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In the North, humans are exposed to a number of unfavourable natural and climatic factors, which can negatively affect the body’s functions. In the process of adaptation, homeostasis is maintained by imposing a strain on the relevant organs and systems, including the immune system, whose disruption is usually accompanied by changes in the cellular composition of the pool of peripheral blood leukocytes and is reflected in leukogram parameters. The purpose of this study was to establish the informative value of integral haematological indices for preventive detection of changes in the immune status. Materials and methods. We examined 75 volunteers, including 52 residents of Konosha settlement and 23 residents of the city of Arkhangelsk (mean age 42 ± 10 and 44 ± 14 years, respectively). The subjects’ complete blood count was performed using the Medonic M20 cell analyser (Boule Medical AB, Sweden), and their leukocyte formula was calculated. The leukocyte intoxication index, nuclear index, allergization index and leukocyte shift index were calculated. Results. It was established that apparently healthy people living in the same region but in areas differing in natural and climatic conditions have statistically significant differences in the cellular composition of the leukocyte pool. In residents of the northern part of the Arkhangelsk Region (the city of Arkhangelsk), lymphocyte and band neutrophil count, as well as mean nuclear index and mean allergization index exceed the upper limits of their reference intervals. At the same time, residents of the region’s southern part (Konosha settlement) had a higher frequency of exceeding the upper limit of the reference interval of the leukocyte intoxication index. Integral haematological indices allow us to identify changes in the immune status at the preventive stage; their calculation can serve as an effective way to assess the degree of allergization, the level of endogenous intoxication and the reactivity of the immune system. Due to the simplicity and accessibility of the analysis, one can quickly obtain results and use them both for population screening and in surveillance studies.

Adaptive restructuring gets disrupted due to a reduction in the body’s reserve capacity at increased stress on the functional systems in response to the combined effects of adverse factors, including climatic. Determination of the state of blood transport systems and immune homeostasis broadens our understanding of how human body systems operate under adverse conditions of the North. The purpose of this article was to assess the state of the transport components of the blood system in relation to the immune status of the population of the European North of Russia. Materials and methods. A survey of 789 residents of the Arkhangelsk Region aged 21 to 55 years was conducted and their blood system parameters were analysed taking into account the levels of haptoglobin, transferrin, immunoglobulins and lipid transport complexes with their structural ligands. Results. Residents of the European North of Russia showed increased levels of transferrin in 31.8 %, IgM in 7.6 %, IgE in 7.8 % and low-density lipoproteins in 10.2 % of cases, as well as a deficit in IgA in 55.6 % and high-density lipoprotein apoA-I ligand in 56.2 % of cases. Elevated blood transferrin concentrations are associated with low CD71+ lymphocyte count, which reflects the inhibition of activation and proliferation processes when the signal from the CD3+ receptor is blocked. A decrease in the level of transferrin CD71+ receptors on lymphocytes is manifested in disturbed immunoglobulin class switching with the formation of IgA deficit, which is compensated by IgM and IgE. Increased immunoglobulin content ensures effective binding of metabolic products with autoantigen properties (low-density lipoproteins) when the functional properties of high-density lipoproteins are impaired due to the structural apoA-I deficit. Determination of the transport components of the blood system in relation to the state of the immune system is informative for assessing the risk of disruption of adaptive mechanisms.

Introduction. Campylobacteriosis is among the leading causes of acute gastrointestinal infections. The severity of campylobacteriosis and the development of long-term complications may be influenced by the genotype of the pathogen, whose biological properties can affect immune response parameters. The aim of the study was to identify common genotypes of epidemic clones of Campylobacter pathogens and to investigate characteristics of the immune response and severity of the disease. Materials and methods. The study included 203 patients aged from 1 month to 17 years with campylobacteriosis who underwent treatment at the clinic of the Federal State Budgetary Institution "DNKCIB FMBA" in 2019–2021. The diagnosis was confirmed using polymerase chain reaction method. Patient samples were also analyzed using culture-based methods. Total DNA was extracted using the QIAamp DNA Mini Kit. Genetic determinants encoding virulence factors and MLST typing were performed using the ResFinder program. The immune status of patients was assessed on days 1 and 7 of the illness. Immunological investigation included measurement of serum immunoglobulin concentrations (IgA, IgM, IgG), C-reactive protein, and cytokines (IL-1β, IL-1, IL-2, IL-4, IL-5, IL-6, IL- 7, IL-8, IL-10, TNF-α, and IFN-γ). Results. When analyzing the frequency of detection of Campylobacter sequence types in children with clinical intestinal infections, it was found that the profile of isolated isolates is most similar to those from countries of North America (USA and Canada), Northern Europe (Great Britain, Holland ) and Scandinavia (Denmark, Sweden, Finland). Identification of a pathogen with the flgE+, cdtA+, cdtC+ genotype was accompanied by a statistically significant increase in the level of IL-8 and a decrease in the content of IgA in the peripheral blood serum, which reflected the low efficiency of the immune response during infection with Campylobacter and predetermined the severe course of the infectious process during the disease.

Background. The profession of firefighters is characterized by the impact of a number of dangerous factors, including toxic fire products, which is currently not taken into account by the medical service and medical and psychological support units. To increase the effectiveness of measures aimed at preventing non-communicable diseases, protecting the health and improving the professional longevity of firefighters, it is necessary to take into account the influence of harmful professional factors that influence the formation of various pathologies. Intention of the study: to determine laboratory parameters characterizing the toxic etiology of the formation of fatty liver degeneration in firefighters. Methodology. To determine the features of the pathogenesis of non-alcoholic fatty liver disease, 246 male patients suffering and not suffering from fatty liver degeneration were examined. The tasks were solved by analyzing the results obtained using toxicological, biochemical, and immunological techniques. Results and Discussion. Laboratory markers of fatty liver degeneration have been determined. The peculiarities of the regulation of the immune system in employees of the GPS FPS of the Ministry of Emergency Situations of Russia suffering from fatty liver degeneration have been revealed. Conclusions. Multidirectional changes in instrumental, biochemical and immunological parameters were revealed in firefighters suffering from fatty liver degeneration compared to the control group with the same pathology, indicating the peculiarities of homeostasis disorders, which determines the difference in pathogenesis caused by chronic toxic damage by fire products.

Cellular immunity plays an important role in the control of SARS-CoV-2. Lymphopenia and a decrease in the functional activity of cells may be among the main reasons for deterioration of clinical outcomes of the disease. Usage of the bacterial therapeutic vaccine Immunovac-VP-4 during the inflammation phase may be promising for immunomodulation of the cellular immunity. The aim of our study was to evaluate the dynamics of lymphocyte subpopulations in hospitalized patients with COVID-19 upon combining the basic therapy with immunotropic drug based on the antigens from opportunistic pathogens. The study included 45 patients (18-70 years old) admitted with a confirmed diagnosis of moderate/severe infection caused by the COVID-19 virus. In addition to basic therapy, 33 persons of this group received Immunovac-VP-4 by a combined nasal-oral method. Subpopulation activity of peripheral blood lymphocytes in patients over time (at baseline, on the 14th and 30th day after hospitalization) was studied by flow cytometry by means of FC-500 Cytomics (Beckman Coulter, USA) using monoclonal antibodies (mAb) (Immunotech, France). In the group receiving only standard therapy, an increased number of T lymphocytes was detected on day 14 (79.9 (75.5-81.6), p = 0.00252), on day 30 from the start of treatment (78.4 (74.25-79. 2), p = 0.03662), and a decrease in B lymphocytes on day 14 (10.6 (7.78-11.63), p = 0.03236), on day 30 (7.85 (6.25-11.1), p = 0.01352) relative to baseline parameters upon admission. We revealed more pronounced changes in the parameters of cellular immunity relative to the initial parameters, i.e., an increased proportion of T lymphocytes on the 14th day (80.1 (73.8-84.2), p = 0.00018), and 30th day from starting the treatment (80.2 (76-81.9)), T helpers at 14 days after treatment (50.2 (43-57), p = 0.00694), cytotoxic T cells by 30th day of therapy (26.35 (24-29.4), p = 0.0114), decrease in B lymphocytes on day 14 (13.1 (8.2-16.9), p = 0 00158), on the 30th day from the start of treatment (8.2 (7.6-9.7), p

Occupational hazards affect immunological reactivity and increase the risk of infection with respiratory pathogens. The purpose of our work was to study the mechanisms and causes of developing carriage of streptococci possessing genetic determinants of resistance to antibiotics as health risk factors for workers engaged in coke production and basic oxygen steelmaking. We examined 136 workers of a ferrous metals industry and compared the prevalence of the carriage of Streptococcus pneumoniae, Streptococcus spp. and macrolide resistance genes (Mef, ErmB) in those engaged in coke production and basic oxygen steelmaking. We also collated the results of immunological examination of the carriers and non-carriers of S. pneumoniae. The control cohort was formed of engineering and technical personnel. We established that, compared with the controls, Streptococcus pneumoniae was a more frequent finding in the workers engaged in coke production and basic oxygen steelmaking (p ˂ 0.05). The cycle threshold value of Streptococcus spp. in them was also statistically higher. The Mef gene was more abundant in the steelmakers, including those carrying Streptococcus pneumoniae (p ˂ 0.05), and a change in immunological reactivity was detected in the cases carrying Streptococcus pneumoniae. In those engaged in basic oxygen steelmaking, significant changes were detected at the cellular level expressed by a reduced absolute number of mature T-lymphocytes (CD3+), T-helpers (CD4+), and T-suppressor/cytotoxic cells (CD8+) (p ≤ 0.05). At the humoral level, both the relative and absolute number of B-lymphocytes (CD19+) and the level of IgM were reduced, while that of IgG was, on the opposite, increased (p ≤ 0.05). In the coke plant workers carrying Streptococcus pneumoniae, the level of IgG was significantly higher than the control and reference values. We conclude that Streptococcus pneumoniae carriage in the steelmakers as a health risk factor was accompanied by a change in immunological reactivity and higher abundance of the Mef gene compared to the controls while in the coke production workers the related differences were detected only in the IgG level.

