[IMMUNOREHABILITOLOGY: A LOOK FROM THE SOURCES TO THE FUTURE. FROM IMMUNOTHERAPY TO PERSONALIZED TARGETED IMMUNOREHABLITATION].

Development and introduction of modern clinical diagnostic tests (that allow to evaluate the functional system of immune homeostasis) into medical practice, a huge body of evidence on the leading role of the immune system in pathogenesis most acute and chronic diseases and even identification of specific nosological forms of immune-mediated diseases forced the scientists to search and develop new tools and techniques that have therapeutic effects on the impaired immune homeostasis and restore it to the normal state. The introduction of a new concept - immunorehabilitation - was an impetus for the accumulation of new knowledge and a catalyst for research in clinical immunology. It was Revaz Sepiashvili who breathed life into the concept of immunorehabilitation. He was lucky to be at its origi. He became not only the founder of the brand new scientific field - immunorehabilitation, but also the founder of a new medical science - immunorehablitology. In this paper, the author returns to the roots and recalls the way that medical science has gone before coming to understand immunorehablitology and tells readers about current successes and its development prospects.

[CRITERIA FOR SELECTION OF TUMOR CELLS AND PROSPECTS FOR SPECIFIC IMMUNOTHERAPY FOR BLADDER CANCER].

Specific antitumor immunotherapy with autologous dendritic cell vaccines is one of the new approaches of modern medicine. For activation of dendritic cells highly immunogenic antigens are used, however optimal antigens in case of bladder cancer (BC) are still not researched. Cancer-testis antigens (CTA) are the most promising target in the context of creation of antitumor vaccines, because they are distinguished by pronounced immunogenicity, they are detected in different types of tumors and have limited pattern of expression in healthy tissues of grown-up organism. Regarding the level of mutational load, bladder cancer (BC) holds the third position among all malignant growths, which creates particular opportunities for use of immunotherapy in case of this disease. At chromosomal level most times the following cytogenetic anomalies specific for BC are detected: hyperploidies at 3, 7 and 17 chromosomes and deletion of 9p 21 locus. Besides, in the literature there is information about possible monosomy at 2, 3, 6, 8, 13, 14, 17 and frequent loss of Y chromosome in case of BC. Development of personified dendritic cell antitumor vaccines (PDAV) against bladder cancer (BC) is a relevant problem, which covers many aspects, necessary for its standardization. In particular, in case of cultivation of tumor cells under in vitro conditions their transformation goes at higher pace in comparison with in vivo tumor development. Moreover, the article presents the results of the study of molecular-genetic features of BC of tumor cultures in case of long-term cultivation, the level of expression of CTA (MAGE, NY-ESO-1, GAGE, BAGE) by urothelial carcinoma cells (UCC). There has been described the karyotypes of cells of urothelial low differentiated carcinoma of high malignant potential at various passages with prolonged cultivation, as well as the correlation between cytogenetic profile and expression of tumor-specific cancer-testis antigens has been identified. There have been developed two verified cell line cultures of muscle invasive and muscle-non-invasive urothelial carcinoma, that are potentially useful for the producing of tumor-associated vaccines against BC.

[SELECTION OF MINI-INVASIVE PALLIATIVE DECOMPRESSION METHOD IN PATIENTS WITH MALIGNANT OBSTRUCTION OF BILIARY DUCTS BASED ON THE STUDY OF BIOCHEMICAL BILE INDEXES].

The article gives our own experience in the determination and study of additional laboratory criteria (total lipids, cholesterol, maximum and area chemiluminescence, antioxidant activity) at the local level (in bile) in patients with bile duct obstruction of malignant etiology. Constellation of metabolic disorders allowed to propose an original method for determining the lithogenicity of bile (integral indicator of lithogenicity). The obtained data made it possible to justify the need to assess the degree of metabolic disturbances in bile, on the basis of which it is possible to predict the risk of lithogenesis and the duration of stent operation, which in turn helped optimize the algorithm for choosing the method of bile ducts decompression aimed at preventing early obturation of endoprostheses.

[ANTIRETROVIRAL THERAPY AND THE RISK OF LIVER FIBROSIS PROGRESSION IN HIV/HCV COINFECTED PATIENTS].

