Many pathogens use metabolic pathway of arginine for successful dissemination. Bacterial arginine deiminase hydrolyzes arginine to form one molecule of ammonia and two molecules of ATP. The activity of the enzyme contributes to the improvement of survival of pathogenic bacteria in conditions of low pH at the site of infection or in phagolysosome, as well as in anaerobic conditions, and also leads to deficiency of arginine. Metabolism of arginine plays an important role in regulating the functions of immune system cells in mammals. Arginine is a substrate of enzymes NOS and arginase. Arginine depletion, potentially contributs to immunosuppression. The review analyzed the literature data on the effect of streptococcal arginine deiminase on the metabolism of arginine eukaryotic cells, and discusses immunosuppressive action of the enzyme.

This article presents the results of immunotoxicity study of a novel slow-release drug for multiple sclerosis treatment based on recombinant human interferon beta-1а. The test article is polyethylene glycol (PEG)-conjugated interferon beta-1a. Performed modification allows to improve pharmacokinetic parameters, decrease immunogenicity and elevate tolerance that significantly increases safety of the test article. The study is performed in nonhuman primates – rhesus monkeys (Macaca mulatta). The species, used in this study, is susceptible to human interferon beta-1a that has previously been shown in specific activity studies. Dynamics of peripheral blood lymphocyte subsets composition, activated lymphocyte count (based on the presence of early activation marker), serum antibodies (IgM, IgG, IgA and IgE) level and ratio were assessed within in vivo experiments. The effect of interferon beta-1a on CD69 expression was examined in mononuclear cells culture. It was shown that the test article causes changes in lymphocyte subsets ratio (decrease of NK-cells relative count with T-lymphocytes relative count elevation) in primates’ peripheral blood. Revealed changes were reversible and dose-independent. It was not shown that the test article have reliable effect on CD69 expression rate. There was no evidence of test article effect on level and ratio of serum antibodies and polymorphonucleocytes phagocytic rate in the absence of additional antigenic exposure. The results obtained during the experiment indicate the absence of pathological effect of the test article on the nonhuman primates’ immune system.

Osteoarthritis (OA) is among challenging problems of clinical medicine, not only due to its high prevalence, but also because of higher burden of comorbidities. Previously we described a clinical phenotype of OA associated with type 2 diabetes mellitus (OADM), which is one of OA phenotypes characterized by increased severity and reduced quality of life. In current literature, there is a lack of data on OADM biomarkers. Based on the current knowledge on type 2 DM and OA pathogenesis, it may be suggested that disturbances of DNA methylation may present the key pathogenetic mechanism for the both diseases. A number of factors, for example, chronic systemic inflammation, or increased levels of advanced glycation end products, may lead to increased articular cartilage degradation in type 2 DM-associated OA. Both OA and type 2 DM are characterized by higher comorbidity burden, thus allowing to suggest that coexistence of these diseases leads to additive effects upon comorbidity indices. In this exploratory study, we evaluated levels of total DNA methylation in peripheral blood mononuclear cells (PBMC), along with biomarkers of serum cartilage degradation and comorbidity features in patients with OA associated with diabetes (OADM). Global DNA methylation in PBMC was assessed as 5-methylcytosine levels using flow cytometry. Circulating aggrecan and anti-CII antibody concentrations were measured by means of ELISA. Comorbidity indices were assessed using Cummulative Illness Rating Scale (CIRS-G). A total of 78 patients with generalized OA were assessed. Fifty two patients had clinical manifestations of OA preceded by DM type II for 1 year (case group), and 26 OA patients were non-diabetic (control group). Patients with OADM had more pronounced joint impairment and higher severity of comorbidity. There were no differences in other measures of comorbidity between the compared groups. In conclusion, further studies on epigenetic control of inflammation and cartilage metabolism in patients with OA will enable to identify new therapeutic targets and to define new treatment strategies for the both basic disorder and comorbidity states. 

Computer analysis of primary structure for >3300 proteins has shown an opportunity for existence of global immune epitope continuum of protein relationships (IECPR) for eukaryotes, prokaryotes, and viruses. On the basis of IECPR, one may provide new interpretations for immune events, and in particular, to consider them as an additional factor determining poly- and autoreactivity of antibodies, and, respectively, extend the concept of regulatory functions of natural antibodies. For medical practice, the IECPR would be especially useful in cases of search for novel vaccines and immune diagnostic preparations.

