Immunologiya

1504-188
INFLUENCE OF TLR-AGONISTS ON EXPRESSION BY ANTIGEN-PRESENTING CELLS OF THE TARGET PROTEIN ANTIGEN ENCODED IN ADENOVIRAL VECTOR
Bagaev A.V., Pichugin A.V., Lebedeva E.S., Lysenko A.A., Shmarov M.M., Logunov D.Yu., Naroditsky B.S., Ataullakhanov Ravshan Inoyatovich, Khaitov R.M., Gintsburg A.L.

«State scientific center "Institute of immunology», Federal medico-biological Agency of Russia, 115478, Moscow; «N.F. Gamaleya Federal research center of epidemiology and Microbiology» Ministry Of Health Of Russia, 123098, Moscow
Abstract: Replication-defective recombinant adenoviral vectors (rAd) represent one of the advantageous platforms for development of genetic vaccines. A target gene inserted into rAd is transcribed in cells of the vaccinated human, namely in macrophages and dendritic cells which are effective antigen-presenting cells (APC). The target antigen production is continued in the human organism during 2-3 weeks following administration of rAd, encoding the antigen. It induces intensive responses of T- and B-cells specific to the target antigen. Immune responses against the rAd-encoded target antigen can be enhanced with a use of immune adjuvants, in particular, agonists of Toll-like receptors which stimulate APC for production of pro-inflammatory cytokines and chemokines as well as expression of co-stimulatory receptors on the cell membrane. We hypothesized that a combined use o f TLR-agonists with the target antigen encoding rAd can enhance a production of the target antigen in APC, along with above mentioned immunostimulation effects. In this work we showed an immunoadjuvant effect of TLR4-agonist (Immunomax) administered in BALB/c mice during their immunization with the rAd-HA construct comprising gene of H1N1 Influenza virus hemagglutinin. Using in vitro cell cultures a direct stimulation of antigen-presenting dendritic cells by the TLR4-agonist was revealed which significantly enhanced the response of interferon-gamma secreting antigen-recognizing T cells. We examined expression of rAd-encoded protein antigens in dendritic cells and macrophages. Using cytoplasmic, membrane-bound and secretory target proteins, we showed that TLR4-agonist enhanced production of these three target proteins in APC. Both the number of APCs producing the antigen and the accumulation of the target protein in each antigen-producing cell were increased under influence of the TLR4-agonist. A comparison of Immunomax with agonists of other TLRs revealed that agonists of TLR2, TLR4, TLR5, TLR7, TLR8 and TLR9 enhanced, but the agonist of TLR3, unexpectedly, suppressed the expression of rAd-encoded target proteins.
Keywords: антиген-презентирующие клетки, рекомбинантные аденовирусные векторы, экспрессия антигенов, агонисты Toll-подобных рецепторов, antigen-presenting cells, recombinant adenoviral vectors, antigen expression, agonists of Toll-like receptors

1504-196
ROLE OF INTERLEUKIN-1 AND MITOGEN-ACTIVATED PROTEIN KINASES IN THE MECHANISMS OF ACTION OF MURAMYLDIPEPTIDE ON CELLS OF INNATE IMMUNITY
Pashchenkov Mikhail Vladimirovich, Pinegin B.V.

“Institute of immunology” FMBA of Russia, 115478, Moscow
Abstract: When you activate glucosaminilmuramildipeptide (Hmtri) gram-negative bacteria, the macrophages produce significantly large quantities of proinflammatory cytokines, particularly tumor necrosis factor (TNF) than dendritic cells (DC), with the same abilities of both types of cells respond to lipopolysaccharide (LPS). Studies have shown that the increased ability of macrophages to respond to Hmtri is not associated with auto - and paracrine mechanisms mediated by cytokines of the family of interleukin-1 (IL-1). At the same time, IL-1a and IL-1β potentiate the response of DC to Hmtri. When comparing macrophages and DCS, activated Hmtri discovered that macrophages have a more pronounced activation of the mitogen-activated protein kinase p38, as well as more prolonged expression of TNF mRNA, all of which, apparently, and determines a more powerful response of macrophages to Hmtri. Thus, new data on the mechanisms of action of muramyldipeptide on cells of innate immunity that could be taken into account in the development and application of muramyldipeptide Immunostimulants and adjuvants.
Keywords: дендритные клетки, макрофаги, фактор некроза опухолей, мурамилпептиды, интерлейкин-1, dendritic cells, macrophages, tumor necrosis factor, interleukin-1, muramyldipeptide

