Activation of immune system cells is accompanied by a profound rearrangement of their metabolism, or metabolic reprogramming. Muramyl peptides, which are fragments of bacterial peptidoglycan, activatie innate immune cells through NOD1 and/or NOD2 receptors. Here, we characterize, for the first time, alterations of carbohydrate and energy metabolism of human macrophages activated by a NOD1 agonist, N-acetyl-D-muramyl-L-alanyl-D-isoglutamyl-meso-diaminopimelic acid (M-triDAP) in comparison with a TLR4 agonist, lipopolysaccharide (LPS). Real-time analysis of cell metabolism showed that both agonists, within 1 h after addition to cells, boosted glycolysis along with a minor reduction of oxygen consumption.

The effect of either agonist on glycolysis was blocked by an Akt kinase inhibitor, but was independent of the mTORC1 kinase complex and elevation of glycolytic enzyme expression. Unlike LPS, M-triDAP caused almost no induction of aconitate decarboxylase 1, an enzyme breaking the Krebs’ cycle. The effect of 2-deoxyglucose (a competitive inhibitor of glycolysis) and Akt inhibitor on M-triDAP-induced cytokine expression was ambiguous. The Akt inhibitor reduced TNF, IL-6 and IL-1β, expression, whereas 2-DG inhibited TNF and IL-6 expression at an early stage (1 h), but enhanced it at a late stage (4-9 h) after addition of M-triDAP. Mechanisms whereby these inhibitors affect cytokine expression are discussed.

Multiple sclerosis is an autoimmune demyelinating inflammatory disorder ofthe central nervous system. In addition to autoimmune mechanisms neurotransmitter glutamate plays a significant role in the destruction of myelin, oligodendrocyte and neuronal death. It was shown that glutamate produced by activated macrophages and microglia by ionotropic and metabotropic receptors mediates excitotoxic process which contributes to the formation and maintenance of neurodegeneration in MS. Recently the evidences were found that glutamate may act as an immunomodulator by control of functions of infiltrated T-cells in inflammation tissues. Furthermore, immunomodulation may be carried out by the glutamate ionotropic receptors, in particular the NMDA-subtype, at the level of peripheral T-lymphocytes. The aim of this study was the investigation of the role of NMDA-receptors in the regulation of immunocompetent cells functions by the comparative analysis of the genes expression profile in peripheral blood mononuclear cells from multiple sclerosis patients using a commercial kit Human Signal Transduction Pathway Finder PCR Array. It has been shown that in peripheral blood mononuclear cells from multiple sclerosis patients the antagonist NMDA-receptors (+)-МК801 caused the alteration of expression of genes which are composed to the closely related and overlapping clusters of biological processes such as apoptosis, phosphorylation, cytokine and chemokine signaling. These data suggest that the NMDA-receptors could be involved in the modulation of some of the key functions of mononuclear cells, as well as in the regulation of chemotaxis of immune cells in patients with multiple sclerosis.

Frequent relapses of inflammatory diseases of the upper respiratory tract (URT) - a condition that goes beyond purely otorhinolaryngological practice. Obviously, in such cases it is a violation of protective mechanisms at the system and/or local level. These patients are increasingly in the field of view of immunologists. Therefore, at the present stage it is necessary to understand both the etiopathogenetic state of this condition and the variants of the immunological dysfunction that forms in this group of patients.

The aim of this study was to determine the spectrum of the microbiological composition of the oropharynx and to investigate the factors of local immunity in patients with frequent recurrences of inflammatory diseases of the URT.

Material and methods. The bacterial microflora of the oropharynx was determined by sowing from throat, tonsils, the presence and concentration of herpes-group viruses in whole saliva (real-time PCR method). The concentration of protective factors of saliva (α-defensins, catelicidin LL-37, lactoferrin, secretory IgA) was also determined in patients with frequent recurrences of inflammatory diseases of the URT outside the exacerbation period.

Results. In a person who is often ill adults, the microbial landscape outside the period of exacerbation is represented by a combined bacterial (less pathogenic, mostly conditionally pathogenic) and viral (mainly EBV, HHV 6) microflora. Also in these patients there is a disturbance in the production of mucosal immunity factors.

Antiretroviral therapy (ART) is able to effectively reduce the plasma viral load in HIV-infected patients. However virus hidden in latent reservoirs is unaccessible for ART and supports the persistence of infection. So the development of approaches to affect the proviral DNA integrasted in host cell genome is of great importance. Perspective strategies of the genome editing technologies for mutagenic deactivation of viral genes, HIV DNA removal from host cell genome and also for latent viral reservoir eradication are being analysed in the review.

