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<article article-type="research-article" dtd-version="1.3" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xml:lang="ru"><front><journal-meta><journal-id journal-id-type="publisher-id">epidemiology</journal-id><journal-title-group><journal-title xml:lang="ru">Эпидемиология и Вакцинопрофилактика</journal-title><trans-title-group xml:lang="en"><trans-title>Epidemiology and Vaccinal Prevention</trans-title></trans-title-group></journal-title-group><issn pub-type="ppub">2073-3046</issn><issn pub-type="epub">2619-0494</issn><publisher><publisher-name>«Numicom» LLC</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.31631/2073-3046-2016-15-3-94-101</article-id><article-id custom-type="elpub" pub-id-type="custom">epidemiology-170</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="ru"><subject>ВАКЦИНОПРОФИЛАКТИКА</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="en"><subject>VACCINAL PREVENTION</subject></subj-group></article-categories><title-group><article-title>Влияние иммуномодуляторов на реактивность клеток иммунной системы при моделировании противотуляремийного вакцинного процесса</article-title><trans-title-group xml:lang="en"><trans-title>The impact of Immunomodulators on Reactivity the immune System cells in Model Vaccinal process against Tularemia</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Кравцов</surname><given-names>А. Л.</given-names></name><name name-style="western" xml:lang="en"><surname>Kravtsov</surname><given-names>A. L.</given-names></name></name-alternatives><email xlink:type="simple">noemail@neicon.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Клюева</surname><given-names>С. Н.</given-names></name><name name-style="western" xml:lang="en"><surname>Klyueva</surname><given-names>S. N.</given-names></name></name-alternatives><email xlink:type="simple">noemail@neicon.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Бугоркова</surname><given-names>С. А.</given-names></name><name name-style="western" xml:lang="en"><surname>Bugorkova</surname><given-names>S. A.</given-names></name></name-alternatives><email xlink:type="simple">noemail@neicon.ru</email><xref ref-type="aff" rid="aff-1"/></contrib></contrib-group><aff-alternatives id="aff-1"><aff xml:lang="ru"><institution>ФКУЗ «РосНИПЧИ «Микроб» Роспотребнадзора</institution><country>Россия</country></aff><aff xml:lang="en"><institution>Federal State institution of public Health «Russian Scientific Research Institute «Microbe» Federal Service for Surveillance on consumer Rights Protection and Human Wellbeing</institution><country>Russian Federation</country></aff></aff-alternatives><pub-date pub-type="collection"><year>2016</year></pub-date><pub-date pub-type="epub"><day>20</day><month>06</month><year>2016</year></pub-date><volume>15</volume><issue>3</issue><fpage>94</fpage><lpage>101</lpage><permissions><copyright-statement>Copyright &amp;#x00A9; Кравцов А.Л., Клюева С.Н., Бугоркова С.А., 2016</copyright-statement><copyright-year>2016</copyright-year><copyright-holder xml:lang="ru">Кравцов А.Л., Клюева С.Н., Бугоркова С.А.</copyright-holder><copyright-holder xml:lang="en">Kravtsov A.L., Klyueva S.N., Bugorkova S.A.</copyright-holder><license xml:lang="ru" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>Данная работа распространяется под лицензией Creative Commons Attribution 4.0.</license-p></license><license xml:lang="en" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>This work is licensed under a Creative Commons Attribution 4.0 License.