Decades of research on the mechanisms of immunological protection against Mycobacterium tuberculosis, the causative agent of tuberculosis (ТВ), did not allow us to draw a final conclusion about the relative importance of specific pathways when forming protective immunological memory. The BCG vaccine, being the only so far approved tuberculosis vaccine protects children from severe forms of ТВ infection. It is still unclear why BCG does not save from primary infection, reactivation of ТВ and latent carrying. At the same time, the association between BCG vaccination and a reduced risk of non-mycobacterial infections, allergies, cancer and general mortality has been demonstrated. Such nonspecific effects of BCG are dependent mostly on the innate immune cells, rather than on specific memory Т cells. There is evidence of an adjuvant effect of BCG vaccination with respect to the humoral immune response to a variety of childhood vaccines. This review is focused mostly on the analysis of works aimed at studying the relatively recently identified mechanism for generating the non-specific effect of the BCG vaccine, i.e., development of induced natural immunity. This phenomenon is mediated by NOD2 signaling and epigenetic macrophage modification and, due to BCG vaccination, leads to enhanced capacity of macrophages to produce TNFa and IL-6 in response to stimulation by BCG-nonrelated microorganisms or TLR ligands. Induced immunity does not only reshape transmission of immunological signals between the cells of innate immune system, but also induces profound changes in the balance of metabolic pathways, such as glycolysis, oxidative phosphorylation, metabolism of amino acids and fatty acids, being accompanied by enhanced ability of innate immune cells to respond to the secondary stimulation. Realizing these intracellular processes opens up new opportunities for therapeutic intervention into the regulation of immune processes accompanying infectious and inflammatory diseases. In general, an in-depth study of the non-specific component of BCG vaccination should lead to emergence of new ideas about the mechanisms of its protective action, as well as affect development of a new ТВ vaccine. This knowledge can stimulate changes in global vaccination policy, aiming for optimization of vaccination benefits and reduction of childhood morbidity and mortality, as well as decrease of the post-vaccinal complications.

Phenotypes of asthma and allergic rhinitis are classified depending on the prevailing direction of the immune response the T lymphocyte profile and spectrum of cytokines that regulate the subpopulations of T lymphocyte helper cells. Therefore, the studies on the pathogenesis in various phenotypes of allergic respiratory diseases, and assessment of structural and functional characteristics of Th17 lymphocytes and interleukin 17 are relevant. The purpose of the present study was to analyze the subpopulations of Th17 lymphocytes and IL-17A, IL-17F interleukins in children with atopic asthma and allergic rhinitis. Materials and methods: a comprehensive assessment of structural and functional characteristics of T helper cells was carried out in 60 children aged 3-11 years with a verified diagnosis of atopic asthma. In 44 children (73.33% of total) bronchial asthma was combined with allergic rhinitis, and 30 healthy peers formed the control group. The population and subpopulation composition of blood lymphocytes was assessed by flow cytofluorimetry using monoclonal antibodies to CD3, CD4, CD8, CD19, CD45RA, CD45RO and CD196. To determine the intracellular content of IL-17, monoclonal antibodies against IL-17A (clone REA1063) labeled with PE-Vio770, isotypic control of antibodies against REA (Miltenyi Biotec GmbH, Germany) were used. The contents of total, specific IgE and interleukins IL-17A and IL-17F were determined by the enzyme-linked immunosorbent assay in the blood serum. Statistical processing of the results was performed using the “Statistica 10” applied software. When studying functional and quantitative characteristics of immunocompetent cells in children with atopic bronchial asthma and allergic rhinitis, a sufficient variability was revealed for relative and absolute numbers of CD3+CD4-CD8+, CD3+CD8+CD45RA+ and CD3+CD4+CD45RA+CD45RO"T lymphocyte subpopulations in peripheral blood, without significant differences with appropriate parameters in healthy controls (p < 0.001). A significant increase in the number of T lymphocytes was found in children with atopic bronchial asthma, with respect to CD3+CD8+CD45RA"CD45RO+ subpopulation (p < 0.001), the differentiated population of CD3CD4 positive T helpers (p < 0.05), and the Th effector subpopulations expressing both isoforms of CD45RA and CD45RO receptor (p < 0.01). The proportion of CD4CD45RO positive memory cells in children with atopic bronchial asthma and allergic rhinitis proved to be lower (p < 0.001), and the number of CD8+CD45RO+T lymphocytes, on the contrary, was higher (p < 0.025) than in the group of healthy controls. A diagnostically significant increase in the absolute and relative amounts of T helper 17 type with detectable changes in their functional characteristics, i.e., by the CCR6 chemokine receptor (CD196) expression levels, and presence of IL17A interleukin in children with atopic asthma and allergic rhinitis. The contents of this T helper 17 type subpopulation, and concentration of interleukins IL-17A, IL-17F in the blood serum of children with atopic asthma and allergic rhinitis showed the variability of functional and quantitative characteristics of cells that depended on the prevalence of allergic inflammation, evident imbalance in the interleukin 17 system, and the influence of Th17 lymphocytes on various aspects of inflammation and bronchial hyperreactivity associated with Th1 and Th2 response.

