The article discusses the determining role of immunopathogenesis of the main diseases of the modern man (cancer, atherosclerosis, autoimmune, allergic and infectious diseases). In this regard, the concept of «immune paradigm» is introduced. There is evidence that any pathology is based on the classical immune response to the antigen, whether auto- or xenoantigen, with all stages of its development and parallel changes in the state of immune tolerance: its breakdown in cases of autoimmune and allergic diseases and atherosclerosis; its establishment in cases of cancer and infectious diseases. In the meantime, it is emphasized that the immunopathogenesis is based on insufficient or increased function of immunocompetent regulatory cells with suppressive activity. Here the concept of «immunosuppressive dominant» is introduced. Finally, we discuss the need for fundamental changes in treatment of these diseases, with a focus on molecular and cellular immunotherapy methods and development of integrated approaches to their application.

The immune system in critical illnesses initiates local inflammation in the damaged area. In the absence of a balance between local and systemic inflammations, an infectious or non-infectious systemic inflammatory response follows, which has a stage of "hyper inflammation - compensatory anti-inflammatory response", that may result in multi-organ failure. The final stage of critical ill-nesses, therefore, will be characterized by induced immunosuppression with the impaired function of neutrophils, monocytes, macrophages and dendritic cells and release of myeloid-derived suppres-sor cells. The aim of the review is to evaluate the contribution of various components of the im-mune response to the formation of induced immune suppression from the perspective of candidate diagnostic markers.

Over the past few decades, thanks to the use of new technologies, the spectrum of functional capabilities of neutrophil granulocytes has been significantly expanded. Their effector potential with respect to infectious agents, including phagocytosis, the production of active forms of oxygen and nitrogen, degranulation with the release of numerous enzymes and antimicrobial peptides, and the formation of extracellular traps were studied in detail. However, it has been found that many of the factors that neutrophils use to directly destroy pathogens have a regulating effect on other cells of the immune system and the neutrophils themselves. In addition, upon activation, neutrophils are capable of synthesizing a number of de novo biologically active molecules. Traditionally considered as inducers of an inflammatory reaction, neutrophils demonstrate the ability to simultaneously incorporate mechanisms that contribute to limiting and resolving inflammation. Ambivalent both helper and suppressor effects of neutrophils on cells of congenital and adaptive immunity testifies to their important immunoregulatory role both in homeostasis and various types of pathology, particularly in the development of malignant tumors.

Cytokines comprise the molecular language of communication between the cells, which is needed to maintain the homeostatic functions of the body (including the immune system) and mediate various diseases. Many aspects of inflammation, autoimmune diseases and neoplasia are associated with cytokine signaling through specific receptors. The establishment of new physiological functions of “old” cytokines and understanding the molecular and cellular mechanisms of their involvement in disease pathogenesis, as well as the search for new therapeutic targets and development of innovative approaches to anti-cytokine therapy, present a fundamental problem. When assessing the tremendous success of anti-cytokine therapy in treatment of certain autoimmune diseases, we should not forget that (a) this treatment does not eliminate the causes of the disease:autoreactive T-cell clones; and that (b) less than half of the patients respond to this therapy; and that (c) anti-cytokine therapy has serious side effects.

Microbicides are antiseptic topical drugs that help directly or indirectly inhibit the penetration of an infectious agent into the human body, thereby preventing the sexual transmission of HIV-infection and other sexually transmitted diseases. Microbicides have an antiviral mechanism of action in the sexual transmission of HIV and affect the components of mucosal immunity in the vagina. In this article, the pharmaceutical and biomedical aspects of microbicide application are examined and diverse classifications of microbicides are presented. For each group of chemicals, the most important representatives and their mechanisms of action are described. This article also presents the structure and function of mucosal immunity, and shows the importance of the mucosal immune response in the sexual transmission of HIV. This work also exhibits the experimental models for testing of candidate microbicides. For each compound described, a review of preclinical research and clinical trials is provided, covering its development as a microbicide. This paper gives an overview of microbicides, a new class of chemically diverse immunobiological medications reducing the risk of sexual transmission of HIV. The use of microbicides is believed to curb the HIV/AIDS epidemic in the nearest future.