1504-200
IMMUNOMODULATOR «IMMUNOMAX» ACTIVATES DENDRITIC CELLS
Pichugin Aleksey Vasil’evich, Bagaev A.V., Chulkina M.M., Berzhitskaya D.A., Shishkova N.M., Ataullakhanov R.I.

«Institute of immunology, Federal medical-biological Agency of Russia, 115478, Moscow
Abstract: Earlier it was reported that immunomodulator «Immunomax» activates monocytes, macrophages and NK cells. In this work, we first studied the effect of Immunomax on dendritic cells of mouse and human. Researched primary dendritic cells isolated by cell sorting from mouse spleen or human peripheral blood, as well as artificially derived dendritic cells differentiated in vitro with GM-CSF from bone marrow of the mouse or human monocytes. It is established that the Immunomax increases the expression of co-activation molecules CD40, CD80, CD86, MHC-II on the surface of dendritic cells, stimulates the production of proinflammatory and regulatory cytokines and chemokines (IL-1, TNFa, IL-10, IL-12, IL-8, McP-1, MIP-1, RaNtES). It is proved that the activation of Immunomax NK cells is mediated by dendritic cells. Discovered effects suggest that the Immunomax activates the main physiological functions of dendritic cells such as antigen presentation T cells, activation of antigen-specific T cells, the involvement of other cell types in the inflammatory focus. It is assumed that the therapeutic effect of Immunomax in patients with various viral, bacterial and fungal infections, and cancer pathology may be due to the influence of dendritic cells.
Keywords: иммуномакс, дендритные клетки, ко-активационные молекулы, секреция цитокинов, NK-клетки, Immunomax, dendritic cells, co-activation molecules, secretion of cytokines, NK cells

1504-206
FEATURES OF ADAPTIVE REACTIONS OF IMMUNE AND ENDOCRINE SYSTEM AT MALES OF MICE OF F1 (C57BL/6 Х DBA/2) AT THE FOOD DEPRIVATION, COGNITIVE TENSION AND IN THE CONDITIONS OF THE ENRICHED ENVIRONMENT
Kondashevskaya Marina Vladislavovna, Diatroptov M.E., Ponomarenko E.A., Serkova V.V., Nikolskaya K.A.

Federal State Budgetary Institution «Scientific Research Institute of Human Morphology» of the Russian Academy of Medical Science, 117418, Moscow, Russia; Lomonosov, Moscow State University, 119991, Moscow, Russia
Abstract: The immune and endocrine system adaptive responses to the food deprivation, cognitive tension and enriched environment were studied insufficiently. The research objective was to study thymus and spleen morphological and functional status, cytokine profile in splenocytes, stimulated by concanavalin A as well as the level of a peptide hormone, leptin in mice F1 (C57BL/6 × DBA/2) at the conditions of food deprivation, cognitive tension and influence of the enriched environment was studied. Using morphometry and enzyme immunoassay analysis, the changes in thymus and spleen morphology and function under the simulated conditions were established testifying activation of immune system. The level of proinflammatory cytokines in splenocytes was raised under the cognitive tension that occurred simultaneously with decrease of the leptin level in blood. Conversely, increasing of a leptin level was combined with decreasing of proinflammatory cytokine secretion in splenocytes under the enriched environment. The combination of these facts can specify that leptin is involved in modulation of psychoemotional state, training, memory, and also the immune reactivity.
Keywords: мыши, тимус, селезенка, цитокины, пищевая депривация, когнитивное напряжение, обогащенная среда, лептин, mice, thymus, spleen, cytokine, food deprivation, cognitive tension, enriched environment, leptin

