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Objective: To investigate the role of dopamine receptor D 1 DR and D 2 DR in the production of cytokines interleukin-6 (IL-6) and IL-1β by monocytes and macrophages in patients with relapsing-remitting multiple sclerosis (MS)., Material and Methods: Ten patients with relapsing-remitting MS and 10 healthy subjects were examined. The level of IL-6 and IL-1β production was assessed in culture supernatants obtained from CD14 + monocytes or macrophages stimulated with interferon-γ (IFN-γ) and lipopolysaccharide (LPS). To study the role of dopamine receptors in the regulation of CD14 + monocytes or macrophages, samples of cells were incubated in the presence of specific D 1 DR or D 2 DR antagonists, after which IFN-γ/LPS were added to the cultures. Levels of cytokines in culture supernatants were measured by enzyme-linked immunosorbent assay., Results: The production of IL-6 and IL-1β by CD14 + monocytes and macrophages was comparable between the groups. Blockade of D 1 DR suppressed cytokine production by CD14 + monocytes and macrophages in both groups. In contrast, blockade of D 2 DR increased the production of cytokines by CD14 + monocytes and did not affect cytokine production by macrophages in both groups., Conclusions: Targeting of dopaminergic receptors could be considered as an additional mechanism of immunomodulation in MS with both pro- and anti-inflammatory effects on cells of the innate immune system.

Objective. Reprogramming of M1 macrophage phenotype with inhibited M2 phenotype transcription factors, such as STAT3, STAT6 and SMAD and assess their impact on the development of Ehrlich carcinoma (EC) in vitro and in vivo. Methods. Tumor growth in vitro was initiated by addition of EC cells in RPMI-1640 culture medium and in vivo by intraperitoneal of EC cell injection into mice. Results. It was found that M1-STAT3/6- SMAD3 macrophages have a pronounced anti-tumor effect in vitro, and in vivo, which was greater than anti-tumor effects of M1, M1-STAT 3/6, M1-SMAD3 macrophages and cisplatin. Conclusion. M1 macrophages with inhibited STAT3, STAT6 and/or SMAD3 effectively restrict tumor growth. The findings justify the development of new anti-tumor cell therapy technology.

There are numerous data in experimental and clinical medicine that convincing evidence on the leading role of the immune system in the pathogenesis of tumor diseases. Exactly immune cells such as cytotoxic T lymphocytes, NK cells, macrophages and dendritic cells have the ability to kill tumor cells. Under normal conditions the activity of these cells is a factor of inhibition proliferation and differentiation of tumor cells. An appearance of tumor itself, as uncontrolled cell growth and clinical manifestation, says that it was changed the cytotoxic activity of the cells causing tumor immunity. The main factor, if not the only reason for the decline of anti-tumor activity of the cells, is the formation of powerful extra- and inside-tumor suppressor mechanisms suppressing cytotoxic activity of anti-tumor immune-competent cells and allowing tumor cells to avoid surveillance by the immune system. It is showed that T and B cells, macrophages, and cells of myeloid origin suppressors possess these immunosuppressive properties. Therefore, in the future, methods to suppress functional activity of cells suppressors of various geneses can be the basis for immunotherapy of tumor growth.

Objective: to analyze the role of inflammatory and immune reactivity in the development of adenomyosis and its associated pain. Methods. For morphological studies it were using fragments of walls of 56 uterus received after hysterectomy in patients with pelvic pain on a background of diffuse adenomyosis II-III degree, and 30 patients with painless form of adenomyosis. To identify, evaluate the amount and spatial distribution of macrophages, T-helper cells and natural killer cells it was using MAbs to CD68, CD4, CD56 respectively. The results of the study showed a significantly high expression of CD68 (49,3 ± 2,3 vs. 21,2 ± 1,7 conv. units, p<0,01), CD56 (47,4 ± 2,7 vs. 17.2 ± 1.8 conv. units, p<0,01, p<0,05) and CD4 (52,1 ± 2,2 vs. 19,9 ± 2,5 conv. units, p<0,01) in patients with painful form of adenomyosis in the regions of ectopic endometrium and in the regions of perivascular growth in myometrium compared to those areas in women with painless adenomyosis. Conclusions: Adenomyosis is a chronic inflammatory disease accompanied by dysfunction of the uterine immune reactivity. Inflammatory and immune processes in the uterus with adenomyosis contribute to the persistence and growth of endometrial implants. In adenomyosis, associated with chronic pelvic pain syndrome, there is increase in the number of activated macrophages, natural killer cells and T-helper cells in the perivascular regions and in areas of remodeling of the myometrium are carriers of the nerves, which leads to increased neurogenic inflammation and sensitivity of nociceptors, activation of peripheral nerve fibers and the generation of pain.