</license-p></license></permissions><self-uri xlink:href="https://www.epidemvac.ru/jour/article/view/170">https://www.epidemvac.ru/jour/article/view/170</self-uri><abstract><p>Исследовали влияние азоксимера бромида (полиоксидония - ПО) и даларгина (ДА) на реактивность клеток иммунной системы при моделировании противотуляремийного вакцинного процесса у мышей линии Balb/c. Животных иммунизировали подкожно дозой 104 живых микробных клеток штамма Francisella tularensis 15 НИИЭГ. ПО или ДА вводили подкожно за 60 мин до вакцинации соответственно в дозах 4 и 2 мкг. На 3-е и 21-е сутки иммуногенеза исследовали периферические органы иммунной системы и содержимое брюшной полости. Клеточную реакцию на вакцинацию и исследуемые иммуномодуляторы оценивали методом проточной цитометрии (CyAn ADP) по двум показателям светорассеяния, а также по изменению количества пролиферирующих клеток и клеток в апоптозе. Кроме того, для характеристики изменений функционального состояния ядер лимфоцитов применяли световую микроскопию и определяли титры специфических антител. Установлена различная реакция лимфоцитов и фагоцитов интактных мышей на введение ПО и ДА. В отличие от ПО, ДА стимулировал пролиферацию лимфоцитов и активировал апоптоз макрофагов, воздействуя на их цитоплазматические гранулы. Особенность эффекта ПО заключалась в способности активировать миграцию фагоцитов с высоким содержанием цитоплазматических гранул из брюшной полости мышей в селезенку. Только при использовании ПО в качестве иммуномодулятора при моделировании противотуляремийного вакцинного процесса регистрировали существенное повышение титров специфических антител на фоне более длительной функциональной активации спленоцитов и пониженной интенсивности повреждения макрофагов в селезенке и брюшной полости.</p></abstract><trans-abstract xml:lang="en"><p>Investigated is the effect of azoximer bromide (polioxidonium - PO) and dalargin (DA) on the immune system cell reactivity in the anti-tularemia vaccine prosess modeling in Balb/c mice. The animals were immunized subcutaneously with a dose of 104 live microbial cells of vaccine strain Francisella tularensis 15 NIIEG. PO or DA subcutaneously administered 60 min before vaccination, respectively, in doses of 4 mg and 2 mg. On 3rd and 21st days of immunogenesis the peripheral organs of the immune system and the contents of the abdominal cavity were investigated. Cell response to vaccination and investigated immunomodulators evaluated by flow cytometry (CyAn ADP) for two light scatter parameters and for changing the proliferating and apoptotic cell number. Additionally, for the characterization of changes in the functional status of lymphocytes nuclei the light microscopy was used and titers of specific antibodies were determined. Installed is the different response of intact mice lymphocytes and phagocytes to PO and DA introduction. As distinct from PO, DA stimulated the lymphocete proliferation and macrophage apoptosis by acting on their cytoplasmic granules. PO activated the migration of phagocytes with high cytoplasmic granules from mice abdominal cavity in the spleen. Only when using the PO as an immunomodulator in anti-tularemia vaccine process modeling recorded a significant increase in specific antibody titers against the background of a long-term functional splenocyte activation and macrophages reduced macrophage damage intensity in the spleen and abdomen.