According to the WHO data, the number of infected people exceeded 765.2 million people during the COVID-19 pandemic. The severity of patient’s condition is determined by immune system hyperactivation. Activation of T- and B-lymphocyte subsets plays a prominent role in the control of infectious process. A content of small circular DNA molecules — T-cell receptor excision circles (TREC — T-cell receptor excision circles) and B-cell (“kappa”) excision rings (KREC — Kappa-deleting recombination excision circles) — in the peripheral blood can be used as a marker of the functionally active T and B cells maturation. The purpose of this work is to quantify peripheral blood TREC and KREC level in patients with the new coronavirus infection COVID-19 of varying severity.Materials and methods.The material consisted of 1028 blood samples from patients with a confirmed diagnosis of COVID-19, as well as 717 blood samples from apparently healthy volunteers. The content of TREC and KREC DNA fragments in the total DNA fraction was assessed by quantitative Real-time PCR using the “TREC/KREC-AMP PS” test system (St. Petersburg Pasteur Institute, Russia). Blood cell phenotyping was carried out using flow cytometry.Results.TREC/KREC levels were significantly reduced in COVID-19 patients (p 0.0001 at 95% CI). A significant direct correlation was established between the levels of peripheral blood TREC molecules and level of CD45+CD3+CD19–T cells (r = 0.59, p 0.0001), as well as between KREC level and count of CD45+CD3–CD19+B cells (r = 0.66, p 0.0001). The level of TREC molecules in patients with severe vs. moderate infection was significantly reduced in patients aged 30–39 years old (p = 0.0404) and 40–49 years old (p = 0.0356). The negative correlation between severity of COVID-19 clinical manifestations and TREC level in the blood of patients in 30–49 year age group indicates about an opportunity of using this analyte as a diagnostic and prognostic laboratory marker of patient’s condition. A simple PCR analysis algorithm makes it relevant to use the described method for assessing a state of immunity in coronavirus patients in the context of systemic negative impact of the SARS-CoV-2 virus on human organism.

The pandemic caused by a new strain of the SARS-CoV-2 coronavirus has swept the whole world but effective methods for treating this severe pathology have not yet been created. It has now been established that a risk of a severe course of COVID-19 is not so much a patient's age itself, but so-called age-related diseases; the renin-angiotensin system (RAS) is directly or indirectly involved into their development. The SARS-CoV-19 virus interacts with one of the main regulatory elements of this system, ACE2, and disrupts the balance between the two RAS branches. This ultimately manifests itself in an increase in levels of angiotensin II, which, through binding to the angiotensin type 1 receptor (AT1R), causes a number of pathological conditions, including hypertension, atherosclerosis, and cardiovascular diseases, enhances cell proliferation, apoptosis, death of vascular endothelial cells, etc. This process has been described in many reviews by Russian and foreign authors. However, cells of innate and adaptive immunity are another less well-described but no less important target of angiotensin II. The consequences of this interaction are analyzed in detail in this review. With COVID-19, dendritic cells are activated, macrophage proliferation and neutrophil infiltration increase with further involvement of CD4-lymphocytes and other cellular elements of the adaptive immunity in this process. Hyperactivation of the immune system is accompanied with the release of a large amount of pro-inflammatory cytokines, which can lead to the occurrence of a cytokine storm. The picture is aggravated by the inhibitory effect produced by the virus itself on the synthesis of signaling interferons at initial stages in its internalization into the cell. A separate section in the review ad-dresses the problem how to predict a risk of a developing serious condition and search for its predictors by analyzing the state of the RAS and ratios of key cellular elements in the immune system. This is extremely important for making decisions concerning the amount of necessary medical care and strategies for subsequent treatment.

The paper presents the results of complex immunological examinations of the patients with purulent inflammatory formations of the uterus appendages. Clinical and immunopathogenetic evidence of choice of the surgical treatment and postoperative immunorehabilitation are provided. Tactics of postoperative immunorehabilitation with use a recombinant interferon-α2b are developed in patients with heavy forms of purulent inflammatory formations of the uterus appendages.

Background. The participation of immune responses in the pathogenesis of degenerative-dystrophic diseases of the synovial joints determines the feasibility of using more rational approaches to assessing the immune status of patients with this pathology. Despite the ongoing immunological studies in patients with degenerative-dystrophic diseases of the hip joint, there are questions related to the functioning of the immune system as a whole, which require additional research.The aim of the study was to establish the features of the relationship between the indicators of the immune status and to identify the factors that determine the nature and severity of immunological disorders in patients with coxarthrosis.Material and methods. The study is based on the results of immunological parameters in 73 patients (mean age – 45.3 ± 2.56 years) with stage III dysplastic coxarthrosis. The data obtained using cluster analysis made it possible to distribute patients into two groups. The first clinical group included 46 patients, the second one – 27 patients. The control group consisted of 28 clinically healthy individuals. Mathematical processing of the results was carried out using the Statistica 6.0 software package (StatSoft Inc., USA) and the mathematical package Mathcad 2001 Pro (MathSoft Inc., USA).Results. The levels of CD4+ and CD8+ cells and IgA were determined as the classification features that make the greatest contribution to the division of the studied groups. Model experiments have shown that a specific combination of the magnitude of each of the noted factors with a certain degree of probability makes it possible to assess the state of the initial immunological reactivity and verify the nature and severity of immunological disorders.Conclusion. The information obtained is of great importance, since it allows predicting the course of the recovery period after surgery and assessing the risk of developing possible postoperative complications in patients with severe articular pathology.

The role of viral infection in bronchial asthma (BA) is well-known being reflected particularly in GINA. An effect of pneumotropic intracellular persistent herpesviruses on the course of BA is of particular interest. The most common viruses of this group are cytomegalovirus (CMV), EpsteinBarr virus (EBV), and human herpesvirus 6 (HHV-6). The CMV role has been discussed in our previous publications allowing us to focus here on EBV and HHV-6. We examined 167 children with BA that was diagnosed and clinically assessed in accordance with the current national clinical guidelines. Patients with controlled asthma (70 patients), partially controlled and uncontrolled asthma (97 patients) were stratified into several groups. The detection of EBV and HHV-6 DNA was carried out in throat swabs by PCR; the level of total and virus-specific IgA, IgM, IgG, IgE as well as serum level of IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-8 and TNF was assessed by enzyme linked immunosorbent assay; lymphocyte subpopulations were analyzed by flow cytometry. The dose of topic GCS was taken into account with reference to the fluticosone equivalent; the function of external respiration was studied by spirometry. It was revealed that EBV DNA was found in 14.2% of cases, whereas HHV-6 in 19.0% of cases, but 14.4% and 52.4% of patients, respectively, shed no pathogen-linked DNA. At the same time, patients with uncontrolled BA are significantly more likely to shed the pathogen DNA, so that EBV is released in 17.1% vs 4.5% of patients with controlled BA, HHV-6 in 19.5% vs 13.6%. On the contrary, children with controlled BA were significantly more often (63.6% vs 51.2%) negative for viral DNA shedding. Moreover, virus shedding was paralleled with higher levels of IL-5: it was as high as 0.91 pg/ml and 0.29 pg/ml for EBV and HHV-6, respectively; those shedding DNA of both pathogens vs no shedding had IL-5 at level of 0.25 pg/ml vs 0.11 pg/ml. Similar pattern was observed for higher total IgE: 184.5 IU for EBV, 113.1 IU for HHV-6, and 371.7 IU shedding both viruses vs 95.2 IU in without DNA pathogen shedding; lower level of FEV1: EBV 96.6%, HHV-6 98.8%, and 106.2% in patients shedding both viruses vs 109.8% in patients not shedding the pathogen DNA. Patients shedding EBV DNA require higher doses of topic GCS to achieve disease control: EBV 325.0 mg, HHV-6 186.4 mg; shedding both viruses 328.1 mg of topic GCS vs 198.6 mg in patients without pathogen DNA shedding. Thus, activation of both EBV and HHV-6 worsens BA control and aggravates its course, but EBV persistence has a more pronounced effect on the course and control of the disease.

