Department and Institute of Pathology, Laboratory for Immunohistochemistry and Immunopathology (LIIPAT), Centre for Immune Regulation (CIR), Oslo University Hospital, Rikshospitalet, Norway.
Benef Microbes. 2010 Sep;1(3):211-27. doi: 10.3920/BM2010.0009.
In the process of evolution, the mucosal immune system has generated two layers of anti-inflammatory defence: (1) immune exclusion performed by secretory IgA (and secretory IgM) antibodies to modulate or inhibit surface colonisation of microorganisms and dampen penetration of potentially dangerous antigens; and (2) suppressive mechanisms to avoid local and peripheral hypersensitivity to innocuous antigens, particularly food proteins and components of commensal bacteria. When induced via the gut, the latter phenomenon is called 'oral tolerance', which mainly depends on the development of regulatory T (Treg) cells in mesenteric lymph nodes to which mucosal dendritic cells (DCs) carry exogenous antigens and become conditioned for induction of Treg cells. Mucosally induced tolerance appears to be a rather robust adaptive immune function in view of the fact that large amounts of food proteins pass through the gut, while overt and persistent food allergy is not so common. DCs are 'decision makers' in the immune system when they perform their antigen-presenting function, thus linking innate and adaptive immunity by sensing the exogenous mucosal impact (e.g. conserved microbial molecular patterns). A balanced indigenous microbiota is required to drive the normal development of both mucosa-associated lymphoid tissue, the epithelial barrier with its secretory IgA (and IgM) system, and mucosally induced tolerance mechanisms including the generation of Treg cells. Notably, polymeric Ig receptor (pIgR/SC) knock-out mice that lack secretory IgA and IgM antibodies show reduced epithelial barrier function and increased uptake of antigens from food and commensal bacteria. They therefore have a hyper-reactive immune system and show predisposition for systemic anaphylaxis after sensitisation; but this development is counteracted by enhanced oral tolerance induction as a homeostatic back-up mechanism.
在进化过程中，黏膜免疫系统产生了两层抗炎防御机制：(1) 分泌型 IgA（和 IgM）抗体进行免疫排除，以调节或抑制微生物的表面定植，并抑制潜在危险抗原的渗透；(2) 抑制机制，避免对无害抗原（特别是食物蛋白和共生菌成分）产生局部和外周过敏。当通过肠道诱导时，后一种现象被称为“口服耐受”，主要依赖于肠系膜淋巴结中调节性 T（Treg）细胞的发育，黏膜树突状细胞（DC）携带外源性抗原并被诱导为 Treg 细胞。鉴于大量食物蛋白通过肠道，而明显和持续的食物过敏并不常见，黏膜诱导的耐受似乎是一种相当强大的适应性免疫功能。当 DC 发挥抗原呈递功能时，它们是免疫系统的“决策者”，通过感知外源性黏膜影响（例如保守的微生物分子模式），将先天免疫和适应性免疫联系起来。需要平衡的本土微生物群来驱动黏膜相关淋巴组织、具有分泌型 IgA（和 IgM）系统的上皮屏障以及包括 Treg 细胞生成在内的黏膜诱导耐受机制的正常发育。值得注意的是，缺乏分泌型 IgA 和 IgM 抗体的多聚 Ig 受体（pIgR/SC）敲除小鼠表现出上皮屏障功能降低和食物及共生菌抗原摄取增加。因此，它们具有过度活跃的免疫系统，并在致敏后表现出全身性过敏反应的倾向；但这种发展被增强的口服耐受诱导作为一种体内平衡的后备机制所抵消。