</p></trans-abstract><kwd-group xml:lang="ru"><kwd>вакцинный штамм Francisella tularensis 15 НИИЭГ</kwd><kwd>полиоксидоний</kwd><kwd>даларгин</kwd><kwd>проточная цитометрия</kwd><kwd>апоптоз</kwd><kwd>пролиферация</kwd><kwd>ядрышковый организатор (AgNOR)</kwd><kwd>антитела</kwd><kwd>vaccine strain Francisella tularensis 15 NIIEG</kwd><kwd>polyoxidonium</kwd><kwd>dalargin</kwd><kwd>flow cytometry</kwd><kwd>apoptosis</kwd><kwd>proliferation</kwd><kwd>nucleolar organizer (AgNOR)</kwd><kwd>antibodies</kwd></kwd-group></article-meta></front><back><ref-list><title>References</title><ref id="cit1"><label>1</label><citation-alternatives><mixed-citation xml:lang="ru">Саяпина Л.В., Соловьев Е.А., Горяев А.А., Бондарев В.П. Изучение иммунобиологических свойств вакцинного штамма Francisella tularensis 15 НИИЭГ в условиях длительного хранения. Проблемы особо опасных инфекций. 2015; 2: 87 - 91.</mixed-citation><mixed-citation xml:lang="en">Sayapina L.V., Solov,ev E.A., Goryaev A.A., Bondarev V.P. Studies of of immunological properties in Francisella tularensis vaccine strain 15 NIIEG under extended storage conditions. Problems particularly dangerous infections. 2015; 2: 87 – 91 (in Russian).</mixed-citation></citation-alternatives></ref><ref id="cit2"><label>2</label><citation-alternatives><mixed-citation xml:lang="ru">Каральник Б.В., Пономаре ва Т.С., Дерябин П.Н., Денисова Т.Г., Мельникова Н.Н., Тугамбаев Т.И. и др. Влияние иммуномодуляции на иммуногенную и протективную активность живой чумной вакцины. Журнал микробиол. 2014; 6: 108 - 112.</mixed-citation><mixed-citation xml:lang="en">Karalnik B.V., Ponomareva T.S., Deryabin P.N., Denisova T.G., Mel,nikova N.N., Tugambaev T.I. The impact of immunomodulation on immunogenic and protective activity  of alive plague. Zhurnal mikrobiol., epidemiol. i immunobiol.2014; 6: 108 – 112 (in Russian).</mixed-citation></citation-alternatives></ref><ref id="cit3"><label>3</label><citation-alternatives><mixed-citation xml:lang="ru">Клюева С.Н., Щуковская Т.Н. Влияние адъювантов нового поколения in vitro на продукцию цитокинов клетками крови вакцинированных против чумы лиц. Российский иммунологический журнал. 2015; 9 (2): 201 - 208.</mixed-citation><mixed-citation xml:lang="en">Klyueva S.N., Schukovskaya T.N. Effect of a new generation of adjuvants in vitro cytokine production by blood cells of vaccinated individuals against plague. Russian Immunological Journal. 2015; 9 (2): 201 – 208 (in Russian).</mixed-citation></citation-alternatives></ref><ref id="cit4"><label>4</label><citation-alternatives><mixed-citation xml:lang="ru">Ляпина А.М., Полянина Т.И., Ульянова О.В., Елисеев Ю.Ю., Телепнев М.В., Мотин В.Л., Федорова В.А. Применение полиоксидония для получения специфических антител к бактериальным антигенам. Современные проблемы науки и образования. 2012;</mixed-citation><mixed-citation xml:lang="en">Ljapina A.M., Poljanina T.I., Ul’janova O.V., Eliseev Ju.Ju., Telepnev M.V.,  Motin V.L., Fedorova V.A. Application polioksidonija to produce specific antibodies to bacterial antigens. Modern problems of science and education. 2012. № 2. http: www.science-education.ru/102-5729 (in Russian).</mixed-citation></citation-alternatives></ref><ref id="cit5"><label>5</label><citation-alternatives><mixed-citation xml:lang="ru">Киселева Е.П. Новые представления о противоинфекционном иммунитете. Инфекция и иммунитет. 2011; 1: 9 - 14.</mixed-citation><mixed-citation xml:lang="en">Kiseleva E.P. New concepts of anti-infective immunity. Infection and Immunity. 2011; 1: 9 – 14 (in Russian).