The dogma of the central nervous system (CNS) as an immune-privileged site has been substantially revised in recent years. CNS is an immunocompetent organ and actively interacts with the immune system. Microglia plays a leading role in a CNS immune response. However, in malignant gliomas, there is M2-polarization of microglia acquiring immunosuppressive and tumor-supportive properties. It occurs under the influence of tumor cytokines, such as transforming growth factor-β, interleukin-10, and prostaglandin E2. M2-polarized microglia exhibits reduced phagocytic activity, changes in the expression of many cellular determinants, or inverse of their functions, STAT3 activation, and production of immunosuppressive cytokines that suppress the function of cytotoxic CD8+ T cells or CD4+ T-helper cells type I. Myeloid-derived suppressor cells and regulatory T-lymphocytes, which have been recruited from peripheral blood into tumor tissue, also have immunosuppressive properties. The development of new treatment options for malignant gliomas must consider the role of the microenvironment in maintaining tumor vitality and progression.

Macrophages play important role in initiation and progression of inflammation in atherosclerosis. Plaque macrophages were shown to exhibit a phenotypic range that is intermediate between two extremes, M1 (proinflammatory) and M2 (anti-inflammatory). Indeed, in atherosclerosis, macrophages demonstrate phenotypic plasticity to rapidly adjust to changing microenvironmental conditions. In plaque macrophages demonstrate different phenotypes, and besides macrophage phenotypes could be changed. Phenotypes M1, M2, M4, Mhem, HA-mac, M(Hb) u Mox are described in the article. Ability of macrophages change their phenotype also considered.

A key role in the ability of immunity to adequately respond to pathogenic factors play macrophages. Depending on the type of infection and the microenvironment macrophages can rapidly change their phenotype towards the proinflammatory M1 or antiinflammatory M2 one. The process of changing the cell phenotype is termed "reprogramming". This process plays a central role in the immune response and therefore its disturbance triggers the development of disease. Reprogramming of macrophages is provided by intracellular signaling pathways. These paths can also control epigenetic, post-transcriptional and metabolic mechanisms of phenotypic activity of macrophages. Epigenetic mechanisms can be divided into the reprogramming mechanisms towards M1 and M2 phenotype. A key component of post-transcriptional regulation is micro-mRNA (miR). On M1- and M2-stimuli macrophages express different sets of miRs. MiRs may form a positive feedback mechanism for quick reprogramming of macrophages and negative feedback mechanisms, to limit excessive inflammation in the case of M1 phenotype and to restrict fall bactericidal activity in the case of M2 phenotype. Reprogramming of macrophages leads to a change in the metabolism of these cells. Formation of M1 phenotype accompanied by a shift of the arginine metabolism towards NO-synthase activation and increased production of NO, an increase in the contribution of glycolysis to ATP production, increased deposition of bacteriostatic iron. Formation of the M2 phenotype is accompanied by a shift of the arginine metabolism towards arginase 1 activation and increasing production of urea, increased ATP synthesis in mitochondria and increased capture of fatty acids, increased the capture of heme iron. Metabolic control of macrophage phenotype also involves the positive and negative feedback. In general, macrophage reprogramming involves very good coordinated and adapted to each other changes in the activity of signaling, epigenetic, post-translational and metabolic mechanisms. A detailed understanding of the mechanisms of reprogramming will assist in selecting the correct effective therapeutic targets to develop new ways for correction of impaired immunity. Keywords: immunity; macrophages; reprogramming

Macrophages are some of key constituents of innate immunity. They possess marked phenotypic and functional diversity. Several subpopulations of "classically" and "alternatively" activated macrophages have been recognized. Tissue heterogeneity of resident macrophages are characterized by great quantity populations of these cells in the lymphoid andnonlymphoid tissues. Macrophages actively take part in responses of acute and chronic inflammation. An imbalance on the activity of these cells leads to cytotoxicity/tissue injury if the balance is tipped toward M1 macrophages, and fibrosis/cancer if it is tipped toward M2 macrophages. Moreover, macrophages can immediately participate in reactions of innate immunity during chronic inflammation.