Current urgency of studying the intrathecal cellular immune response to infections of central nervous system is determined by limited knowledge on existing data about mechanisms of the brain immune protection in normal and diseased state. Implication of multi-colour flow cytometry in clinical laboratory diagnostics allowed to perform detailed studies of biological liquors, including cerebrospinal fluid (CSF). Currently, however, there are only scarce data on the lymphocyte subpopulations in CSF. Appropriate reference values remain a challenging issue. A study of CSF lymphocyte pool in absence of definite results at previous examination may be a potential way to resolve this problem. These clinical conditions include acute respiratory viral infections (ARVI), presenting with pseudomeningitidis (meningism) syndrome. The aim of this work was to characterize the subsets of lymphocytes from CSF of the children with ARVI with the meningism symptoms in order to get basic (control) values for diagnostics of inflammatory brain diseases. We have studied subpopulation composition of the CSF lymphocytes form in 27 children with ARVI complicated by the meningism (pseudomeningitidis) by means of flow cytometry using FACSCalibur analyzer with BD MultiTEST IMK Kit reagents. The data evaluation was performed with FlowJo software. We have studied relative contents of the main subsets, i.e., total Т cells (CD3⁺); Т helpers (CD3⁺CD4⁺Th); cytotoxic T cells (CD3⁺CD8⁺CTL); natural killers (СD3^-CD16⁺CD56⁺NK); В cells (CD3^-CD19⁺), and minor lymphocyte subpopulations: double-positive (DP) (CD3⁺CD4⁺CD8⁺); double-negative (DN) (CD3⁺CD4^-CD8^-) T cells; NKT (СD3⁺CD16⁺CD56⁺); CD3⁺CD8^bright, CD3⁺CD8^dim, CD3^-CD8⁺NK. Statistical evaluation was carried out with standard GraphPad Prism 5 software. Among the main lymphocyte populations in CSF, T cell were predominant (96.2%), as well as their subpopulations, i.e., CD4Th (53.4%), and CD8⁺CTL (28.2%), with low amounts of NK (2.2%) and B cells (0.7%). The mean relative content of minor subpopulations (DN or DP T cells, and NKT cells) was, respectively, 5.3, 4.0, and 9%. Age dependence was revealed for the contents of major and minor lymphocyte subsets. With advancing age of the children, the relative numbers of CD3⁺ and CD4⁺Тh cells in CSF increase, as well as CD4/CD8 ratio, associated with decreased share of NK cells, like as DN and CD3⁺CD8^dimТ cells. The results obtained are reflect some features of lymphocyte pool in CSF of the children without inflammatory process in CNS. Thus, they may be referred as control values (inflammation-free brain disorders) when studying immune pathogenesis of neuroinfections and other inflammatory diseases of CNS in the children from different age groups.

It is known that the immunological component of nearly any dysregulatory pathology is manifested by the development of new functional systems providing adaptation reactions, as well as by the presence of allostasis, reflecting other forms that are different from the normal parameters, and variants of mutually supporting relationships that occur at different structural and functional levels of the body. A long stay in the areas of military campaigns inevitably has a negative impact on the re-adaptation for civilian life, and it is accompanied by occurence of pathological functional connections that lead to dysregulation of the basic functions, including those of nervous and immune systems. In this regard, we studied the features of immune cell functioning in the patients with early forms of chronic cerebral ischemia accompanied by hyperlipoproteinemia, and we have made a comprehensive assessment of the factors characterizing morphological and functional state of endothelium. A representative survey included 87 patients who participated in the Afghan campaign with early forms of cerebral circulatory failure. The subjects exhibited objective and subjective signs of underlying vascular disease, typical to the earliest manifestations of chronic cerebrovascular insufficiency (CVVN) manifesting as headache, dizziness, noise in the head, memory impairment, decreased performance. All the patients underwent a comprehensive examination, i.e., expanded lipidogram, determination of vasoactive factors in the blood and cultural fluid, the number of circulating desquamated endotheliocytes, thus reflecting morphological signs of endothelial damage, additional ultrasound Doppler sonography of the main vessels, transcranial Doppler and electroencephalography were carried out.

It is known that endothelial cells are independently capable of modulating vascular tone, depending on the current clinical condition, and it may be also subjected to remodeling rearrangements with involvement into the pathological process, e.g., in atheromatosis. In this regard, endothelial dysfunction is a key factor in developing vascular pathology, affecting the systemic level. According to results of the study, it has been established that the main progression mechanism for the early forms of CVVN is the development of endothelial dysfunction. The condition has multifactorial genesis in which immune mechanisms are directly involved. Hyperlipoproteinemia established in more than 90% of cases, is one of the most important metabolic triggering factors for development of immune reactions, which is also promoted by imbalance of vasoform and thrombogenic factors, by presence of oxidative and nitrosative cellular stress markers which generally contribute to increase in cerebral vascular remodeling and the basis for the formation of organic pathology of the central nervous system.

Hormonal and immunological characteristics of have been studied in individuals with initial autoimmune thyroiditis who have first- and second-degree relatives with autoimmune diseases. The age of the studied group of patients was 31±14 years, 60 women and 7 men. All the patients were examined by clinical, laboratory and instrumental methods in accordance with examination standards for autoimmune thyroiditis and type 1 diabetes mellitus. In addition, A, M, and G serum immunoglobulins and autoantibodies to insulin, pancreatic cells were determined. In patients with autoimmune thyroiditis, regardless of the presence / absence of a family history of autoimmune diseases, we have found an increase (p < 0.01) in total cholesterol content (by 63.6-65.9%), basal hyperglycemia (by 20-25%), higher thyroid-stimulating hormone (by 79-104%) in presence with decreased thyroglobulin levels (by 8-17.8%; p < 0.01), in comparison with the control group. There was a significant increase in postprandial glucose and glycated hemoglobin (p < 0.01) in patients with autoimmune thyroiditis and type 1 diabetes, in cases of familial autoimmune diseases, as compared to the controls. In all patients of the study group, there was a significant (p < 0.001) increase in autoantibodies to thyroperoxidase, compared with controls, and within the subgroup with co-existence of type 1 diabetes and autoimmune diseases in the family (p < 0.005).