</mixed-citation></citation-alternatives></ref><ref id="cit6"><label>6</label><citation-alternatives><mixed-citation xml:lang="ru">Silva M.T. When two is better than one: macrophages and neutrophils work in concert in innate immunity as complementary and cooperative partners of a myeloid phagocyte system. J. Leukocyte Biology. 2010; 87: 1 - 14.</mixed-citation><mixed-citation xml:lang="en">Silva M.T. When two is better than one: macrophages and neutrophils work in concert in innate immunity as complementary and cooperative partners of a myeloid phagocyte system. J. Leukocyte Biology. 2010; 87: 1 – 14.</mixed-citation></citation-alternatives></ref><ref id="cit7"><label>7</label><citation-alternatives><mixed-citation xml:lang="ru">Pham C.T. Neutrophil serine proteases fine-tune the inflammatory response. Int. J. Biochem. Cell Biol. 2008; 40 (6 - 7): 1317 - 1333.</mixed-citation><mixed-citation xml:lang="en">Pham C.T. Neutrophil serine proteases fine-tune the inflammatory response. Int. J. Biochem. Cell Biol. 2008; 40 (6 – 7): 1317 – 1333.</mixed-citation></citation-alternatives></ref><ref id="cit8"><label>8</label><citation-alternatives><mixed-citation xml:lang="ru">Пинегин Б.В., Некрасов А.В., Хаитов Р.М. Иммуномодулятор полиоксидоний: механизмы действия и аспекты клинического применения. Цитокины и воспаление. 2004; 3: 41 - 47.</mixed-citation><mixed-citation xml:lang="en">Pinegin B.V., Nekrasov A.V., Haitov R.M. Immunomodulator polyoxidonium: mechanisms of action and aspects of clinical application. Cytokines and inflammation. 2004; 3: 41 – 47 (in Russian).</mixed-citation></citation-alternatives></ref><ref id="cit9"><label>9</label><citation-alternatives><mixed-citation xml:lang="ru">Балачевский Б.В., Курзанов А.Н., Славинский А.А. Даларгин-индуцируемая модуляция функционально-метаболической активности нейтрофильных лейкоцитов. Успехи современного естествознания. 2008; 5: 75 - 77.</mixed-citation><mixed-citation xml:lang="en">Balachevskiy B.V., Kurzanov A.N., Slavinskiy A.A. Dalargin-induced modulation of the functional-metabolic activity of neutrophils. The success of modern science. 2008; 5: 75 – 77 (in Russian).</mixed-citation></citation-alternatives></ref><ref id="cit10"><label>10</label><citation-alternatives><mixed-citation xml:lang="ru">Silva T.M., do Vale A., dos Santos N.M. Secondary necrosis in multicellular animals: an outcome of apoptosis with pathogenic implications. Apoptosis. 2008; 13: 463 - 482.</mixed-citation><mixed-citation xml:lang="en">Silva T.M., do Vale A., dos Santos N.M. Secondary necrosis in multicellular animals: an outcome of apoptosis with pathogenic implications. Apoptosis. 2008; 13: 463 – 482.</mixed-citation></citation-alternatives></ref><ref id="cit11"><label>11</label><citation-alternatives><mixed-citation xml:lang="ru">Mares C.A., Ojeda S.S., Morris E.G., Li Q., Teale J.M. Initial delay in the immune response to Francisella tularensis is followed by hypercytokinemia characteristic of severe sepsis and correlating with upregulation and release of demage-associated molecular patterns. Infec. Immunity.2008; 76: 3001 - 3010.</mixed-citation><mixed-citation xml:lang="en">Mares C.A., Ojeda S.S., Morris E.G., Li Q., Teale J.M. Initial delay in the immune response to Francisella tularensis is followed by hypercytokinemia characteristic of severe sepsis and correlating with upregulation and release of demage-associated molecular patterns. Infec. Immunity.2008; 76: 3001 – 3010.</mixed-citation></citation-alternatives></ref><ref id="cit12"><label>12</label><citation-alternatives><mixed-citation xml:lang="ru">Фримель Х. Иммунологические методы. Москва. Медицина; 1987: 472.