The purpose of the study is to determine the nature of the impact of antiretroviral therapy on the development of liver fibrosis in patients coinfected with human immunodeficiency virus (HIV) and hepatitis C virus (HCV), depending on the order of pathogens acquisition. The fact is that the HIV/HCV coinfection is one of the most common pathological conditions worldwide and liver disease is a major cause of death for these patients. We have previously described the phenomenon, according to which the order of viral pathogens acquisition in HIV/HCV coinfected patients has a significant impact on the degree of progression of liver fibrosis. Introduction to clinical practice of antiretroviral therapy greatly increased the life expectancy of HIV-infected patients, however, the impact of ART on a progressive course of liver fibrosis in HIV/HCV coinfected patients have not yet been definitively established.

CORRELATION BETWEEN SPIROMETRY DATES AND SPECIAL ALLERGEN- SPECIFIC IGE IN PATIENTS WITH BRONCHIAL ASTHMA IN WEST GEORGIA.

The study aimed to establish correlation between airway obstruction and specific IgE specificity, managing future treatment in the patients with bronchial asthma, among the population of west Georgia. In the study have been involved 56 patients (among them 24 males and 32 females) of different ages, with diagnostic bronchial asthma (according to GINA recommendation). On the ground of the aim the study included the following steps of allegro-diagnostics: I step - Computerized spirometry by apparatus ,,SPIROLAB 3". II step - To detect allergenization degree, total serum IgE levels, specific IgE and concentration of Phadiatop, using modern automated system - "Immuno CAP 100", were estimated in the patients. III step- future treatment recommendations. All 56 patients were undergone the spirometry measurement. Our results show that of 56 patient 21 (38%) had very severe obstruction by spiromatry: Pretest: FEV 1 - 28%; FEF-45%; FEV1/FVC ratio -55% on average. Post test: significant bronchodilatation was revealed FEV1> +12%( >200 mL) after the inhalation of four puffs of a short - acting beta2 sympathomimetic agent, e.r., 400 µg of salbutamol. In 19 (33%) patients severe bronchoobstruction was established. By spiromometry was revealed: Pre test: FEV 1 - 42%; FEF-55%; FEV1/FVC ratio -67% on average. Post test: significant bronchodilatation was revealed FEV1> +12%( >200 mL) In 14 (25%) patients moderate bronchoobstruction was diagnosed, the spiromatry results were. Pretest: FEV 1 - 52%; FEF-65%; FEV1/FVC ratio - 67% on average. Post test: It was revealed significant bronchodilatation FEV1> +12%( >200 mL). Only in 2 (4%) patients were diagnosed the normal spiromatry. In the patients with bronchial asthma of a specific positivity of specific IgE to the weeds (Wx2) - ambrosia, plantain, clasp/tarragon, atriplex - in 23 (53%) on average; tree dust (Tx9) - alder, lactarius piperatus, nuts, oak, willow - 11 (19%); and cereals (Gx1) - festuca pratensis, lolium temulentum, timoti grass, poa - 9 (16%); Mx2 -Penicillium notatum, Cladosporium herbarum, Aspergillus fumigatus, Candida albicans, Alternaria alternate- 15 (21%) was revealed, only in 5 (9%) patients we cannot established the allergy specific IgE. It was established the correlation between spiromatry dates and special allergen specific IgE in patient with bronchial asthma. The latter is of great importance for providing the effective and safe allegro-specific immunotherapy (ASIT) and successful preventive measures.

[MOLECULAR BIOLOGY OF HEPATITIS B VIRUS AND IMMUNOPATHOGENESIS OF CHRONIC VIRAL HEPATITIS B].

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

[MECHANISMS OF INTERACTION OF VIRAL CAUSATIVE AGENTS IN PATIENTS CO-INFECTED WITH HUMAN IMMUNODEFICIENCY AND HEPATITIS C VIRUSES].

In patients infected with human immunodeficiency virus (HIV) in 20 - 30% of cases co-in- fection with hepatitis C virus (HCV) is observed, that is associated with common routes of transmis- sion for these causative agents. The main cause of lethal outcome for co-infected patients is liver damage. Thus, analysis of mechanisms of mutual influence of HIV and HCV under the conditions of co-infection gains special attention, that can be examined from both standpoints of direct inter- molecular interaction of 2 viral causative agents, as well as from the position of their immune- mediated effect. Negative effect of HIV on the course of fibrosis process in liver during HCV infection is associated with the feature of this virus to cause deep alteration in the immune system by direct damage of CD4+ cells, disruption of mechanisms of immunological memory, suppression of functions of liver fraction of NK and NKT, as well as its ability of co-receptor interaction with hepatocytes and stellate cells, enhancing progress of fibrosis alterations and HCV replication in liver. HCV.is also established to effect replication of HIV, stimulate infection of macrophages with this virus. All these events facilitate the rise in lethality during HIV and HCV co-infection.

