В литературе достаточно подробно описаны морфологические аспекты патогенеза туберкулеза (ТБ). В то же время многое известно об основных этапах развития и формирования специфического адаптивного иммунитета. Однако, с нашей точки зрения, недостаточно уделено внимания участию системы иммунитета в патогенезе возникновения клинически значимых туберкулезных поражений, а также различных форм заболевания. Тем не менее, не подвергается сомнению, что разнообразие клинических проявлений любого заболевания, связанного с проникновением в организм чужеродного агента, в частности, микобактерий туберкулеза (МБТ), обеспечивается совокупностью взаимодействия инфекционного агента и индивидуальной ответной реакции макроорганизма на его внедрение. Мозаика такого взаимодействия обычно накладывает свои коррективы на развитие разных форм процесса, скорость и направленность течения, а также исходы. Безусловно, что ответная реакция макроорганизма на внедрение МБТ является составной частью патогенеза и складывается из многих общего плана компонентов, одними из которых являются реакции, связанные с механизмами естественного и приобретенного иммунитета. Выраженность этих реакций зависит как от особенностей раздражителя (т.е. МБТ), так и макроорганизма. Для развития заболевания ТБ основное значение имеют, во-первых, массивность инфекции, доза и длительность поступления МБТ в организм человека, а также их вирулентность, и, во-вторых, состояние протекции организма в период воздействия инфекционного агента. Патогенез ТБ несколько различается при первичном и повторном заражении МБТ. При первичном инфицировании у 88–90% лиц клинические проявления не развиваются, и о наступившем заражении свидетельствует только переход отрицательной туберкулиновой реакции в положительную (вираж туберкулиновых проб). В ряде случаев ограниченные поражения могут завершиться спонтанным излечением без применения противотуберкулезных препаратов с минимальными остаточными изменениями в легких, внутригрудных лимфатических узлах и тканях других органов нередко в виде кальцинатов и ограниченных участков фиброза в более поздних случаях. Только у 10–12% впервые инфицированных лиц развивается ТБ с выраженными клиническими проявлениями, требующий проведения противотуберкулезной терапии. Отсутствие клинических проявлений первичной туберкулезной инфекции может быть объяснено высоким уровнем естественной резистентности организма человека к ТБ, а иногда может быть следствием приобретенной протекции в результате вакцинации БЦЖ. В настоящем обзоре предпринята попытка обсудить участие механизмов иммунитета в патогенезе как при начале развития самого заболевания, так и в процессе его различных проявлений. В рамках данного обзора широко не обсуждаются проблемы генетически обусловленной резистентности или чувствительности к ТБ.
Ключевые слова: иммунитет, туберкулез, патогенез.
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The morphological aspects of TB pathogenesis are well described in the publications. Much is also known about the main stages of development and formation of specific adaptive immunity. However, from our point of view, not enough attention is being paid to the involvement of the immune system in the pathogenesis of clinically relevant TB abnormalities, as well as various forms of the disease. Nevertheless, there is no doubt that the variety of clinical manifestations of any disease associated with the penetration of a foreign agent into the body, and Mycobacterium tuberculosis (MTB) in particular, is due to the collective interaction of the infectious agent and the individual response of the macroorganism to this infectious agent. The mosaic of such interactions usually imposes its own adjustments on the development of different forms of the process, its speed and direction, as well as the outcomes. Certainly, the response of a macroorganism to MTB is an integral part of pathogenesis and consists of many general components including the responses associated with the mechanisms of natural and acquired immunity. Intensity of these reactions depends on the characteristics of an agent (MTB) and a macroorganism. For the development of TB disease, massiveness of TB infection, dose and duration of MTB exposure to the human body, as well as virulence of MTB and the level of body's protection during the exposure play a very important role. TB pathogenesis is somewhat different in primary MTB infection and re-infection. With primary infection, 88–90% of individuals do not have clinical manifestations, and only the tuberculin skin test conversion signals the onset of infection. In some cases, without any use of anti-TB drugs limited abnormalities may result in spontaneous cure with the minimal residual changes in the lungs, intrathoracic lymph nodes and tissues of other organs, often in the form of calcifications and limited areas of fibrosis in more advanced cases. Only 10–12% of newly infected individuals develop TB with severe clinical manifestations requiring TB therapy. The absence of clinical manifestations of primary TB infection can be explained by a high level of natural resistance of the human body to tuberculosis, and sometimes can be an effect of acquired protection due to BCG vaccination. This review attempts to discuss the role of immune mechanisms in the pathogenesis both at the beginning of disease development, and in the process of its various manifestations. Issues of genetically determined resistance or susceptibility to TB are not being covered in detail in this manuscript.
Key words: immunity, tuberculosis, pathogenesis.
Список литературы
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11. Martineau AR, Newton SM, Wilkinson KA, Kampmann B, Hall BM, Nawroly N, Packe GE, Davidson RN, Griffiths CJ, Wilkinson RJ. Neutrophil-mediated innate immune resistance to mycobacteria. J Clin Invest. 2007 Jul;117(7):1988-94. doi: 10.1172/JCI31097
12. Easton DM, Nijnik A, Mayer ML, Hancock REW. Potential of immunomodulatory host defense peptides as novel anti-infectives. Trends in Biotechnology. 2009;27(10):582-90. doi: 10.1016/j.tibtech.2009.07.004
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Авторы
В.Я. Гергерт, М.М. Авербах, А.Э. Эргешов
ФГБНУ «Центральный научно-исследовательский институт туберкулеза», отдел иммунологии, Москва, Россия
________________________________________________
V.Ja. Gergert, M.M. Averbakh, A.E. Ergeshov
Central TB Research Institute, Department of Immunology, Moscow, Russia