At the same time, the patients with autoimmune thyroiditis and type 1 diabetes mellitus with aggravated family history for autoimmune diseases have shown a significant increase of insulin autoantibodies, and to own pancreatic components (p < 0.005) when comparing with subgroup of patients without type 1 diabetes and, compared with a subgroup of patients without family history of type 1 diabetes mellitus and other autoimmune disorders.

Increased IgA and IgG in blood serum (p < 0.05-0.001) can be traced, regardless of the presence of type 1 diabetes and familial autoimmune anamnesis. Increase of humoral immunity indices was significant in the persons with autoimmune thyroiditis accomplished by the type 1 diabetes in families with autoimmune diseases, in comparison with patients without type 1 diabetes (p < 0.005) and without burdened family history (p < 0.01). Hence, we have registered more pronounced changes in thyroid hormones, the contents of autoantibodies to a number of surface and internal structures of endocrine organs, as well as serum immunoglobulins in the persons with autoimmune thyroiditis accomplished by type 1 diabetes in hypothyreosis with first- and second-degree relatives with autoimmune diseases, in comparison with patients without burdened family history. Therefore, the diagnosis of at least one autoimmune disorder in a family member increases the alertness of patients and doctors, thus contributing to the early detection of autoimmune diseases.

The level of thyroid stimulating hormone is one of the diagnostic indicators of thyroid function. In subclinical hypothyroidism, its concentration in the blood serum increases, while the level of thyroid hormones remains normal. One of the reasons for this is the phenomenon of macrotyrotropinemia, in which the macro isoforms of thyrotropin (a complex of thyrotropic hormone with immunoglobulin) are present in the blood. It is assumed that the biological activity of macrotyrotropin is low, and may accumulate in the circulation, causing a falsely elevated level of thyroid-stimulating hormone in serum. The aim of this study is to identify the nature and prevalence of the macrothyrotropinemia phenomenon among patients with subclinical hypothyroidism in presence of autoimmune thyroiditis and a group of healthy donors. Materials and methods: Fifty serum samples of venous blood served as the material for the study: 30 patients with subclinical hypothyroidism in presence of autoimmune thyroiditis; 10, with manifesting hypothyroidism, 10 conditionally healthy donors without thyroid gland pathology (control group). The group was derived from results of the clinical laboratory at the Clinical Hospital at the Kazan station railway. Patients’ blood serum was screened for the presence of macrotrorotropin by polyethylene glycol precipitation method, followed by analysis by gel filtration chromatography. Results of this study were as follows: screening of blood sera was performed by gel filtration and affinity chromatography. Polyethylene glycol was shown to precipitate 50 to 100% serum thyrotropin, of which true macrotrothropin makes 56-98%. In the patients with subclinical hypothyroidism with a thyroid-stimulating hormone level of more than 10 pIU/ml, a trend towards an increase in the level of macrothyrotrophinaemia has been shown. The content of macrotyrotropin complex in patients with subclinical hypothyroidism, in whom the level of antibodies to thyroperoxidase is > 500 U/L, is significantly higher if compared to the patients with manifesting hypothyroidism. Elevated levels of antibodies to thyroperoxidase can lead to the generation of macrotyropin. Our findings have shown that the phenomenon of macrothyrotropinemia is quite common in patients with subclinical and manifesting hypothyroidism with Hashimoto thyroiditis (53.3%) and in control group (25%). Macrotyrotropin complex probably consists of thyrotropin and IgG. Patients with a thyroid-stimulating hormone level of > 10 pIU/ml are candidates for screening for the presence of the macrotyrotropin complex.

The activity of the autoimmune process may correlate with the phenomenon of macrothyrotropinemia. The results can be used to develop an additional tool when choosing therapy in clinical practice.

Immunopathogenesis of rheumatoid arthritis (RA) is characterized by polyclonal activation of B lymphocytes, changes in their subpopulation composition, impaired peripheral tolerance, increased activation and differentiation of B cells, as well as deficient negative selection. Peripheral blood phenotypes of B1 and B2 lymphocytes, their correlation and response patterns in seronegative variant of articular RA type A decrease in B1 lymphocytes along with increased degree of clinical activity and duration of RA has been revealed. B2 lymphocytes remained the predominant subpopulation in peripheral blood. The studied parameters of B2 lymphocytes in the patients with disease duration of up to 5 years and more were higher than the data obtained in a control group. However, no significant changes in their dynamics were revealed upon comparative analysis. With increasing degree of clinical activity, the decreased activation potential of B2 lymphocytes was revealed, along with reduction of costimulatory signal transmission via the CD40/CD40L complex. Hence, detection of B1 and B2 lymphocytes in various types of RA may be used as diagnostic and prognostic markers.