In the review the information, concerning questions of interpreting sameness of medical monoclonal antibody products, intended for treatment rare (orphan) of diseases with the account regulatory requirements, concerning to orphan drags is resulted. The general principles of the proof of similarity of biotechnological medical products, features regulatory requirements to preparations on a basis unmodified monoclonal antibody products, the modified antibodies, antibody conjugates, fragments of an antibody, fusion proteins etc. The data on the features of the criteria underlying definition of two monoclonal antibody drugs, as biosimilar, in the case of their use for the treatment of orphan diseases, based on the information provided in the regulatory documents.

The number of patients suffering from bronchial asthma all over the world is convinced of the seriousness and importance of this problem. Despite the attempts of scientists to unite efforts in the fight against this disease, the level of deaths and hospitalizations is growing every year. The bulk of the research is devoted to the study of the molecular mechanisms of the pathogenesis of bronchial asthma. This review describes the role of Toll-like type 4 receptors (TLR4) in the pathogenesis of bronchial asthma, the processes of signal transfer involving adapter proteins, as well as the effect of ubiquitination processes and the role of ubiquitin A 20 on the activation of the inflammatory response are examined.

The maternal immune system is involved in all stages of the reproductive process from conception to the implantation of the embryo and the development of the placenta and fetus. Cells of the immune system recognize antigens and other signaling molecules of seminal fluid, embryos and placenta. In experiments on mice, it was found that when conceiving, seminal fluid in the reproductive tract of females induces an immune response that allows or cancels pregnancy, i.e. controls the quality of preimplantation embryos, as well as a chain of events that affect the subsequent development of the fetus. In particular, the seminal fluid initiates the processes of immune adaptation necessary for the development of tolerance to the father's transplantation antigens (antigens of the major histocompatibility complex or human HLA), represented in the seminal fluid and inherited by the fetus. The decidualized endometrium of the uterus plays an important role in assessing the quality of preimplantation embryos, as well as in their selection. In the process of decidualization, endometrial stromal cells (ESCs) acquire a unique ability to recognize and eliminate implantable defective embryos, that is, to function as a biosensor for the quality of embryos. The success of implantation depends on the close interaction of the blastocyst and the endometrium of the uterus mediated by locally secreted factors. An important function of the decidualized endometrium is the temporary acquisition of the receptive phenotype, which is necessary for the introduction of the blastocyst into the uterus. It is believed that the abolition of sensory function is associated with the inability of the endometrium to achieve receptive status, which is one of the causes of infertility. In studies on the nature and mechanisms of habitual miscarriage, evidence was obtained in support of the hypothesis that the root cause of this pathology is abnormal quality control, which allows defective embryos to be removed to implant freely in the uterus and manifests clinically as a recurrent miscarriage. It is believed that this pathology can be based on an imbalance of regulatory signals that control the differentiation of ESCs into specialized decidual cells.

The analysis shows that, despite numerous clinical studies of prognostic significance of infiltrating lymphocytes (TIL) in various types of malignant tumors, there is no single point of view on this problem. The greatest material was accumulated in the evaluation of TIL as a prognostic factor for the duration of General and relapse-free survival and the effectiveness of neoadjuvant therapy in breast cancer patients. Although the meta-analysis carried out in the review publications showed a high level of correlation between the intensity of tumor infiltration by lymphocytes and survival of patients with breast cancer, as well as with the effectiveness of neoadjuvant therapy, similar patterns were noted not for all variants of this pathology. Even more contradictions arise in the evaluation of the predictor role of various lymphocyte subpopulations. In particular, various studies have shown a positive correlation between the percentage of both cytotoxic CD8⁺ TIL and suppressor FOXP3⁺ TIL. Obviously, for this reason, according to the recommendations of the German Breast Group, it is proposed to evaluate the infiltration of tumor lymphocytes using standard histological staining with hematoxylin-eosin without isolation of individual lymphocyte subpopulations. An even more complex and ambiguous interpretation of the prognostic significance of TIL and their subtypes is observed in other localizations of malignant tumors, which is obviously due to the small number of patients included in the study.

Along with the predictive value of TIL for chemotherapy, tumor-infiltrating lymphocytes can also be predictive biomarkers of immunotherapy effectiveness. In particular, new immunotherapy drugs pembrolizumab, nivolumab, etc. can effectively enhance the antitumor effect of CD8⁺ TIL. Therefore, the degree of severity and subpopulation composition of lymphoid infiltration of the tumor can be considered not only as a prognostic factor in the course of cancer, but also be important for the selection of individualized treatment, including modern immunotherapeutic drugs. Literature analysis and clinical trials were conducted on databases Scopus, WebofScience, PubMed, Clinical trial. gov and RISC.