[BASIC PRINCIPLES AND METHODS TO THE USE IMMUNOMODULATING PREPARATIONS IN CLINICAL PRACTICE: CLASSIFICATION, INDICATIONS AND CONTRAINDICATIONS].

This paper is devoted to one of the most pressing issues in modern clinical medicine, the problem of immunomodulators and immunotropic therapy. The materials presented are the logical sequel of the papers published by Revaz I. Sepiashvili in 2001-2015. In these articles, the author proposed the first classification of immunotropic preparations, a brief historical background and chronological emergence of the concept of therapies, as well as definition of immunomodulators. This paper presents an updated classification of immunomodulatory drugs which is valid for January 2015. The paper also outlines basic principles for therapies that allow the clinician not only to select a proper immunomodulator but also to develop strategy and tactics in treatment of the patient, taking into account his/her individual characteristics and the need to use in clinical practice only officially registered immunotropic preparations.

[MODERN CONCEPT OF PATHOGENESIS OF ALLERGIC DISEASES AND NEW POTENTIALITIES OF IMMUNOTHERAPY].

Despite the undoubted success of specific immunotherapy of allergic diseases (desensitization), one should confess that its effectiveness is not always satisfactory, and this explains the ongoing search for new approaches to immunotherapy. This conclusion is based on the results of basic research in immunology and allergy which provide new opportunities for therapy. The analysis of relevant work related to the study of allergic processes makes it possible to allocate two items: 1) specific hyposensitization-therapeutic approach that is primarily aimed at the final stage of the allergic reaction development; 2) development of allergic phenotype begins at early stages of B lymphocyte development while its final stage, IgE hyperproduction, depends on multiple of pre- and accompanying factors. Unfortunately, we should say that there are many issues in the development of allergic reaction that are beyond our understanding. Nevertheless, today new mechanisms of pathogenesis are revealed and there is a real opportunity for new approaches to the treatment of this pathology. Some of such various mechanisms will be discussed below.

[IMMUNOLOGICAL AND NON-IMMUNOLOGICAL PATHOGENETIC MECHANISMS OF DEVELOPMENT OF COMPLICATED FORMS OF ATOPIC DERMATITIS (REVIEW)].

Difficult to control atopic dermatitis (AD) presents a therapeutic challenge and often requires combinations of topical and systemic treatment. Causes of severe AD are individual in each patient (e.g. genetic, barrier function, allergies). In this review, we will examine the highly complex interplay among skin barrier abnormality, allergy, immune dysregulation and antimicrobial peptide as a trinity in the development of AD. Studying of pathogenesis of formation of the complicated current the AD is a key problem of successful control as contamination of skin, and allergic inflammation.

[AEROPOLINOLOGIC MONITORING AND DISTRIBUTION OF ALLERGOALLERGENS IN WESTERN GEORGIA].

Climate and geographical conditions such as: air temperature, humidity and plant diversity represented in the region is of great importance for prevalence of allergic diseases. All these factors will maintain growing of allergization/sensitization of the body. It is known that allergic diseases (pollinosis, bronchial asthma), the highest percentage comes on the allergens- aeropolutants, that are represented in many plants and herbs in the form of dust (ragweed pollen, alder, birch, maple, walnut, mallow, cotton plant etc.). Thus, aeropolinologic study acquires special importance helping the clinicians to solve the following issues: which plant is common for the concrete region; what is the source of dust allergy; when are they particularly dangerous for the patient; when their dust is revealed and its concentrations in air pool or how they look. Georgia is the country with diverse flora and landscapes; the climate in Georgia varies across different parts of the country. Clinical and epidemiological studies have shown that the Western Georgia is characterized by the frequency of allergic diseases. The above raises the need to create a calendar of flowering plants in Imerety region of Georgia. 69 patients with allergic rhinitis and bronchial asthma from 7 to 60 years old (34 men and 35 women) were observed. The patients underwent allegro-diagnostic investigation. The results revealed high titers on weeds (WX2). On the basis of the conducted research annual calendar of aero-allergens spread in Imerety region was composed.

[Bronchial asthma pathogenesis and genetic prognosis development].

