IMMUNOLOGICAL MEMORY: THE ROLE OF REGULATORY CELLS (TREGS)

Memory T cells are necessary for development of the immune response and represent one of the most numerous population of human T lymphocytes. On the contrary, suppressive regulatory T cells (Tregs) may terminate the immune response and help to maintain tolerance to self-antigens. These important groups of cells are consisting of different subpopulations and retaining throughout life. However, today there is yet no clear understanding of how the relations between these two groups of cells are formed. In this work we consider possible ways of development and maintenance of CD4+ T cell memory and role of Tregs in these processes. Mechanisms of a differentiation of memory T cells, Tregs and recently described memory Tregs are discussed. The functional and genetic characteristics of these cells are compared. Division of cells according to the functional profile allows drawing parallels between memory T cells and Tregs. These two groups are consisted of central circulating populations (Tc), effector which can migrate toward specific tissues (Te) and tissue-resident cells (Tr), which are staying in peripheral tissues. The similar structural organization of Tregs and memory T cells, existence of transitional forms of tissue-resident Treg subpopulations with properties of memory cells assumes existence of close interrelation between these groups of lymphocytes. The conversion of CD4+ memory T cells into FoxP3-expressing Tregs is one of possible mechanisms of communication between these two groups. The memory Treg-cells with T cell and memory Treg-cell properties can represent a transitional stage of differentiation. On the other side, Treg cells can differentiate independently of memory T cells and accumulate during life in the form of memory Treg cells. The supressor function of Tregs is also necessary as well as function of memory T cells to develop the immune response. It is possible, that a subset of Treg cells undergoes selection in thymus and constitutively express TCR-receptors having affinity with peripheral tissues. Further, these committed cells can be settled into tissues and become tissue-resident Treg cells which maintain regional T cell memory. Tregs can represent the “mirror image” of the structural organization of memory T cells, but with the return sign – the sign of suppression. The quantitative ratio of Tregs and memory T cells (CD4+CD45RO+CD25hiFoxP3+/CD4+CD45RO+CD25-FoxP3-), perhaps, is important criterion for functional assessment of immune system. The balance between these functionally opposite cell subsets has to provide stable functioning of immune system

Muon pair creation from positronium in a circularly polarized laser field

We study elementary particle reactions that result from the interaction of an atomic system with a very intense laser wave of circular polarization. As a specific example, we calculate the rate for the laser-driven reaction $e^+e^- \to \mu^+\mu^-$, where the electron and positron originate from a positronium atom or, alternatively, from a nonrelativistic $e^+e^-$ plasma. We distinguish accordingly between the coherent and incoherent channels of the process. Apart from numerical calculations, we derive by analytical means compact formulas for the corresponding reaction rates. The rate for the coherent channel in a laser field of circular polarization is shown to be damped because of the destructive interference of the partial waves that constitute the positronium ground-state wave packet. Conditions for the observation of the process via the dominant incoherent channel in a circularly polarized field are pointed out

Analysis of complex singularities in high-Reynolds-number Navier-Stokes solutions

Numerical solutions of the laminar Prandtl boundary-layer and Navier-Stokes equations are considered for the case of the two-dimensional uniform flow past an impulsively-started circular cylinder. We show how Prandtl's solution develops a finite time separation singularity. On the other hand Navier-Stokes solution is characterized by the presence of two kinds of viscous-inviscid interactions that can be detected by the analysis of the enstrophy and of the pressure gradient on the wall. Moreover we apply the complex singularity tracking method to Prandtl and Navier-Stokes solutions and analyze the previous interactions from a different perspective

The method of surgical access while treatment of nonclostridial anaerobic infections of soft tissues of tongue and oral cavity floor

The author analyzed the methods of operational interventions in the area of soft tissues of oral cavity floor and tongue while treatment of nonclostridial anaerobic infections. Twenty-nine of the forty-two analyzed patients were operated, using the authors’ method of T-shaped incision. The number of lethal outcomes has decreased almost twice. Treatment results allow us to recommend the proposed method for wider use in clinical practic

Tumor microenvironment: the formation of the immune profile

Tumor microenvironment (TME) is formed as a result of interaction and cross-linking between the tumor cell and different types of surrounding cells. Recent studies have shown that the tumor reprograms the microenvironment so that TME promotes the development of primary tumors, their metastasis and becomes an important regulator of oncogenesis. Under the influence of the tumor, the immune profile in the TME undergoes significant changes, “editing". An immunosuppressive network is formed, which suppresses the activity of the main effector of cellular immunity — T lymphocytes. T cells in TMA are in a state of anergy and exhaustion. T cells in TME are characterized by increased expression of inhibitory receptors, decreased secretion of cytokines and cytolytic activity. Blocking inhibitory receptors with specific antibodies can lead to the restoration of the functions of exausted T cells. Therefore, the restoration of the functional activity of T lymphocytes is one of the important strategies in cancer immunotherapy. The formation of the immune profile is influenced by genetic aberrations accumulating in the tumor. They play an important role in creating a specific, characteristic only for this tumor immune environment in the TME. Genetic changes in tumor cells lead to phenotypic and functional rearrangements of lymphocytes, which allows the tumor to escape the reaction of immune cells. Since many tumors occur after prolonged inflammation or exhibit characteristics of chronic inflammation as they progress, inflammation is considered an important factor in the formation of immune profile in TME. Immune infiltrates from different human tumors associated with inflammation may contain valuable prognostic and pathophysiological information. Macrophages in the TME now began to be regarded as descriptive marker and as a therapeutic target. One of the main mechanisms by which tumor cells reprogram surrounding cells is the release of exosomes — small vesicles that carry and deliver proteins and nucleic acids to other cells. When exosomal cargo is absorbed, molecular, transcriptional and translational changes occur in the recipient non-tumor cells in the TME. Therefore, tumor exosomes are an effective means by which the functions of immune cells in TME are purposefully changed. Thus, along with individual molecular and genomic testing of the tumor, attention should be paid to a deeper analysis of the immune profile of TME. It is a large resource of biomarkers and targets for immunotherapy