Sarcoidosis is an inflammatory disease of unknown etiology, characterized by development of necrosis-free epithelioid cell granulomas, resulting in hyperactivation of various cells of the immune system. The role of humoral mechanisms in the pathogenesis of sarcoidosis is less studied than cell-mediated. It is necessary to study the role of activation or the anergy of the B cell development of immunity in sarcoidosis, the degree of its activity and the characteristics of the clinical course of the disease. Our study was aimed at investigating the characteristics of the B cells subsets in the peripheral blood of patients with chronic sarcoidosis (n = 41), depending on the activity of the disease. The control was peripheral blood samples from healthy volunteers (n = 43). Objective clinical and instrumental criteria, angiotensin converting enzyme (ACE) were used to determine the activity of the disease. Using flow cytometry analysis of peripheral blood cell B cells were determined based on two approaches: expression of IgD/CD38 (“Bm1-Bm5” classification) and IgD/CD27. In patients with sarcoidosis there was a significantly higher relative number of Bm2 "activated" naive cells" (IgD⁺CD38⁺) than in conditionally healthy volunteers, 65.38% versus 55,66% (p < 0.001). The relative and absolute contents of eBm5 (IgD^-CD38⁺) and Bm5 (IgD^-CD38⁺) memory cells were significantly lower in the group of patients with sarcoidosis relative to the control group. Relative values: 6.59% versus 13.31%, (p < 0.001), and 3.43% versus 8.49%, (p < 0.001), respectively. It was shown that with an increased level of ACE in the peripheral blood of patients, the number of naive Bm1 cells (IgD⁺CD38^-) was significantly reduced, r = -0.557, p < 0.001. The relative content of memory B cells that did not switch the class of synthesized antibodies (IgD⁺CD27⁺) in the group of patients was reduced to 6,25%, and in the control group — 12,95% (p<0.001). The number of memory cells that switched the class of synthesized antibodies (IgD^-CD27⁺) was also significantly reduced in patients with sarcoidosis and amounted to 6.75% versus 16.50% in the control group (p < 0.001). In patients with high levels of ACE, there was an increase in the relative content of naive B cells (IgD⁺CD27^-), r = 0.532, p < 0.001. An inverse relationship was established between the number of memory B cells (IgD⁺CD27⁺) and ACE levels, r = -0.565, p < 0.001. These results indicate the important role of the B cell immune response in the pathogenesis of sarcoidosis and make it possible to evaluate the characteristics of the humoral response with various degrees of disease activity.

Disturbances of programmed cell death are at the heart of many immunopathological processes in tuberculosis. The relationship between activity of apoptosis and severity of immune response is of particular interest in the patients with fibrous-cavernous drug-resistant pulmonary tuberculosis at different extent of the process. The paper concerns features of apoptosis, proliferative activity of lymphocytes, cytokine’s production and subpopulation composition of peripheral blood lymphocytes in the patients with uni- and bilateral fibrous-cavernous drug-resistant pulmonary tuberculosis. It was shown that apoptotic rates in the examined patients is closely related to extent of pathological process. Extent of early and late apoptosis and, accordingly, the number of living cells reflected the progression degree of destructive process in the lungs affected by fibrous-cavernous tuberculosis. The possibility of predicting the extent of destructive changes in affected lungs based on expression of apoptosis markers is presumed. Index of activity for early apoptosis of T lymphocytes, exceeding normal values by 25% and higher were clinically significant. A clear relationship between the immune response and apoptosis level was revealed. Ambiguous changes of immunological parameters were shown with increasing apoptosis associated with the severity of destructive changes. Increased apoptotic cell death in all patients with fibrous-cavernous tuberculosis, regardless of extent of the process, was associated with inhibition of antigen-specific proliferative response, decrease in CD25⁺ lymphocytes, increased numbers of B cells, along with decreased production of IFNγ, IL-8, and increased IL-2 response to PPD. In cases of unilateral destruction, increased apoptotic rates were accompanied by a decrease in the CD95⁺ cell numbers, and a decrease in TNFα production. On the contrary, in patients with bilateral destruction it was characterized by a high content of CD95⁺ lymphocytes, increased production of TNFα and IL-10. An index of extremely unfavorable course of the process is a combination of high apoptosis levels and low antigen-specific response with low expression of CD25⁺ cells, increased number of CD19⁺ and CD95+ lymphocytes, decreased production of IFNγ, IL-8 and increased production of IL-2, TNFα, IL-10. The relationships found in the work indicate that the combined assessment of apoptosis indexes, together with immunological parameters, has a higher informative value when assessing the state of immunocompetent cells, the origin of the process and trends for its development. Detecting the features of programmed lymphocyte death, in conjunction with immune parameters, allows to evaluate the role of apoptosis in each single case and to predict the course of the process, with subsequent justification of immunotherapy administration.

The aim of this study was to evaluate production of cytokines by the blood immune cells in patients of different age groups with invasive non-specified type mammary ductal carcinoma, with or without metastases. Production of cytokines by periphery blood immunocompetent cells, either spontaneous and stimulated with polyclonal activators, was assessed in 82 patients with invasive mammary ductal carcinoma. The concentrations of IL-6, IL-8, IL-10, IL-17, IL-18, IL-1p, IL-1ra, TNFa, IFNy, G-CSF, GM-CSF, VEGF и MCP-1 were determined by solid-phase enzyme-linked immunosorbent assay. The patients were divided into 2 age groups: the first group consisted of 48 patients from 45 to 60 years old; the second group consisted of 34 older patients (61 to 75 years old). Metastases in local lymph nodes were documented in twenty patients from the first group and nine patients from the second group. The younger patients (45-60 years old) with metastases in local lymph nodes showed higher polyclonal activation index of IL-4 and IL-1ra production, when compared to the patients without lymphatic metastases. As for the older patients (61 to 75 years old), their polyclonal activation index of IL-6, IL-8, IL-1ra, G-CFS, GM-CSF production was significantly lower in cases of local lymph nodes metastases. The latter was due to higher level of spontaneous production, which suppressed the influence of polyclonal activators. The index of polyclonal activation upon production of cytokines in patients with lymphatic metastases was shown to be significantly higher for the age group of 45 to 60 years than in the age group of 61 to 75 years old. This fact suggested a highly stimulating effect of polyclonal activators in patients younger than 60 years. It was found that correlation between the index of polyclonal activation of cytokine production, and the indexes of ER, PR, HER2/NEU and Ki-67 receptor expression, which are used for the determination of molecular genetic subtype of the tumor, differ significantly for the distinct age groups.

