte counts in lymphoid structures of ileum. Treatment of experimental animals with Simvastatin and ARIL-1 during the development of experimental pathology was accompanied by decrease of RORγt+ and T-bet+ lymphocytes, along with increasing total numbers of FoxP3+ lymphocytes. 

Simvastatin and antagonist of IL-1 receptors seem to exert a beneficial effect upon the course and outcomes in the indomethacin-induced rat ileitis model, via changing expression of pattern-recognizing receptors on lymphocytes and modulation of balance between different T helper cell subsets of intestinal tissues.

Production kinetics and some functional properties of long-lived marrow plasma cells were studied in mice immunized with T-independent type 2 antigens. Alpha (1→3) dextran was used as an antigen for immunization. The mice were immunized by dextran, and the numbers of IgM antibody producing cells were determined by ELISPOT method. The cell phenotype was determined by cytofluorimetric technique. In the area of normal bone marrow lymphocytes ~4% of T and ~85% of B cells were detected. About 35% of the cells expressed a plasmocyte marker (CD138); 3% were CD138+IgM+, and about 6% of the lymphocytes were double-positive for CD138+IgA+. Among spleen lymphocytes, 50% of T and 47% of B cells were detected. About 1.5% lymphocytes were CD138+, and 0.5% were positive for CD138 and IgM. 

Time kinetics of antibody-producing cells in bone marrow and spleen was different. In spleen populations, the peak amounts of antibody-secreting cells have been shown on the day 4; the process abated by the day 28. Vice versa, the numbers of the antibody-producing cells in bone marrow started to increase on the day 4. The process reached its maximum on day 14, and after 28th day became stationary. The in vitro experiments have shown that supplementation of bone marrow cells from immune mice with dextran did not influence their functional activity. It was previously shown for cells responding to T-dependent antigens only. 

A specific marker for the long-lived plasma cells is still unknown. However, these cells possess a common CD138 marker specific for all plasma cells. A method for isolation of bone marrow CD138+ cells was developed. The CD138+ cells were of 87-97% purity, being enriched in long-lived bone marrow cells, and produced monospecific antibodies. 

We studied biological effects of Human Leukemia Differentiation Factor (HLDF), first derived from the cultural media of human myelogenous HL-60 leukemia cells, on the production of IL-1β, IL-1ra and IL-8 by immune cells from the patients with chronic atrophic gastritis, adenomas and adenocarcinomas of the stomach. To evaluate the influence of HLDF on cytokine-producing function of the whole blood cells, the latter were incubated with this factor or without it. The levels of IL-1β, IL-1ra and IL-8 were determined in supernates of these cells. The stimulation indices of HLDF upon cytokine production were estimated as a cytokine production ratio of stimulated versus resting cells. Histological analysis of gastric mucous tissue samples and removed tumors was also performed. It was revealed that, in chronic atrophic gastritis, HLDF significantly increased IL-1ra and IL-8production. In patients with stomach adenomas and adenocarcinomas, HLDF increased IL-1ra, IL-8 and IL-1β production. In cases of stomach adenomas, the indices of HLDF stimulation upon blood cells cytokine production are significant higher than in patients with chronic atrophic gastritis. Interdependence study between the stimulation indices of HLDF and histological parameters of gastric mucosa and tumor samples have shown a negative correlations between the stimulation index of HLDF upon IL-1ra production and the grade of intestinal metaplasia and dysplasia of the adenoma epithelium, and a positive correlation between the stimulation index of HLDF on IL-8 production and the intensity of lymphoid infiltration of the adenomas. In patients with gastric adenocarcinomas, a positive correlation between the stimulation index of HLDF on IL-8 production and number of blood vessels with tumor embolus was revealed. One may presume that immune cells activation caused by HLDF may exert following actions: (1) triggering some processes of chronic inflammation that underly malignancy development, and (2) the mechanisms restricting the disturbances of epithelial regeneration. Finally, the results of HLDF effects depend on balance between proand antioncogenic cytokines produced by immune cells. 

The aim of present study was to investigate the relationship between phenotypic features of monocytes and intensity of “respiratory burst” in the patients with renal cell carcinoma (RCC). A total of 73 patients with RCC (Т3N0М0, clear cell type) participated in the study. Phenotyping of blood monocytes was performed by flow cytometry. The level of “respiratory burst” in monocytes was determined using spontaneous and zymosan-induced luminol- and lucigenin-dependent chemiluminescence. Suffficient changes in phenotypic structure and intensity of “respiratory burst” were identified in peripheral blood monocytes of the patients. Alterations of monocytic subpopulations in RCC were characterized by increased numbers of cells with the CD14lowCD16+ (“non-classical”) phenotype. The imbalance in expression of activation markers was found among monocyte populations from cancer patients; we have revealed a reduced number of monocytes expressing HLA-DR-antigen, and increased number of CD64-positive cells. Meanwhile, intensity of “respiratory burst” in the total monocyte population proved to be reduced in RCC patients. In this case, the characteristic features of the “respiratory burst” intensity distribution among monocytes were as follows: in RCC, a reduced “respiratory burst” activity was found in monocytes with CD14+CD16- phenotype, being, however, increased in the monocytes with CD14+CD16+ and CD14lowCD16+ phenotypes. Such redistribution may be due to increasing role of the given monocyte subsets in immunopathogenesis of renal cell carcinoma. 