Increasing attention is being paid to methods for detecting primary and secondary T and/or B cell immunodeficiencies. Their implementation into laboratory diagnostics would contribute to the early diagnostics of immunodeficiencies. Currently, the number of identified adult patients with immunodeficiencies of various origins is steadily increasing. Age, gender and ethnicity of patients may be significant factors of immunity. Hence, determination of the population reference intervals for TREC and KREC DNA excision rings in peripheral blood of adult persons is an urgent laboratory task for in-depth examination of both congenital and acquired immunodeficiency conditions. Our purpose was to determine the reference intervals for the quantitative assay of TREC and KREC fragments in peripheral blood among the adult population of St. Petersburg. We studied whole blood samples obtained from 717 apparently healthy volunteers aged 18 to 108 years within the program of population immunity assessment among residents of St. Petersburg. The exclusion criterion included immunodeficiency of any origin, viral hepatitis A, B, C, HIV infection. Quantitation of the target TREC and KREC DNA fragments was carried out using a set of reagents for the quantitative determination of excisional rings TREC and KREC by Real-time PCR (TREC/KREC-AMP PS). The reference intervals were determined by the direct method according to the recommendations of the International Federation of Clinical Chemistry and the Russian State Standard (GOST) R 53022.3-2008. The volunteers were divided into six age groups: 18-29, 30-39, 40-49, 50-59, 60-69 years old, and the persons over 70. The amounts of TREC and KREC in each blood sample were determined for all age groups. Upon correlation analysis, we have revealed a negative relationship between the concentration of TREC molecules in blood samples, and the age of study participants (Spearman correlation coefficient r = -0.80 (p-value < 0.0001)). Significant differences in TREC levels between different age groups were revealed. No correlations were detected between KREC contents in blood samples and age as well as any differences between age groups. Reference intervals of the TREC level were determined for each mentioned age group. A unified reference range was established for the KREC levels. The established reference intervals for TREC and KREC molecules in adults are significantly lower than in newborns. The obtained results enable determination of reference intervals for TREC and KREC levels among adults, thus contributing to effective personalized laboratory diagnosis of immunodeficiency states of various origins.

Introduction. The immune status is a multifaceted parameter quantitatively and qualitatively analyzing functional activity immune system state in immune organs as well as some non-specific mechanisms of antimicrobial protection. Peripheral blood level of T-receptor excision rings (TREC) and B-cell excision rings (KREC), respectively, can serve as surrogate markers of T- and B-cell maturation. Currently, the diagnostic kits available on the market have two significant disadvantages: i) the kits are aimed at diagnosing immunodeficiency conditions only in newborns and children, while keeping adult patients uncovered; ii) essentially, use solely single reference normalization gene for data normalization resulting in increased variability and decreased sensitivity of the assay data. The aim: to develop a highly sensitive method for laboratory assessment of the state of immunity in immunodeficient patients by using real-time PCR for assessing TREC and KREC level in children and adults. Materials and methods. There were used whole blood and dry blood spot samples obtained from newborns and adults, apparently healthy individuals as well as patients with verified PID and HIV-infection. A total of 2577 samples were examined. Commercial kits were used as comparison methods. Results. Multiplex PCR was carried out, analyzing the number of target molecules TREC and KREC, as well as fragments of the HPRT and RPP30 normalization genes analyzed with the developed series of plasmid calibrators. The established analytical range of TREC/KREC DNA measurements comprised 103 to 109 copies/mL. The accuracy of measurements on a tablet-type instrument (CFX) was 95.84%, on a rotary-type instrument (Rotor-Gene 3000) 95.11%, which corresponds to the standard indicator. The equivalence between the data obtained after assessing whole blood samples and dry blood drops was shown. The data analysis allowed to find out 100%-diagnostic specificity and sensitivity of the method proposed. Conclusion. The method developed by us allows to diagnose decline in T- and/or B-cell immunity in children and adults and can be used to detect TREC and KREC molecules both in peripheral whole blood samples and dry blood spots using Guthrie cards. Moreover, the uniform values of reference norms can be used regardless of the type of analyzed clinical material. The study data evidence about potential for effective use of multiplex PCR diagnostics both for complex primary testing/screening of newborns and assessing state of immunity to identify adult patients with PID and as a part of the diagnostic monitoring of patients with secondary immunodeficiencies, e.g., HIV infection.

In the context of the COVID-19 pandemic, scientific interest is growing in studying the impact of the proposed vaccination on women’s reproductive health. As is known, alterations in the state of the immune system and activation of an autoimmune response can lead to reproductive failure in women and potential complications of subsequent pregnancy. Objective: to evaluate the effect of the “Gam-COVID-Vac” on the immune status parameters, the relationship of their changes and the specific immune response to vaccination with the dynamics of the level of autoantibodies in women of reproductive age.The prospective study included 120 women who were vaccinated against COVID-19 with the “Gam-COVIDVac”. The criteria for inclusion in the study were: the age from 18 to 49 years, the absence of COVID-19 in the anamnesis, a negative result of a study on SARS-CoV-2 by PCR and negative results of tests for antibodies of classes G and M to SARS-CoV-2 before vaccination, the absence of pregnancy and serious somatic diseases. The patients were examined twice: immediately before vaccination and 90-100 days after the introduction of the 1st component of the vaccine. The level of IgG antibodies to SARS-CoV-2 after vaccination was assessed using ELISA. Before and after vaccination, the levels of antiphospholipid, anti-nuclear, organ-specific and antihormonal autoantibodies were determined, peripheral blood lymphocytes were immunophenotyped to determine the main subpopulations (CD3, CD4, CD8, CD19, CD5, CD16, CD56), as well as the expression of activation markers of lymphocytes (HLA-DR, CD25, CD147) using monoclonal antibodies.The effectiveness and safety of the combined vector vaccine against COVID-19 were high. Specific IgG antibodies to SARS-CoV-2 were produced in 98.3% of vaccinated women, no serious adverse reactions were observed. After vaccination, there was an increase in the level of some autoantibodies within the reference ranges, only IgM antibodies to phosphatidylethanolamine (PE) and IgG antibodies to DNA increased above the reference values. However, this increase was transient. After vaccination, the following changes in the parameters of the immunogram were observed: an increase in the content of cells with CD3+CD25+, CD19+ phenotype in peripheral blood and a decrease in the content of cells with CD56+CD16+ phenotype within the reference ranges, a decrease in CD147+/CD3+. Weak correlations were noted between these changes in immunogram parameters and the levels of some autoantibodies. The specific antiviral immune response to vaccination did not correlate with the autoimmune response.Vaccination with “Gam-COVID-Vac” is effective and safe and does not lead to disorders in the immune system. The observed increase in the level of autoantibodies to PE and DNA is transient. Changes in the parameters of the immune status within the reference ranges may be due to vaccination and the development of a specific antiviral immune response.

Aim. One of the important tasks in solving the problem of improving the efficiency of sheep breeding is the rational use of fodder lands in the North Caucasus and the South of Russia, a significant part of which is located in different natural and climatic conditions. The complexity of solutions lies in insufficient knowledge of the mechanisms of adaptation of farm animals, in particular sheep, to the ecological and geographical features of these regions. The purpose of this research was to study the genetic polymorphism of genes, the degree of genetic variability and immune status in sheep of different breeds, since genetic polymorphism is a measure of its adaptability and the hematopoietic function of blood is the basis of the life of the organism.Material and Methods. The genetic structure of the GH/Hae III, GDF9/AsplEI genes and immune status, was studied by the methods of genetic‐statistical and immune analysis in sheep of different breeds kept in different climatic zones of Dagestan and the Krasnodar Territory.Results. As a result of DNA genotyping of the studied samples of sheep of different breeds, it was found that polymorphism of GH/HaeIII, GDF9/AsplEI genes is represented by three genotype variants: homozygous GH/HaeIIIАА, GH/HaeIIIВВ; GDF9/AsplEIАА, GDF9/AsplEIGG; heterozygous GH/HaeIIIAB; GDF9/AsplEIAG and two alleles: A and B – of the GH/HaeIII gene; A and G – GDF9/AsplEI gene with different frequency of occurrence, respectively.Conclusion. For the first time, genetic variability has been studied in the context of the immune status of sheep populations of different breeds bred in the foothills of the Republic of Dagestan and Krasnodar Territory. The information obtained about the role of the degree of genetic variability and the immune status of sheep of different breeds is answered in the formation of adaptive‐compensatory mechanisms to specific conditions of the breeding environment. A deeper study of the adaptive characteristics of sheep of different breeds for their further improvement allows the use of molecular genetic and hematological methods.

The purpose is to characterize the clinical picture, immune status and the natural history of HIV infection in the stage of secondary diseases in vertical and parenteral infected children.Materials and methods. A clinical, laboratory, instrumental, immunological examination of 132 children in the stage of secondary diseases infected with HIV in a vertical way (90; I group) and parenteral way in infancy (42; II group) was carried. Results. The clinical picture of HIV infection in the stage of secondary diseases included various combinations of HIV-associated symptoms, opportunistic infections, tumors, which determines the symptomatology of a particular stage. The use of the Cox regression mathematical model of proportional intensities demonstrated a reduction in the duration of stage 4A (RR 5.8; 95% CI 1.4—10.5; P < 0.001), 4B (RR 3.4; 95% CI 1.8—4.3; P < 0.001) and 4V (RR 4.8; 95% CI 1.2—8.9; P < 0.001) in children of group I. Using the method of multiplying Kaplan-Meier estimates, the significant differences between the time curves from the beginning of the 4A stage (Р = 0.044), 4B (P < 0.001) and 4V (Р = 0.029) before the transition to the subsequent stage in children of groups I and II were established. The content of CD4 lymphocytes in the blood in patients of group I was higher as compared with group II at the time of debut of stages 4A (Me 37.5%, IQI 33—40% and Me 22%, IQI 18—24%; Р < 0.001), 4B (Me 25%, IQI 22—28% and Me 20%, IQI 18—22%; Р < 0.001) and 4V (Me 14%, IQI 12—18% and Me 11%, IQI 10—14%; Р = 0.047).Conclusion. HIV infection in the stage of secondary diseases in children infected with the vertical way is characterized by more rapid progression compared with parenteral infected in infancy patients, which is associated with the immaturity of the immune system.