There exists a real hazard of transferring zoonotic influenza A viruses, either swine, or avian, into human population. In such case, severity of such pandemics depends on the pathogen-specific immunity in the population. Virtual absence of such immunity in humans was declared in the literature. In this work, we assessed systemic, local, and T-cell immunity to potentially pandemic H3N2sw, H5N1, H5N2, H7N3, H7N9 and H2N2 influenza A viruses in a group of healthy adults of different age. Our results indicate that these subjects develop the following immune reactions: (i) local (i.e., nasal IgA) and cellular (CD4+ and CD8v memory T cells) heterosubtypic immunity, in absence of detectable virus-specific serum antibodies to avian influenza A viruses; (ii) Local immune responses (as nasal IgA) to human A (H2N2) virus which circulated in 1957-1968 were detected both in subjects who could be primed at that time, but also in subjects born after 1968; (iii) full-scale systemic and local immunity to potentially pandemic А (H3N2sw) swine virus was found in the group. Conclusion. In order of proper epidemiological forecasts and planning appropriate preventive measures for potentially pandemic Influenza A viruses, a regular monitoring of collective immunity should be performed using different adaptive markers. In this respect, any conclusion based on molecular analysis only could lead to considerable mistakes, and should be accomplished by the mentioned immunological studies.

At the present time, systemic lupus erythematosus (SLE) takes the leading place among systemic autoimmune disorders. Despite considerable progress in understanding basic pathogenesis of this disease, many subtle mechanisms of progressive inflammation in SLE are still unknown. It has been discovered that the persistent self-maintenance factors of autoimmune inflammation could be represented by lipopolysaccharides or endotoxins of Gram-negative intestinal bacteria. The objective of this study was to assess the levels of major lymphocyte subpopulations, and their probable relation to specific anti-endotoxin antibodies and endotoxin-neutralizing receptors of granulocytes and monocytes in peripheral blood of SLE patients. The study involved forty-eight patients with SLE. The levels of lymphocyte subpopulations, expression of monocyte and granulocyte anti-endotoxin receptors, amounts of total and endotoxin-specific immunoglobulins were determined by means of, respectively, cytometric analysis and enzyme immunoassay techniques. The results of study have shown an increase in overall numbers of activated and cytotoxic T lymphocytes, a decrease in lymphocytes and NK-cells, diminished levels endotoxin-binding receptors on the monocytes and granulocytes, along with increased anti-endotoxin IgG antibodies. Our study revealed correlations between the levels of the leukocyte endotoxin-binding receptors, and B-lymphocyte contents, like as some associations between anti-endotoxin IgM antibodies, and the levels of B-lymphocytes, and cytotoxic T-lymphocytes. A correlation was also found between anti-endotoxin IgG antibodies and CD4+ lymphocyte levels. Significant alterations of the endotoxin-specific immunity among SLE patients suggest that this imbalance might play an important role in the mechanisms of onset and progression of autoimmune diseases.

Contact sensitivity reaction (CSR) to 2,4-dinitrofluorobenzene (DNFB) in mice is a model of in vivo immune response, being an experimental analogue to contact dermatitis in humans. CSR sensitization phase begins after primary contact with antigen, lasting for 10-15 days in humans, and 5-7 days, in mice. Repeated skin exposure to the sensitizing substance leads to its recognition and triggering immune inflammatory mechanisms involving DNFB-specific effector T lymphocytes. The CSR reaches its maximum 18-48 hours after re-exposure to a hapten. There is only scarce information in the literature about effects of flavonoids on CSR, including both stimulatory and inhibitory effects. Flavonoids possessed, predominantly, suppressive effects against the CSR development. In our laboratory, a model of contact sensitivity was reproduced in CBA mice by means of cutaneous sensitization by 2,4-dinitrofluorobenzene. The aim of the study was to identify the mechanisms of immunomodulatory action of quercetin dihydrate and modified bioflavonoids, using the method of adoptive transfer contact sensitivity by splenocytes and T-lymphocytes. As shown in our studies, a 30-min pre-treatment of splenocytes and T-lymphocytes from sensitized mice with modified bioflavonoids before the cell transfer caused complete prevention of contact sensitivity reaction in syngeneic recipient mice. Meanwhile, this effect was not associated with cell death induction due to apoptosis or cytotoxicity. Quercetin dihydrate caused only partially suppression the activity of adaptively formed T-lymphocytes, the contact sensitivity effectors. It was shown that the modified bioflavonoid more stronger suppress adoptive transfer of contact sensitivity in comparison with quercetin dehydrate, without inducing apoptosis of effector cells. Thus, the modified bioflavonoid is a promising compound for further studies in a model of contact sensitivity, due to its higher ability to suppress transfer of CSR with T-lymphocytes, as compared to quercetin dihydrate.