</mixed-citation><mixed-citation xml:lang="en">Frimel X. Immunological methods. Moscow. Medicine; 1987: 472 (in Russian).</mixed-citation></citation-alternatives></ref><ref id="cit13"><label>13</label><citation-alternatives><mixed-citation xml:lang="ru">Сибиряк С.В., Хайдуков С.В., Зурочка А.В. Оценка апоптоза в иммунологических исследованиях. Вопросы современной проточной цитометрии. Клиническое применение. Челябинск. Бумажный двор; 2008:195.</mixed-citation><mixed-citation xml:lang="en">Sibiryak S.V., Khaidukov S.V., Zurochka A.V. Evaluation of apoptosis in immunological research. Clinical application. Chelyabinsk. Paper Yard; 2008:195 (in Russian).</mixed-citation></citation-alternatives></ref><ref id="cit14"><label>14</label><citation-alternatives><mixed-citation xml:lang="ru">Bi Y., Du Z., Yang H. Guo Z., Tan Y., Zhu Z., Yang R. Reduced apoptosis of mouse macrophages induced by yscW mutant of Yersinia pestis results from the reduced secretion of YopJ and relates to caspase-3 signal pathway. Scand. J. Immunol. 2009; 70 (4): 358 - 367.</mixed-citation><mixed-citation xml:lang="en">Bi Y., Du Z., Yang H. Guo Z., Tan Y., Zhu Z., Yang R. Reduced apoptosis of mouse macrophages induced by yscW mutant of Yersinia pestis results from the reduced secretion of YopJ and relates to caspase-3 signal pathway. Scand. J. Immunol. 2009; 70 (4):358 – 367.</mixed-citation></citation-alternatives></ref><ref id="cit15"><label>15</label><citation-alternatives><mixed-citation xml:lang="ru">Iritani B.M., Eisenman R.N. C-Myc enhances protein synthesis and cell size during B lymphocyte development. PNAS. 1999; 96 (23): 13180 - 13185.</mixed-citation><mixed-citation xml:lang="en">Iritani B.M., Eisenman R.N. C-Myc enhances protein synthesis and cell size during B lymphocyte development. PNAS. 1999; 96(23): 13180 – 13185.</mixed-citation></citation-alternatives></ref><ref id="cit16"><label>16</label><citation-alternatives><mixed-citation xml:lang="ru">Sklar L.A., Oades Z.G., Finnay D.A. Neutrophil degranulation detected by right angle light scattering: spectroscopic methods suitable for simultaneous analysis of degranulation or shape change, elastase realease, and cell aggregation. J. Immunology. 1984; 133 (3): 1483 - 1487.</mixed-citation><mixed-citation xml:lang="en">Sklar L.A., Oades Z.G., Finnay D.A. Neutrophil degranulation detected by right angle light scattering: spectroscopic methods suitable for simultaneous analysis of degranulation or shape change, elastase realease, and cell aggregation. J. Immunology. 1984; 133 (3): 1483 – 1487.</mixed-citation></citation-alternatives></ref><ref id="cit17"><label>17</label><citation-alternatives><mixed-citation xml:lang="ru">Коржевский Д.Э., Гиляров А.В. Основы гистологической техники. Санкт-Петербург. СпецЛит; 2010: 96.</mixed-citation><mixed-citation xml:lang="en">Korzhevskij D.Je., Giljarov A.V. Basics of histologic techniques. St. Petersburg: Ltd. Publishing SpetsLit; 201: 96 (in Russian).</mixed-citation></citation-alternatives></ref><ref id="cit18"><label>18</label><citation-alternatives><mixed-citation xml:lang="ru">Howell W.M., Black D.A. Controlled silver staining of nucleolus organizer regions with a protective colloidal developer: a one-step method. Experientia. 1980; 36: 1014 - 1015.</mixed-citation><mixed-citation xml:lang="en">Howell W.M., Black D.A. Controlled silver staining of nucleolus organizer regions with a protective colloidal developer: a one-step method. Experientia. 