The aim of the study was to study the effectiveness of the use of immunomodulators and antioxidants in the correction of immune status parameters in patients with adenomyosis. 70 patients were examined, including 57 women (the main group), who were diagnosed with adenomyosis according to the results of a comprehensive clinical, ultrasound and hysteroscopic examination. The control group consisted of 23 gynecologically healthy women. After verification of the diagnosis, all patients with hypertension received standard treatment (SL) (clinical recommendations of the Ministry of Health of the Russian Federation from 2016). Among the female patients, 19 women received only SL (1st subgroup). 38 exhaust gases examined, in addition to SL, received various combinations of antioxidant, immunomodulator, and membrane protector and were divided into two subgroups. The second subgroup included 20 patients in addition to the SL receiving sodium ribonucleate; Hypoxene and phospholipids. The third subgroup included 18 patients who additionally received Inosine + Nicotinamide + Riboflavin + Succinic acid; Meglumine acridone acetate, and glycyrrhizic acid + phospholipids. The analysis of the cytokine status and the compliment system was performed at the time of admission and by the 15th day of observation. Detected changes of the cytokine status, complement system activation, increased oxygen-dependent activity of neutrophils in the peripheral blood (increased production of active oxygen forms as a result of respiratory burst) confirm the presence of immune inflammation on the systemic level. Insufficient clinical-laboratory efficacy of ST in the correction of immune changes has justified the use of drugs with immunomodulating, antioxidant, and membrane protective properties in the pharmacological therapy of adenomyosis, which have been successfully used in the treatment of other diseases with similar disorders.Optimal combinations of immunomodulators and antioxidants in the correction of the immune status of patients with adenomyosis were revealed. The study performed demonstrates the efficacy of correcting immune status parameters in patients with adenomyosis when the standard treatment is combined with antioxidant and immunomodulating agents.

Specific prevention is one of the most effective methods for the control of infectious diseases causing considerable economic damage to commercial pig farms, among which is porcine pleuropneumonia. In order to improve the effectiveness of preventive vaccination, various immunomodulators that differ in their origin and mechanism of action are used. The paper presents the results of the study of the effect of such products as biferon-S and prostimul containing species-specific recombinant interferons on the immune status of piglets during specific prevention of porcine pleuropneumonia. Tests were carried out in clinically healthy 30–35-day-old piglets immunized with Ingelvac® APPX vaccine (Boehringer Ingelheim Vetmedica GmbH, Germany). It was found that the use of biferon-S and prostimul together with the vaccine administration is accompanied by immune status improvement in the animals, which is manifested as an increase, in comparison with vaccinated animals that received no interferon-containing products (base case), in serum levels of γ-globulins – by 34.6 and 53.7% (in case of prostimul and β-globulins – by 10.1%), total immunoglobulins – by 32.8 and 37.8%, large circulating immune complexes – by 37.5 and 52.6%, a less significant increase in the levels of small complexes and, as a result, pathogenicity coefficient reduction by 5.4 and 12.4%, respectively. Tests for post-vaccination immunity levels in piglets showed a 3.8-fold increase in the levels of specific antibodies against the antigen of porcine pleuropneumonia agent, and in case of the vaccine administration in combination with biferon-S and prostimul – a 4.0-fold and 4.9-fold increase, respectively. The use of prostimul was accompanied by a more considerable improvement of immune status in the piglets, and this is attributable to the fact that vitamins А, Е and С, which have antioxidant properties and improve the effectiveness of interferons, natural resistance and specific immunity, are included in its composition in addition to recombinant type 1 cytokine.

Increased incidence of ulcerative colitis (UC) is a prerequisite for searching new therapeutic approaches, primarily with an opportunity of site-directed impact on the colon lesion. UC pathogenesis is associated with dysregulated immune response, and limited effectiveness of basic therapy for the disorder. Vitamin D3 exhibits antioxidant, anti-inflammatory, immunomodulatory and other properties, it has been shown to be effective in some autoimmune diseases, thus prompting us to study its effect on immune status in UC. We aimed for studying the effect of vitamin D3, as a component of original rectal suppositories, upon clinical course and indexes of immune status in experimental UC. UC in rats was modeled with 3% oxazolone solution. The vitamin D3-containing suppositories (1500 IU) weighing 300 mg were administered per rectum every 12 hours for 6 days. On days 2, 4 and 6 of UC, the clinical features were assessed as well as blood leukocyte counts, numbers of CD3+, CD45RA+; absorbing and NBT-reducing abilities of blood neutrophils were determined; IgM, IgG, IL-6 and IL-8 concentrations in serum were also studied.The DAI index increased in non-treated UC, along with raised neutrophil numbers in blood, their absorption and NBT-reducing activity was also increased, the total number of lymphocytes, including CD3+, CD45RA+ became higher, serum concentrations of IgM, IgG, IL-6, IL-8 increased. Local use of vitamin D3 in UC reduces DAI parameters, causes decrease in blood neutrophil counts, reducing and partially restoring absorptive and NBT-reducing abilities of neutrophils, decline of total lymphocyte counts in blood, partially restoring the CD3+ and CD45RA+ numbers, causing decline and partial restoration of serum IgM, IgG, IL-6, IL-8 concentrations. An association between clinical signs and indexes of immune status in UC was established under the conditions of vitamin D3 use. Conclusions: The protective effect of vitamin D3 in UC can be mediated by its antioxidant effect, changes in production of immunoregulatory cytokines, modulation of Th1-, Th2-, Th17-dependent reactions and Treg activity, being a pre-requisite for further studies to clarify the mechanism of vitamin D3 immunotropic action in UC,with an opportunity of using it in clinical practice.

Background. The effect of geomagnetism on human immunity has so far been studied through long-term observations. We set ourselves the goal of detecting the immediate immunotropic effects of the Earth's magnetic field by analyzing the relationships between immunity parameters and the geomagnetic Ap-index. Material and methods. The object of observation were 74 patients with multiple sclerosis and 14 patients with radiculopathies, who in the period from September 2014 to November 2018 conducted a one-time assessment of immune status by the relative content in the blood of lymphocytes of CD3+, CD4+, CD8+, CD25+, CD56+ and CD19+ phenotypes and serum level of Immunoglobulines M, G, A as well as CIC and IL-1β. On the day of blood capture and during the previous 7 days, retrospectively recorded the geomagnetic Ap-index, using a publicly available information resource http://wdc.kugi.kyoto-u.ac.jp/kp/index.html. Results. During the week, the average level of Ap-index ranged from 12÷20 nT. The correlation coefficients between the Ap-index on the day of blood collection and 1, 3 and 7 days before it and the level of CD3+CD4+ lymphocytes were -0,57; -0,48; -0,55 і -0,52 respectively, while on other days were in the range of -0,35÷0,05. In contrast, with the level of CD56+ lymphocytes Ap-index correlates positively and almost mirror (0,56; 0,43; 0,54 і 0,57 respectively and 0,34÷-0,08), due to the reciprocity of their levels (r=-0,80). Also positive, but much weaker, correlates the Ap-index with the level of CD25+ lymphocytes (0,35; 0,25; 0,45 і 0,31 respectively and 0,22÷-0,14). In contrast, with the level of IL-1β Ap-index correlates significantly only on the day of blood collection and 2 days before (r=0,21 and 0,31 respectively), and with other registered parameters of immunity the correlation is insignificant. The canonical correlation between Ap-indices for 7 days before and on the day of blood collection, on the one hand, and the levels of CD4+, CD56+, CD25+ and CD8+ lymphocytes and the concentration of IgM and IL-1β - on the other hand, was very strong: R=0,741; R2=0,549; χ2(42)=130; p-6. Conclusion. Disturbances of the geomagnetic field (Ap-index) has a significant immediate modulating effect on the level of immune parameters in the blood, mostly T-helpers (suppressor) and natural killers (enhancing).

The aim of the study was to identify a relationship between gene polymorphisms associated with developing coronary heart disease and pathogenetic features of opisthorchiasis invasion. There were compared laboratory parameters assessing the immune system functioning (lymphocyte immunophenotyping evaluated by flow cytometry, serum immunoglobulin and cytokine concentrations, non-specific resistance indices) in patients with chronic opisthorchiasis (caused by Opisthorchis felineus) of various genotypes with/without mutations in loci associated with predisposition to developing coronary heart disease. It was found that opisthorchiasis invasion leads to altered immune response in patients bearing mutations in genes encoding adenosine monophosphate deaminase 1, hypoxia induced factor 1 alpha, and apolipoprotein E affecting relevant protein functions compared to those without minor alleles. Upon that, patients carrying mutation in the adenosine monophosphate deaminase 1 gene, turned out to have lowered cellular (decreased count of cytotoxic lymphocytes) and humoral immunity (decreased immunoglobulin A level). Patients with opisthorchiasis bearing a rare allele in the hypoxia-induced factor 1 alpha gene were featured with activated adaptive immunity and reduced activation of innate immunity. Moreover, mutated apolipoprotein E gene was coupled to decreased activity of cellular immune response, which exacerbates the course of opisthorchiasis invasion, whereas minor allele of the rs1333049 polymorphism in the cyclin-dependent kinase inhibitor gene results in no significantly altered immune response. Thus, gene-related dysfunction of certain proteins may allow opisthorchiasis invasion to elicit multidirectional changes in immune response, so that approaching the normal range of diverse immune-related parameters during chronic parasitic invasion may not necessarily be interpreted as a “protective” effect exerted by any of gene polymorphisms. The most prominent changes in immune response of patients with chronic opisthorchiasis were detected in case of polymorphism in the factor-induced hypoxia-1 alpha gene. The data obtained suggest that the aforementioned genetic polymorphisms may predispose to manifestation of certain opisthorchiasis clinical forms.

