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Hepatitis B is an infectious disease resulting from infection with the hepatitis B virus. Chronic hepatitis B (CHB) is characterized by prolonged inflammation in the liver, the development of fibrosis, liver cirrhosis and hepatocellular carcinoma. Factors of the immune system play a critical role in the pathogenesis of CHB. Thanks to chemokines, immune cells migrate to the site of inflammation to implement their effector functions. The CX3CL1/Fractalkine chemokine is the only member of the CX3C family of chemokines with unique structural and functional properties. Its receptor CX3CR1 is expressed mainly on the surface of cytotoxic effector lymphocytes such as NK cells, TNK and cytotoxic T lymphocytes. The purpose of our study was to analyze the content of CX3CL1/Fractalkine in the blood plasma of patients with CHB and the analysis of this chemokine with liver fibrosis. The concentration of CX3CL1/Fractalkine was determined in the blood plasma of patients with CHB using a multiplex assay based on xMAP technology. Blood plasma from patients with chronic viral hepatitis C (CHC) and autoimmune liver diseases (AILD) was used as a comparison group. The control group consisted of healthy individuals. For statistical analysis of data, nonparametric statistics methods were used: Kruskal–Wallis test, Spearman correlation coefficient ROC-analysis. It was shown a reduced level of CX3CL1/Fractalkine in patients with CHB compared with the control group (p = 0.0003) and with the comparison groups of CHC (p 0.0001) and AILD (p = 0.0005). A reduced concentration of CX3CL1/Fractalkine was shown in the blood plasma of CHB patients with initial fibrosis (p = 0.0092) and severe fibrosis/cirrhosis (p = 0.0009), while in patients with severe fibrosis/cirrhosis, a significantly reduced level of this chemokine was established compared with the initial degree of liver fibrosis (p = 0.0081). Correlation analysis revealed a highly significant inverse relationship between the severity of liver fibrosis and the content of CX3CL1/Fractalkine in the blood plasma of patients with CHB (Spearman r = –0.33; p = 0.02). Thus, the chemokine CX3CL1/Fractalkine is included in the immunopathogenesis of CHB; its reduced content is characteristic only of CHB and does not change in other chronic liver diseases. It is involved in the processes of liver fibrosis during infection with the hepatitis B virus. The concentration of the chemokine CX3CL1/Fractalkine depends on the stage of liver fibrosis in CHB, and a decrease in the level of CX3CL1/Fractalkine in the blood plasma can serve as a negative factor in the development of CHB.

Relevance. Hemorrhagic fever with renal syndrome (HFRS) is a natural focal viral infection with a high probability of severe course, the possibility of death, a long recovery period after infection, low effectiveness of therapy and vaccine prevention. In the Russian Federation, HFRS is most often caused by the Puumala orthohantavirus. The aim of the study — to evaluate the immunophenotypic composition of lymphocytes and cytokine profile in the blood of patients with hemorrhagic feverwith renal syndrome in comparison with acute respiratory viral infections and with the prospect of developing immunological criteria for early diagnosis of HFRS. Matherials and Methods. There were examined the blood of 24 patients with a verified diagnosis of HFRS who were hospitalized in the infectious diseases department of the Samara Medical University Clinics and admitted in the first days of the disease, 18 patients with acute respiratory viral infections of established etiology, as well as 15 healthy people. Results and Discussion. Analysis of the results of lymphocyte phenotyping and cytokine levels in the blood revealed that the percentage of B lymphocytes in the blood was 12.6 %, cytotoxic CD8+ T lymphocytes expressing the activating lectin receptor NKG2D (CD3+CD8+CD314+), 25 %, regulatory T cells with CD3+CD4+FoxP3+ phenotypes 7.8 % and CD3+CD8+FoxP3+ 9.5 %, as well as IL-6 24 pg/ml, TNFß 55 pg/ml, IL-10 11.3 pg/ml with high diagnostic significance, judging by the results of ROC analysis, indicates in favor of GLPS, but not ARVI. Conclusion. The results obtained can be used as criteria for early immunodiagnosis of HFRS. The development of a new hypothesis on the mechanism of CD8+ immunological memory formation may contribute to the discovery of new potential targets for HFRS immunotherapy and the creation of new principles for the production of vaccine preparations for the prevention of this disease.

Aim. To develop and evaluate the effectiveness of complex therapy of vulvar lichen sclerosus (VLS), considering the clinical and immunological variant (CIV) of the disease. Materials and methods. A randomized prospective study included 292 patients 20-70 years old with different CIVs of the VLS course: atrophic (n=101), sclerosing (n=154), scleroatrophic (n=37), as well as 35 females with VLS in the comparison group of the same age category. Based on the clinical, immunological, and morphological features of the VLS course, a complex anti-relapse therapy was developed, the effectiveness of which was evaluated after a year of follow-up in comparison with the standard of care (SoC) of patients (from the comparison group) based on the number of disease relapses and the results of the Vulvar Quality of Life Index Questionnaire (VQLI) survey of women with vulvar diseases. Results. In patients with the sclerosing variant of VLS, short courses of topical glucocorticoids during exacerbations are justified; in patients with the scleroatrophic variant – topical calcineurin inhibitors, in the atrophic variant – a protein-peptide complex from porcine blood leukocytes (vaginal suppositories and cream-balsam with lanolin) containing interleukin-1, 6, tumor necrosis factor α, transforming growth factor, macrophage migration inhibitory factor. Patients with any variant of VLS are instructed to follow household and hygienic recommendations, use emollients daily, take prophylactic doses of vitamins A, E, and D to correct its deficiency or insufficiency, as well as use local enzyme therapy, as indicated, aimed at preventing or treatment of cicatricial changes. Local estrogens were prescribed only to women with genitourinary menopausal syndrome in the peri- and postmenopausal period. The developed complex anti-relapse therapy of VLS showed greater clinical efficacy compared to SoC: 3.7-fold decrease in episodes of disease exacerbation, as well as a significant (p=0.001) 1.3-fold decrease in the negative effect of VLS on the QoL of patients in the main clinical group (15.4 points according to the VQLI assessment – a mild effect on QoL) compared to SoC with the average score of 27.6, which corresponded to a strong negative effect of the disease on QoL. Conclusion. The results of the study support the distinction of VLS CIVs and the need to consider their features when choosing an effective therapy for the disease. Properly selected complex, supportive therapy of VLS can significantly increase the QoL of patients, minimize the number of relapses, and prevent the development of complications, including, probably, the risk of malignant transformation.

