Lamm M E
Institute of Pathology, Case Western Reserve University, Cleveland, Ohio 44106, USA.
Annu Rev Microbiol. 1997;51:311-40. doi: 10.1146/annurev.micro.51.1.311.
Infections often involve the mucosal surfaces of the body, which form a boundary with the outside world. This review focuses on immunoglobulin A (IgA) antibodies because IgA is the principal mucosal antibody class. IgA is synthesized by local plasma cells and has a specific polymeric immunoglobulin receptor-mediated transport mechanism for entry into the secretions. By serving as an external barrier capable of inhibiting attachment of microbes to the luminal surface of the mucosal epithelial lining, IgA antibodies form the first line of immune defense. In addition to this traditional mode of extracellular antibody function, recent evidence suggests that IgA antibodies can also function in a nontraditional fashion by neutralizing viruses intracellularly, if a virus is infecting an epithelial cell through which specific IgA antibody is passing on its way to the secretions. IgA antibodies are also envisaged as providing an internal mucosal barrier beneath the mucosal lining. Antigens intercepted by IgA antibodies here can potentially be ferried through the epithelium and thereby excreted. In addition to the polymeric immunoglobulin receptor on mucosal epithelial cells, IgA antibodies can bind to receptors on a variety of leukocytes and have been shown, in some experimental systems, to be capable of activating the alternative complement pathway, making IgA antibodies potential participants in inflammatory reactions. Although the relationship of IgA antibodies to inflammation is not entirely clear, the bias presented is that IgA is basically noninflammatory, perhaps even anti-inflammatory. According to this view, the major role of the Fc portion of IgA antibodies is to transport IgA across mucosal epithelial cells and not, as in the case of the other classes of antibody, to activate secondary phenomena of the kind that contribute to inflammation. Because of IgA's key role as an initial barrier to infection, much current research in mucosal immunology is directed toward developing new vectors and adjuvants that can provide improved approaches to mucosal vaccines. Finally, because of advances in monoclonal antibody technology, topical application of antibodies to mucosal surfaces has significant potential for preventing and treating infections.
感染常常累及身体的黏膜表面，这些黏膜表面构成了与外界的边界。本综述聚焦于免疫球蛋白A（IgA）抗体，因为IgA是主要的黏膜抗体类别。IgA由局部浆细胞合成，具有特定的多聚免疫球蛋白受体介导的转运机制以进入分泌物中。通过作为一种能够抑制微生物附着于黏膜上皮内衬管腔表面的外部屏障，IgA抗体形成了免疫防御的第一道防线。除了这种细胞外抗体功能的传统模式外，最近的证据表明，如果病毒正在感染特定IgA抗体在分泌途径中经过的上皮细胞，那么IgA抗体也可以通过在细胞内中和病毒以非传统方式发挥作用。IgA抗体还被设想为在黏膜内衬下方提供内部黏膜屏障。在此处被IgA抗体拦截的抗原可能会被转运穿过上皮细胞从而排出。除了黏膜上皮细胞上的多聚免疫球蛋白受体外，IgA抗体还可以与多种白细胞上的受体结合，并且在一些实验系统中已表明其能够激活替代补体途径，这使得IgA抗体成为炎症反应的潜在参与者。尽管IgA抗体与炎症的关系尚不完全清楚，但目前的观点倾向于认为IgA基本上是非炎症性的，甚至可能是抗炎的。根据这一观点，IgA抗体的Fc部分的主要作用是将IgA转运穿过黏膜上皮细胞，而不像其他类别抗体那样激活有助于炎症的继发性现象。由于IgA作为感染的初始屏障的关键作用，黏膜免疫学的许多当前研究都致力于开发新的载体和佐剂，以提供改进的黏膜疫苗接种方法。最后，由于单克隆抗体技术的进步，将抗体局部应用于黏膜表面在预防和治疗感染方面具有巨大潜力。