The prevalence of bronchial asthma has shown its steady increase in the world in recent years. Despite all the achievements of Allergology, control of the disease can be achieved only in two-thirds of patients even if all social risk factors and the influence of concomitant diseases are excluded. Thus, it is necessary to study endogenous factors that modify the pathogenesis of the disease. Toll-like receptors are the main molecules for recognizing pathogenic patterns in the human immune system. Since any Allergy is a recognition error, mutation of the genes of the recognizing molecules can have a direct and multidirectional effect on the nature of the inflammation and its clinical manifestations in bronchial asthma (BA). To detect this effect, 65 patients with BA were examined, and mutations of Toll-like receptor genes were detected: TLR2-Arg753Glu, TLR4- Asp299Gly, TLR4-Ghr399Ile, TLR9-T1237C, TLR9-A2848G, lymphocyte subpopulations CD3, CD19, CD4, CD8, CD16, phagocytosis indicators, levels of IgA, IgM, IgG, IgE and IL-6, IL-7, IL-9. The assessment of the severity of asthma and its level of control were conducted according to clinical recommendations of the Ministry of health of the Russian Federation in 2019 criteria. We have shown characteristic clinical manifestations of the studied mutations. A lighter course of the disease, more complete control over it and a better response to therapy were found in single-nucleotide substitutions in the Toll-like receptor 4 and 9 (TLR4-Asp299Gly, TLR4-Ghr399Ile, TLR9-T1237C, TLR9-A2848G). On the contrary, a heavier course and a worse response to therapy were detected in the TLR2 mutation with Arg753Glu replacement. In the studied groups, the features of immunity indicators characteristic of genotypes with a lighter and more controlled course of BA were determined: a higher absolute number of T-helpers, with multidirectional changes in the number of T-killers, but with invariably preserved higher ratio of CD4/CD8 in such genotypes. Higher levels of phagocytosis indicators (primarily characterizing chemotaxis) and IL-7, IL-9 were also detected. The exception is the TLR9-A2848G mutation, in which greater disease control and better response to therapy are combined with no changes in the studied laboratory characteristics. At the same time, a specific feature of the genotype of the studied patients with BA was revealed – a combination of Toll-like receptors 4 and 9 mutations. This suggests the presence of genetic patterns that characterize groups of patients with BA that differ in severity, response to therapy, and degree of control, which makes it possible to personalize approaches to diagnosis, prevention, and therapy of the disease.

Objective: to evaluate the effectiveness of the application of bee products in correction of signs of fatigue during the recovery period in athletes of complex coordination sports. Materials and methods: 40 athletes of complex winter sports 15-21 years old (mean age - 19.05±3.42 years (M±m)) were examined: the main group (24 people) received 10% aqueous-alcoholic extract of bee moth larvae during 25 days of the recovery period; rantrol group (16 persons) received dry adsorbed royal jelly. The parameters of hematopoiesis, immune and hormonal status, physical working capacity were studied. Results: a decrease in the concentration of TNF-a and IL-4, and increase in IL-1ß and IL-6 within the reference values was established after the course of beekeeping products intake in both groups of athletes. The administration of the bee moth larva extract resulted in a decrease in the CIC (p = 0.010), an increase in the CD3 +, CD 19- lymphocytes (p = 0.028), CD3 +, CD4 + lymphocytes (p = 0.016), and signs of stimulation of erythropoiesis in the form of an increase in erythrocytes (p = 0.016) and reticulocytes (p = 0.027), as well as an increase in testosterone (p = 0.038) and physical performance (p = 0.041; p = 0.034), that was more pronounced in comparison with the royal jelly intake. Conclusions: the use of bee moth larva extract in the recovery period resulted in more significant improvement in the state of the oxygen-providing blood system, correction of the immunological imbalance and hormonal parameters of adaptation, and preservation of the level of physical fitness achieved in the competitive period in comparison with royal jelly.

Treatment of chronic viral infections accompanied by permanent virus persistence in the target epitopes of the oral cavity, skin, urogenital tract is complicated by virtual lack of available drugs exerting combined systemic virulicidal and immunomodulatory effects. Here we demonstrate clinical and immunological efficacy of combined therapy in treatment of Epstein–Barr virus (EBV)-associated chronic infections. The aim of the study was to evaluate the clinical and immunological efficacy of combined etiopathogenetic therapy using the Acegram cosmetic product in patients with EBV-associated chronic infections. Materials and methods. There were enrolled 40 patients monitored before treatment as well as 20 patients followed up after combination therapy (cycle therapy consisted of oral valaciclovir (Valtrex) applied at dose of 500 μg twice a day for 10 days, glucosaminylmuramyldipeptide (Licopid) — 10 mg 2 twice a day for 10 days, topical irrigation for mucous membranes with granulocyte-macrophage colony-stimulating factor active center-derived peptide (Acegram-spray) 3 times a day for 10 days. If necessary, treatment courses were repeated 20 days after the onset. All patients were examined for the presence of EBV genomes in the oral fluid and blood using the qualitative and quantitative polymerase chain reaction (PCR) using the DNA technology test system (Russia) on a DT-Lite device prior treatment and 30, 60 days post-therapy time points. In addition, serum samples were analyzed for level of class G immunoglobulins specific to the EBV nuclear and capsid antigens by using enzyme immunoassay (test systems manufactured by CJSC Vector Best, Russia) as well as immune status (clinical methods, enu flow cytometry evaluation of the phagocytic activity of neutrophils, ELISA method). Results. Use of single or two course combination therapy in subjects with fully eradicated EBV carriage associated with reversed clinical symptoms was accompanied by recovered immune system status (T and B cells, T-helper cells, CD3+ CD25+ cells, phagocytosis parameters). A non-invasive approach proposed for controlling virus elimination in the oral fluid by using polymerase chain reaction method may serve as to objectively monitor therapeutic efficacy.

Crohn’s disease is an urgent problem of modern gastroenterology due to increasing prevalence, severity of complications and side effects of the basic therapy, in particular upon treatment with 5-aminosalicylic acid (5-ASA). Searching, development and trials of new effective drugs with minimal side effects in Crohn’s disease is an urgent task. Curcuma longa is one of the initial substances containing curcumin with antioxidant, cytoprotective, anti-inflammatory properties. Its effectiveness has been demonstrated in few studies with its systemic use in Crohn’s disease treatment. Our aim was to perform a comparative analysis of curcumin and 5-ASA effect applied as a composition of rectal suppositories, studying clinical signs and indices of immune status in experimental Crohn’s disease. The study was performed on 70 Wistar male rats. Crohn’s disease was modeled by introduction of a 50% alcohol solution of trinitrobenzene sulfonic acid (TNBS) per rectum, and verified by clinical and morphological methods. Rectal suppositories, each containing 50 mg of 5-ASA and original suppositories containing 0.075 mg of curcumin were used over 12 hours during 7 days. The studies were performed on the 3rd , 5th and 7th days of Crohn’s disease.In the course of experimental TNBS-induced Crohn’s disease in animals, an increased frequency of bowel motility, appearance of blood in the stool, decreased body weight progressed from the 3rd to the 7th days of observation, along with increased number in CD3+, CD45RA+ lymphocytes in blood, higher number of segmented neutrophils, lower absorption and NBT-reducing activity of blood neutrophils, increased serum concentrations of IL-23, IgM, IgG. Composition of the new medication form was justified; production technology and standardization of the suppositories containing curcumin for the treatment for Crohn’s disease were developed. Usage of rectal suppositories with curcumin is associated with decreased severity of clinical signs, decrease and partial restoration of segmented neutrophils, CD3+ lymphocyte numbers in blood, recovery of absorption and NBT-reducing ability of blood neutrophils, and decrease of IL-23, IgM, IgG concentrations in serum. The effectiveness of rectal suppositories with curcumin is compared to the effectiveness of the use of rectal suppositories with 5-ASA in terms of disease activity index, the number of neutrophils and CD3+ lymphocytes in the blood, serum concentrations of IL-23, IgM and IgG, in, at lesser extent, in terms of absorption and NBT- reducing ability of blood neutrophils.The composition and production technology of rectal suppositories with curcuminwas developed; the leukocyte populations, CD3+, CD45RA+ lymphocytesin blood were assesed, neutrophil absorption and NBT-reducing ability, IL-23, IgM and IgG concentrations were determined; the use of rectal suppositories with curcumin in experimental Crohn’s disease is comparable with the effectiveness of rectal suppositories with 5-ASA.