 Interrelationship between a malignant tumor and the immunity are provided by the involvement of both adaptive and innate immune systems. Monocytes are major participants in nonspecific immune response and mediate their key function through refilling the pool of tumor-associated macrophages, dendritic cells and myeloid suppressor cells. All these populations regulate the relationship of tumor-infiltrating immunocompetent cells with tumor cells and with other components of the microenvironment, as well as tumor cell proliferation, angiogenesis, and dissemination. Monocytes, being direct participants of the chronic persistent inflammation, are involved in the inflammation impact on both tumor origin and progression. The study of the molecular mechanisms of monocyte recruitment and differentiation in malignant neoplasms seems to be a promising direction, both for a diagnostic purpose and as a search for targeting molecules for the control of macrophages and dendritic cells in the tumor microenvironment. In this review, the characteristics of peripheral blood monocytes are given, taking into account the heterogeneity of their population. Tie2+ cells and macrophage-polarized CD163+ and CD204+ -monocytes, as well as cancer-associated macrophage-like cells (CAMLs), are described as contributors to cancer disease progression and outcome. The involvement of monocyte subpopulations in the pathogenesis of oncological diseases of different localizations at the stages of the formation of monocyte precursors in the bone marrow, circulation in peripheral blood and differentiation in tumor tissue is shown.

Over the last decade the role of innate immunity has been known to be crucial for the activation of adaptive immune system. The main triggers that upregulate reactions of innate immunity are small exogenous molecules with conserved motifs, molecular patterns. The article discusses a variety of possible roles of molecular patterns in the immune mechanisms, including the participation of Allergen Associated Molecular Patterns (AAMPs) in allergic processes.

Cytokines represent a unique family of endogenous polypeptide mediators of intercellular interaction. From an immunopharmacological point of view cytokines can be marked out as a new, separate immunoregulatory molecule system and have some common biochemical properties and pleiotropic type of biological activity. In the cytokine regulatory system both reduction and elevation of cytokine levels can cause pathology. Several endogenous systems exist to control cytokine elevation and prevent tissue pathology. When synthesized simultaneously, cytokines form a cytokine chain. Deletion of any unit of this chain leads to the break in the formation of immunopathology. Cytokines as therapeutic preparations have evident advantages but also some limitations such as pharmacokinetics with short circulation period, adverse effects due to pleiotropic mode of action, and injectable drug forms. Rational design for clinical cytokine application could be linked with the development of prolonged and local drug forms or personalized cytokine therapy.

The problem of iodine deficiency remains relevant all over the world due to the widespread prevalence and the negative impact it has on human health in all agegroups. Iodine deficiency leads to a decrease in the intellectual potential of children, the development of reproductive disorders at a young age, as well as the formation of multinodular toxic goiter as the last stage of goiter transformation, accompanied by heart rhythm disturbances in middle and old age. The article covers the issues of monitoring iodine deficiency in the regions of Russia and provides data on the situation in the world on the development of future prevention programs and current prevention programs. A detailed analysis of each criterion for the severity of iodine deficiency and the effectiveness of preventive programs was carried out. Particular attention is paid to the criterion of neonatal hyperthyrotropinemia as a promising indicator for monitoring iodine deficiency.

The review is devoted to the analysis of molecular mechanisms of action of S. pyogenes virulence factors aimed at overcoming the protective functions of macrophages. The review describes in detail the main protective functions of macrophages and the mechanisms of their implementation in the course of streptococcal infection. The virulence factors of S. pyogenes, which prevent the recruitment of macrophages to the site of infection, are examined. Particular attention is paid to the analysis of molecular effects that suppress the pathogen by the process of phagocytosis, intracellular bactericidal activity and the production of cytokines by macrophages. The analysis of molecular genetic mechanisms of regulation of the expression of S. pyogenes virulence factors that provide adaptation of the pathogen to changing conditions in the site of inflammation is carried out.

Host genetic factors influencing the intracellular part of HIV live cycle and regulating of HIV-specific immune response are reviewed. Its include genes coding proteins which support viral replication and assembly of new virions, genes coding antiviral defense proteins, HLA genes and some others. Variants of these genes and its compositions affect individual succeptibility/resistance to HIV infection, influence the pathogenesis of the disease and also associate with efficacy of antiretroviral therapy.