Metabolic activity of innate immunity cells infected by various doses of Gram-negative (Yersinia pseudotuberculosis, Salmonella enteritidis) and Gram-positive (Staphylococcus aureus, Listeria monocytogenes) bacteria has been investigated. Using various animal models we found that during the initial period (up to 2 days) changes of infection in cellular responses depend on the type of the pathogen. In response to infection caused by Gram-negative bacteria predominant neutrophil accumulation in the foci of inflammation was observed, while Gram-positive bacteria induced preferential accumulation of macrophages. The study of metabolism of these cells showed that the response of terminally differentiated primed phagocytes to pathogen appearance was higher than in cells circulating in blood. In addition to the priming state the phagocyte reactivity is influenced by the bacterial load. At a low phagocyte/microbe ratio the cells reaction is almost undetectable, while an excess of microorganisms causes (despite of the increase of the phagocytic parameters) the hyperactivation of cell metabolism and production of maximal amounts of bactericide agents, which exhibit a damaging effect on the cell itself.

Macrophage is a key cell of immune system, it participates in antiviral, antimicrobial and antitumor defense of the organism, also in regeneration and reparation of tissues. Macrophage coordinates functioning of immune system, participates in tumor growth progression. The process of inflammation consists of two stages. Cytotoxical potential of immunocompetent cells will be realized in the first stage, to avoid a bacterial infection. The second stage of inflammatory process is associated with reparation and regeneration. During inflammation, according it stages, macrophages change functional state, switching from cytotoxical M1 to M2, that associated with reparation. We suppose, that rapamysin, a suppressor of mTOR, causes completely different effects on tumor associated macrophages and cells of microglia. Rapamycin transforms tissue macrophages into M1 phenotype, promoting the tumor regression. While in microglial cells of the central nervous system it induces transformation into M2 phenotype, facilitating the course of the neurodegenerative disease and slowing down the aging.

Predisposition to tumors is often determined by how effectively the genotype of an individual forms an immune defense. An important factor of such protection is macrophage NO. We assumed that the body's vulnerability to the development of tumors may depend from the characteristics of the NO generating systems. The content of NO in the tumor changed by ITU, inhibitor of iNOS, c-PTIO, traps and SNP, donor NO. Production of macrophage NO were evaluated by nitrites in the culture media. iNOS was assessed using the Western blot analysis. Phenotype of macrophages was assessed using cytometry for CD labels. Life span of mice C57BL/6N with Ehrlich tumor was 25% greater than that of the C57BL/6J. Reducing the content of NO in the tumor reduced life expectancy of high-resistance to tumor subline C57BL/6N at 23%. Increase of NO increased life expectancy of low-resistance subline C57BL/6J at 26%. Macrophages of C57BL/6N were 1.5 times higher contents of iNOS and NO production, as compared with macrophages of C57BL/6J. CD phenotype markers determined the macrophage phenotype C57BL/6N as M1 and C57BL/6J mice macrophage phenotype as M2. Thus, the body's vulnerability to the development of tumors may depend from the characteristics of the NO generating systems. C57BL/6J, unlike C57BL/6N does not synthesize NNT (nicotinamide nucleotide transhydrogenase) and have differences in the single nucleotide polymorphism (SNP). The important role of NO in the resistance to Carcinoma, NNT and SNP deserve attention in the development of new methods of antitumor therapy.

The changes in the numerical density of macrophages of maternal (basal decidua) and fetal (Kashchenko-Hofbauer cells) origin were studied in the placenta of women with opportunistic (Ureaplasma urealyticum and Mycoplasma hominis) and pathogenic (Chlamydia trachomatis) urogenital microflora. Histological study of placenta was performed and CD68-immunoreactive cells were detected immunohistochemically in the basal decidua and in the chorionic villi obtained during artificial abortions for non-medical reasons in the 6-8th week of pregnancy (n=136). The results showed no changes in the numerical density of macrophages of maternal origin and a significant decrease in the numerical density of macrophages in the stroma of the chorionic villi, which was associated in Chlamydial infection with a delayed, and in Ureaplasma and Mycoplasma infection - with an accelerated development of the villous tree.

Purpose of the investigation was microscopic examination of changes in cyto architectonics of the spleen and jejunum lymph (immune) tissue in 19-20-week C57BL/6N male mice exposed to some conditions their counterparts had lived in during the 30-d Bion-M1 mission (ground experiment). Local deviations in reactions of the morphofunctional zones of these organs were found. In the spleen, reaction in the centers of lymph nodules generation or the B-lymphocytes maturation zone grows strong. Changes in the cell composition of periarterial lymph sheaths that constitute the morphological site of T-lymphocytes accumulation suggest inhibition of its functional activity. Cell composition of the jejunum wall structure implies a decline of the jejunal immune activity. Our investigation of the organs taken from the ground control mice maintained in the flight BIOS-MLZh module evidences that unceasing noise, hypokinesia, isolation, and paste-like feed weaken general immunity of laboratory animals.