The aim of the review is to give a brief characteristic of cell cultures obtained from mammalian tissues and to consider the current possibilities and prospects for their use in virology. The analysis of the literature data presented in the main databases, such as Web of Science, PubMed, Scopus, Elsevier, Google Scholar and RSCI (as of July 2023), indicates that various types of cell cultures are currently used in virological studies. The use of cell culture has a number of advantages over other in vitro and in vivo methods of virological research. The review provides numerous examples on the development of new methods of obtaining cell cultures for the cultivation of viruses. Among them are sensitive and reporter cell systems, the design of which can be a promising tool for diagnostics of existing and new unknown viral infections. Cell cultures are characterized as potential in vitro models in virology for developing new diagnostic test-systems and antiviral drugs. An important area of cell cultures application is their use as a substrate for the production of culture-derived vaccines. Another aspect of the cell cultures application is also highlighted, such as the study of the effect of the viruses on the host immune system or the mechanisms of immunopathogenesis of viral infections. It is concluded that the use of cell cultures remains currently and in the near future one of the most important methods in practical virology and in scientific research.

Aim to evaluate the pathogenetic role of T-lymphocytes carrying the natural killer marker CD56 in hemorrhagic fever with renal syndrome (HFRS). Material and methods. The study group included 65 patients with HFRS receiving the inpatient treatment in the Clinics of SamSMU, and 15 healthy people were chosen for the control group. The following examinations were scheduled for all patients in the different stages of the disease: a clinical blood test, flow cytometry with a given set of monoclonal antibodies, enzyme-linked immunosorbent assay of blood serum to determine the cytokine profile. For statistical analysis we used the SPSS v.23 software. Results. The percentage of CD3+ CD56+ NKT blood content in comparison with those for cells of innate immunity (neutrophil granulocytes, monocytes, natural killers) and lymphocytes of adaptive immune response, as well as the level of cytokines in the blood serum showed that in polyuric and convalescent periods, the number of these cells significantly increases and remains closely embedded in correlations with other components of the immune system. Conclusion. A new hypothesis has been proposed to interpret the role of NKT in the development of the immune response in HFRS.

The aim of the work is to determine the relationship between the levels of cytokines of proinflammatory and anti-inflammatory action during the clinical course of hemorrhagic fever with renal syndrome (HFRS) and the previously described characteristics of the phenotypic composition of blood lymphocytes in disease of various severity. Materials and methods. 65 patients with a serologically verified diagnosis of HFRS were under observation. The control group included 15 conditionally healthy people. Determination of cytokines in the blood of patients with HFRS was carried out by the enzyme immunoassay method at the different stages of the disease. The phenotypic composition of blood lymphocytes was assessed by flow cytofluorimetry. Results. At the different stages of the disease, there was a quantitatively different increase in the content of cytokines in the blood associated with cytotoxic immune reactions (IL-12, IFN, TNFa, TNF), as well as IL-10 and IL-6 correlated with each other in severe cases, against the background of a drop in blood levels of IL-4 and IL-1. In the moderate course of HFRS, correlations of IL-12 and IL-4 with NKG2D+ CTL, the relationship of IL-12 with almost all other cytokines, and the correlation of CD8+ Treg with IL-6 and TNF levels were observed. In severe cases, the formation of a complex that included interconnected IL-6 and IL-10 correlating with the number of NKG2D+ CTL, CD8+ Treg, NKT was noted. Conclusion. The pathogenetically significant mechanism of HFRS is realized with the predominant participation of cytokines of the cellular immune response and IL-6, correlatively associated with NKG2D+ CTL, CD8+ Treg, NKT, which, in case of a favorable outcome, contribute to the active formation of a pool of CD8+ memory cells, disrupted presumably by excessive secretion of IL-10.

Alopecia areata is an autoimmune disease characterized by non-scarring hair loss with preservation of the hair follicle. Hair loss in alopecia areata can be either focal with the appearance of clearly defined foci of alopecia, or diffuse or complete hair loss in any area of the skin where hair follicles are present. Data on the role of food allergy in the development of alopecia areata and the nature of the sensitization spectrum are extremely scarce. Objective: to study the features of the spectrum of sensitization to food and pollen (cross-reacting) allergens in patients with alopecia areata.The study involved patients with alopecia areata (n = 17), who were divided into groups according to age: group 1 — children (n = 9) and group 2 — adults (n = 8). All patients underwent a specific allergological examination: collection of an allergic history, skin prick testing with food and pollen allergens (Allergopharma, Germany).Analysis of the spectrum of sensitization to food allergens in patients with alopecia areata revealed features depending on their age. Thus, in the group of sick children, the highest frequency of sensitization to whole chicken eggs, food cereals, yeast, soybeans and cow's milk proteins was noted. In the group of sick adults, the most significant food allergens were: egg protein, rye flour, oats. Among the pollen allergens in the first group of patients, the most common allergens were a mixture of weed and grass pollen, in the second group, a mixture of meadow grass pollen. All patients, taking into account allergological testing, were administered an individual elimination diet with the exclusion of causally significant allergens, taking into account crossreacting allergens. The elimination effect was assessed 2 months after the start of the elimination diet. 70% of patients showed a clinical improvement, i.e., the growth of vellus was noted (vellus depigmented hair) in the foci of alopecia, as well as terminal pigmented hair. Complete regression of alopecia foci occurred on average within 3-6 months from the start of therapy.The sensitization to food and pollen (cross-reacting) allergens in patients with alopecia areata and the positive effect of the elimination diet revealed in our study well supports the role of food allergy in the development of this disorder. Therefore, the study of the causal relationship between food allergy and alopecia areata is of particular relevance and creates prerequisites for the discovery of new diagnostic and therapeutic options.

Introduction. The immunopathogenesis of the novel coronavirus infection COVID-19 is usually associated with the development of imbalance in the immune response to its causative agent, SARS-CoV-2 virus (Coronaviridae: Coronavirinae: Betacoronavirus: Sarbecovirus). This is manifested, in particular, by interferons’ (IFNs) deficiency at the beginning of the disease followed by hyperproduction of pro-inflammatory cytokines. The virus causes a decrease in IFN types I (α/β) and III (λ) levels; changes in IFN type II (γ) are less studied. In this regard, it is relevant to assess the functional bioactive IFN (interferon status) in COVID-19. The aim of the study was to assess the antiviral potential of the body by testing the biologically active IFNs in COVID-19. Material and methods. We used biological serum samples of COVID-19 patients taken in the acute phase (110 patients on the 1–5 days of the disease) and during rehabilitation (47 patients during 1–3 months after the disease onset). Assessment of interferon status was performed according to the technique developed by the authors and described earlier. Results. The IFN status of patients with COVID-19 in the acute period and in the phase of post-infection rehabilitation was studied during the observation period. It was found that SARS-CoV-2 causes a pronounced inhibition of biological activity of IFN types I and II compared to the reference values by more than 20 and 7 times, respectively. During the post-COVID period, incomplete recovery of the IFN system activity was registered, which proceeded very slowly. No cases of reaching physiological indicators of interferon status were identified during the observation period. Conclusion. The obtained data on deficiency of the functional biologically active IFN confirm the hypothesis about the predominant role of impaired IFN production of different types in the immunopathogenesis of the novel coronavirus infection.