At the present time, there is no common point of view to the role of circulating neutrophils (NP) in emergence and development of neoplasia. It is suggested that due to high functional plasticity, the neutrophils may exhibit both pro- and antitumor activity. In order to study the NP phenotype at different stages of cervical neoplasia (CN), we have evaluated their absolute and relative amounts, myeloperoxidase activity, spontaneous and induced NST-test markers, and the level of intracellular cationic proteins. Spontaneous production of elastase and active forms of matrix metalloproteinases, the levels of IL-2, IL-8, IL-18, IFNy, G-CSF were determined in the NP cell lysates and in blood serum. The formation of extracellular traps (NET) was evaluated using 1-day cultures of Saccharomyces cerevisiae as an inducer. We examined 31 patients with cervical intraepithelial neoplasia (CIN) and 21 primary patients with cervical cancer (CC, Ia stage according to FIGO scale), as well as 25 practically healthy women. We revealed increased spontaneous and inducible oxygen-dependent cytolytic and phagocytic activity and spontaneous production of NET if compared to normal values, along with decreased absolute NP numbers in patients with CIN, thus suggesting the antitumor activity of NP. The levels of “pro-tumor” cytokines (MMP-9, IL-2 and G-CSF) become increased over normal levels as early as at the CIN stage, both for the neutrophils and blood plasma. High levels of regulatory IFNy and neutrophil-priming IL-8 in blood plasma do not presume any use of exogenous NP-activating factors at the stage of cervical dysplasia. At the initial stage of cervical cancer, the absolute NP amounts are significantly increased compared to normal counts. However, despite increased spontaneous oxygen-dependent cytolytic activity, the NPs have a significantly reduced activity of phagocytosis and sharply increased spontaneous production of NET, thus, generally, being characteristic to the “pro-tumorous” NP phenotype. IL-2 levels are elevated, and MMP-9 values are still increased in NP and blood plasma of patients with CC (stage Ia). Hence, the obtained results suggest some changes of NP phenotype to a pro-tumorous pattern during transition from intraepithelial dysplasia to cervical cancer. These results allowed us to design an algorithm for examining women with suspected cervical cancer, including IL-2 measurement in blood serum, and MMP-9 amounts in the NP lysates.

We performed a comparative evaluation of natural antibodies (e-At) to glutamate and GABA, the bioregulators of, respectively, excitatory and inhibitory systems in the people who differ in physical activity and its duration. The study included those athletes who are intensely engaged in Greco-Roman wrestling (22 cases), ice hockey (42 cases). The control group consisted of volunteers performing a complex of fitness exercises (42 persons). The relative contents of natural neurotransmitter antibodies in blood serum was determined by the solid-phase ELISA technique, using a synthetic conjugated glutamate and GABA antigens for sorption on the analytic plates. With increasing physical activity determined by the coaching schedule, a significant increase in the level of GABA and glutamate antibodies was found in the groups subjected to strenuous exercise, compared to the controls. For wrestling athletes, a consequent measurement of glutamate and GABA antibodies was performed, with an interval of 14 days for each period. The zero point of the first stage was characterized by the absence of physical activity, being increased at later terms. We have established experimentally an interrelation between changes in immunological parameters and physical loads at different time periods of Greco-Roman wrestling. There was a gradual increase in antibodies to these neurotransmitters after the first stage of sport exercises. However, a statistically significant change in their level was observed only by the end of the third training period. In hockey players, a comparative ELISA testing of natural antibodies to glutamate and GABA showed a significant change in the level of antibodies to neurotransmitters compared with appropriate parameters of control group. We have also noted distinct features of the antibody content in hockey players if compared with Greco-Roman fighters. The content of GABA and glutamate antibodies for the group of hockey players examined was initially significantly higher than in control group, and remained on these levels throughout the entire training process. These results may indicate a different functional state of the body before exercise. Statistical evaluation of the data obtained has revealed some individual patterns of serum antibody contents in athletes. At initial terms, most hockey players, either at rest and under physical load, showed a scatter in the contents of GABA antibodies. After enhanced physical loads, the number of athletes with higher levels of glutamate antibodies was increased. The data obtained may indicate to a degree of GABA-and glutamate-dependent regulatory systems involvement into various stages of physical training.