The article reports the results of studying the lymph tissue of mesenteric and cervical lymphatic nodes in C57BL/6N mice after the 30-day orbital flight onboard biosatellite Bion-M1. Histological and morphometric investigations revealed changes in the ratio of the nodes structural-functional zones and microstructure. Reductions in reticular cells, plasmocytes, macrophages and blasts in the nodes point to degradation of both humoral and cellular immunity.

Macrophages play a key role in the pathogenesis of many human diseases. Both evaluation of M2/M1 macrophage ratio and discovering definite roles of macrophage phenotypes in this diseases may be used as criteria for assessment of effectiveness of treatment and for predicting prognosis of patients. Moreover, macrophage reprogramming seems to be a perspective therapeutic strategy for the diseases with inflammatory component in their pathogenesis. This review is based on articles published mainly in last five years and describes the results of the studies for some substances, most of them being used in current medical practice. This agents have been proven to have determined affection on macrophage polarization, its signal pathways, etc. Influencing macrophage reprogramming by such agents seems to be an important strategy in modern medicine.

The paper presents evidence on the important contribution of the peripheral serotonin system in the process of immunomodulation. The main components of the system - serotonin, receptors and serotonin transporter - are described. Possible mechanisms of serotonin regulation of activity of immune cells - lymphocytes, macrophages and dendritic cells - are reviewed.

The immunomodulatory properties of perspective prebiotics--beta-galactose-containing--polysaccharides arabinogalactan, arabinogalactan with flavonoids, carrageenan, galaktomannan have been studied. It was established that oral administration of the studied beta-polysaccharides to experimental animals leads to a significant activation of immune cells and the synthesis of humoral factors in their organism which significantly increases the cytotoxic activity of blood serum. The most pronounced immunomodulatory effect exhibits arabinogalactan with flavonoids and carrageenan.

In review provides information about the function oft the body of chaperones and their role in the development of pathological processes, including--atherosclerosis and coronary heart disease. Marked comminications systems chaperones to the immune and endocrine systems, and inflammation.

The examination was applied to sampling of 17 patients with stable implants after 18-36 months after endoprosthesis replacement of knee joint and to sampling of 17 patients with developed within this time-frame aseptic instability of endoprosthesis within the same time-frame. The typing of lymphocytes of peripheral blood was implemented using laser flow cytometry. The detection of immunoglobulins, cytokines, circulating immune complexes was made applying the technique of enzymoimmunoassay. In case of development of aseptic instability the signs testifying moderate activation of immune system and starting dysfunction of monocyte macrophage component of immune system. At that, IL-6, TNFα, CD14+HLA-DR provided the most complete information on the side of diagnostic of developing aseptic instability of joint.

Based on their studies and literature analysis, the authors offer a hypothesis for the adaptive pattern of chronic immune granulomatous inflammation occurring in infectious diseases that are characterized by the development of non-sterile immunity. The authors' proposed hypothesis holds that not every chronic inflammation is a manifestation of failing defenses of the body exposed to a damaging factor. By using tuberculosis and leprosy as an example, the authors show the insolvency of a number of existing notions of the pathogenesis and morphogenesis of epithelioid-cell and leprous granulomas. Thus, the authors consider that resident macrophages in tuberculosis maintain their function to kill mycobacteria; thereby the immune system obtains information on the antigenic determinants of the causative agents. At the same time, by consuming all hydrolases to kill mycobacteria, the macrophage fails to elaborate new lysosomes for the capacity of the pathogens to prevent them from forming. As a result, the lysosome-depleted macrophage transforms into an epithelioid cell that, maintaining phagocytic functions, loses its ability to kill the causative agents. It is this epithelioid cell where endocytobiosis takes place. These microorganisms destroy the epithelioid cell and fall out in the area of caseating granuloma necrosis at regular intervals. Some of them phagocytize epithelioid cells to maintain non-sterile immunity; the others are killed by inflammatory macrophages. The pathogenesis and morphogenesis of leprous granuloma, its tuberculous type in particular, proceed in a fundamentally similar way. Thus, non-sterile immunity required for tuberculosis, leprosy, and, possibly, other mycobacterioses is maintained.