To date, despite significant advances in the study of the immunopathogenesis of chronic hepatitis C (CHC), many open questions remain in the diagnosis, prediction and course of treatment. In the context of the study of this infection, the Toll-like gene family of innate immune system receptors (TLRs) is of considerable interest. The article analyzes and summarizes the data of professional scientific sources on the role of the TLR-4 gene in the functioning of the natural human immune system, as well as Asp299Gly polymorphism of this gene in the immunopathogenesis of CHC. The relevance of the study is due to the fact that the innate immune system is crucial in the primary protection of the macroorganism from pathogens, the recognition of which largely depends on the TLRs receptor gene family, and genetic analysis is a modern and promising direction in personalized medicine. The importance of determining genetic markers lies in the fact that regardless of age and other factors of the external and internal environment, they carry information about the predisposition to various diseases, which can be used in the formation of a genetic passport. The data concerning the influence of the Asp299Gly polymorphism of the TLR4 gene on the immunopathogenesis of CHC are contradictory and require further investigation. An in-depth study of this issue will improve the therapeutic and diagnostic tactics of this disease based on a comprehensive assessment of the features of the immune response, which are caused by the carriage of the indicated polymorphism in the human genome. [ABSTRACT FROM AUTHOR]

Alopecia areata is a common inflammatory immune-mediated disorder in which autoimmune response is triggered against hair follicles, thus leading to non-scarring hair loss on the scalp, face and other parts of the skin. Despite numerous studies concerning this issue, today there is no consensus on the etiology and pathogenesis of focal alopecia. In the literature, special attention is paid to association of focal alopecia with autoimmune diseases, such as rheumatoid arthritis, celiac disease, type 1 diabetes, psoriasis, autoimmune thyroiditis, vitiligo. Recent studies have identified the association of focal alopecia with atopic diseases (allergic rhinitis, bronchial asthma, atopic dermatitis) and the early debut of severe forms of hair loss. The aim of this study was to present a clinical case of focal alopecia in an 8-year-old girl with atopic bronchial asthma and seasonal allergic rhinitis. As based on detection of eosinophilia in peripheral blood and a high concentration of total IgE in serum, one may assume that atopic alopecia is the cause of focal hair losses in a child with atopy. The patient underwent skin prick testing, in order to determine sensitization for food components, pollen and fungal allergens. As a result of skin testing, a hyperergic reaction (> 15 mm in diameter) to tree pollen was revealed, a positive response (6-9 mm) to oatmeal, a weakly positive reaction (3-5 mm) to whole chicken egg, carrots, tomato, apple, pear, pollen of meadow, cereal, weed grasses was also revealed. With regard of these allergological data, an individual diet was recommended with the elimination of causally significant allergens (including those eliciting weakly positive reactions), external treatment, i.e., topical calcineurin inhibitors administered for 1 month. One month later, an improvement of the pathological process was registered, and 6 months from the start of therapy, complete restoration of hair follicles was noted in the focus of alopecia. The patient was monitored for a year, no complaints of hair loss were noted. The positive effect of elimination against the background of the appropriate elimination diet with respect to causally significant allergens, was also noted when treating her for respiratory allergy, i.e., the patient did not have seasonal manifestations of hay fever over the next pollination period. This clinical case is demonstrated in order to draw special attention of dermatologists, allergologists, immunologists, general practitioners to the issues of focal alopecia in children against the background of typical allergic diseases.

This brief analytical review is devoted to spreading, etiology, pathogenesis, prophylaxis, and treatment of COVID-19 and “swine flu” causing pandemics in the 21st century. Both pandemics were caused by respiratory viruses belonging to different families, i.e., Coronaviridae (SARS-CoV-2) and Orthomyxoviridae (influenza A(H1N1)pdm09 virus), respectively. In most cases, pathogens enter human organisms via epithelial cells of the upper airways. Sometimes, these viruses infect intestinal epithelium. Given that symptoms of influenza and COVID-19 are similar, its diagnostics should always be based on laboratory results, especially, PCR evidence for specific RNA presence in clinical material. The paper describes similarities and differences in immune pathogenesis of the diseases. The main characteristics of two pandemic courses caused by SARS-CoV-2 and influenza A(H1N1)pdm09 are revealed. The presence of influenza vaccine and etiotropic chemotherapeutic agents, as well as preexisting immunity to influenza virus among elderly people in 2009 had a significant influence on morbidity and mortality during the influenza pandemic. The presence of antibodies to A(H1N1)pdm09 virus in sera of elderly people before the pandemic can be explained by the fact that some antigenic properties of A(H1N1) virus which circulated before 1957 were similar to that of A/California/07/09 (H1N1)pdm09. Consequently, morbidity and mortality among people older than 65 (main risk group) were low, while children and young adults suffered more often. The opposite pattern is observed for COVID-19, since mortality among the elderly population is high, while the children and young adults have an asymptomatic or mild form of a disease. A suggestion is made that population in the South-East Asia may have immunity against SARS-CoV-2, since coronaviruses with antigenic features similar to the pandemic one could circulate in that region and infect population without evident symptoms, while one or several recent virus variants caused severe disease and COVID-19 outbreak in Wuhan.

Aim. Assessment of the features of cellular immunological mechanisms at the early stage of HFRS of varying severity and development of prognostic criteria for the risk of a severe course of the infectious process. Materials and methods. An immunological blood test (flow cytofluorimetry method) was performed in 12 patients with severe HFRS and 53 patients with moderate course in the dynamics of the disease. Statistical data processing was performed based on the SPSS software package. Results. At the initial stages of HFRS, immunological features of the severe course of the disease were established in the form of a higher content of T-helper and regulatory T-cells in the blood and a reduced number of CTL, including their activated pool. Based on these changes, an immunological prognostic coefficient of HFRS was developed, which allows determining the risk of severe course in the early days (febrile period) of the disease with high prognostic accuracy. Conclusion. The results obtained allowed us to identify previously unknown features of the immune process at the initial stages of HFRS development, which allowed us to propose a new approach to predicting the severe course of the disease.

Candidiasis is the most common fungal infection predominantly affecting the mucous membrane. The fungus Candida causes these lesions. There are strains resistant to modern antimycotic drugs among Candida spp. Due to the increase in candidiasis prevalence and the widespread use of antifungal agents, the issue of effective treatment is becoming increasingly important.Liability of C. albicans to antigenic mimicry and suppression of the immune response mediates the evasion of the fungus from the immune response and development of excessive inflammation. The evasion of the fungus Candida from the local nonspecific immunity factors contributes to the breakdown of the antibody response initiation and cellular reactions of the acquired immunity, which are of key importance for anti-candidiasis protection. Therefore, the lack of an adequate local immune response from the mucous membranes is a possible reason for the development of a recurrent vulvovaginal candidiasis.Modern treatment for recurrent candidiasis in the formed risk groups involves the use of prophylactic aggressive etiotropic therapy, but at a lower dose, and the pathogenetically substantiated treatment involves regulating the local immune response in the vagina through the use of immunomodulatory drugs that inhibit the growth of fungi by activating the innate and acquired components of mucosal immunity. In addition, local immunomodulators contribute to the recovery of damaged mucous membranes and additional lubrication of tissues in contrast to antimycotics, which tend to increase the clinical manifestations of infection and dryness of mucous membranes when applied topically in the early stages of treatment.