Osteomyelitis of the jaw bones is an infectious inflammatory process of odontogenic or post-traumatic nature, which in recent years has significantly changed its clinical picture. The purpose of the study was to study the relationship between the parameters of the immune status in patients with chronic osteomyelitis of the lower jaw and the clinical course to elucidate the prospects for the use of immunotropic drugs. Results. It is concluded that the study of the parameters of systemic immunity in patients with chronic osteomyelitis followed by appointment of immunotrophic polyoxidonium preparation, increases the effectiveness of complex treatment of patients.

Aim. To compare by flow cytometry the cellular immune status indicators in persons, living on the territory of the Caspian sandy natural plague focus for epidemic indications. Materials and methods. Whole blood leukocytes of 120 people were examined by flow cytometry with using the two four-color labeled monoclonal antibody reagents (Cyto-Stat CD45-FITC, CD4-PE, CD8-ECD, CD3-PC5 и Cyto-Stat CD45-FITC, CD56-PE, CD19-ECD, CD3-PC5) and by means of CD95-FITC reagent. The results were taken into account before and in a month and 6 months after vaccination. We were determined in the blood the relative content of lymphocytes, monocytes, granulocytes, leukocytes carrying an early apoptosis marker (CD95), T and B- lymphocytes, NK cells as well T – lymphocyte helpers (Th) and cytotoxic T-lymphocytes (Tcyt) for immunoregulatory index (IRI) calculation. Results. Before anti-plague vaccination in 14 people (11,7%) were found abnormally low immunoregulatory index values characterized the immunodeficiency state (IRI

Oral mucosal lesions hold one of the lead places in the structure of dental diseases. Oral lichen planus (OLP) considered as a multifactorial disease is of top priority among dermatoses of oral mucosa and red lip border. Diverse putative concepts behind developing lichen planus pathogenesis are discussed including immunoallergic, viral, genetic and membrane-destructive theories. However, an immune theory is thought to play a crucial role in developing lichen planus. Despite documented induction of immune mechanisms, complex interaction between pathological process and normal defense response as well as stirred interest to it, multiple aspects of immunological conflict in lichen planus remain unclear. Few data describing altered immune parameters depending on clinical picture of lichen planus are currently available that suggested to perform the study aimed at examining immune status in patients with various forms of oral lichen planus. There were enrolled 286 oral lichen planus patients (248 females and 38 males), aged 27–84 years. Based on clinical picture, all OLP patients were divided into 6 groups: a typical type, exudative-congestive, erosive-ulcerous, hyperkeratotic, atypical, bullous type. An immune status in peripheral blood samples was evaluated by analyzing innate defense mechanisms as well as humoral and cellular immunity. Multiple altered immune parameters characterized by impaired phagocytic capture and metabolic activity, disimmunoglobulinemia, altered ratio of major immunocompetent cell types and subsets were documented during the study. Moreover, OLP patients with typical, hyperkeratotic, exudative hyperemic, atypical and erosive ulcerous forms were found to have increased amount of CD4+ helper T cells associated with a self-sustained immune response due to suppressed elimination of pathogenic agents consequently resulting in developing autoimmune process. While analyzing immune status in OLP patients, it allowed to find a relationship between dysphagocytosis signs, impaired humoral and cellular immunity as well as various clinical forms of the disease. Thus, it suggests imbalanced mechanisms responsible for pathogen elimination might play a role in OLP pathogenesis, including infectious agents being involved in its development.

Apoptosis is defined as a highly regulated form of programmed cell death with typical morphological and biochemical features. A variety of factors, including heavy metals, may influence the intensity of programmed cell death. The aim of the work was to simulate apoptosis in an in vitrosystem under the conditions of stable strontium exposure. The children’s population consuming drinking water with high strontium (Sr2+) content (n = 49) was observed. The level of lymphocyte apoptosis was determined with flow cytometry technique, by means of labeled annexin V-FITC conjugate (AnnV-FITC) and propidium iodide (PI) staining. AnnV-FITC+PI- cells were regarded as early apoptotic forms, whereas late apoptotic and/or necrotic cells were AnnV-FITC+PI+. The isolated leukocytes were incubated with Sr2+ at a concentration of 7.0 mg/l, the maximal permitted concentration (MPC) for water of aqueous objects, for 4 hours at 37 ºC. Expression of CD95 and p53 apoptosis markers was performed by flow cytometry using labeled monoclonal antibodies.In vitroexposure to strontium was associated with significantly decreased expression of apoptosisregulating factors, i.e., membrane marker CD95 and intracellular transcription protein p53, 1.56- and 1.68-fold, respectively. Meanwhile, we revealed a significantly (4.68-fold) decreased amounts of AnnV-FITC+PI--cells, as well as a statistically significant (1.35-fold) increase of the AnnV-FITC+PI+-cells. Moreover, the amounts of AnnV-FITC+ PI--lymphocytes in all samples were below the physiological ranges and control values. The number of samples with higher contents of AnnV-FITC+PI+-lymphocyte exceeding the established standards and control values, was 30.8%. Thus, it has been experimentally proven that strontium, at a concentration corresponding to MPC for water objects may significantly inhibit cell death along apoptotic pathways, with switching to necrotic cell death mechanisms, according to phosphatidylserine contents, as detected by annexin V binding test. The data have revealed an ability of strontium to have a significant effect upon the parameters of regulation and maintenance of cellular homeostasis, by influencing the apoptosis intensity, due to shifting a balance towards necrosis and reducing expression of apoptosis-regulating factors. The results of this study may be used in order to identify some marker indexes of immune disorders potentially induced by external influence of strontium upon human health under specific environmental factors.

The aim of this prospective randomized clinical study was to investigate the role of preoperative carbohydrate admnistration in surgery-induced metabolic, immune and inflammatory reactions after thoracoabdominal operations. At the Surgical department I (B.V. Petrovsky National Research Center of Surgery), we investigated a modulatory role of carbohydrate preload upon surgical stress observed after major thoracoabdominal operations (thoracoscopic and open esophagectomy, retrosternal colonic esophagoplasty) followed by the enhanced recovery protocol. The study was performed in 2014-2017, it included 30 patients, divided into 2 groups. Group A patients (n = 16) received carbohydrates preload (12.5% maltodextrin solution per os or enterally). In patients with dysphagia, the 12.5% dextrose solution was used intravenously in equal volumes. Group B patients didn’t receive any additional preload with carbohydrates. The groups were age- and gendermatched, similar for disease and surgery types. Glucose and insulin levels (with HOMA insulin resistance index, HOMA-IR) were measured before surgery and on day +1, interleukin levels (IL-6, IL-10, IL-8) and index IL-8/IL-10 were assessed before surgery, and on days +1 and +5 after surgery. Cell-mediated immunity was investigated before surgery and on day +5.The stress-induced hyperglycemia (> 7.8 mmol/L) was detected more frequently in group B (50%), than in group A (6%), p = 0.012. Insulin resistance measured by HOMA-IR in group B was detected in 71% of patients and in 25% patients of group A only, p = 0.027. Individual analysis of immune response demonstrated that a trend for immune recovery was detected by the day +5 post-op in the group A. Postoperative levels of IL-6 and IL-10 were lower on day +1 and +5 in group A. Morbidity rates and the terms of hospitalization were similar in both groups. Local postsurgical infections in group A were developed in 6% of the patients vs 35.6% in group B (p = 0.072).In conclusion, a complex study of surgical stress, i.e., metabolic, immune and inflammatory reactions after esophageal surgery has shown that the carbohydrate preload decreased the incidence of postoperative insulin resistance and stress-induced hyperglycemia, being accompanied by lower release of proinflammatory cytokines and provides positive effects upon the patient’s immune system.

Research objective. Statistical data concerning patients with opportunistic infections depending on parameters of immunity and the description of a number of clinical cases of development of opportunistic lesions in patients with HIV infection in the absence of the expressed immunodeficiency. Materials and methods. Medical records of the patients with HIV infection hospitalized in 2012-2015 in the Infectious Diseases Clinical Hospital No. 2 of Moscow, and the clinical cases of patients with development of opportunistic lesions with satisfactory indicators of the immune status. Results. The distribution of patients with HIV infection who had opportunistic infections, depending on the number of CD4+ lymphocytes at the time of development of the disease revealed a significant group of patients with a sufficiently large number of CD4+ cells. Statistical data on the development of various opportunistic lesions with different parameters of the immune status are presented. The authors describe a number of relevant clinical cases. Discussion. The possible causes of the development of opportunistic diseases and their recurrence in patients with HIV infection with a satisfactory amount of CD4+ lymphocytes are discussed. In the pathogenesis of this phenomenon are important not only quantitative but also qualitative parameters of immunity, as well as the characteristics of the causative agents of opportunistic lesions.

Background. Pneumonia in newborns is a topical problem of pediatrics because of its significant morbidity, high disability. At present, there is no doubt that the immune system plays a leading role in the pathogenesis, clinical manifestations and outcome of respiratory diseases in newborns. The purpose of the study was to investigate immune status in newborn children with pneumonia. Material and methods. Immune status was studied in 20 healthy newborns and 32 children with neonatal pneumonia. Results. The state of immunity in newborn infants with infectious inflammatory diseases of the lung is characterized by an increase in the early precursors of T and B lymphocytes, immature T-lymphocytes and neutrophils, lack of mature immunocompetent cells (T and B lymphocytes, monocytes and neutrophils). Conclusions. In newborns with pneumonia there are significant changes in the immune system and factors of nonspecific protection, leading to secondary immune deficiency.