1504-211
COMPARISON OF CYTOKINES LEVELS IN PATIENTS WITH HEART RHYTHM DISORDERS OF VARIOUS GENESIS
Bekbosynova M.S., Kovzel Elena Fedorovna, Abdrahmanov A.S., Rashbaeva G.S., Nuralin O.M., Alzhanova A.B., Smagulov Z.H., Tursunbekov A.B.

National Medical Holding, Astana, Kazakhstan
Abstract: We studied the levels of cytokines TNFalpha, MCP-1, IL1beta, IL-6, IL8, IL-10, VEGF and IFN gamma and a marker of fibrosis - metallopeptidase inhibitor 1 (TIMP1) in serum of patients with coronary heart disease (CHD), dilated cardiomyopathy (DCM ) and idiopathic cardiac arrhythmias (ICA) with ventricular tachycardia and atrial fibrillation. A comparative analysis of the indicators was performed to determine the most significant markers, which control potentially fatal arrhythmias in patients with heart failure of different genesis. There was detected a significant increase in the levels of IL 6 and IL 8, which correlate with levels of CRP and the development of ventricular tachycardia in patients with DCM and CHD. Also a prognostic indicator of severe arrhythmia in patients with CHD was significantly higher activity of angiogenesis with increased VEGF level in the serum of patients predominantly with ventricular arrhythmias. Significantly high values of marker of fibrosis (TIMP 1) found in patients with CHD regardless of the nature of the arrhythmias. The most unfavorable prognostic marker at idiopathic arrhythmias is determined to increase in the serum ofpatients of the monocyte chemoattractant protein-1 (MCP 1).
Keywords: цитокиновый статус, ингибитор металлопротеиназы-1, дилятационная кардиомиопатия, желудочковая тахикардия, фибрилляция предсердий, идиопатические нарушения ритма, cytokine status, TIMP1, dilated cardiomyopathy, ventricular tachyarrhythmia, atrial fibrillation, idiopathic arrhythmias

1504-216
INVESTIGATION OF ERGOFERONTO SUPPRESS ACTIVITY OF RESPIRATORY SYNCYTIAL VIRUS IN VITRO
Shilovskiy I.P., Prozorova Mariya Sergeevna, Khaitov M.R.

National Research Center-Institute of immunology of Federal Medico-Biology Agency, 115478, Moscow
Abstract: Viral infections of the lower respiratory tract are a major cause of morbidity and mortality among children, elderly and patients with immunodeficiency statements. Respiratory syncytial virus (RSV) - is the most common cause of bronchitis, bronchiolitis and pneumonia in infants. Up to 1 million deaths are annually registered worldwidedue to RSV infection. Most of the existing drugs against RSV are either not effective enough ortoo expensive. Ergoferonis a drug based on a mixture of polyclonal antibodies in release-active form against interferon gamma, CD4 receptor and histamine. Inthisstudyweexa minedtheabilityofErgoferonto suppress RSV infection in vitro. WeshowedthatpreincubationofErgoferonwithvirusleads to two-fold decrease in RSV titer. SucheffectofErgoferonisprobablycaused byalterations in viral proteins RSV-G and RSV-F, which are involved in entry of the virus into the cell.
Keywords: респираторно-синтициальный вирус, РСВ-инфекции, противовирусные препараты, respiratory syncytial virus, RSV infection, antiviral drugs

1504-220
PROMPT PROTECTION AS THE FUTURE OF VACCINOPROPHYLAXY
Sergeev V.A., Sergeyev Oleg Vital’evich