Succeptibility to HIV and the dynamics of HIV infection progression to AIDS are dependent on unique individual factors. Revealing genetic features of natural resistance to HIV infection is of great importance for the development of effective strategies for disease control. This review presents an analysis of host gene alleles coding receptors and their ligands participating in viral entrance to target cell. These allelic variants and their combinations can have a significant influence on the individual resistance/sensitivity to HIV infection and may be associated with the HIV infection progression to AIDS.

This literature review is devoted to the analysis of the role of macrophages in the immunopathogenesis of infectious lung diseases of bacterial etiology. The article summarizes information about the origin of macrophages, their phenotypic and functional heterogeneity. The mechanisms of impaired protective function of innate immunity are associated with the polarization of the program of maturation and activation of macrophages in the direction to tolerogenic or immunoregulatory cells with phenotype of M2. Alveolar macrophages perform a variety of functions (from pro-inflammatory to regenerative) in the development of inflammation in the respiratory organs. Their inherent plasticity suggests that the same macrophages can change their phenotype and function depending on the microenvironment in the inflammatory focus at different stages of the disease. Understanding the mechanisms that regulate macrophage plasticity will be an important step towards realizing the potential of personalized immunomodulatory therapy.

The aim of the study was to investigate the features of T-lymphocyte apoptosis induced by components of autologous apoptotic cultures in vitro in norm and rheumatoid arthritis in the context of «cellular neighborhood».

Materials and methods. Subjects of the study were blood samples of patients with rheumatoid arthritis (RA) and healthy women of comparable age. Developed protocol allowed to differentially evaluate the parameters of proliferation, early and late stages of apoptosis in the «primary» (CFSE-) and «secondary» (CFSE+) induced apoptotic T-lymphocyte cultures. It was estimated the effect of cellular and humoral components of unstimulated, anti-CD3- and dexamethasone-stimulated cells under the conditions of overcrowding and depleted culture media on autologous lymphocytes, cultured under physiological conditions, in norm and RA.

Results. Comparative qualitative analysis revealed the features of the processes of T-lymphocyte apoptosis in norm and pathology. Also, the parameters of early and late stages of apoptosis of a «primary» induced culture and «secondary» induced cells after transferring the cellular and humoral components of apoptotic cultures did not differ significantly either initially or during culturing in both investigated groups. But it was a significant increase in the amount of living T-cells in «primary»-induced unstimulated and dexamethasone-stimulated RA patients’ cultures compared to similar donors’ cultures.

Conclusion. There was no difference between stimulated with anti-CD3 antibodies cells and the «secondary» induced cultures. Taking into account the absence of significant differences in the parameters of activation apoptosis, the increased number of living cells in RA patients’ cultures relative to donors’ is evidence of contribution of non-autonomous apoptosis effects to cellular homeostasis in RA.

Objective. The purpose of this study was to evaluate the length of telomeres in the arms of individual chromosomes in patients with bronchial asthma (BA).

Materials and methods. The study included patients with BA (n = 10, the mean age (44 ± 8.2) years) and healthy donors (n = 10, the mean age (44 ± 8.4) years). Metaphase spreads obtained from peripheral blood mononuclear cells were used. At the time of sampling BA patients received treatment at the Clinic of Immunopathology, Novosibirsk. BA was diagnosed by physicians according to GINA-2016. For measurement of telomere length on individual chromosome arms we used quantitative fluorescent in situ hybridization with a PNA-probe specific for telomeres. We used inverted DAPI banding for chromosome identification (according to ISCN-2013). For each individual 5 metaphase cells were analyzed. We applied the newly developed MeTeLen software to estimate the telomere repeats quantity (http:// www.bionet.nsc.ru/en/development/application-development/development-of-a-computer/metelen.html) in metaphase images. For enhanced image analysis compared with the previously developed programs, we included estimation of background signal and correction of defects of the optical system.

Results. Comparing of telomere length show, that telomeres in the certain chromosome arms (4q, 5q, 9p, 10 q, 11p, 13p, 15q, 18q, 19q) in BA are significantly shorter than in corresponding group of donors (p < 0.05, Mann – Whitney U-test). For both studied groups we also evaluated telomere sequences shortened and elongated relative to the average telomere length in the group (p < 0.05, Wilcoxon-signed-runk test). The following differences and similarities between the telomere profiles of patients and donors were determined: the telomere sequences 4p, 6q, 8p were elongated and 2q, 9q, 11p, 15q were shortened relative to the average telomere length in BA patients. Moreover, this telomere sequences did not differ from the average telomere length in the group of donors. At the same time, the telomere sequences 12p, 16p, 17p, 19p were significantly shorter, and 3p was longer than the average telomere length in both groups.