The aspects of virus hepatitis C immunopathogenesis are discussed. The main attention is paid to higher production of Th1 cytokines providing active protection of the host from HCV. The up-to-date approaches to the therapy of chronic hepatitis C, described in the literature and the original ones, including the triple therapy with immunomodulators of various mechanisms of action, i.e. cycloferon (injections and tablets), galavit and derinat are presented. The comparative efficacy of the therapy is estimated. Cycloferon is shown to be the drug of choice in the treatment of patients with virus hepatitis addicted to narcotics. The clinical and laboratory efficacy of the metabolic hepatoprotector remaxol with antioxidant activity is described. Its high effictivity and satisfactory tolerability (side effects requiring discontinuation of the drug use were recorded only in 0.3% of the cases), as well as the minimal risk of no biochemical remission after its use allow to conseder remaxol as a highly efficient metabolic hepatoprotector for pathogenetic therapy of chronic hepatitis.

Immunological memory and tolerance represent major achievements and advantages of adaptive immunity. Organisms bearing adaptive immunity display prominent competitive advantages in the fight against infections. Memory immune cells are preserved for decades and are able to repel a second attack of an infectious agent. However, studies performed in the XXI century have shown that even unrelated pathogens may be quickly and effectively destroyed by memory cells. This type of response is called heterologous so that heterologous immune response is mainly typical to viral infections and other intracellular infections, where T-cells play a lead role in protection. This review will discuss various mechanisms involved in implementing T-cell cross-reactivity, describe molecular prerequisites for heterologous T-cell responses. Experimental evidence of memory T-cell potential to heterologous immune response in mouse models and in human infections are also discussed. Heterologous immune response is an important immune arm in adults and the elderly when the yield of naive cells to the periphery declines due to thymus involution. Along with obvious advantages, heterologous immune response leads to imbalanced memory T-cell repertoire, replacement of immunodominant epitopes with minor ones allowing viruses to evade immune response that results in virus persistence, or, conversely, fulminant infection course. Another threat of heterologous immune response due to switch in dominant repertoire of recognizable epitopes is presented by random self-epitope recognition, which can lead to development of autoimmune pathology. Heterologous immunity can also disrupt drug-induced tolerance in organ and tissue transplants and lead to graft rejection. Heterologous immune response should be taken into consideration while developing and using new vaccines, especially in adults and the elderly.

Based on the III International Consensus on the definition of Sepsis and Septic Shock (Sepsis-3), the modern definition of septic shock was proposed: “Septic shock is a type of sepsis that is accompanied by severe hemodynamic, metabolic and cellular disorders, and these disorders are associated with a higher risk fatal outcome”. Despite the classic idea of septic shock development (proinflammatory, immunosuppressive phases and, finally, multiple organ failure with distinct shock organs), the theory of activation of the caspase, endocannabioid system and system of protein of programmed death-1 in evolving septic shock are promising approaches to development of new diagnostic and therapeutic methods. Lymphopenia is already observed at an early stage of septic shock, which further leads to deep immunosuppression. Previous experimental studies have revealed some treatment methods to reduce the pro-inflammatory stage, which, however, did not show desired results in clinics. Now it is necessary to look for ways to inhibit apoptosis, depletion of lymphocytes, macrophages and other immune cells in the course of septic shock. It is known that caspases mediate innate detection of pathogenic microorganisms, cause pyroptosis, activation of monocytes. It has been proven that inhibition of caspase-8, caspase-11 leads to decreased monocyte functioning and cytokine release, which plays an important role in immunopathogenesis of septic shock. Associations of PD-1 and PD-2 expression on CD4+ lymphocytes and monocytes are also shown to be connected with immune dysfunctions, decrease in lymphocyte proliferation, and increased interleukin-10 concentration. Stimulation of the cannabinoid receptors is able to reduce inflammation by inhibiting cytopathic and immunosuppressive effects of pathogens. It has been shown that classic septic shock biomarkers (pro-inflammatory, anti-inflammatory cytokines; procalcitonin, lactate, etc.) do not have predictive power in relation to the outcome of the disease. Circulating and citrullated histones, determined by mass spectrometry, may serve as potential diagnostic markers of septic shock, but they require further study. Use of oxidized phospholipid oxPAPC (Oxidized 1-palmitoyl-2-arachidonoyl-snglycero-3-phosphocholine), hydrogen sulfide and Fasciola hepatica fatty acid binding proteins (hepatic fluke) prevents oxidative stress, synthesis of pro-inflammatory cytokines and provides maturation of macrophages and dendritic cells. Further study of immunological reactions during septic shock is of great importance for substantiation of new approaches to the diagnostics and therapy of septic shock.

Here, we review the data on mechanisms inhibiting cytotoxic effect of anthrax toxin on the immune system cells. Various disease forms, immunopathogenesis and contemporary methods for anthrax treatment are discussed. In addition, an anthrax toxin was outlined, whereas structural and functional organization of the protective antigen, lethal and edema factors was detailed. A mechanism for association of a protective antigen and lethal factor, protective antigen and edema factor leading to formation of a lethal toxin and edema toxin, respectively, was described. Participation of protective antigen domains in the process of interaction with surface receptors of imunocompetent cells as well as features of binding a protective antigen with lethal factor and edema factor are discussed. A mechanism of endosomal toxin complex internalization and subsequent transfer of effector molecules to the cytosol are described. Effects of the lethal factor and the edema factor on components of eukaryotic cells as well as cytotoxicity mechanisms are analyzed. The approaches to block anthrax toxin action at various stages of toxicoemia have been analyzed based on previously uncovered sequential signs of cytotoxic activity for Bacillus anthracis toxins. Currently available chimeric and humanized monoclonal antibodies are capable of neutralizing B. anthracis toxins at diverse assembly stages, particularly considering the drugs inhibiting: inter-receptor interaction between protective antigen with eukaryotic cells; furin-like enzymes activating prepore assembly; protective antigen oligomerization; binding of the lethal factor or edema factor to the protective antigen; translocation of the lethal factor or the edema factor into cell cytosol; transport of protective antigen with lethal factor or edema factor from endosomes; enzymatic activity of lethal factor or edematous factor. The anti-toxin agents approved for anthrax prevention and treatment in Russia and worldwide are discussed. The limitations of anti-toxin agents and perspectives for their improvement are also described including inhibition of lethal factor activity, interference with integration of toxin components, blockade of interactions between toxic complexes and immune cell receptors.