The aim of our work was to investigate the herd immunity to influenza viruses among population of Russia during autumn 2918; evaluation of severe cases of the infection over the season of2018-2019 epidemics, and confirmed cases of influenza in vaccinated persons. A total of 1835 samples of blood serum were studied. Neither sample did react in hemagglutination inhibition test with highly pathogenic A(H5N8) and A(H7N9) viral strains. 41 to 58% of samples, dependent on sampling region, showed significant antibody titers (> 40) against против вакцинного штамма the vaccinal A/Michigan/45/2015 strain (H1N1pdm09). 40 to 63% of the same sera were positive for epidemic A/Lipetsk/1V/2018 strain (H1N1pdm09), isolated at the start of epidemic season (26.11.2018). From 26 to 46% of the samples were seropositive towards vaccinal strain A/Singapore/ INFIMH-16-0019/2016 (H3N2), and 10 to 23% towards Yamagata influenza B genetic strain. Severe influenza cases during the 2018-2019 epidemic season were caused, mainly, by influenza A virus, with predominance of A/H1N1pdm09 (52.5%), with only 3% of cases caused by influenza A viruses. 217 cases of influenza with lethal outcome were confirmed, of them about a half of these cases (44.7%) affected older persons (> 60 years old), 29% were diagnosed in the group of 46-59 years old. Eight lethal cases of influenza infection (3.7%) were documented in the persons vaccinated before the vaccination season. Over 75% of patients with lethal influenza cases had concomitant diseases, with cardiovascular disorders, obesity, diabetes, urogenital diseases, infectious diseases (HIV, hepatitis) being most often. Hence, vaccination against influenza remains the most effective protective tool, especially in the risk groups. The study was performed in the frames of the state task contract (ГЗ-1/16 and ГЗ-2/18).

We provide the data on distribution of IL-1β and IL-1ra cytokine concentrations in nasal secretions from the patients with different forms of chronic polypous rhinosinusitis. The control group (group 1) included healthy persons. The second group consisted of patients exhibiting chronic polypous rhinosinusitis (CRS-NP), free of clinical signs of purulent inflammation in paranasal sinuses and/or bronchial asthma. The patients of group 3 were diagnosed with chronic purulent polypous rhinosinusitis (CPRS-NP). Group 4 consisted of the patients with chronic polypoid rhinosinusitis complicated by bronchial asthma (CRS-NP + BA). Cytokine concentration was determined by means of ELISA tests for all the patient groups. We have found that the local concentrations of IL-1ra and IL-1β cytokines were significantly different (p < 0.05) from the group of healthy individuals, dependent on the clinical forms of chronic polyposis. IL-1β concentrations in the group of patients with CRS-NP (No. 2) were increased 5-fold, for group of CPRS-NP patients (No. 3), these levels showed a 15.5-fold increase. In the group of patients with CRS-NP + BA (No. 4), the Il-1 levels were 13fold higher in comparison with healthy controls. The IL-1ra concentration in the group of healthy people (No. 1) was 1825.64+463.70 pg/ml. Upon development of CRS-NP (No. 2), an increase in its values up to 3646.21±263.39 pg/ml was registered. Upon development of CPRS-NP (No. 3), an increase in appropriate values up to 2305.33±282.86 pg/ml was noted, and, in cases of CRS-NP + BA, a decrease in its values to 956.15±213.02 pg/ml was observed.

Meanwhile, a conflicting character was revealed for the changes in these cytokines, thus preventing their usage as an indicator of polyposis severity. At the same time, estimation of the CIL-1ra/CIL- 1β ratio in nasal secretions of the patients in groups 1, 2, 3 and 4 based on two-dimensional projection of the spatial CIL-1ra/ CIL-1β distribution provides a basis for discrimination of the patient groups. The CIL-1ra/ CIL-1β ratio as assessed for nasal secretions of patients belonging to groups 1, 2, 3, and 4 shows a general, statistically significant decrease with increasing severity of chronic polyposis (p < 0.001), thus making this parameter indiformative for intensity of the pathological process. The resulting 95% confidence intervals confirm that the cytokine ratios are promising parameter in order to estimate the efficiency of immune therapy.

The incidence of glaucoma is rather high in different countries, being the leading cause of visual loss in the population, thus presuming relevance of the search for new and informative methods of diagnosing this disease. According to modern views, changes of local interleukins seem to be important for the glaucoma pathogenesisis. The aim of present study was to improve diagnosis and prognosis of primary open-angle glaucoma on the basis of information content of interleukins at the local level. The study was conducted on the basis of S. Fyodorov Intersectoral Research and Technology Complex “Eye Microsurgery”. The main group of patients consisted of 109 patients with primary open-angle stage II glaucoma. The age of glaucoma patients ranged from 58 to 75 years with a median of 62.4±2.5 years. The control group consisted of 52 persons without glaucoma at present and in past, the average age of which did not differ significantly from the members of the main group, i.e., 59.6±2.8 years (p > 0.05). The studies of interleukin content in lacrimal fluid was carried out by means of the Multiscan enzyme immunoassay (Finland) using common sandwich-variant of solid-phase enzyme immunoassay with R&D Diagnostic Inc. test systems (USA). The diagnostic significance (informativeness) for local interleukins was calculated according to the generally accepted formula. Statistically significant changes in the levels of lacrimal interleukins were revealed in the patients with primary open-angle glaucoma. The highest increase in the content of local interleukins was found for IL-2 (8.4-fold) and IL-17 (8.3-fold). The content of IL-8 was also increased significantly in the lacrimal fluid of patients with primary open-angle glaucoma. However, the changes in the studied local anti-inflammatory interleukins proved to be multidirectional: the level of IL-4 in the formed primary open-angle glaucoma was significantly increased, and the level of IL-10, on the contrary, was decreased. Evaluation of diagnostic significance by the local interleukin levels showed the maximal informative value for IL-2 (J = 637.4), and IL-17 (J = 612.8), which indicates their leading role for diagnostics of primary open-angle glaucoma. High level of information content is typical for IL-8 (J = 572.5). Using regression analysis for the most informative interleukins in lacrimal fluid, we have developed a mathematical model that provides a high-probability prediction (P < 0.001) of primary open-angle glaucoma. Lacrimal concentrations of IL-2, IL-7 and IL-8 are the most informative indexes of lacrimal fluid for the diagnosis and prediction of primary open-angle glaucoma.