Conclusions. We guess, that the observed significant shortening of telomere length on individual chromosome arms in BA, as compared to donors, is relevant in pathogenesis of this disorder. The revealed features of telomere profile of patients with BA may be a result of different telomere length maintenance mechanisms and may influence to the development of asthma that needs further study.

Purpose. The subpopulation composition of peripheral blood lymphocytes was evaluated in patients with alcoholic liver fibrosis (ALF).

Materials and methods. The study included 62 patients with ALF; 15 patients abusing alcohol without liver fibrosis and 20 conditionally healthy donors. In samples of lysed peripheral blood, the number of cells bearing surface markers was determined by flow cytometry. In patients with ALF at terminal stages of fibrosis, significant lymphopenia was recorded with a change in the composition of the main subpopulations of lymphocytes relative to the values of conditionally healthy donors and the comparison group.

Results. We identified in the blood of ALF patients with terminal (III–IV) stage (relative to control and comparison group) of the relative number of naive (TN) and central memory T-lymphocytes (TCM) associated with an increase in the number of effector cells (TEM and TEMRA) allows us to suggest in this category of patients the direct differentiation of TN and TCM lymphocytes to effector (TEM and TEMRA), which can aggravate the course of the tissue-destructive process due to the high biocidal activity of the latter. Elevated levels of hematopoietic (CD34 and CD133) cells in the peripheral blood at the initial and moderate stages. (I–II) fibrosis (relative to control and comparison group) may be due to persistent inflammation in the liver parenchyma and an increasing imbalance between the processes of its damage and reparative capabilities. Whereas the decrease in their number at the terminal station fibrosis may indicate an increasing decompensation and depletion of the regenerative potential of the organism in the final stages of the degenerative process.

Conclusions. In general, the obtained data demonstrate new aspects of the immune regulation of the processes of fibrogenesis in chronic alcoholism.

Objective: to study the immunophenotype of the macrophage population and the mechanisms of their vectorial redistribution in fibrous cavernous pulmonary tuberculosis.

Materials and methods. The material for the study was fragments of the fibrous cavern wall and pericavernous lung tissue of the dead or surgical patients diagnosed with fibrous cavernous tuberculosis (n = 163). All patients were divided into 2 main groups: patients with active bacteria excretion (MTB+, n = 84) and patients with clinical abacillation (MTB–, n = 79) for immunohistochemistry with a panel of markers for: macrophages and histiocytes – CD68; vascular growth factor A – VEGF-A; T-helpers – CD4, and T-cytotoxic lymphocytes – CD8.

Results. Following the analysis of CD68 expression, the population heterogeneity of macrophages was revealed depending on the intensity of the cytoplasmic reaction, functional activity, localization and quantitative characteristics. Three groups were identified: highly active, moderately active and weakly active. Based on the reaction with vascular growth factor A, it was determined that VEGF+ cells correspond to weakly active CD68+ macrophages and are located on the border between the specific granulation tissue and fibrous layer as well as in the pericavernous zone and intact lung tissue with a statistically significant predominance in patients with MTB– (p < 0.05). Regardless of the scope of bacterial secretion, the number of VEGF+ cells in the lymphoid follicle zone directly correlates with that of CD68+ macrophages in the pericavernous zone (R = 0.68) and indirectly correlates with the number of diffusely scattered VEGF+ cells in the fibrous capsule (R = –0.75). In the meantime, CD68+/VEGF+ are visualized in the zone of CD8+ T-lymphocytes, and CD68+/VEGF- – in the zone of CD4+ cell clusters. Such correlation indicates the redistribution of macrophages into type 2, which has a remodeling effect on the surrounding tissues with the potentiating participation of lymphoid cells.

Aim. The study of the mechanisms of atopic disease formation and a model of immunopathogenesis of the atopic diseases.

Methods. Determination of surface lymphocytes receptors in peripheral blood of atopic bronchial asthma and atopic dermatitis patients with the help of monoclonal antibodies using the indirect immunofluorescence method. Expression of genes encoding TLR2, TLR4 and TLR9 receptors of airborne epithelial cells by real-time polymerase chain reaction, as well as determination of cytokine TSLP, IL-33, IL-4 and TGFβ (eBioscience) in airway flushes in atopic asthma patients and healthy people.