The report presents the results of own research of the most important factors in the genesis of various forms of sterility. A married couples (n = 50) was examined with regard to possible etiological structure of these forms of pathology — infections of the family herpes (Herpes simplex types 1, 2, Cytomegalovirus hominis (CMV), Epstein–Barr virus (EBV) and genetic distribution for the second class of histocompatibilit (HLA II class): HLA-DRB1, HLA- DQA1 и HLA-DQB1. The authors present own data on genetic typing of the couples for the second class of histocompatibility, which allow to correlate these data with clinical and laboratory associations with infectious agents (infections of the herpes family). The genetic characteristics that determine the reproductive ability of the couple are associated with susceptibility to certain infectious markers. It is shown that the dominant majority of couples determined the HLA- DRB1 gene, which is more frequently associated with infections of the herpes family. Despite the fact that the level of positive PCR results in the group of couples with primary infertility was higher than in couples with secondary sterility (100 and 92%, respectively), maximum titers of specific antibodies to infections of the herpes family, including the frequency of markers of exacerbation, definition of IgM was higher than in the group of couples with primary infertility, and significantly higher than in couples with normal fertility. So, this antigen histocompatibility (HLA-DRB1) is associated with significant frequency of sterility, especially the secondary one, and infectious contamination infections of the family of herpes — HSV 1, 2 types, CMV, EBV in the study group — couples with secondary infertility. Marker HLA-DRB1, the most frequent in coup les with infertility, including idiopathic, associated in this group not only with significant contamination of infectious of the herpes family, but the presence of a chronic infectious process at the stage of reactivation. Conducted clinical and immunological studies clearly demonstrate the need for a comprehensive survey of women with disabilities in the system of immunogenesis with the mandatory assessment of the level of infectious (viral) contamination. Analysis of the results of their clinical and immunological studies allows us to propose an algorithm of complex examination in functional disorders in the system of immunogenesis, including the study of viral load as a necessary component.

The carried out research revealed negative impact of chronic T-2 toxin intoxication on immune status of white rats vaccinated against Salmonellosis. This is illustrated by erythropoiesis inhibition and amenia development. The immunized animals and animals chronically exposed to T-2 toxin typically demonstrate a decrease in the number of erythrocytes by 13% and in the level of hemoglobin by 9.6% due to reduced hemolotic action of xenobiotics and hematopoiesis depression. The use of aminoseleton in the vaccination scheme enhances adaptive immunity and natural resistance of the organism under these conditions. On day 30 post vaccination the vaccinated rats demonstrated an increase (in comparison to the control animals) in the number of erythrocytes - by 14.1%; hemoglobin - by 11.7%, number of leukocytes - by 6.5%, absolute number of segmentonuclear neutrophils - by 23%, immature neutrophils - by 11.1%. It is related to active formation of neutrophils in the marrow and their further migration to the blood circulation system for phagocytosis. The detected morphological changes in blood of the vaccinated and exposed animals suggest hematological disorder associated with T-2 toxicosis demonstrated as erythropoiesis inhibition and leucopenia. Decrease in specific humoral immunity and natural resistance caused by chronic T-2 toxicosis following experimental infection with Salmonella cholerae suis had a negative effect on the animal lifetime and safety.

The basis for the development of atopic dermatitis (AtD) is a complex interaction between genetic disorders, environmental factors, lack of the skin barrier and immunological disorders. In view of the importance of immunological disorders in the etiopathogenesis of atopic dermatitis, the study of these parameters in patients with AtD is a necessary aspect to assess the severity of the course, prognosis of complications and recurrence.Purpose. Comprehensive assessment of clinical and immunological parameters in adolescents with atopic dermatitis.Materials and methods. The study included examination of 28 patients with atopic dermatitis aged from 12 to 16 years, with disease duration from 10 to 15 years, which included analysis of complaints and anamnesis data, evaluation of disease severity on the SCORAD scale, General clinical and immunological studies. The peculiarities of cellular and humoral immunity in the relapse stage were determined. The main indicators of phagocytic activity of blood neutrophils were also investigated.Results. In the analysis of anamnestic data of patients, a history of diseases associated with atopia in 16 (57.1%) of 28 adolescents (AtD, bronchial asthma in relatives of the first and second line of kinship) was revealed. When assessing the disease severity on a scale of SCORAD, prevailed patients with moderate to severe atopic dermatitis over — 19 (67,9%) patients, the average score of the assessment of the severity of AtD amounted to 29.3 ± 1,25. The conducted immunological examination with assessment of cellular and humoral immunity showed significant changes in immunological reactivity in patients with AtD. On the part of the cellular immunity level it is necessary to note a clear decrease in CD3+ and CD8+, as well as an increase in the subpopulation of T-lymphocytes — CD4+ and b-lymphocytes — CD20+ in most patients compared to normal indicators characteristic of this age group. Compared to healthy adolescents, there were high rates of IRA and NK cells (CD16+). In all patients there was an increase in immunoglobulin M and G, a high content of immunoglobulin E. The formation of secondary immunodeficiency, manifested by a decrease in phagocytic activity of leukocytes and incomplete phagocytosis, which is a factor predisposing to the development of pyoderma.Conclusion. Changes in immune status in patients with AtD are expressed by imbalance of population Of T-lymphocytes, increase of various classes of immunoglobulins and considerable oppression of practically all indicators of functional activity of neutrophils of blood.

A comparative analysis of the changes in the immune and genetic status in patients with metabolic syndrome (MetS) combined with thyroid pathology has been performed in comparison with patients only with MetS or thyroid gland (TG) dysfunction.Materials and methods: 90 patients were recruited and assigned to one of three groups: A group of patients with MetS and TG dysfunction; a group of patients only with MetS; group of patients only with TG dysfunction. All patients underwent immune status assessment – CD3, CD4, CD8, CD16, CD4 +/CD8 +, and tumour necrosis factor (TNF) and C-reactive protein (CRP) levels were studied in a biochemical blood test. Genetic analysis consisted in determining the frequencies of alleles and genotypes of four polymorphic markers: rs10865710 of the PPARG3 gene, rs1042713 and rs1042711 of the ADRB2 gene and rs5443 of the GNB3 gene. Results: The combination of MetS with TG dysfunction regardless of the presence or absence of autoimmune thyroid diseases was characterized by aggravation of disorders in the Tand B-cell components of immune system, an increase in IgG, CRP, and TNF levels. Genetic analysis showed frequent detection of the A allele, the AA genotype of the polymorphic marker rs1042713 of the ADRB2 gene, coding β2-adrenoreceptor in the Kazakh population.

Aim. Evaluate immune status in patients with chronic hepatitis (CH) depending on type of causative agent and severity of the infectious process. Materials and methods. 232 residents of Yakutia including 127 patients with various forms of chronic hepatitis and 105 healthy individuals were examined. Relative levels of mature T-lymphocytes (CD3+), T-helpers (CD4+), T-suppressors (CD8+), B-lymphocytes (CD72+) and natural killers (CD16+) were studied by flow cytometry, as well as concentration of sera immune globulins of classes A, M and G by ELISA. Results. In patients with chronic hepatitis of various forms, a decrease of expression of differentiating antigens - CD3+, CD4+, CD72+ on the surface of lymphocytes and concentration of sera immune globulins was established. In CHD patients in phase of monoreplication high activity of the infectious process is accompanied by a shift of immune regulatory index to the increase of activity of cytotoxic cells with simultaneous development of deficiency of mature functionally active T-lymphocytes. In the group of patients with hepatitis D virus with liver cirrhosis normal concentration of sera immune globulins is retained against the decrease of the number of T-helpers and B-lymphocytes. Conclusion. In patients with various forms of viral hepatitis acquired immune deficiency can emerge, which is often accompanied by enhancement of NK-cell activity. The noted reduction of the number of mature functionally active T-cells, as well as main classes of sera antibodies could be connected with immune system load during a chronic infectious process.

Проанализированы результаты изучения статуса цитокинов, интенсивности перекисного окисления липидов (ПОЛ), тяжести эндогенной интоксикации (ЭИ), функционального состояния печени при разных формах синдрома системной воспалительной реакции (ССВР) у 82 больных острым калькулезным холециститом (ОКХ). У 68 больных выявлены признаки ССВР, у 14 - их не было. В сыворотке крови больных в динамике определяли содержание провоспалительных (фактор некроза опухолей-α - ФНО-α, интерлейкинов-6 - ИЛ-6) и противовоспалительных (ИЛ-4, ИЛ-10) цитокинов, диеновых конъюгат (ДК), малонового диальдегида (МДА), С-реактивного протеина (CPП), общего белка, альбумина, общего билирубина, активность каталазы (КАТ), аланинаминотрансферазы (АЛТ), аспартатаминотрансферазы (АСТ), щелочной фосфатазы (ЩФ), гаммаглутамилтрансферазы (ГГТ). Установлено, что выраженность дисбаланса цитокинов, интенсификации ПОЛ, тяжести ЭИ, нарушений функционального состояния печени зависела от числа критериев ССВР.

Alpha-fetoprotein is one of the best known embriospecific proteins, which is used to diagnose fetal abnormalities and tumor processes of the gastrointestinal tract and liver and has a pronounced immunotropic and detoxifying effect, and also a direct apoptotic effect on tumor cells. The appointment of AFP mice at the oldest age in our experiments, dramatically increased survival and markedly increased the relative weight immunotropic bodies, apparently, due to the characteristic of the AFP general effect of improving the functions of tissues and detoxifying action. Thus, AFP has a significant bioactivity and anti-aging effectname, that allows to consider it as a candidate for a geroprotective agent.