N.F. Gamaleya Federal research Centre of Epidemiology and Microbiology (FRCEM) Ministry of Health of Russia
Abstract: Hypervaccination against infectious diseases is a radically new efficient strategy of preventive vaccination. Its objective is specific abrogation of innate susceptibility of the organism to the disease achieved by blockage of the pathogen specific binding sites (receptors) on the surface of target cells by the anti-receptors of the vaccine. The new strategy is based on competition between the anti-receptors of the vaccine and those of the pathogen for the receptors on target cells. The mechanism of hypervaccination is a rapid maximal saturation of the target cells receptors with a massive dose of anti-receptors contained in a live or inactivated vaccine. Protection of the naturally susceptible organism against infection initially occurs by the mechanism of homologous interference at the stage of the pathogen’s binding to the target cell rather than by reactions of adaptive immunity. At a later stage, early protection is followed by a long-term intense immune response with a marked seroconversion. Thus, a high dose vaccination confers protection in two stages, interference at the receptor binding level and immune response. Administering a safe vaccine with a high content of anti-receptors protects naturally susceptible animals against disease and death at challenge 12-72 hrs after vaccination with no chronic infection establishing. An apparent resistance of the organism against a severe challenge soon after vaccination is likely to be due to a full or virtually full saturation of the target cells receptors with the vaccine anti-receptors. The efficiency of prompt protection in field conditions has first been shown in the eradication of classical swine fever (CSF) in two countries, Russia and Belarus.
Keywords: вакцинация, доза вакцины, защита, иммунитет, vaccination, protection, immune response, immunity

1504-227
EFFICACY AND SAFETY OF VACCINES FOR THE PREVENTION OF HEPATITIS A
Shevcov Vladimir Aleksandrovich, Volgin A.R.

Federal State Budgetary Institution «Scientific Centre for Expert Evaluation of Medicinal Products» Ministry of Health of the Russian Federation, 127051, Moscow, Russian Federation
Abstract: Specific prophylaxis based on vaccination is currently the most effective preventive measure of a viral A hepatitis (HAV). Hepatitis A inactivated vaccines developed last year’s successfully used in many countries. Hepatitis A inactivated vaccines licensed in Russian Federation are safe, have low reactogenicity and are highly immunogenic according to National Regulatory Authorities. However, epidemiological experience show different effectiveness of vaccines and absence of desired protection of population in some extreme conditions after vaccination. It is clearly confirmed by a single administration of HAV vaccines to individuals in epidemic outbreaks of A hepatitis. Safety parameters and immunogenic potency of Hepatitis A inactivated vaccines licensed in Russian Federation were analyzed. It is established that single-dose vaccination using the most effective vaccine can provide high prophylactic effect in early epidemic outbreaks with high individual vaccination level. Regular monitoring of the duration of protection induced by single and double doses of vaccine is permanently needed.
Keywords: вирусный гепатит А, вакцинопрофилактика, иммуногенность, viral hepatitis А, vaccination, immunogenicity

1504-231
CROSS- RECTIVITY BETWEEN FOOD AND ANIMAL ALLERGENS IN CHILDREN WITH ATOPY
Mokronosova M.A., Bass E.A., Arefyeva I.A., Zheltikova Tat’yana Mikhaylovna

I.I. Mechnikov’s Research Institute for Vaccines and Sera, 105064, Moscow, Russian Federation; N.N. Burdenko Institute For Neurosurgery, 125047, Moscow, Russian Federation
Abstract: Background: Some patients who are sensitized to cat allergens have allergic reactions to pork. This is associated with crossreacting of IgE-antibodies to cat serum albumin (Fel d 2) with pork albumin and was described as “pork-cat syndrome”. The aim: To investigate frequency of IgE-aB to animal allergens (Fel d1, Fel d2, Can f1, Can f3) and some food allergens of animal origin (pork, beef, milk) in children and adolescents. Methods: The study included 37 children aged 5 to 14 years with clinical manifestations of respiratory allergy after the contact with cat and dog. Results: The occurrence of IgE-aB to major cat allergen uteroglobin (Fel d 1) were positive in 84% of cases (31/37). The positive levels to major dog allergen (Can f 1) were detected in 1.4 times less than to Fel d1. IgE-aB to lipocalins Fel d2 and Can f3 were identified even rarer - 7.6 and 5.3 times, respectively. Positive levels of IgE-aB to food allergens have been detected in 14-38% of children. Statistically significant positive correlation of IgE-aB to pork was found only in patients with positive IgE-aB to cat (Fel d2) or dog (Can f3) allergens - r = 0,6881 and r = 0,5573, respectively. Conclusion: In patients with allergic manifestations to cat the cross-reactivity between IgE-aB to pets and pork serum albumin was found.
Keywords: молекулярная компонентная диагностика, аллергены кошки, свинина, молекулярные компоненты, molecular component diagnostics, cat allergens, pork, molecular components