Results. During the exacerbation of atopic diseases in peripheral blood lymphocytes, an intensive activation process develops with impaired lymphocytes activating apoptosis aimed at the formation of plasma cells capable of developing intensive IgE synthesis. To search for signals that could explain the mechanism of rearrangement of the B-cell part of the immune system during atopy, the epithelium cells of the airways were examined in a group of patients with atopic asthma and found an increase in gene expression coding for TLR2, TLR4, TLR9 in 6, 3 and 2.5 times respectively. Along with increased expression of TLRs genes in patients with bronchial asthma, an increased content of TSLP and IL-33 cytokines secreted by epithelial cells of the airways was detected. These cytokines have an immunoregulatory action - their nearby antigen presenting functions format the Th2 type of immune response, promote the production of cytokines (IL-4, IL-9, IL-13) and cause the development of an allergic type of inflammation.

Conclusion. We suppose that the main link in pathogenesis is a disruption of the interaction of TLRs with the corresponding ligands caused by spontaneous dimerization of TLRs under the malonic dialdehyde influence. The intake of slowly metabolized dimers of TLRs into epithelial cells is a signal for genome activation, which leads to the synthesis of allergic cytokines IL-33 and TSLP. Thus, the main immunopathogenesis pathway of atopic diseases is the pathological functional interaction between epithelial cells and peripheral blood B-lymphocytes.

Aim of the research – to analyze secretion of vascular endothelial growth factor (VEGF) and epidermal growth factor (EGF) by blood eosinophilic granulocytes in vitro, together with an expression of VEGFR and EGFR in tumor tissue in gastric and colon cancer in association with tissue eosinophilia.

Materials and methods. A total of 52 patients with gastric cancer and 50 patients with colon cancer were examined. The material of the research included supernatants of eosinophil cultures and samples of malignant tumors tissues of the stomach and colon. Enzyme-linked immunosorbent assay was used to determine the contents of VEGF and EGF in the eosinophil culture supernatants in vitro. The expression of VEGFR and EGFR in tumor tissue was evaluated by immunohistochemistry. The results were analyzed by statistical methods.

Results. An increase in basal and r-IL-5-induced secretion of VEGF by eosinophilic granulocytes of blood in vitro was found in patients with gastric cancer accompanied by tissue eosinophilia. The concentration of EGF in the culture of blood eosinophils in vitro with the addition of r-IL-5 increased in patients with eosinophilic infiltration of tumor tissue, regardless of the localization of the pathological process,both in patients with gastric cancer and colon cancer. Eosinophilic infiltration of the tumor tissue in gastric cancer and colon cancer was combined with hypo-expression of EGFR by tumor cells; VEGFR receptor expression was not dependent on the presence of eosinophilic granulocytes in the tissue of tumors.

Conclusion. Hypersecretion of vascular endothelial growth factor VEGF and epidermal growth factor EGF (upon stimulation with r-IL-5) by blood eosinophils in vitro in patients with gastric and colon cancer with tissue eosinophilia indicates an increase in the activity of these cells. Deficiency of expression of VEGF and EGFR receptors in tumor tissue causes violation of cooperative interaction of eosinophilic granulocytes and tumor cells in malignant tumors of the stomach and large intestine.

The purpose of this study is to evaluate mRNA levels of genes encoding CD16A (FCGR3A) and CD16B (FCGR3B) in peripheral blood and tumors of colorectal cancer patients (CRC).

Materials and methods. The study included 66 CRC patients from Nizhny Novgorod Regional Clinical Oncology Center and 111 people without cancer as a comparison group from Nizhny Novgorod Regional Blood Center named after N.Ya. Klimova. The mRNA relative levels in peripheral blood and tumor was detected by reverse transcription real-time polymerase chain reaction. The mRNA levels correlation and association with CRC clinical characteristics were assessed by statistic methods.