1980; 36: 1014 – 1015.</mixed-citation></citation-alternatives></ref><ref id="cit19"><label>19</label><citation-alternatives><mixed-citation xml:lang="ru">Бугоркова С.А., Щуковская Т.Н., Курылина А.Ф. Ядрышковый аппарат лимфоцитов - как индикатор функциональной активности лимфоидных органов при доклинической оценке вакцин. Проблемы особо опасных инфекций. 2015; 2: 75 - 78.</mixed-citation><mixed-citation xml:lang="en">Bugorkova S.A., Schukovskaja T.N., Kurylina A.F. Nucleolar apparatus of lymphocytes - as an indicator of the functional activity of lymphoid organs in the preclinical evaluation of vaccines. Problems particularly dangerous infections. 2015; 2: 75 – 78 (in Russian).</mixed-citation></citation-alternatives></ref><ref id="cit20"><label>20</label><citation-alternatives><mixed-citation xml:lang="ru">Комбарова Т.И. Алгоритм отбора и предварительной оценки кандидатов в вакцинные штаммы туляремийного микроба. Автореф.: дис.. канд. биол. наук. Оболенск; 2013.</mixed-citation><mixed-citation xml:lang="en">Kombarova T.I. Selection algorithm and preliminary evaluation of candidates for vaccine strains of tularemia microbe. Doctorate of biol. sci. diss. Obolensk; 2013 (in Russian).</mixed-citation></citation-alternatives></ref><ref id="cit21"><label>21</label><citation-alternatives><mixed-citation xml:lang="ru">Houghton A.M., Hartzell W.O., Robbins C.S., Gomis-Rth F.X., Shapiro S.D. Macrophage elastase kills bacteria within murine macrophages. Nature Letters. 2009; 460: 637-642.</mixed-citation><mixed-citation xml:lang="en">Houghton A.M., Hartzell W.O., Robbins C.S., Gomis-Rüth F.X., Shapiro S.D. Macrophage elastase kills bacteria within murine macrophages. Nature Letters. 2009; 460: 637 – 642.</mixed-citation></citation-alternatives></ref><ref id="cit22"><label>22</label><citation-alternatives><mixed-citation xml:lang="ru">Steen H.B., Boye E. Escherichia coli growth studied by dual parameter flow cytophotometry. J. Bacteriology. 1981; 145 (2): 1091 - 1094.</mixed-citation><mixed-citation xml:lang="en">Steen H.B., Boye E. Escherichia coli growth studied by dual parameter flow cytophotometry. J. Bacteriology. 1981; 145 (2): 1091 – 1094.</mixed-citation></citation-alternatives></ref><ref id="cit23"><label>23</label><citation-alternatives><mixed-citation xml:lang="ru">Marohn M.E., Barry E.M. Live attenuated tularemia vaccines: recent developments and future goals. Vaccine. 2013; 31(35):3485-3491. doi: 10.1016/j.</mixed-citation><mixed-citation xml:lang="en">Marohn M.E., Barry E.M. Live attenuated tularemia vaccines: recent developments and future goals. Vaccine. 2013; 2; 31(35):3485 – 3491. doi: 10.1016/j.</mixed-citation></citation-alternatives></ref><ref id="cit24"><label>24</label><citation-alternatives><mixed-citation xml:lang="ru">Фирстова В.В., Павлов В.М., Горбатов А.А., Комбарова Т.И., Караулов А.В., Дятлов И.А. Формирование антитуляремийного клеточного и гуморального иммунного ответа, индуцированного у мышей F. tularensis 15 НИИЭГ. Иммунология. 2014; 35 (3): 147 - 150.</mixed-citation><mixed-citation xml:lang="en">Firstova V.V., Pavlov V.M., Gorbatov A.A., Kombarova T.I., Karaulov A.V., Dyatlov I.A. The development of cellular and humoral immune responses, induced in mice by Francisella tularensis 15 NIIEG. Immunology. 2014; 35 (3): 147 – 150 (in Russian).</mixed-citation></citation-alternatives></ref></ref-list><fn-group><fn fn-type="conflict"><p>The authors declare that there are no conflicts of interest present.</p></fn></fn-group></back></article>