1504-234
FEATURES SUBPOPULATION COMPOSITION OF LYMPHOCYTES AND CYTOKINE PROFILE IN PATIENTS WITH PSORIASIS TREATED BY VARIOUS METHODS OF PHOTOTHERAPY
Pinegin B.V., Teplyuk N.P., Murugin V.V., Smirnov K.V., Marshani Z.B.

I.M. Sechenov First Moscow state medical University; «Institute of immunology» FMBA of Russia, 119991. Moscow
Abstract: The work studied the effect of different methods of phototherapy (PUVA therapy or UVB-311 nm therapy as monotherapy and combination therapy: the combination of PUVA therapy with excimer lamp 308 nm or UV-b (311 nm) therapy with excimer lamp 308 nm) on subpopulation composition of lymphocytes and cytokine status in patients with psoriasis. It is shown that in all cases of phototherapy there is a significant improvement on clinical, registered on the index of severity of psoriasis (PASI). With this treatment there was a significant reduction in the overall level of T-cells and activated T-cells (CD3+HLA-DR+). A significant reduction of CD3+CD4+CD161+. T-cells, the major producers of IL-17. In parallel with the clinical improvement observed a significant reduction of almost all Pro-inflammatory cytokines (TNF-α, IL-1β, IL-6, IL-8). There was a significant reduction of cytokines IFN-γ, IL-17 and IL-22, which are pivotal in the initiation and maintenance of psoriatic inflammation. It is assumed that the phototherapy, causing a reduction in functional activity, does not affect the expression of differentiation antigens in Th17 cells.
Keywords: псориаз, фототерапия, субпопуляции лимфоцитов, цитокины, psoriasis, phototherapy, subpopulations of lymphocytes, cytokines

1504-237
AUTOANTIBODIES AGAINST HORMONES AND PHOSPHOLIPIDS IN PREGNANT WOMEN WITH SYSTEMIC LUPUS ERITHEMATOSUS
Menzhinskaya Irina Vladimirovna, Fedorova E.V., Van’ko L.V., Kashentseva M.M., Kosheleva N.M., Klimenchenko N.I., Sukhikh G.T.