The reactions of rat regional lymph nodes, caused by implantation of the autologous multipotent mesenchymal stromal cells of a bone marrow origin (AMMSCBM) for acceleration of bone defect regeneration in bottom jaw experiment were studied by methods of fluorescent light microscopy. After introduction in an injury site of a bottom jaw bone of polyhydroxyalkanoate with adsorbed AMMSCBM with a transfected GFP gene the numerous large macrophages with a set of oval fluorescent inclusions in cytoplasm appear in lymph nodules of submandibular lymph nodes. The number of such macrophages increases within 2 weeks after operation, and further starts decreasing. Probably, entered via such way the AMMSCBM partially are phagocytized by macrophages. At destruction of the structures created from AMMSCBM, debris also are phagocytized by macrophages. In that and other case these macrophages appear in the germinative centers of lymph nodules in lymph nodes where initiation of immunity reactions against DNA and same GFP isn't excluded.

Using the immunohistochemical method, mononuclear phagocytes (MNPs) were detected in the liver, lung, kidneys and spleen of rats after a single intravenous injection of a suspension of magnetoliposomes and magnetic microspheres prepared on the basis of nanoscale magnetite particles of (NMPs). The dynamics of the of the number and topography of CD68(+)- and CD163(+)-cells in liver, lung and kidneys was characterized during 120 days after the intravenous injection of the suspension of modified NMPs. It was shown that NMPs surface modification reduced the degree and duration of macrophage activation. Signs of MNPs activation after the infusion of nanomaterial decreased in the following series: unmodified NMPs, magnetoliposomes, magnetic microspheres.

Is established that at intestinal dysbacteriosis in the organism of experimental animals develop reactions of inflammatory type (early and late), leading to an accumulation in the blood serum of humoral immunity factors, blocking reactions mediated by lymphocytes ormacrophages, while maintaining their cytotoxic activity. Introduction of animals of tne probiotic endosporin promotes restoration of quantitative and qualitative indicators of intestinal microbiocenosis and the normalization of the immune system.

On the basis of morphological and immunological study of biopsies of the colon in patients with diverticulosis was revealed that microscopic inflammation of the mouth of the diverticulum is characterized by several features that include excessive proliferation of the epithelium, the predominance of macrophage reaction in the development of the immune response, increased cell adhesion and unusual ratio between the expression of cytokines and other regulatory molecules. Changes in the structure of the formed diverticula tissue are associated with dysregulation of many processes of tissue metabolism and morphogenesis. These include the dysregulation of cell renewal of the epithelium (increased level of proliferation of epithelial cells and inhibition of apoptosis), degradation of extracellular matrix components, moderate vascular reaction. All these processes take place on the background a particular form of immune protection and adaptation mechanisms.

This review describes and summarizes the data of ESX secretory system peculiarities characteristic of mainly mycobacteria. This system is involved in the secretion of small proteins of the WXG100 family. Some of these proteins represent virulence factors of Mycobacterium tuberculosis and other pathogenic mycobacteria. The role of these proteins in pathogenesis apparently consists of protecting mycobacteria from lysis in the macrophages that absorb them; the cytolysis of macrophages; and, hence, mycobacterium output into the surrounding tissue. A number of proteins that make up this secretory system are homologs of proteins involved in the conjugation process in saprophytic Mycobacterium smegmatis.

Anaferon and pediatric anaferon based on release-active antibodies to interferon-gamma (R-A antibodies to INF-gamma) proved to be efficient in the treatment of many viral infections. Immunomodulating (immunotropic) properties of the drugs were revealed in the preclinical studies at many Russian and foreign research medical institutions and are reviewed herein. Anaferon and pediatric anaferon stimulated the humoral and cellular immune responses and increased the neutrophil and macrophage activity. The crucial mechanism of the immunotropic action of R-A antibodies to INF-gamma was the effect on the system of interferons and in particular on INF-gamma and functionally conjugated cytokines, resulting in normalization of the functional activity of the innate factors of the immune defense and increasing of the antiviral action. The broad spectrum of the immunotropic activity provided the success of anaferon and anaferon pediatric for more than 10 years in the treatment and prophylaxis of the diseases associated with disorders in the immune system functional state.

In the review of the literature modern data on mechanisms phagocytes protection of periodontium, sold monocytes-macrophage system and neutrophil are resulted. The opportunity of programming of a morphological amd functional phenotype of macrophage is analyzed by change of concentration of whey of blood. Data on functioning in gingival sulcus or periodontal pocket << extracellular neutrophil traps>> are resulted. Opportunities to operate by the nonspecific protective answer of fabrics periodontium on microbic aggression are shown.

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.

Chronic inflammatory processes have long current during which there is a change of remission by an aggravation of disease. Until recently was considered, that occurrence and activation of chronic inflammatory process is caused by one signal of danger. Most often it are served with microorganisms. The sum of our end literary data shows that activation is connected with accumulation in the center of an inflammation of macrophages and their hyperactivation as a result of action of two signals of danger--microorganisms and xenobiotics.