Purpose: To Study immune status in patients with coxarthrosis consequent to treatment of congenital hip dysplasia and Perthes' disease as well as to determine additional variables indicating arthrosis progression.Materials and methods: The authors analyzed results of preoperative immune examination of 13 male patients aged 11,4±0,7 years (10-13) with coxarthrosis of type I-II developed consequently to treatment of hip dysplasia and Perthes' disease. Based on obtained anatomical and functional outcomes the authors divided the patients into two groups. First group included 8 patients with postoperative improvement of joint function and absence of disease progression. Second group (5 patients) was featured by functional deterioration and arthrosis advancing.Results: Patients of the second group demonstrated statistically significant elevation in certain parameters of humoral (circulating immune complex) and cellular immunity (CD3+HLA-DR (%), CD3+HLA-DR (109/l)) as well as interleukin-6.Conclusion: Obtained results have proven that initial immune parameters (IL-6, circulating immune complex, lymphocytes with activation markers) can be used as additional variables for decision making in regard to option and advisability of reconstructive joint preserving procedures in patients with coxarthrosis consequent to treatment of hip dysplasia and Perthes' disease.

The paper confirms long-time opisthorhis invasion role as a risk factor of host immune system reconstitution as well as an important factor in holangiocarcinomas development. It was shown that opisthorhosis invasion primal stage induce host immune system reconstitution. Host immune B-cells system is activated by metacercaria antigens, while the same antigens inhibits T-cells activity. Opisthorhis metabolites stimulate proliferative mithogen-induced T-cells acti vity. Chronic opisthorchis invasion leads to immune system disbalance. It means: decrease of specific and non-speci fic natural killers activity, number of high proliferative activity T-lymphocytes and the shift of regulatory T-cells subset to suppressors prevalence. At the same time specific as well as non-specific T-suppressors functional ability is very low. It was shown T-cells helper-amplifier activation. Despite of circulating B-cells decrease the antibody produced cells number is spleen increases significantly at the same time with circulating immune complexes accumulation. Even 3–6 month after dehelmintisation the immune system disbalance decreases but lefts. In addition, chronic opisthorhis invasion leads to the proliferative processes activation in ductal epithelium, liver, lymph nodes and in other organs which leads to cancer proliferation. According to the results obtained the opisthorhis infected patients needs to be immunocorrected before as well as after dehelmintisation for holangiocancerogenesis profylaxis.

The feature of rheumatoid arthritis (RA) is the predominant clinical picture of chronic synovial joint inflammation accompanied by progressive cartilage and bone destruction, the pathogenesis of which is greatly due to autoimmune mechanisms. Some investigations demonstrate that a set of poor climatic and geographical factors may influence the development of immune disorders that are a trigger in the development of RA.Objective: to comparative analyze immunological parameters in RA in dwellers from different regions of Uzbekistan.Subjects and methods. The study enrolled RA patients from three Uzbekistan zones: 1) Tashkent (n = 25), 2) Xorazm Region (n = 25); 3) Namangan Region (n = 28).Results and discussion. Comparative analysis of the immune status indicated that the patients living in Zone 2 exhibited a significantly reduced T cell immune response (p < 0.05), a considerably higher count of B lymphocytes (p < 0.001), and significantly lower levels of CD11b+, CD18+, CD25+, and CD95+ cells (p < 0.05) than did those from the two other zones. Examination of the frequency of the monomorphic determinant of histocompatibility Class I (HLA-I) antigens revealed its significant decrease in the patients residing in Zones 1 and 3 (p < 0.05) whereas the RA patients from Zone 2 had a significantly higher frequency of HLA-DR (p < 0.05).Conclusion. The comparative analysis shows that the immunological parameters differ in the patients from the three zones of Uzbekistan, which may suggest that the climatic and geographical factors of the environment may influence the course of the disease.

The aim of the study is to enable rapid development of forecasting human disadaptation disorders caused by stress factors change living conditions. The developed method allows for the values of salivary immunoglobulin A, ceruloplasmin and proportion of lymphocytes in the blood leukocyte formula to recognize nosological class of diseases which are based on the failure of adaptation processes. Application of the method allows early adaptation period to identify individuals with poor adaptive skills and to predict the likely nosological form disadaptation disorders, which are essential for effective preventive measures.

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Purpose: assessment of the free radical oxidation system and antioxidant protection, immune and cytokine status in patients with pulmonary infiltrative tuberculosis, depending on the type of inflammatory tissue reaction. Materials and Methods: the study included 60 patients with infiltrative pulmonary tuberculosis with exudative and productive type of inflammation.Statistical analysis of the data was performed using the program Statistica 6.0. Results: the patients with productive type of inflammation are mainly characterized by a limited process with poor bacterioexcretion, moderate disturbances in the free-radical oxidationsystem, antioxidant protection, immune and cytokine status. In patients with exudative type widespread destructive process with massive excretion of Mycobacterium tuberculosisprevails, as well as severe disturbances in the free-radical oxidationsystem, antioxidant protection, immune and cytokine status. Summary: the clinical and laboratory characteristics of infiltrative tuberculosis with different types of inflammatory tissue reaction should be considered duringprescription of pathogenetic treatment and prediction of the course and of the outcome of tuberculosis process.

Chronic periodontitis is one of the most common diseases in dental practice, which shows annual tendency to increase. Nowadays, mechanisms of the formation of this pathology have been substantially studied. However, chronic periodontitis often occurs in combination with a concomitant pathology, in particular, pneumonia. Mechanisms of their formation under conditions of combined pathology and the role of the immune system have not been studied completely, prompting topicality of this research. The results of investigation of the peculiarities of changes in phagocytic leukocyte activity, indices of immune status in the blood, prooxidant and oxidant systems in the periodontium and lungs of guinea pig males in early (6th and 10th days) and late (20th day) periods of chronic periodontitis and in combination with experimental pneumonia have been presented in the article. It has been shown that early and late periods of chronic periodontitis formation, as well as in combination with experimental pneumonia pathology were characterized by increased phagocytic leukocyte activity, which was manifested by an increase (p

The purpose of the study – the optimization of clinical diagnosis of chronic course of Ixodes tick-borne borreliosis based on indicators of immune and cytokine status of patients.Materials and Methods: clinical and immunological study of patients with chronic Ixodes tick-borne borreliosis in the Krasnoyarsk region. The observations were made on 205 patients for 1,5 years. The diagnosis was based on clinical and epidemiological data confirmed the identification of specific antibodies to borrelia by ELISA. The indices of cellular and humoral immune system, phagocytosis, cytokine (interleukin-1β, 4, 8 , tumor necrosis factor-α).Results: Show Part chronicity of infection after an noneritemic form of the disease (37,5%) and combined forms of Ixodes tick-borne borreliosis with tick-borne encephalitis (33,2%). Clinical manifestations were characterized by the involvement in the pathological process of the musculoskeletal system (42,9%) and combined lesions to the nervous system (38.5%). A rare variant of the chronic course of borreliosis was central nervous system as the onset of the disease (3,5%). Common infectious syndrome relapse accompanied by autonomic dysfunction with prevalence parasimpatotonus (59,0%) and simpatotonus (41,0%), and febrile reactions (71,2%) were more subfebrile with fever (51,2%).Conclusion: pathogenetic mechanisms of chronic course of Ixodes tick-borne borreliosis closely associated with inflammation and immune-mediated reactions of the organism , and are characterized by the presence of cellular immunodeficiency, insolvency phagocytosis, suppression of the synthesis of interleukin-4 and interleukin-8 intensive products.

Tendency to chronization of infectious process is characteristic of a current the Ixodes tick-borne borreliosis. Early identification of laboratory signs of risk of development of a chronic process of disease will allow to correct in due time therapy and to prevent a disease failure.Research objective: search of criteria for chronization in the retrospective analysis of the immune status of patients with various clinical forms of sharp ixodes tick-borne borreliosis.Materials and methods: clinical trials are executed at 161 patients with a chronic current and 420 patients with a sharp process of disease. Results of the retrospective analysis of the immune status and cytokines taking into account recovery and disease chronization are given.Results of research: predictive criteria of chronization of an erythema form of Ixodes tick-borne borreliosis were decrease in absolute quantity of lymphocytes, a phagocytic index, number of the phagocytic neutrophils, the raised level of the total IgM. Significant criteria of chronization of an illness after the ended non-erythema’s form of a disease were decrease in an expression of cytotoxic CD8+ of cells, decrease CD4+/CD8+ of cells and decrease in number the phagocytic neutrophils. For all clinical forms of a sharp process of Ixodes tick-borne borreliosis the increased synthesis interleukin-8 during the convalescence period at patients with the subsequent chronization of a disease was characteristic. Preservation of high level of interleukin-1β secretion and a neoplasm necrosis factor-α after the ended non-erythema’s form of an illness was predictive criterion of chronization of a disease. Characteristic of production cytokines at patients with the combined course of a borreliosis-encephalitis infection in the sharp period of a disease was high level of synthesis interleukin-4.Conclusion: adverse predictive criteria of development of a chronic process of Ixodes tick-borne borreliosis are failure of a phagocytic link to immune system, decrease in an expression of cytotoxic CD8+ of the cells, the increased synthesis interleukin-8 and interleukin-4.