Research Center for Obstetrics, Gynecology and Perinatology named after V.I. Kulakov, Ministry of Health of the Russian Federation, 117997, Moscow; Scientific Research Institute for Reumatology named after V.A. Nasonova, 115522, Moscow
Abstract: SLE often develops in women of reproductive age and is characterized by the production of autoantibodies against multiple autoantigens, mainly against the components of the nucleus. Pregnancy in patients with SLE is high risk for both mother and fetus. Objective: to study the prevalence of autoantibodies against hormones and phospholipids in pregnant women with SLE and their association with pregnancy complications. Antibodies (IgM, IgG) against hormones and ntiphospholipid antibodies (aPL) were determined in the blood serum of pregnant women with SLE (n=40) and healthy pregnant women (n=43) using ELISA. Those and other antibodies are often detected in SLE (respectively, 65% and 27.5%). Antibodies against human chorionic gonadotropin (ahCG), progesterone (aPg), cardiolipin and β2-glycoprotein-I were found in patients with SLE more frequently, and their levels were higher than those in healthy pregnant women (p<0,0001). Antibodies against hormones were found in different forms of SLE, more often in lupus flare during pregnancy and in the presence of antibodies against the components of the nucleus (70,6%), and correlated with the last (r=0,3407; p=0,0363). In patients with antibodies against hormones the pregnancy was often complicated by early threatened abortion (50%) and preterm delivery (30,8%), activation of intravascular coagulation during pregnancy (57,7%) and in the postpartum period (73,1%); ahCG IgG were associated with early threatened abortion (AUC=0,722; p=0,0105). Thus, aPL and antibodies against hormones were often found in pregnant women with SLE, the last detected more frequently in the presence of antinuclear antibodies and in lupus flare during pregnancy; ahCG IgG were significantly associated with early threatened abortion.
Keywords: системная красная волчанка, аутоантитела к кардиолипину, аутоантитела к β2-гликопротеину-I, аутоантитела к хорионическому гонадотропину, аутоантитела к прогестерону, осложнения беременности, systemic lupus erithematosus, autoantibodies against cardiolipin, autoantibodies against β2-glycoprotein-I, autoantibodies against human chorionic gonadotropin, autoantibodies against progesterone, pregnancy complications

1504-242
PHENOTYPIC AND FUNCTIONAL CHARACTERISTICS OF THE ALTERNATIVE ACTIVATED MACROPHAGES: POTENTIAL USE IN REGENERATIVE MEDICINE
Sakhno Lyudmila Vasil’evna, Shevela E.Ya., Chernykh E.R.

«Research Institute of Clinical immunology» SB RAMS, Novosibirsk, Russia
Abstract: Macrophages are cells of innate immunity and play an important role in protecting the body from pathogenic impact, maintaining tissue homeostasis, elimination of aging, neoplastic or damaged cells) and the healing process. Cells of the monocyte-macrophage series are characterized by the diversity of response to a changing microenvironment, which indicates a high plasticity of macrophages. Analysis of literature data reveals at least two functional type macrophages - classical proinflammatory and anti-inflammatory macrophages, called M1 and M2 cells, respectively. M1 and M2 cells have phenotypic features and characteristics for each type cytokine profile. Study of the functions of macrophage cells showed that the activity of M1 and M2 macrophages boxer by nature: inflammatory versus anti-inflammatory, immunogenic against tolerogenic activity, tissue-destructive against reparative activity. The involvement of M2 macrophages in the resolution of inflammation and stimulation of reparative processes demonstrates the therapeutic potential of these cells and allows to consider them as potential candidates for the stimulation of reparative processes.
Keywords: макрофаги, функциональная дихотомия, фенотип, продукция цитокинов и хемокинов, репаративная активность, macrophages, functional dichotomy, phenotype, production of cytokines and chemokines, reparative activity

1504-247
SAFETY OF MEDICINES OF MONOCLONAL ANTIBODIES CONNECTED WITH MANIFESTATION OF THEIR IMMUNOGENICITY
Avdeeva Zhanna Il’darovna, Alpatova N.A., Soldatov A.A., Bondarev V.P., Mosyagin V.D., Medunitsyn N.V.