Decrease of oxygen concentration, i.e. hypoxia, in organism tissues and cells is an important pathogenetic component in a large number of diseases. In these cases hypoxia is not only an important component of diseases pathogenesis, but can also influence immune reactions determining the outcome of diseases. Thus, concentration of macrophages in hypoxic areas and their reaction to hypoxia are the key moments in understanding the mechanisms of hypoxia influence on immunity. Macrophages are of the utmost importance in the congenital immune startup and define the vector of development of the adaptive response. In this review we present updated data on influence of hypoxia on macrophages phenotype and their plasticity, and we also analyze genetic trait of macrophages reaction to hypoxia. Molecular mechanisms of immune cells reaction on hypoxia and the role of transcription factors, HIF-1 and NF-kappaB, are analyzed. As a whole, it allowed to describe an important biological phenomenon - hypoxia-regulated control of macrophages phenotypic plasticity, and to define ways of search of new effective approaches to the management of diseases with hypoxic disturbances.

The State Education Institution of Higher professional education "The Orenburg State Medical Academy of Federal Agency in Public Health and Social Development". In the experiment on mice (CBA x C57Bl6) F1 and Wistar rats is shown the protective effect of triterpenoid plant--miliatsina (3-beta-methoxy-delta18-oleanena) in relation to the humoral immune response and clearance macrophage function hepatic xenobiotic conditions of use--methotrexate. The results define the term as used miliatsina immunoprotector with adverse effects on the body of environmental and industrial chemical factors that form the secondary immunodeficiency.

Excessive poorly differentiated epitheliocytes were detected in the crypts and subepithelial regions of the colorectal mucosa during the regeneration process in the majority of patients with diverticular disease. The compensatory reaction of the sigmoid mucosa decreased, which was seen from rarely detected cryptic hyperplasia. Disorders in the epitheliocyte proliferation and differentiation were paralleled by changes in tissue levels of proinflammatory cytokines (elevation of TNF-α and IFN-γ and reduction of IL-1β and IL-8) and increase of IL-4, regulating lymphocyte activation.

Current knowledge of immunocellular and lipoprotein mechanisms of the liver-induced anti-endotoxin tolerance has been summarized. The role of T regulatory cells, different macrophage phenotypes, high density lipoproteins, oxidized low density lipoproteins and their receptors as the key players in mechanism of tolerance to endotoxin has been discussed.

Aim: To assess efficacy of combined immunocorrection in the treatment of patients with chronic viral hepatitis C (CVHC)., Material and Methods: Routine clinicobiochemical tests, examination of immunological homeostasis (cellular immunity, the level of circulating immune complexes - CIC and their molecular composition, macrophagal phagocyting system - MPS) were made in two groups of CVHC patients: the study group (n=68) and control group (n=66). The control patients received standard treatment, the study group received also cyclopheron in combination with reamberin. Cyclopheron was given per os in a single daily dose 600 mg 2 days, then 3 times a week in a dose 150 mg for 48 weeks. Reamberin infusions in a single daily dose 400 ml were made for 5 - 7 days., Results: CVHC in exacerbation phase is characterized by the presence of secondary immunodeficiency running with T-lymphopenia, low count of peripheral blood lymphocytes with CD4+ phenotype and low immunoregulatory index CD4/CD8, depression of functional activity of T-cells as evidenced by lymphocyte blast transformation test with phytohemagglutinin, inhibition of phagocyting activity of monocytes and inhibition of dermal macrophages. This shows subnormal functional activity of MPS. CVHC runs with accumulation of CIC in blood serum primarily due to increased content of most pathogenic mid- and low-molecular .ifactions of immune complexes. Addition ofcyclopheron and reamberin in combined treatment of CVHC patients promotes normalization of immunological homeostasis which clinically occurs in parallel with achievement of persistent and long-term CVHC remission., Conclusion: The results of the above investigation support pathogenetic validity and prospects of cyclopheron and reamberin inclusion into combined treatment of CVHC.

The synthetic mesh is widely used for treatment of hernias. We conducted a comparative study of the morphological pattern of inflammation, the cellular composition of tissues and dynamics of scar formation in mice when using implants "Esfil" and "Unifleks" under influence of single and double injection of cultured fibroblast and without such injection to the region of stents location. A more pronounced inflammatory reaction during the study period of investigation was observed in the case of "Esfil". In the late period of the study, a higher percentage of fibroblasts was observed in the case of the prosthesis "Unifleks" compared to the prosthesis "Esfil". Injection of cultured fibroblasts modifies the curve of the dynamics of the inflammatory process by making it smoother in the case of both prostheses. So, more preferred is the use of prostheses "Unifleks".