Results. The study suggests that in the peripheral blood of CRC patients the levels of mRNA FCGR3A and FCGR3B were statistically significantly lower than in healthy individuals. The mRNA levels remained low at 7–10 days after surgery. The FCGR3A mRNA normalized level in the blood and tumors of CRC patients, as well as in the blood of healthy individuals, was several times higher than the FCGR3B mRNA level. At the II stage of tumor development in CRC patients, the FCGR3A and FCGR3B mRNA levels were statistically significantly decreased, but as the tumor progressed is normalized. Moderate degree of tumor differentiation was also characterized by a drop in mRNA levels of the tested genes. Reduced FCGR3A and FCGR3B mRNA levels in the blood of patients were observed in the absence of metastases. In tumor samples, FCGR3A mRNA was tested in 95.5% of cases, FCGR3B mRNA in 68.2% of cases. Progression of CRC was accompanied by an increase in FCGR3A mRNA level in tumors, the FCGR3B mRNA level did not change. Positive correlation of FCGR3A mRNA level with TNF and FOXP3 mRNA levels was found, which indicates the possible involvement of FCGR3A in the regulation of chronic inflammation in tumors of CRC patients.

Conclusion. Changes in mRNA levels of genes encoding CD16A (FCGR3A) and CD16B (FCGR3A) molecules were detected in blood and tumor samples. The results indicate the potential for their use as monitoring immunological markers in CRC.

Aim. In this study we aimed to investigate circulating blood cells during experimental virus-induced asthma exacerbation vs baseline.

Materials and methods. Rhinovirus 16 (RV16) experimental infections were induced in RV16-seronegative moderate and mild atopic asthmatic and healthy non-atopic subjects. PBMC from 8 mild, 12 moderate asthmatics and 6 normal subjects obtained at baseline (14 day) and at day 4 after infection with RV16 were analyzed by flow cytometry. B-cells were identified as CD19+. Monocytes were identified as MHC II, CD14high cells. The MHC II, CD14neg-low cells were further classified by CD123 and CD11c expression into myeloid DC (CD11chigh, mDC), plasmacytoid DC (CD123+, pDC).

Results. There were no differences at baseline in frequencies of blood monocytes, mDC and pDC in asthmatic compared to normal subjects, but we found increased amount of B-cells in asthma group (p < 0.05). At day 4 after RV16 infection we found decreased percentages of pDC in both moderate and mild asthmatics (p < 0.05) compared to baseline.

Conclusion. These data suggest an increased migratory potential of circulating pDCs during virus-induced asthma exacerbation. In patients with asthma pDCs could be recruited to the airways. It is possible that the distinct subsets of DCs may be recruited at different time points to the effector sites of allergic inflammation.

The aim of the study was to study the relationship between the condition of mast cells of testes and spermatogenesis in normal and with various types of testicular damage.

Materials and methods. The studies were carried out on male rats of the Wistar line. Two experimental models of testicular damage were used puncture and compression. Morphological and morphometric methods of investigation were used to study the relationship between spermatogenesis and mast cells. To assess the functional state of the testicles by chemiluminescence, a study was made of the level of total testosterone in the blood.

Results. The similar destructive processes develop in the testicle with various injuries, characterized by the presence of necrotic tubules, seed balls, a decrease in the number of spermatogenic epithelial cells, an increase in the number of non-functioning tubules, and a change in a number of morphometric parameters. The reaction of mast cells to various types of damage is manifested in the enhancement of their functional activity. So after a puncture against the background of a decrease in the number of mast cells activation of their synthetic function occurs, while in squeezing the cells respond not only with an increase in functional activity, but also with an increase in their number in the organ.

The conclusion. Disturbance of spermatogenesis in various injuries of the testis is accompanied by activation of the functional activity of mast cells, regardless of the nature of the damage. However, the increase in the number of mast cells in the body occurs only with the preservation of the blood–testis barrier. Since normal spermatogenesis is carried out against the background of a sufficiently high synthetic activity of mast cells, this reaction of increased synthesis and degranulation can be considered as compensatory.

Background. The reason why HIV-infected patients receiving highly active antiretroviral therapy (HAART) suffer from the increased immune activation remains elusive. Regulatory T-cells (Treg) are able to control immune activation, but their quantity may vary due to the infection. The aim of this work was to estimate the number and subsets of Tregs in HIV-positive patients receiving virologically effective HAART.

Materials and methods. The CD4+ T-lymphocyte (CD3+CD4+) and Treg (CD3+CD4+FOXP3+) quantities were determined by flow cytometry. Treg subsets were assessed based on the FOXP3 expression level. The state of T-cell activation was established according to the simultaneous expression of CD38 and HLA-DR molecules.