Ischemic heart disease (IHD) represents significant medical issues, due to high prevalence of the disorder, permanent progressive course, being a leading cause of mortality. With respect to important role of vascular wall inflammation in IHT sipported by the inflammatory macrophages, Т cells and NK cells, one should conclude that their activation markers may play certain role in evaluation of intensity of immune inflammation, and, therefore, they could be used for prediction of health consequences for the patients. Hence, the aim of this study was to assess diagnostic value of soluble co-stimulatory molecules, as well as adhesion molecules in the patients with effort angina and acute coronary syndrome. In the course of controlled clinical study, we have examined 48 patients with IHD, of both genders at the age of 55 to 70 years, as well as 15 healthy persons aged 50 to 70 лет. The main group of IHD patients was divided into 2 subgroups: the 1st subgroup included 25 cases with effort angina, functional class 2-3; the 2nd subgroup consisted of 23 patients admitted to the clinic with acute coronary syndrome with ST elevation on ECG, and GRACE score of 125 to 140 points. The mean age of the observed patients was 68.5±5.0 years old). In the course of the study, serum contents of adhesion molecules (sICAM-1, sVCAM-1, leukocyte (L) and platelet (P) selectins), like as sCD28, sCD40, sCD40L, sCD80, sCD152, sFas, sFasL were measured by means of immunoenzyme technique. The data analysis has shown an increase of sCD152 levels by 77.8% (р = 0.026); sCD40 elevated by 22.2% (р = 0.038), and sVCAM was increased 1.98-fold (р = 0.011) in the effort angina patients. Similarly, we revealed a decrease in L- and P-selectins, respectively, by 51.6% (р = 0.029), and 29.0 % (р = 0.04), as well as decrease of sСD80 by 77.1% (р = 0.026); sCD40L by 30.8% (р = 0.041), sFas by 54.4 (р = 0.038), sFasL на 32.5% (р = 0.043). In acute coronary syndrome, if compared to control group, an increase in sCD152 was found by 61.1% (р = 0.029); sCD40 by 29.6% (р = 0.041); sVCAM-1 was elevated 3.16-fold (р = 0.001), along with decreased concentrations of L-selectin by 71.6% (р = 0.025); P-selectin by на 32.1% (р = 0.043); sCD80 by 76.4% (р = 0.023); sCD28 by 48.1% (р = 0.038); sCD40 by 29.6% (р = 0.046); sCD40L by 28.2% (р = 0.045); sFas by 48.5% (р = 0.041); sFasL by 12.5% (р = 0.05). The patients with acute coronary syndrome, in comparison with effort angina, exhibited a diminished L-selectin expression by 41.3% (р = 0.033); sCD28 by 30.1% (р = 0.036); sFasL by 29.6% (р = 0.041); sFas by 12.5% (р = 0.06), whereas sVCAM-1 levels were increased by 59.0% (р = 0.027). The examined patients with IHD exhibited increased levels of serum sCD152, sCD40 and sVCAM-1, along with decreased expression of L- and P-selectins, sCD80, sCD40L, as well as sFas and sFasL. In presence of acute coronary syndrome, a more pronounced drop in L-selectin, sVCAM-1, sCD28, sFasL and sFas expression like as relative increase of FasL over Fas levels. L-selectin is the most precise marker of acute coronary syndrome, with informativity of 91% and diagnostic threshold of 7.7 ng/mL (95% CI, 78-98%), as well as FasL with informativity of 93% (84-99%) and diagnostic value of 3.1 ng/mL. The detected changes of the markers studied in acute coronary syndrome, in particular, increased FasL levels and diminished CD28 presume a possible pathogenetic relation between development of the IHD exacerbation and imbalance between T-regulatory lymphocytes and Th17 helper cells as well as pronounced apoptosis activation of endotheliocytes in coronary arteria.

Prevalence of threatened miscarriage is 16-25% of all pregnancies. The symptomatics of the threatened miscarriage in the first trimester may develop due to conversion of initial inflammatory reaction that disturbs the intersystemic and local interactions in the endometrium, followed by placental insufficiency, intrauterine fetal affection and spontaneous abortion. The aim of our work was to study the association between single nucleotide polymorphisms (SNPs) of some cytokine genes, e.g., IL-1β (C511T, rs16944), IL-17A (G197A, rs2275913), IL-12B (A1188C, rs3212227), TNFα (G308A, rs1800629), and IL-4 (C589T, rs2243250) and the risk of early reproductive losses among residents of Adyghe Republic (RA). The work was carried out at the Immunogenetic Laboratory of our Research Institute of Complex Problems. The allelic variants of cytokine genes were detected by SNP-method in 106 samples of genomic DNA in women with the threatened abortion in 1st trimester (n = 58) and the uncomplicated gestation (n = 48). SNP-typing of polymorphic variants of cytokine genes IL-1β, IL-17A, IL-12B, TNFα and IL-4 was carried out by PCR (polymerase chain reaction) with allele-specific primers and electrophoretic detection of results on test systems of (Litech, Moscow). Statistical analysis of experimental data was carried out by SPSS Statistical program 17.0. The correspondence of SNP distributions to expected values at Hardy—Weinberg equilibrium and comparison of allelic variants/ genotypes frequencies were performed using the χ² criterion (Chi-square with Yates correction), odd ratios (OR) detected at significance level p < 0.05 and 95% confidence interval (95% CI). Reliability of the differences for the SNP frequencies for small samples was evaluated using the Fisher’s exact criterion. Heterozygous variant (C511T; OR = 3.46; 95% Cl: 1.04-11.54) and homozygous “mutant” genotypes (T511T; OR = 5.71; 95% Cl: 1.12-29.09) of the main proinflammatory IL-1β was significantly associated (p < 0.05) with the risk of developing threatening miscarriage in the Adygea residents. The -511Т allele of IL-1β gene, and -1188C variant of IL-12B gene increase the risk of the early termination of pregnancy, respectively, 5.8-fold (95% Cl: 2.4213.92; p = 0.00004), and 2.97-fold (95% Cl: 1.23-7.19; p = 0.01). The “mutant” -511T allelic variant of the IL-1 p gene is associated with the risk of developing a symptome complex of threatening miscarriage in Russian ethnic group (p = 0.0001; OR = 14.09), and in Adygea ethnic group (p = 0.02; OR = 8.17), which is almost undetectable in women with normal pregnancy in the first trimester. Thus, only С511Т (rs16944) in IL-1β gene and A1188C (rs3212227) in IL-12B gene of the five typed cytokine genes may be used as marker polymorphisms of gestational distress for the women in Adygea.