Scientific data and data obtained by us regarding new innate immunity receptor agonists from sea hydrobionts are presented. Highly efficient and low toxic biologically active substances isolated from sea organisms are inductors of dendritic cells maturation, activate neutrophils, monocytes/macrophages and NK-cells, have an anticomplementary (fucoidans) and pro- and anti-inflammatory effects. Protective properties of biologically active substances are exhibited when various pathogens entering the organism--bacteria, viruses, protozoa, fungi. These substances may become a basis for the creation of new pharmaceutical preparations.

This article reviews modern concepts of the most common types of macrophage activation: classical, alternative, and type II. Molecular mechanisms of induction and regulation of these three types of activation are discussed. Any population of macrophages was shown to change its properties depending on its microenvironment and concrete biological situation (the "functional plasticity of macrophages"). Many intermediate states of macrophages were described along with the most pronounced and well-known activation types (classical activation, alternative activation, and type II activation). These intermediate states are characterized by a variety of combinations of their biological properties, including elements of the three afore mentioned types of activation. Macrophage activity is regulated by a complex network of interrelated cascade mechanisms.

Thrombosis and inflammatory complications are concomitant to the post-surgery period of splenectomy due to the traumatic damage to the spleen. Therefore morphological analysis of the spleen residue after the partial spleen resection is of particular theoretical and practical interest. Total of 36 white rats, male, body mass 130-150 g., underwent partial resection of the spleen under the ether narcosis. Rats were withdrawn from the experiment on the first, 7-th, 15-th, 30-th, 90-th and 180-th day after the surgery. Spleen tissue samples were fixed in the 10% formaldehyde solution and stained with the use of routine methods. Homory method was used to reveal the argyrofilous fibers and ink injection was used to reveal blood vessels respectively. Spleen parameters were calculated morphometrically. Microsoft Excel program was used for statistical analysis of the data obtained. Partial disorder of blood microcirculation in the spleen after partial splenectomy was registered and in same time relative increase in the mass of the spleen and lymphatic follicles was shown concomitant to these disorders. The presence of the clusters of macrophages and lymphocytes capable of phagocytosis, as well as haemociderosis is considered as morphological criterion of the immune reaction. We can suppose that remainder spleen cells can induce immune response as regards autoantigens as response to the operational trauma and directed to restore the homeostasis.

The protein pattern of mouse macrophage strain (J774) has been investigated using 2D electrophoresis after combined action of bacterial endotoxins (LPS), heat shock treatment (HS) and administration of recombinant human Hsp70. The investigation demonstrated significant protective effect of HS and recombinant Hsp70 treatment applied before LPS introduction. This effect is apparently realized by means of several signal transduction systems. In the course of the investigation, we have identified eight proteins, which exhibited pronounced changes in their synthesis due to combined treatment. The data accumulated may shed light on molecular mechanisms underlying protective antiseptic action of HS and/or recombinant Hsp70 applied before LPS administration.

The structure of Wistar rat subcutaneous adipose tissue and axillary (regional) lymph nodes (LN) was studied by the methods of light microscopy after the subcutaneous implantation of the fragments of silicone mammary implant in the area of right scapula in animals treated with interleukin-2 (IL-2). Subcutaneous implantation of sterile silicone plates to rats was found to induce chronic granulomatous inflammatory process with the formation of connective tissue capsule. Implants placement to rats treated with IL-2 resulted in the formation of a thicker capsule with the signs of sclerosis, fibrosis and hyialinosis; all the capsular structures were heavily infiltrated with macrophages, which contained phagocytozed silicone fragments. After the introduction of silicone implants, the volume of the capsule and connective tissue in the regional LN progressively increased, while after IL-2 treatment the intensity of sclerotic processes was significantly decreased. The relative area of lymphoid nodules without the germinal centers in LN sections was increased 1 month following the induction of chronic inflammatory process in rats treated with IL-2, but by 6 months the proportion of nodules both with or without germinal centers become less, as compared to the initial data.

Using a complex of morphological methods, the peculiarities in the reaction of jejunum lymphoid structures were studied in 105 Wistar rats with reference to their behavioral characteristics (stress tolerance). Initially, in passive (stress prone) rats the number of lymphoid and plasma cells was higher than in active animals, together with the macrophage reaction, which may indicate greater activity of immune structures in this group of animals. In behaviorally active rats, the negative impact of stress was less pronounced; rehabilitation processes were faster, as compared to those in passive animals. By day 14 after the end of the experiment, the restoration of cell population of lymphocytes was observed in the wall of the intestine in the active animals, while in the passive rats, the processes of destruction of lymphocyte cell line was increased together with the macrophage response.