Macrophage polarization in sarcoidosis

Sarcoidosis is a systemic inflammatory disease of unknown etiology, characterized by the formation of epithelioid cell granulomas, multisystem lesions with a certain frequency of involvement of various organs, mainly the lungs (up to 90% of cases). Over the past decade, significant progress has been made in understanding the pathogenesis of sarcoidosis, the important role of immunological, genetic and environmental factors in the development of this pathology has been established. It is believed that the leading mechanism in the pathogenesis of sarcoidosis is the aberrant activation of the innate and adaptive immune response to unidentified antigen(s), which leads to the development of granulomatous inflammation and the formation of granulomas. However, despite the huge number of studies that has been carried out, the mechanisms and signaling pathways that control the development of the inflammatory process during the formation of granulomas and the progression of pathology have not been fully determined.This literature review examines the important role of various cytokines and T helper subpopulations in sarcoidosis. Particular attention is paid to the cells of innate immunity – macrophages in the pathogenesis of this disease. These cells play a key role in the formation of sarcoid granulomas and in the pathogenesis of sarcoidosis. The macrophage population is characterized by plasticity and functional heterogeneity. In response to various signals from the microenvironment, macrophages are able to acquire certain phenotypes. The review considers the issues of polarization of macrophages, changes in the phenotype of these cells to subpopulations M1 (M1 phenotype; classically activated; pro-inflammatory) and M2 (M2 phenotype; alternatively activated, anti-inflammatory). These two cell populations are characterized by the expression of different markers on their surface, which allow these cells to differentiate from each other. The analysis of literature data on the levels of key polarizing cytokines for macrophages and cells-producers of these cytokines that patients with sarcoidosis have, in acute and chronic course of the disease, was carried out.Important aspects of the alternative activation of macrophages of the M2 phenotype and their division into subtypes: M2a, M2b, M2c, M2d are noted. The features of various subtypes’ activation of macrophages in this granulomatosis and their importance in the development and progression of pathology are considered. Studying the role of macrophages’ phenotypes, understanding the mechanisms by which the phenotypes of these cells are activated and modulated in various microenvironmental conditions, can contribute to the development and implementation into clinical practice of new therapeutic approaches for the treatment of sarcoidosis and many other forms of pathologies

Somatoform disorders in the family doctor's practice.

Somatoform disorders – psycho­genic diseases are characterized by pathological physical symptoms that resemble somatic illness. Thus, any organic manifestations, which can be attributed to known diseases are not detected, but there are non-specific functional impairments. Somatoform disorders include somatization disorder, undifferentiated somatoform disorder, hypocho­n­driacal disorder, somatoform dysfunction of the autonomic nervous system and stable somatoform pain disorder. The first part of the article reviewes features of the clinical manifestations of somatization disorder and undifferentiated somatoform disorder. Role of non-benzodiazepine tranquilizers (ADAPTOL) and metabolic drugs (VASONAT) in the treatment of patients with somatoform disorders is discussed. In review article data of neurologists and cardiologists on the effectiveness of anxiolytic drug ADAPTOL and metabolic drug VASONAT in different clinical groups of patients (coronary artery disease, chronic ischemia of the brain), which can significantly improve quality of life, increase exercise tolerance, improve cognitive function and correct mental and emotional disorders are presented

Features of Social Services for Elderly Citizens Age in the Context of a Charitable Organization

Currently, various charitable organizations and foundations that implement activities in the field of social services for elderly citizens are successfully functioning on the territory of the Russian Federation. Due to the individual specifics of each of them, the authors conducted an analysis that allows us to identify and summarize the main directions of their activities in this area. The study included such charitable organizations as the Charity Fund (hereinafter referred to as the Charity Fund) for Helping the Elderly and Disabled people “Old Age in Joy”, the Charity Fund for Supporting the Elderly “Dignity”, the Charity Fund “Longevity”, the Charity Fund “Give Care”, the Charity Fund “Metallurg”, etc.В настоящее время на территории Российской Федерации успешно функционируют различные благотворительные организации и фонды, реализующие деятельность в сфере социального обслуживания граждан пожилого возраста. В силу индивидуальности специфики каждого из них авторы провели анализ, позволяющий выделить и обобщить основные направления их деятельности в указанной сфере. Изучению подверглись такие благотворительные организации как, Благотворительный фонд (далее — БФ) помощи пожилым людям и инвалидам «Старость в радость», БФ поддержки пожилых людей «Достоинство», БФ «Долголетие», БФ «Дари заботу», БФ «Металлург» и др