Results. It was shown that HIV-positive patients compared to healthy people have reduced CD4+ T-lymphocyte counts despite virologically effective HAART. At the same time in HIV-infected people, Treg absolute numbers were only slightly decreased. Moreover, the major part of Treg pool in their blood consisted of lymphocytes with a high level of FOXP3 expression that corresponded to the phenotype of cells with the highest suppressor activity. However, an increased relative amount of activated CD4+ T-lymphocytes was retained in the HIV-infected individuals’ blood.

Conclusion. In HIV-infected patients who received HAART in time and whose treatment resulted in an effective HIV viral load suppression and a satisfactory CD4+ T-cell counts increase, a relatively large pool of peripheral Tregs is maintained. However, these lymphocytes are not enough to fully control immune activation that develops against the background of chronic lentivirus infection.

Purpose. To study the content of cytokines and growth factors in the intraocular fluid of patients with developed stage of primary open-angle glaucoma (POAG).

Materials and methods. 56 patients with a verified diagnosis developed stage of primary open-angle glaucomawere examined. The control group consisted of 30 patients with a diagnosis of uncomplicated cataract. A concentration of 17 cytokinesand 3 isoforms of the transforming growth factor (TGF) β was determined using a Bio-Plex Pro™ Human Cytokine 17-plex Assay and Bio-Plex Pro™ and TGFβ 3-plex Assay kit by flow-through fluorometry on a Bio-Plex 200, Bio-Rad double beam laser analyzer, USA.

Results. Astatistically significant increase was shown in the concentrations of cytokines and growth factors (interleukins (IL) 4, 6, 7, 8, 12, 17, TGFβ 1, 2, 3, macrophage inflammatory protein 1 β) in the intraocular fluid of patients with developed stage of the primary open-angle glaucoma in respect to data obtained from the study of the intraocular fluid of the persons with uncomplicated cataract, as well as a statistically significant decrease in the concentrations IL-2, IL-10, granulocyte-macrophage colony-stimulating factor.

Conclusion. In the pathogenesis of primary open-angle glaucoma, the activity of the local chronic inflammatory process is determined. This is confirmed by statistically significant changes in the studied cytokines and growth factors. Increase in the concentrations of the studied representatives of the superfamily of transforming growth factors-beta, which have anti-inflammatory activity, the ability to stimulate proliferation, cell growth, synthesis of extracellular matrix proteins, etc., attests to their importance in the mechanisms of primary open-angle glaucoma development. Increase concentrations of IL-7 in the intraocular fluid of patients with primary open-angle glaucoma allows us to assume participation in the pathogenesis of the primary open-angle glaucoma of this autocrine mediator of activation of the growth of lymphatic structures.

The aim of the study was to analyze the relationship between monocyte subpopulations and phenotype/ functions of monocyte-derived dendritic cells (DCs), as well as DC sensitivity to the tolerogenic effect of dexamethasone.

Materials and methods. The study included 15 healthy donors. DCs were generated by cultivating enriched fractions of CD14+ monocytes with or without CD16+cell depletion (CD16-Mo-DCs or CD16+Mo-DCs, respectively) in the presence of interferon alpha (IFNα) and granulocyte-macrophage colony-stimulating factor (GM-CSF). Monocyte subpopulations were obtained by immunomagnetic negative selection.

Results. CD16+Mo-DCs were characterized by higher percentage of mature (CD83+CD14-) and lower number of semi-mature (CD14+CD83+) cells, but were similar to CD16-Mo-DCs by HLA-DR and CD86 expression, involved in the presentation of antigens and activation of naive T-cells. and also to co-inhibitory/ tolerogenic molecules B7-H1 and TLR-2. CD16+Mo-DCs displayed higher allostimulatory activity, which was positively correlated with CD86 expression (rS = 0.69; p = 0.027) and negatively – with TLR-2 expression (rS = -0.72; p = 0.1). Allostimulatory activity of CD16-Mo-DCs was positively correlated with the number of mature CD14-CD83+DCs and semi-mature CD14+CD83+DCs. Addition of dexamethasone (10-6 M) into CD16-Mo-DCs and CD16+Mo-DCs cultures led to the delay of DC maturation, the decrease of CD86 and the increase of TLR-2 expression, as well as the increase of cells with co-inhibitory CD86- B7-H1+ phenotype that was positively correlated with the reduction of DC allostimulatory activity. The decrease of CD86+/TLR-2+ index in CD16+Mo-DC population was due to the reduction of CD86+DCs and in CD16-Mo-DC population – to the increase of TLR-2+cells. Dexamethasone possessed higher inhibitory effect on DC maturation in the CD16+Mo-DC cultures.