The review is dedicated to an actual problem--genetic prognosis of risk of bronchial asthma development that is quite a complex aspect of studies from a methodological viewpoint. Bronchial asthma--heterogeneous disease by both etiology and clinical characteristics. At the same time genetic prognosis is based on the unity of pathogenetic mechanisms of development, though in immunological reactions that are the base of this disease, alternative variants are possible. The aim of this review is carrying out parallels between modern achievements in the field of deciphering trigger mechanisms of bronchial asthma pathogenesis and object of genetic studies based on these mechanisms. Among the examined conceptions--role of epithelial tissue in trigger mechanisms of bronchial asthma, variants of key role of immune system cells, first of all, T-helpers of various types for further development of inflammatory-effector reactions with damage characteristic for this disease. Compliance of contemporary approaches of genetic studies and novel concepts of bronchial asthma pathogenesis is shown.

[Intestine infections, inflammation and autoimmunity. Lymphoid apparatus of intestine in interaction with intestine microflora].

Topicality of interrelation between intestine infections, inflammation diseases of intestine and autoimmune processes is widely discussed in scientific literature of recent years. Thereby a review of literature on the designated aspect of the problem is dedicated to the analysis of interconnection between structural-functional features of lymphoid apparatus of intestine and its ability to react to antigen load from both commensal and pathogenic intestine microflora. During description of structure and functions of lymphoid formation of intestine a particular attention is paid to difference of subpopulation characteristics of lymphocytes and antigen-presenting cells composing intra-epithelial lymphocytes, elements ofimmune system lamina propria, Peyer's patches, mesenteric lymphatic nodes. The role of normal microflora and infectious agents in trigger mechanisms of reaction of immunocompetent cells is underscored; key aspects of cellular-molecular mechanisms of mucous membrane immune system functions are discussed.

[Intestine infections, inflammation and autoimmunity. Trigger and effector mechanisms of autoimmune disease development as an outcome of intestinal infections].

Problem of interconnection of intestine infections, inflammatory intestine diseases and autoimmune illnesses in this article is examined from the position of their trigger and effector mechanisms. Among trigger mechanisms special attention is given to mechanisms by which the presence of pathogenic microbial causative agent in the organism is transformed into an autoimmune process. The phenomenon of antigen mimicry, carriage of superantigens by pathogenic agents, the role of cell apoptosis are accentuated. Autoimmune diseases are examined in the same way as genetically determined phenomenon with designation of main genes, polymorphism of which is involved in the development of this pathology. Among effector reactions accompanying the development of autoimmune process againstthe background of intestine infections the role of B1 lymphocytes, Th17 and Th1 are analyzed in more detail. Special attention is given to pathogenetic and protective role of natural killers which is recognized as relatively understudied.

[Serotonin and its immune and physiological effects].

Now that the neurotransmitter serotonin modulates the immune system cells, and its main sources for antigenpresenting cells and lymphocytes are enterochromaffin cells of the gut, peripheral nerves, platelets and mast cells in case of inflammation. Immune cells uptake serotonin because they express receptors for this monoamine and intracellular serotonin transporters. The dendritic cells have a mechanism to transfer serotonin to T lymphocytes during antigen presentation. The macrophages and T cells have the ability to serotonin synthesis. Serotonin can influence mobility and proliferation of lymphocytes, phagocytosis, cytolytic properties, synthesis of chemokines and cytokines. Diversity of immunomodulating effects of serotonin is determined by heterogeneity of serotoninergic receptors. Immunomodulating action of serotonin is evidence of the close relationship between nervous and immune systems.

[The effect of water with modified isotope content on the parameters of free radical oxidation in vivo].

With the use of nuclear magnetic resonance we investigated the effect of consumption of water with the modified isotope content on the composition of deuterium in the blood, assessed the state of pro-oxidant-antioxidant system in the blood and lyophilized tissues (liver, kidneys) under prolonged oxidative stress. Possible mechanisms of direct and indirect antioxidant effects of the water with modified isotope content and the perspectives of its use for nutritional correction of abnormalities of oxidative metabolism during special physiological conditions and in clinical practice are discussed.

[Is antiviral therapy in gastroduodenal pathology necessary?].

Mucous membrane of the gastroduodenal region of 104 patients with different pathologies (gastritis and erosive ulcerative alterations) was investigated by polymerase chain reaction (PCR). Examination of the biopsy material revealed frequent occurrence of pathogenic strains of Helicobacter pylori (up to 80%) and Herpesviridae (EBV, HHV 6, HHV 7, HHV 8) in various combinations. In such cases it is necessary to use adequate antibacterial and antiviral therapy with individual choice of immunomodulators.