The aim of the present study was to evaluate the clinical efficacy of a standardized combination of three muramyl peptides containing a residue of meso-diaminopimelic acid (Polymuramyl), as well as effects of this immunomodulator on the lymphocyte subpopulation profile, function of circulating neutrophils, and concentrations of serum immunoglobulins in the patients with chronic recurrent pyoderma. Thirty-five men (34.5±10 years) with exacerbation of chronic pyoderma (osteofolliculitis, folliculitis, sycosis, furunculosis) were randomized into two groups matched by age and clinical manifestations of the disease. In the comparison group (n = 17), the patients received standard treatment. In the main group (n = 18), in addition to the same standard treatment, the patients received intramuscular injections of Polymuramyl at a dose of 200 mg daily from day 1 to 5 of the study. The overall assessment of the treatment efficacy was performed on the day 14, and at 1 and 6 months of observations. Induction and maintenance of complete clinical remission were assessed as “significant improvement”; induction and maintenance of partial remission were considered to be “improvement”; persistent signs of skin inflammation and lack of remission were assessed as “lack of effect”. Immunological parameters were studied on days 0 and 14, and then at 1 and 6 months of the study. Addition of Polymuramyl to the standard treatment caused a marked tendency towards increased proportion of the patients with «significant improvement» or «improvement» on the day 14: total ratio of the patients with any clinical improvement was 24% higher, and the relative number of the patients with "lack of effect" was five-fold lower than in the comparison group (p=0.076). A trend towards improved clinical efficacy, according to the above criteria, was maintained after 1 and 6 months of the study. At 6 months of the follow-up, the proportion of patients without pustules/furuncles in the main group (9 out of 18) exceeded that in the comparison group (3/17, p = 0.047). Significant inter-group differences and dynamics of indicators of neutrophil functions, subpopulation composition of lymphocytes and concentrations of immunoglobulins in serum were not detected. However, in the main group after the 6-month observation, there was an upward trend in the absolute number of T-cells due to CD3⁺CD4⁺ subpopulation, as well as serum IgA concentration. The results of this study are in accordance with previously published data, thus indicating the ability of Polymuramyl to accelerate regression of clinical manifestations of chronic pyoderma and induce sustained remission of this disease. At the same time, the design of present investigation and the timing of taking biological samples for laboratory tests did not allow to register significant changes in most of the studied systemic immunological parameters under the influence of immunomodulator, except for the previously described modulation at the level of pro- and anti-inflammatory cytokines.

Disturbances in the nervous system during chronic mercury intoxication (CМI) are accompanied by regular changes in the immune system. Diagnostic use of neurospecific protein markers of various pathological changes in the central nervous system is one of the promising areas of modern neuroimmunology. Prolonged exposure to the mercury vapors may cause disturbances of both CNS neurons and peripheral nerves. At the same time, the neuroimmune relationships underlying the evolving disease are not studied to sufficient grade, especially in the later post-contact period of chronic mercury intoxication. The aim of this work was to identify the relationship between the contents of antibodies to neurotrophic proteins of the nervous tissue, and changes of the neurophysiological indices characterizing the state of central and peripheral pathways in the nervous systems of the patients after chronic mercury intoxication (CMI). Our study immunological study included 30 males in the post-contact period of the CМI, who previously worked in contact with metallic mercury vapors. The clinical patterns of patients were dominated by encephalopathy, the main manifestation of which are mental disorders (more often in the form of organic asthenic disorder, or organic personality disorder with cognitive and emotional-volitional disorders of varying severity). The criteria for inclusion in the study were: verified diagnosis in all patients, written informed consent to participate in the study, a history of the harmful effects of metallic mercury vapor under production conditions. Statistical evaluation was carried out using Statistica for Windows 6.0 software. The levels of neurotrophic antibodies (AT), somatosensory evoked potentials (SSEP), electroneuromyography (ENMG) data were studied in terms of assessing the relationship between changes in specialized structures of the nervous tissue, and the state of the central and peripheral neural pathways in the patients after chronic mercury exposure. The following correlations were found: those between the concentrations of antibodies to endorphin p ф-END) and changes in central conducting structures, as well as between antibodies to proteins S-100, MBP, GFAP, NF-200, VG calcium channel, MAG, p-END, AH-R, Ser-R, M-OR and the speed of axonal impulse conduction within various peripheral neural structures. The interrelations revealed in this study indicate to pathological changes in specialized structures of the nervous tissue, which may be used as diagnostic indicators for clinical course of CМI in the post-contact period.