Conclusion. CD14+ monocytes, both contained and depleted by CD16+ cells, can differentiate into DCs when cultured with IFNα. The presence of CD16+ cells in whole blood monocyte pool is associated with generation of DCs showed a more mature phenotype and higher allostimulatory activity. Both CD16- and CD16+ monocyte-derived DCs are sensitive to suppressive effect of dexamethasone. However, dexamethasone tolerogenic effect involves different mechanisms in CD16-Mo-DCs and CD16+Mo-DCs.

The aim of the work is to establish general regularities and features of differentiation of blood monocytes into 4 subpopulations in diseases associated with circulatory and respiratory hypoxia.

Materials and methods. 18 patients with ischemic heart disease (IHD), 12 patients with ischemic cardiomyopathy (ICMP), 14 patients with chronic obstructive pulmonary disease (COPD), 15 patients with newly diagnosed infiltrative pulmonary tuberculosis (PTB) and 12 healthy donors were examined. In whole blood, we determined the relative number of different subpopulations of monocytes by flow cytometry. The results were analyzed by statistical methods.

Results. It is shown that an increase in the number of classical (80.56 [77.60; 83.55]%) and the deficit of intermediate (10.38 [9.36; 11.26]%), non-classical (6.03 [5.24; 6.77]%) and transitional (2.14 [1.41; 3.92] %) monocytes in the blood is determined in patients with COPD when compared with the group of healthy donors (p < 0.05). In groups of patients with PTB and IHD, an increase in the number of intermediate monocytes (26.24 respectively [22.38; 42.88] % and 25.27 [15.78; 31.39]%) and the lack of transitional cells (1.77 [1.36; 3.74]% and 2.68 [2.63; 4.0]%) at the normal content of classical and non-classical forms of monocytes (p < 0.05) is detected. In patients with ICMP, a decrease in the number of non-classical monocytes (up to 5.05 [4.08; 6.58]%) is combined with the normal cell content of other subpopulations (p < 0.05). The interrelation between the number of classical and intermediate monocytes in patients with COPD (r = –0.63; p < 0.05), PTB (r = –0.72; p < 0.01), IHD (r = –0.59; p < 0.05), ICMP (r = –0.58; p < 0.05) was established.

Conclusion. In COPD associated with generalized hypoxia, an increase in the number of classical monocytes is combined with a deficiency of their other subpopulations in the blood. In PTB and IHD, antigenic stimulation of the immune system mediates accelerated differentiation of monocytes from classical to intermediate forms with a decrease in the number of transitional cells regardless of the etiology of the disease (infectious or non-infectious) and the type of hypoxia (respiratory or circulatory).

Aim. The aim of this study was the investigation of the influence of humoral factors of homeostatic proliferation IL-7 and IL-15 on T-regulatory cells in healthy donors.

Materials and methods. The study included 15 conditionally healthy donors. Phenotyping and evaluation of expression changes of transcription factor FoxP3 and the main functional molecules on T-regulatory cells such as PD-L1, CTLA-4 and HLA-DR during cultivation under IL-7, IL-15 and anti-CD3 stimulation combined with IL-2 were performed by flow cytometry. Also, we estimated proliferation intensity of T-regulatory cells in the course of cultivation.

Results. We revealed that humoral factors of homeostatic proliferation can effectively support a pool of T-regulatory cells during cultivation by number and phenotype and can maintain expression of important molecules such as PD-L1 and HLA-DR on regulatory T-cell surface. In addition, our study showed that IL-7 and IL-15 can cause relatively low T-regulatory cells proliferation in comparison to CD4+- lymphocytes.

Conclusion. The observed ability of homeostatic proliferation factors to maintain T-regulatory cells pool presumably can play an important role in lymphopenic conditions when the number of effector cells is decreased and the insufficiency of interleukin IL-2 is observed, which plays a primary role in the homeostasis of T-regulatory cells in normal conditions.