A search for associations between allelic variations of immune response genes, and mitral stenosis associated with rheumatic heart disease, represents an important task when studying the pathogenesis of cardiovascular disorders among inhabitants of large industrial regions in Western Siberia. Among multiple polymorphisms of interleukin-encoding genes, a particular attention should be paid to association studies of some intronic polymorphisms with variable numbers of tandem repeats (VNTR). In this respect, genotyping of interleukin 1 receptor antagonist genes (IL-1ra86bp VNTR) and interleukin 4 (IL-470bp VNTR) has shown positive associations between the intron 2 IL-1ra*3R/3R microsatellite polymorphism, intron 3 IL-4*2R/2R variant, and the risk of mitral stenosis development in patients with rheumatic heart disease (OR = 12.71; p = 0.0001). 

The goal of present study was a search for pathogenetical reasoning of an opportunity for prolongation of pregnancy complicated by premature rupture of membranes at a gestational term of 22-34 weeks. The patients were subject to due observation and expectant treatable of pregnancy with prevention of possible infectious and inflammatory complications, as well as monitoring of systemic inflammatory response markers, immune state, and cytokine profile of blood in pregnant women with this disorder. 

We conducted a comprehensive clinical and laboratory examination of fifty pregnant women, whose pregnancy was complicated by premature membrane rupture at 22-34 weeks of gestation. A control group consisted of 40 women with normal pregnancy. For assessment of cellular composition of the blood, a BC3000+ hematological analyzer was used. Distinct subsets of peripheral blood lymphocytes were studied by flow cytometry using monoclonal antibodies («FACS Calibur» «Becton Dickinson», USA). Blood levels of cytokines (IL-2, IL-6, IL-8, TNFα, IL-4, IL-10) were determined by ELISA using test systems (ZAO “VectorBest”, Novosibirsk, Russia). Stereoultrastructural study of membranes was performed with a scanning electron microscope «Hitachi S-450”. 

The findings suggest that the failure of membranes emerging du to systemic metabolic disorders and changes in peripheral blood cells (leukocytosis, lymphopenia due to CD19+ B lymphocytes). Moreover, one could observe reduced counts of CD16+CD56+ T cells (natural killer cells) that showed certain parallelism with increased levels of proinflammatory cytokines (IL-6, IL-8, TNFα) in blood from pregnant PROM, as well as a decrease in IL-10 and IL-4 contents antagonized their proinflammatory effects to certain extent. An opportunity of incomplete pregnancy prolongation for patients with premature rupture of membranes was based on thorough assessment of their somatic and obstetric status and general condition of the fetus, when adequate and comprehensive therapy was applied. In the course of pregnancy prolongation, we found a progressive increase in pro-inflammatory cytokine levels (IL-2, IL-6, IL-8, TNFα), a steady decrease in CD19+ B cell counts, CD3+СD4+ helpers, natural killer cells, increased levels of cytotoxic CD3+CD8+ T cells .The pathogenesis-based criteria for necessary termination of the pregnancy for women with PROM are identified, including an increase in acute-phase proteins levels in blood, development of neutrophilic leukocytosis, lymphopenia, increase of pro-inflammatory cytokine levels in blood (IL-1β, IL-6, IL-8, TNFα), along with progressive reduction of CD3+СD4+ lymphocytes, CD16+CD56+ and CD19+ В lymphocytes. 

Fifty patients with chronic autoimmune urticaria (CAU) and forty-eight patients with chronic idiopathic urticaria (CIU) have been examined. Blood serum contents of IL-4, IL-10 and IL-17A, spontaneous and induced cytokine production in blood cells, as well as polymorphism of IL-4 (C-589T), IL-10 (G-1082A), IL-17A (G-197A) cytokine genes has been studied. No differences have been detected when studying IL-4 levels, depending on genetic variants of IL-4 gene in patients with CAU and CIU. Increased IL-10 amounts in patients with CIU still did not show any correlations with IL-10 genotype (G-1082A). Increased IL-17A levels in patients with CAU were associated with homozygous genotype of AA in comparison to control group, and with heterozygous GA genotype, in comparison to CIU group. The revealed differences of cytokines` genes polymorphism in CAU and CIU provide a molecular-genetic evidence for different clinical forms of chronic urticaria. 

The study deals with parameters of luminol-dependent and lucigenin-dependent chemiluminescence (CL) of peripheral blood neutrophils from patients with bladder cancer (BC) prior to surgical treatment.

We examined sixty patients (45 to 55 years old) with advanced bladder cancer (TNM) prior to the operation, and forty-six patients at 10 days after surgical treatment. A control group consisted of 56 healthy donors. Luminol-dependent and lucigenin-dependent chemiluminescence of blood neutrophils was assessed according to De Sole et al. (1983).

Chemiluminescence assays of peripheral blood neutrophils from the patients with bladder cancer revealed changes in production of reactive oxygen species (ROS), both for initial stage of oxidation reaction, and total level of active oxygen radicals. We have found disturbed values of primary-to-secondary ROS ratio in the cells.

In the patients with bladder cancer, some changes in oxidative metabolism of the blood neutrophils have been registered. These alterations may play an important role in promotion of potential effector cell functions, thus, probably, affecting the whole-scale development of a cytopathic effect exerted by neutrophilic granulocytes. 

The work is dedicated to studies of interrelations between the cytokine contents in the liquid from anterior eye chamber (AEC), and development of systemic immune response to ocular tissue antigens, described in terms of an anterior eye chamber-associated immune disturbance (ACAID phenomenon). The immune assays were conducted in parallel, using multiplex cytokine analysis (flow cytometry technique), and leukocyte inhibition migration reaction. Twenty-six patients with different forms of ophthalmic pathology were examined, including cases of uveitis (18), keratouveitis (3), glaucoma (5). It is shown that the reduced TGF-β1 levels and increased concentrations of proinflammatory, chemotactic cytokines in AEC liquid are associated with development of organ-specific immune sensitization. 

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