Psoriatic arthritis is a chronic progressive systemic inflammatory disease of joints and spine, which leads to the development of erosive arthritis, bone resorbtion, multiple enthesitis and spondylitis. Severe clinical course, resistance to therapy, high prevalence of disability, increased mortality of patients determine a need for further study of the disease. Psoriatic arthritis is a multifactorial disease including immune pathogenic factors representing a complex process of interaction between cellular and humoral components of immune system. The most important way of activating epidermal cells and synovial membrane proliferation in psoriatic arthritis is an imbalance of proinflammatory and anti-inflammatory cytokines. It is noted that the features of clinical course in psoriasis are age-dependent. The study of immune response indices in different age groups allows to reveal distinct progression features of the psoriatic pathology.The purpose of this study was to compare concentrations of proinflammatory and anti-inflammatory cytokines, cellular and humoral immunity, and to conduct a comparative analysis in young and adult patients with psoriatic arthritis.The study included a group of patients with psoriatic arthritis (n = 101) who were divided by their age: group 1, from 18 to 44 years (n = 43); group 2, over 44 years (n = 58). The control groups (3 and 4) included virtually healthy people (n = 103) matched for sex and age with the patients. Populational and subpopulation profiling of blood lymphocytes was performed by flow-cytometry using monoclonal antibodies to CD3, CD4, CD8, CD16, CD19 (LLC “Sorbent”, Moscow, Russia). Phagocytic activity of peripheral blood neutrophils was assessed microscopically by uptake of latex particles. Concentrations of IgA, IgM, and IgG immunoglobulins, circulating immune complexes, cytokines (IL-4, IL-6, IL-10, TNFα) in blood serum was determined by enzyme-linked immunosorbent assay. Statistical evaluation of the results obtained was performed using applied “Statistica 6.0” software.In all the age subgroups of patients with psoriatic arthritis, we have revealedstatistically significant differences against controls, i.e., increased relative and absolute number of CD3-CD16+ lymphocytes in peripheral blood, higher concentration of CIC-C1q, with decreased concentrations of IgA, IgM, IgG in blood serum. The analysis of the main cellular and humoral indicators of immunity in psoriatic arthritis patients revealed a statistically significant differences for psoriatic arthritis in young and adulthood. E.g., the serum concentration of IL- 10 was statistically significantly lower in psoriatic arthritis at a young age in comparison with adult psoriatic arthritis. Phagocytic number and IgG concentration in serum were statistically significantly lower in adults with psoriatic arthritis adulthood than in young patients.In conclusion, The revealed changes in immunological indices in psoriatic arthritis in young and adult patients indicate to differences against healthy controls, as well as intergroup differences. Previous studies have not revealed statistically any significant differences in immunological parameters between young and adult patients with psoriatic arthritis in, thus suggesting a presence of immune disorders associated with psoriatic pathology, but not with the age of patients. However, changes of immunological reactivity are observed with increasing age of patients with psoriatic arthritis and development of severe clinical forms, and they can be considered as markers of psoriatic disease progression, such as increased concentrations of IL-10 and lower IgG amounts in blood serum, a decreased phagocytic number.

Studying immunological aspects of pathogenesis of retinopathy of prematurity (ROP) helps develop new approaches to prevention, rational diagnosis and increase of the effectiveness of treatment of the disease. Purpose: to analyze the level of growth factors in blood serum of premature infants belonging to the group of ROP risk at the pre-clinical stage and find out how this level is related to further development and course of the disease. Material and methods. 85 prematurely born infants of the ROP risk group were examined. The average gestational age at birth was 27.7 ± 2.2 weeks, the average birth weight - 1086.1 ± 266.1 g. The examination included dynamic ophthalmoscopy and determination of the content of VEGF-A in blood serum (using a flow cytometer BD FACS Canto II) and TGF- β1, IGF-I, IGF-II (by enzyme-linked immunosorbent assay (ELISA) using a c-test system Bender MedSystems, Austria). Results. During the first ophthalmoscopic examination, i.e. before the clinical manifestation of the disease, blood serum of children who later developed ROP that subsequently required laser coagulation of avascular retinal areas, was found to have relatively higher concentrations of VEGF-A (above 1300 pg/ml) and IGF-II (above 140 pg/ml) and lower IGF-I concentrations (below 24 pg/ml) and TGF- β1 (below 8000 pg/ml) as compared with the groups of "safe" children. A dynamic study of VEGF-A content and, simultaneously, TGF- β1 content showed uniform changes in the concentration of these growth factors at all observation times. Conclusion. It was shown for the first time that high IGF-II and low TGF- β1 concentrations revealed before the clinical manifestation of the disease can be viewed as prognostically unfavorable as far as subsequent development of severe ROP is concerned. Uniform changes of TGF- β1 and VEGF-A level in blood serum during ROP development may indicate to the synergistic participation of these growth factors in the pathological vasoproliferation. Further studies are required to determine the details of how this mechanism works // Russian Ophthalmological Journal, 2017; 1: 20-5. doi: 10.21516/2072-0076-2017-10-1-20-25

When dactylitis is detected in a patient with psoriatic arthritis (PsA), it is necessary to use active treatment as soon as possible, since in the absence of therapy the disease progresses to joint erosion and functional disorders. The paper considers the clinical signs and diagnosis of PsA and notes the importance of differential diagnosis in this sign with other joint inflammatory diseases. It points to the necessity of elaborating common approaches to an objective assessment of the severity of dactylitis. Its immunopathogenesis and main treatment areas, including the use of biological agents (BAs), are detailed. There are data of clinical trials that have evaluated the efficiency of treatment for dactylitis and established that in most cases, the use of BAs considerably reduce not only the severity of its clinical signs, but also concomitant bone marrow edema. It is noted that the development of new pathogenetic treatments targeting a number of currently established biologically active molecules that play an important role in the pathogenesis of dactylitis will enhance the efficiency of treatment in patients with PsA.

The purpose of the study was to determine the level of proinflammatory cytokines: IL-12, IL-8 and IFNγ, neopterin and lipopolysaccharide-binding protein in the serum of patients with acute brucellosis before and after antibiotic therapy. The clinical data from 32 patients with laboratory-confirmed diagnosis — “acute brucellosis” admitted to the diagnosis, treatment and examination of occupational diseases brucellosis GBUZ SC “City Clinical Hospital No. 2”, the city of Stavropol were used in the study. The concentrations IL-12, IL-8, IFNγ cytokines and acute-phase proteins in serum was determined by ELISA. In the acute phase of brucellosis infection (before treatment) had high levels of pro-inflammatory cytokines IL-8 and IFNγ, but despite holding a course of antibiotic treatment in the serum of patients with preserved high levels of IL-8, indicative of active inflammation in the absence of clinical manifestations. IL-12 level, a key cytokine in the initiation of lymphocyte-dependent immune response was lower than in the control group. Evaluation of the cytokine status (IL-8, IL-12, IL-18) and proteins of acute inflammation phase (neopterin and lipopolysaccharide-binding protein) will provide valuable information for monitoring the effect of pharmacotherapy of acute brucellosis. Indicators of lipopolysaccharide-binding protein and neopterin in the serum of patients with brucellosis should be considered as a marker of inflammatory activity and as a predictor of outcome of acute brucellosis.