Federal State Budgetary Institution «Scientific Centre for Expert Evaluation of Medicinal Products» of the Ministry of Health of the Russian Federation, 127051, Moscow, Russia
Abstract: The review is devoted to questions safety of clinical application of medicines of monoclonal antibodies associated with the manifestation of their unwanted immunogenicity. When using medicines of monoclonal antibodies patients with cancer, autoimmune, infectious, allergic, cardiovascular diseases forming an unwanted immune response may be the cause of reduction of clinical efficacy of a drug or of serious adverse reactions. This review describes the factors that affect the frequency and severity of the immune response to medicines of monoclonal antibodies. Determine the factors associated with MAb preparation (molecular structure, biological properties etc.) and the production process (the presence of impurities and related compounds, the presence of aggregates, the composition of excipients etc.), as well as features of the underlying disease state of the patient, concomitant therapy. A study on the potential immunogenicity of medicines of monoclonal antibodies, including the use of suitable species are required at the stage of pre-clinical studies. However, their results do not fully predict the manifestation of the immunogenicity of drugs in the clinical application. Only at the stage of clinical trials can be adequately assess the immunogenic potential of a particular medicines of monoclonal antibodies at a certain diseases, and the pattern of use. Reduce the risks associated with the safety of the clinical use of medicines of monoclonal antibodies, promote activities aimed at early identification of risks and earlier actions to minimize such risks, and the development of new drugs based on modified MAb to improve their efficiency.
Keywords: лекарственные препараты моноклональных антител, иммуногенность, клинические и доклинические исследования, нежелательные реакции, безопасность применения моноклональных антител, medicines of monoclonal antibodies, immunogenicity, clinical studies and pre-clinical studies, adverse reactions, safety issues medicines of monoclonal antibodies

1504-257
NEUTROPHILIC GRANULOCYTES: A NEW LOOK AT "OLD PLAYERS" ON THE IMMUNOLOGICAL FIELD
Nesterova Irina Vadimovna, Kolesnikova N.V., Chudilova G.A., Lomtatidze L.V., Kovaleva S.V., Evglevsky A.A.

“Russian University of Friendship of Peoples” of Ministry of Education and Science of Russia, 117198, Moscow, Russia; SBEI HPE «Kuban State Medical University» of Ministry of Health Development of Russia, 350063, Krasnodar, Russia
Abstract: Modern basic researches demonstrated that neutrophilic granulocytes (NG) are effector and regulatory cells of the innate and adaptive immunity, and play a crucial role in the immunopathogenesis of a wide range of diseases. NG have potent receptor repertoire, providing a connection between them, cells of the immune system, as well as communication with endothelial cells, epithelial and other tissues. NG inducing stimuli activate and promote the translocation of cytoplasmic granules and vesicles surface molecules on the cytoplasmic membrane the secretion of a large spectrum of pro-and anti-inflammatory, immunoregulatory cytokines, colony, angiogenic factors and fibrogenic, TNF superfamily members, chemokines, regulatory protein, etc. Chromatin nuclei NG capable of restructuring under the influence of inducing stimuli, which is associated with the expression of multiple cytokine genes. NG receiving complex cytokine influence not only acquire new features, but also in various stages of activation and differentiation processes involved in intracellular intraphagosomalis degranulation and killing of implementing elimination microorganisms and extracellular neutrophil degranulation in the formation neutrophil extracellular traps (NET), while this dying through NETosis. Features NG phenotype and their functional properties, demonstrate the existence of subpopulations of NG with different capabilities: equipment of different receptor, the ability to restructure chromatin expressing cytokine genes and secrete cytokines to implement the contents of the granular system, produce reactive oxygen species, implement cytotoxicity form NET. In our opinion, there subpopulation NG: regulatory; suppressor; proinflammatory - initiating an inflammatory response; inflammation with a positive potential microbicidal (antibacterial, antiviral, antifungal); inflammatory cytotoxic potential of the negative - “aggressive”; anti-inflammation regulating regression; antitumoral - TAN1; pro-tumoral - TAN2; hybrid, combining the characteristics of NG and dendritic cells. The absence of adequate response, or hyperactivation blockade NG functions leads to the development of low-intensity infectious and inflammatory diseases, do not respond to conventional therapy of autoimmune diseases/chronic immune-dependent processes. Remodeling dysfunctions NG - the key to new immunotherapeutic strategies.
Keywords: нейтрофильные гранулоциты, иммунофенотип, микробицидность, реструктуризация хроматина, экстрацеллюлярные сети, цитокинопродукция, neutrophil granulocytes, immunophenotype, microbicide, extracellular traps, restructuring скromatin ’ cytokineproduction