Abstract
Review covers modern data on relationships of normal intestinal microbiota and immune system. Possibility to maintain the residence of large numbers of symbiotic bateria at mucosal surfaces of the body is regarded as a separate and independent immunological function named acceptive immunity. Basic effector arms of protective (defense against pathogens) and acceptive immunity (symbiotic relationships) are compared. Acceptive immunity differs from protective one in the absence of inflammation where all complex of immune reactions occurs in the context of physiological process. Several homeostatic mechanisms that provide crosstalk with symbiotic bacteria at the epithelial surfaces, innate and adaptive immunity are described. The main immunological strategies towards symbiotic bacteria are support of microbial community from one hand, and providing of host defense, from the other hand. The key step of this interaction is sensing of soluble microbial products via pattern-recognition receptors on the host cells. Basic innate immune response consists of mucus production and synthesis of antimicrobial peptides by barrier epithelial cells as well as maintenance of specific anti-inflammatory microenvironment. The main adaptive response is synthesis of secretory immunoglobulin A that is produced to the intestinal lumen and interacts with bacteria. At the same time, immunoglobulin A does not make any damage for commensals. Moreover this factor plays important role in symbiotic relationships. The following promicrobial functions of immunoglobulin A are suggested: participation in biofilm formation, discrimination of intestinal bacteria for fixed and free-living populations as well as facilitation of microbial transport through M cells. Mucosal homeostasis is supported by the development of immunological tolerance with participation of T regulatory cells. Main mechanisms of the development and maintenance of specific tolerance towards antigens of normal microbiota are discussed. Modern data on the participation of two main populations of T-regulatory cells are cited — thymic cells and cells induced in periphery. It is now accepted, that development of specific tolerance to microbial and food antigens plays important role in prevention of autoimmune and allergic diseases.
Highlights
За последние два десятилетия появилось большое число публикаций по мукозному иммунитету
Нижний плотный слой слизи препятствует контакту микроорганизмов с клетками организма, поэтому здесь нет зон индукции иммунного ответа, а иммунорегуляторное влияние микробиоты осуществляется посредством различных метаболитов, из которых наиболее хорошо изучены короткие жирные кислоты [43]
IL-9 promotes IL-13-dependent Paneth cell hyperplasia and up-regulation of innate immunity mediators in intestinal mucosa
Summary
Механизмы становления микробиоценоза и его взаимоотношения с иммунной системой у человека и других млекопитающих недостаточно изучены. В качестве известной модели используются безмикробные животные — гнотобионты, выращенные в стерильных условиях. Что такие животные имеют недоразвитую лимфоидную систему кишечника [49, 63]. Что продукты нормальной микробиоты влияют на созревание иммунной системы у человека и животных — на размер Пейеровых бляшек и мезентериальных лимфоузлов, на развитие в них зародышевых центров, на формирование мукозо-ассоциированной лимфоидной ткани кишечника (GALT — gut-associated lymphoid tissue). В эксперименте показано, что бактерии участвуют в развитии и поверхностной дифференцировке эпителия, и эти изменения обеспечивают создание ниши для проживания бактерий [26]. У безмикробных животных нарушена деградация слизи из-за отсутствия бактерий, которые это осуществляют [24], и образование некоторых антибактериальных пептидов
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