Aim. To study the semiotics of neurological lesions in patients with tick-borne encephalitis, Ixodes tick-borne borreliosis (ITBB) and mixed infection (MI), their immunopathogenesis, and the possibilities of current pathogenetic pharmacological correction. Subjects and methods. A total of 220 patients with tick-borne encephalitis, ITBB, and MI concurrent with the syndromes of central nervous system lesions were examined. The immunological studies encompassed the examination of mononuclear cells in the cerebrospinal fluid (CSF), the population and subpopulation composition of lymphocytes, and nitroxidergic processes in the serum and CSF from the total level of final stable nitric oxide metabolites. For pharmacotherapeutic correction, the metabolic drug cytoflavin was used as newly indicated. Results. Cytofluorometric analysis of the CSF cellular composition showed the mononuclear cell predominance of CD3+ (58.6%), CD4+ (57.2%), CD8+ (16.8%) lymphocytes and monocytes (34.4%), which expressed the phenotypic marker CD14+. This reflects the nature of a local immune response: an increase in the immunoregulatory index CD4+/CD8+ from 3.4 to 5.6, respectively, while the normal proportion of these cells in the blood ranges from 1.5 to 2.2. CSF lymphocytes were found to be ready for Fas-mediated apoptosis dependent on the receptor (CD95+ was 64.3%).There was a correlation using the pair correlation coefficient between the total concentration of the metabolites of the nitroxide molecule and the percentage of CD14+ (r=0.5; p

Chronic hepatitis C (CHC) represents a significant public health concern. In the majority of cases, the infection progresses to a chronic form, which is characterised by the development of fibrosis and cirrhosis of the liver. A plethora of cytokines and chemokines are generated as a consequence of inflammatory processes within the liver. These can exert a dual effect, both protective and damaging, particularly in relation to the death of hepatocytes and the progression of liver fibrosis. Furthermore, a number of growth factors have been identified as playing a role in the pathogenesis of CHC. The objective of the study was a comprehensive evaluation of a wide range of cytokines, chemokines and growth factors in the blood plasma of patients with CHC at varying stages of liver fibrosis. The study cohort comprised 63 patients diagnosed with CHC, who were divided into three groups according to the stage of liver fibrosis. The control group comprised healthy individuals (n=32). Concentrations of the following cytokines were determined in plasma: Interleukins and some cytokines (IL-1α, IL-1β, IL-1RA, IL-2, IL-4, IL-5, IL-6, IL-7, IL-9, IL-10, IL-12 (p40), IL-12 (p70), IL-13, IL-15, IL-17A, IL-17-E/IL-25, IL-17F, IL-18, IL-27, IFNα, IFNγ, TNFα, TNFβ); chemokines (CCL2/MCP-1, CCL3/MIP-1α, CCL4/MIP-1β, CCL7/MCP-3, CCL11/Eotaxin, CCL22/MDC, CXCL1/GROα, CXCL8/IL-8, CXCL9/MIG, CXCL10/IP-10, CX3CL1/Fractalkine) and growth factors (EGF, FGF-2, Flt-3L, G-CSF, M-CSF, PDGF-AA, PDGF-AB/BB, TGFα, VEGF-A) by multiplex analysis based on xMAP technology. Nonparametric statistics methods were used for statistical analysis. As a result of the study, increased concentrations of cytokines IL-12 (p40), IL-15, IL-17E/IL-25, IL-27, IFNγ, TNFα, chemokines CXCL9/MIG and CXCL-10/IP-10 and growth factors FGF-2 and M-CSF were found at all stages of liver fibrosis. Elevated concentrations of cytokines IL-1α, IL-1β, IL-2, IL-6, IL-9, IL-10, IL-17F, IFNα, TNFβ, chemokines CCL2/MCP-1, CCL11/Eotaxin, CCL22/MDC and growth factors G-CSF, TGFα, Flt-3L were found in severe liver fibrosis/cirrhosis. Correlation analysis revealed a relationship of high significance between the severity of liver fibrosis and the content of cytokines IL-6, IFNγ, TNFα, IL-7, chemokines CCL2/MCP-1, CCL11/Eotaxin, CXCL9/MIG, CXCL10/IP-10, CXCL1/GROα, growth factors TGFα, PDGF-AA, PDGF-AB/BB. Thus, a certain profile of cytokines characteristic for CHC was revealed, cytokines, chemokines and growth factors significant for liver fibrosis in CHC were found.

This review presents our own and literature data dedicated to predisposing and pathogenetic factors involved in development of a common comorbidity, diabetes-associated osteoarthritis (DAOA). So far, there is no wide-accepted clinical or scientific viewing of DAOA as a distinct clinical phenotype of osteoarthritis (OA). To our knowledge, the role of genetic factors in DAOA development was not discussed in details. Therefore, we have drawn attention to the cross-acting genes involved in both OA and diabetes, i.e., PPARγ, FTO, ADIPOQ, and AGE. These genes encode proteins which can contribute to the pathogenesis of both OA and diabetes. However, some controversies exist about genetic predisposal for OA and diabetes. We review the studies which concern various clinical characteristics of DAOA. We describe a role of chronic hyperglycemia, insulin resistance, advanced glycation end-products (AGE) in development of OA and micro- and macrovascular complications of diabetes. The mechanisms of low-grade inflammation, humoral and cellular immune responses to cartilage antigens, and their role in OA progression are discussed. We underline a similarity of low-grade inflammation in OA and microvascular complications in diabetes. In conclusion, OA and diabetes comorbidity is not a mere coincidence of these diseases. They share some common genetic and pathogenetic factors, a distinct phenotype, and may change thinking of physicians and scientists towards a holistic (personalized) approach to prevention, diagnosis, treatment and prognosis of this comorbidity. We discuss opportunities of DAOA pharmacotherapy based on the key comorbidity feature, i.e., emergence of a new disease property by coexistence of several diseases. One may hypothesize that studying genetic, molecular, and cellular networks in comorbidities may lead to new treatment strategies (‘network pharmacology”) based on targeting the network hubs. We provide examples of such approach in some polypathies (e.g., phenofibrate, a PPARα agonist; simvastatin, a GMGCoA reductase in OA, rheumatoid arthritis and psoriasis), and its potential discuss usefulness is discussed for DAOA. In particular, we provide an example of a pilot study of ademethionine, a methyl group donator.

