Mestecky J, McGhee J R
Department of Microbiology, University of Alabama, Birmingham 35294-10005.
Adv Exp Med Biol. 1992;327:13-23. doi: 10.1007/978-1-4615-3410-5_3.
The selective induction of antibodies in external secretions and mucosal T cell-mediated immunity are desirable for the prevention of various systemic as well as predominantly mucosa-restricted infections. An enormous surface area of mucosal membranes is protected primarily by antibodies that belong, in many species, to the IgA isotype. Such antibodies are produced locally by large numbers of IgA-containing plasma cells distributed in subepithelial spaces of mucosal membranes and in the stroma of secretory glands. In humans and in some animal species, plasma-derived IgA antibodies do not enter external secretions in significant quantities and systemically administered preformed IgA antibodies would be of little use for passive immunization. Systemic administration of microbial antigens may boost an effective S-IgA immune response only in a situation whereby an immunized individual had previously encountered the same antigen by the mucosal route. Immunization routes that involve ingestion or possibly inhalation of antigens lead to the induction of not only local but also generalized immune responses, manifested by the parallel appearance of S-IgA antibodies to ingested or inhaled antigens in secretions of glands distant from the site of immunization. Convincing evidence is available that antigen-sensitized and IgA-committed precursors of plasma cells and T cells from IgA inductive sites (e.g., BALT, GALT, and tonsils) are disseminated to the gut, other mucosa-associated tissues, and exocrine glands. However, due to the limited absorption of desired antigens from the gut lumen of orally immunized individuals, repeated large doses of antigens are required for an effective S-IgA response. Novel antigen delivery systems for the stimulation of such responses has been briefly reviewed here. These, of course, include genetically engineered bacteria and viruses, CT/CFB, liposomes and microspheres. Live attenuated or genetically manipulated bacteria expressing other microbial antigens have been used for selective colonization of GALT. Unique antigen packaging and the use of adjuvants suitable for oral administration hold promise for an efficient antigen delivery to critical tissues in the intestine and deserve extensive exploration. The oral immunization route appears to have many advantages over systemic immunization; however, one must consider alternate IgA inductive sites and compartmentalization within the Common Mucosal Immune System. In addition to providing immunity on mucosal surfaces, which are the most common sites of entry of infectious agents, the mucosal routes of administration are more acceptable and do not require stringent criteria applicable for injectable vaccines, storage problems may be simplified, and large populations of individuals can be immunized simultaneously without the assistance of highly trained health personnel.
诱导外分泌液中的抗体以及黏膜T细胞介导的免疫反应具有选择性，这对于预防各种全身性感染以及主要局限于黏膜的感染是很有必要的。黏膜表面面积巨大，主要由许多物种中属于IgA同种型的抗体保护。此类抗体由大量含IgA的浆细胞在黏膜上皮下间隙和分泌腺基质中局部产生。在人类和一些动物物种中，源自血浆的IgA抗体不会大量进入外分泌液，全身给予预先形成的IgA抗体对被动免疫几乎没有用处。只有在免疫个体先前已通过黏膜途径接触过相同抗原的情况下，全身给予微生物抗原才可能增强有效的分泌型IgA免疫反应。涉及摄入或可能吸入抗原的免疫途径不仅会诱导局部免疫反应，还会诱导全身性免疫反应，表现为在远离免疫部位的腺体分泌物中出现针对摄入或吸入抗原的分泌型IgA抗体。有确凿证据表明，来自IgA诱导部位（如支气管相关淋巴组织、肠道相关淋巴组织和扁桃体）的浆细胞和T细胞的抗原致敏且IgA定向的前体细胞会扩散到肠道、其他黏膜相关组织和外分泌腺。然而，由于口服免疫个体从肠腔中吸收所需抗原的能力有限，为了产生有效的分泌型IgA反应需要重复给予大剂量抗原。本文简要综述了用于刺激此类反应的新型抗原递送系统。当然，这些系统包括基因工程细菌和病毒、霍乱毒素/霍乱弧菌B亚单位、脂质体和微球。表达其他微生物抗原的减毒活细菌或基因改造细菌已用于肠道相关淋巴组织的选择性定植。独特的抗原包装以及使用适合口服的佐剂有望将抗原有效递送至肠道中的关键组织，值得深入探索。口服免疫途径似乎比全身免疫具有许多优势；然而，必须考虑共同黏膜免疫系统内的替代IgA诱导部位和区室化。除了在感染因子最常见的进入部位即黏膜表面提供免疫外，黏膜给药途径更易接受，不需要适用于注射用疫苗的严格标准，储存问题可能会简化，并且无需训练有素的卫生人员协助就能同时为大量个体进行免疫。