Combination of bronchial asthma (BA) with gastroesophageal reflux disease (GRD) is now most prevalent among combined pathology of the respiratory and gastrointestinal tracts. Interaction of these diseases is stated basing on clinical picture and pathogenetic aspects of BA development in the presence of GRD and GRD in the presence of BA. Development of combined affection of gastrointestinal and respiratory tracts occurs in secondary immunodeficiency. Main lines of the paradigm of macrophage phenotypes M1/M2 and mechanisms of alternative development of the immune response Th1/Th2 in combination of GRD with BA are presented. Investigation of macrophage functional activity and Th1/ Th2 balance gives ground for development of the method of macrophage phenotype reprogramming which is a promising approach to effective treatment of combined pathology of the respiratory tract and upper gastrointestinal tract including cases resistant to pharmacological treatment.

Interacting with erythrocytes which transport immune complexes and xenogenic antigens myelocariocytes and leukocytes of circulating blood produce from them erythroclasic clusters in bone marrow and autorosettes in circulating blood. Formation of these cellular associations is completed with exocytic lysis of included in them erythrocytes by myelocariocytes and leukocytes. It is supposed that the lysis of erythrocytes within erythroclasic clusters and autorosettes is the final stage of erythrocytic clearance of immune complexes and xenogenic antigens.

The community acquired pneumonia (CAP) falls into the category of the most frequent human diseases and is one of the leading causes of death from infectious diseases. The main components that characterize the inflammatory process in the lungs at CAP include an increase in vascular permeability, and migration of neutrophils and monocytes/macrophages to the foci of infectious agents inoculation, and the reactivity of these cells defines the upshot of the disease. In the present work, a significant increase in the number of neutrophils and an increase in the number of perishing cells depending on the gravity of current CAP were determined. Herewith, the contents of necrotic neutrophils and macrophages in foci of inflammation dependent on the gravity of current CAP, while the difference between the factors of apoptosis in these patients was not reliable. Apoptotic cell death was mainly revealed in population of macrophages. Analysis of the phagocytic and enzymatic activities of cells of the local defense of CAP patients showed that the state of unspecific resistance of their organisms largely determined the severity of the disease and antibiotic treatment did not affect the normalization of neutrophils and macrophages functions.

Evidence on the studying of the effectiveness the low intensive laser radiation influence as complex treatment of patient with maxillofacial phlegmons with using of the cytological method were presented. Results of the laser therapeutist were in acceleration of the inflammation stage. The neutrophil granulocytes and macrophages settled down in wound earlier then in the control. This led to acceleration of the wound healing.

The immune-competent cells of placenta play the important role in protection of developing fetus against infectious agents; but their dysfunction can lead to development of placental insufficiency that affects health both fetus and mother. The aim of this study was the comparative analysis of presence of immune competent cells in villous chorion of mature placenta, taken from women with diabetes of different age groups. In our study we found three subpopulations of immune cells in villous chorion of mature placenta: natural killer cells (NK), B-lymphocytes and macrophages. Prevailing subpopulation are macrophages, they are detected 1,8 times more often than B-lymphocytes, and 2,3 times more often than NK. The quantity of immune competent cells in groups with diabetes of various types is different. Thus, the greatest number of macrophages was detected in group with diabetes type II of middle age (29-35 years)-- 4.62 +/- 0.93%, B-lymphocytes in group of women with diabetes type I of younger age (18-28 years)--2.50 +/- 0.30%, NK-cells in group with diabetes type I of younger age--1.98 +/- 0,42%. Analysis of received data showed the differences in expression of markers of immune cells in women of different age groups, which brings about the conclusion of various reactance of immune system of women with diabetes depending on age.

Morphological, cytological, morphometric changes were studied in single lymphoid nodules and in grouped lymphoid nodules (Peyers patches) of small intestine in albino rats after the dehydration lasting 3, 6, and 10 days and correction by administration of sodium chloride isotonic solution. In was found that the dehydration resulted in the decrease of lymphoid nodule dimensions, changes in the cellular proportions, enlargement of reticular fiber loops in the nodule stroma. On days 6 and 10 of dehydration, the percentages of macrophages, lymphocytes, cells showing the mitotic figures, mast cells and plasma cells were significantly decreased by factor of 1,4-4, indicating a depression of immune reactions.