Hronic hepatitis B belongs to a category of socially significant diseases due to its wide abundance in the world and high frequency of unfavourable outcomes of this disease. Features of interaction of hepatitis B virus with human immune system, accompanying development of mechanisms of escape from immunological control, is the basis of development of chronic hepatitis B. Molecular-biological features of hepatitis B virus are the basis of the indicated mechanisms, and the content of this review is their examination. Herewith, stages of immunopathogenesis of this disease is the basis of characteristics of interaction of viral proteins with cells of immune system, and isolation of those is accepted in contemporary foreign literature.

Aim. To determine the significance of immune factors in the pathogenesis of kidney injuries in HIV infection, by investigating the cellular and cytokine components of an immune response. Subjects and methods. Thirty HIV-infected patients (mean age 31.7±6.2 years) with chronic kidney disease (CKD) were examined. A comparison group consisted of 10 HIV-infected patients without signs of kidney injury. A control group included 24 healthy individuals to analyze immune status and 15 people to estimate the normal values of the cytokine composition. The cellular composition of lymphocytes on a typical immunogram was determined on a flow cytofluorometer; the serum concentrations of cytokines were measured on a multichannel photometer. Results. The HIV-infected patients with kidney injury displayed significant reductions in the absolute (0.2·109/l and 0.4·109/l, respectively; р=0.015) and relative (14.75 and 22%, respectively; р=0.005) counts of CD3+/CD4+ cells and in the immunoregulatory index (0.2 and 0.4, respectively; р=0.014) as compared to those in HIV-infected patients without kidney disease (р≤0.05) with a rise in the number of cytotoxic T cells (CD3+/CD8+). The HIV-infected patients showed a preponderance of immunosuppressive cytokine compositions, as indicated by the high levels of transforming growth factor-β (a more than 50-fold increase) and by a statistically significant rise in the level of tumor necrosis factor-α (TNF-α) (with CD4+ lymphocyte counts more or less than 200 cells/µl — 19.0 and 24.2 pg/ml, respectively; p=0.017; with HIV RNA levels more and less than 100,000 copies/ml — 24.4 and 19.7 pg/ml, respectively; p=0.012). Conclusion. The HIV-infected patients with CKD developed kidney injury in the presence of a more pronounced decrease in blood T helper lymphocyte subpopulation levels with a predominance of proinflammatory and immunosuppressive responses. TNF-α in combination with immunosuppression and high viral loads was established to play a leading role in the development of kidney injury in HIV infection.

The article analyzes the immunomodulatory therapy as part of pathogenetic treatment of community-acquired pneumonia. Immunological monitoring of patients with severe community-acquired pneumonia demonstrated a disbalance of natural resistance factors, cellular component of immune system and humoral stress factor, which required immunotherapy. Immunomodulatory therapy included azoximer bromide (Polyoxidonium) according to the prescribed regimen and demonstrated immunological efficacy.

Contemporary problems of hemorrhagic fever with renal syndrome (HFRS), being one of hantaviral infection nozoforms and wide-spread on Euro Asiatic continent are considered. Annual increase morbidity with of natural foci expansion, often severe course and a high mortality rate determine the importance of HFRS for health of many countries and in particular the Russia. This article presents of long standing results obtained during the study of epidemiologic, clinical and laboratory diagnostic, immunopathogenesis, treatment trials in Primorsky region of Russian Federation, being the endemic area of co-circulation of several pathogenic hantaviruses.

The diagnostic value of the serum levels of proinflammatory (TNF-α, IL-1β, IL-6, and IFN-γ) and anti-inflammatory (IL-4 and IL-10) cytokines of the immune system was studied in 54 patients with breast cancer (BC). Analysis identified the increased concen- trations of proinflammatory cytokines, such as IL-1β, TNF-α, and IL-6, in the peripheral sera of BC patients.Analysis of anti-inflammatory cytokines in the peripheral sera of patients with BC also revealed a significant increase in the values of IL-4 and IL-10. The findings suggest that there is imbalance between cellular and humoral immunity factors, the study of which will be an important diagnostic criterion for BC.

Significance of psoriasis (PS) research is determined by increasing incidence of this disorder, higher frequency of severe clinical forms, e.g., psoriatic arthritis (PsA). Clinical course and outcomes of psoriasis and psoriatic arthritis depend on degree of immunological disturbances and imbalance of cytokine regulation of intercellular interactions. The leading immune disorders involved in pathogenesis of psoriasis and PsA are those characterized by alterations of Th1-type cytokine profile (TNFα, IL-2, IFNγ, etc.). We have analyzed publications that reveal some features of PS and PsA immunopathogenesis associated with nature of the diseases. The review draws attention to relatively new and scarcely studied data concerning the role of cytokines produced by Th17- and Th22-cells (IL-17, IL-22, IL-23, IL-26), IL-19 subfamily (IL-19, IL-20, IL-24) in development of psoriasis and PsA. Search for the immunological markers predisposing for risk of psoriasis and PsA is an important step in personalized approach to their prediction and planning of preventive measures, in order to prevent progression of this pathology.

Abstract. Multiple parameters of immune system were studied in patients with various clinical forms of tickborne encephalitis (TBE). The patients were examined in acute phase of the infection. It is shown that early immunopathogenesis of TBE, in its feverish form, corresponds to general immunological mechanisms of viral infection. Meanwhile, in focal clinical forms of TBE with favorable outcome, we revealed a deficiency of T-cell immunity, disimmunoglobulinemia, and low Th1-cytokine production. In a focal form with fatal outcome, an early hyperproduction of Th1-cytokines and complement components, as well as increased numbers of activated T-lymphocytes have been noted, along with reduced levels of cytotoxic lymphocytes. The changes observed may be considered as early prognostic criteria of a severe infection.

The aim of review. To present analysis of data on immunopathogenesis of inflammatory bowel diseases.Key points. At genetically sensitive animals inflammatory bowel diseases (IBD) develop at various effects on innate and adaptive systems of immune defense (knock-out and transgenic mice), causing changes of expression of significant immunologic factors with distortion of pro- and anti-inflammatory cells and molecules ratio at their contact to microbiota structures. The physiological state of intestine is characterized by balanced interaction of effector (Th1, Th2, Th17) and regulatory (Treg) cells determining presence of immune tolerance to resident microflora antigens. Innate immunity changes revealed in last years, related to mutations of genes of bacterial structures receptors (NOD2, toll-like receptors, autophagy), cause disorder of endocellular signal processes and pathological activation of cells of adaptive immunodefense of intestinal mucosa and conforming profile of cytokines with development of chronic inflammation which will be mediated: at Crohn's disease – by Th1-and Th17-cells, cytokines IL-12, interferon-γ etc., at ulcerative colitis – by Th2-and NKT-cells, cytokines IL-4 and IL-3 in combination to incompetence of suppressor function of regulatory Т-cells and their cytokines TGF-β (transforming growth factor) and IL-10.Conclusion. Investigations of experimental enterocolites and human IBD confirm immunologic hypothesis of pathogenesis: relation of their development to defects of innate and adaptive immune system.

Cytokines and their receptors belong to a significant role in the initiation and the subsequent course and outcome of autoimmune thyroid disease. Interleukin-2 (IL-2), interleukin-4 (IL-4) and tumor necrosis factor-alpha (TNF-α)-cytokines, which have a multifaceted impact on the various stages of the immune response: the development of inflammatory response, cell proliferation, antibody and acute phase proteins synthesis. Pre-existing pattern of development of autoimmune thyroiditis (Hashimoto's thyroiditis) and Graves' disease (GD) as a state with two opposite positions of the predominant profile of Th1/Th2-lymphocyte activation. The study evaluated the cytokine production by Th1- and Th2-lymphocytes in patients with GD, assessment of lymphocyte receptor system and identified lymphocytes subpopulation in patients with BG, and the impact on the functional state of thyroid gland. It was shown that the immunoregulatory cytokines as Th1(IL2)- and Th2(IL-4)-helper lymphocytes are involved in the immune mechanism of BG. The level of IL-2, IL4, and TNF-α, and the number complementary lymphocyte receptors were not significantly changed in euthyroid or hyperthyroid GD patient. Nevertheless, there are strong correla! tions between production of immunoregulatory cytokines (IL-2, IL-4) with the functional state of the thyroid gland and increase of its volume in GD patient, what confirms the “functional synergies” of these cytokines in autoimmune inflammation in the GD.

Aim. To elucidate the role of Th1/Th2 polarization of immune response in LADA patients in the realization of the clinical phenotype of the disease. Materials and methods. 70 patients aged 21-61 (mean 41.3?1.0 yr) with DM diagnosed based on WHO criteria (1999). Groups 1 and 2 included 13 DM1and 57 DM2 patients (34.6?7.2 and 43.6?7.6 yr respectively). 27 DM2 patients (41.2?1.6 yr) presumably had LADA (P. Zimmet's criteria).Serum anti-GAD65, ICA, and IAA antibodies along with C-peptide were measured in fasting sera and 120 min after GTT by solid phase immunoenzymeassays following manufacturer's instructions with the use of a photometer for Multiscan EX microplates (ThermoLabSystems, Finland) at405 nm (for GAG and ICA) and 450 nm (for IAA and C-peptide). GAD, IAA, and C-peptides levels were calculated automatically from calibrationcurves. Mononuclear leukocytes were isolated by centrifugation in the ficoll-verographin density gradient. The cells thus obtained were resuspendedin the complete nutritient medium reducing their concentration to 2.0x10^6/ml. Phytohemagglutinin (Difco, Germany) was added (10 mcg/1 ml) tothe samples to stimulate mononuclear leukocytes; cell suspensions were further incubated for 24 hr. Initial and PGA-induced levels of IL-2, 4, 10 insupernatants of cell cultures were measured by solid phase immunoassay at 450 nm. Results. At least one type of autoantibodies (GAD, ICA or IAA) was identified in 24.3% of all DM patients (17/70) and in 18% of the DM2 patients(10/57). The level of anti-GAD and ICA ABs and percentage of AB-positive patients were higher in the LADA group while that of anti-IAA ABs amongDM1 patients without LADA. Two AB types at a time were found in 17% (4/23) of the patients with autoimmune DM in the absence of significantdifference between LADA and DM1. Patients with LADA had a significantly lower basal C-peptide level than DM2 patients. The was a tendencytoward lower level of stimulated C-peptide secretion in LADA patients compared with DM2 ones. It suggests impairment of beta-cell secretory functionaffected by the autoimmune process. We observed enhanced basal production of IFN-y by blood mononuclear leukocytes in all DM patients in theabsence of significant difference between the groups. Mitogen-activated production in all CD patients was lower than normal without inter-groupdifferences. Patients with DM2 had the inverted type of IL-2 secretion unlike those with autoimmune diabetes. In both cases it was significantly differentfrom normal values. There was a tendency toward higher basal production of IL-4 by mononuclear leukocytes in LADA and DM2 comparedwith CD1 which reflects pathogenetic peculiarities of beta-cell function in LADA differing from those in DM1 and responsible for slower impairment ofbeta-cell function in this condition. Basal and PGA- induced production of IL-10 was higher in LADA and DM2 than in DM1. It suggests enhancedsuppressor activity of leukocytes that may protect beta-cells from autoimmune destruction and determines gradual development of clinical symptoms ofinsulin deficiency. In contrast, low production of IL-10 in DM1 gives evidence of polarization of the immune response. Conclusion. The loss of functional parenchyma and manifestation of insulin deficiency in LADA occur at a relatively low rate due to the peculiarcharacter of cytokine-mediated cell interactions. It suggests the necessity of an active and careful diagnostic strategy with the use of immunologicalmethods for examination of elder patients presenting with a variety of pathogenetic variants of DM.

The characteristics of tick-borne borreliosis agents and borrelia reservoir hosts and vectors are presented in the article. Considered is participation of ticks' saliva components and superficial spirochete antigens in the mechanisms of mammals infectioning with borrelia. Immunopathogenesis of tick-borne borreliosis is described. The available methods of diagnostics and vaccine prophylaxis of tick-borne borreliosis are evaluated.

The review article provides information about the features of the Varicella-zoster virus (VZV), about the clinical manifestations of CNS damage in acute and chronic VZV infection in children and adults, about the mechanisms of interaction of the pathogen with the immune system during the development of the disease. The question of whether to consider neurological disorders in VZV infection as a complication or manifestation of the disease caused by a defective virus or the presence of subclinical immunodeficiency is discussed, which is confirmed by modern scientific studies. The critical mechanisms of immune defense against VZV, which are the main reason for the penetration of the virus into the CNS and the development of neurological disorders, as well as the relationship between VZV genotypes, the presence of mutations in the gE gene and the nature of the course, the identification of rare variants of the POLR3A, POLR3C, POLR3E and POLR3F genes associated with violation of IFNs induction, and the development of severe VZV infection, in which vasculopathy also occurs, which is the basis for the use of vascular drugs of complex action, such as Cytoflavin, the effectiveness of which has been proven by the authors. A special place is given to the analysis of intrathecal immunopathogenesis, which is likely to be associated with the presence and severity of neurological manifestations, their relapses. The issue of the causes of the development of a severe course of the disease in patients vaccinated against chickenpox, as well as the issue of resistance to specific antiviral drugs, probably associated with the presence of mutations responsible for the resistance of the virus to therapy, is discussed.

General pathophysiological mechanisms of inflammation are reviewed on the models of atherosclerosis, calcinating aortic stenosis, cardiac failure and osteoporosis widely encountered at old age.

A review of the current problems of nasal polyposis has been presented. The results of an analysis mainly of foreign literature have been given, which is reflected in EPOS 2012.