Brandtzaeg P
Laboratory for Immunohistochemistry and Immunopathology (LIIPAT), Centre for Immune Regulation, University of Oslo, Division and Institute of Pathology, Oslo University Hospital, Rikshospitalet, Oslo, Norway.
Scand J Immunol. 2009 Dec;70(6):505-15. doi: 10.1111/j.1365-3083.2009.02319.x.
Prevention of infections by vaccination remains a compelling goal to improve public health. Most infections involve the mucosae, but the development of vaccines against many of these pathogens has yet to be successful. Mucosal vaccines would make immunization procedures easier, be better suited for mass administration, and most efficiently induce immune exclusion - a term coined for non-inflammatory antibody shielding of internal body surfaces - mediated principally by secretory immunoglobulin A (SIgA). The exported antibodies are polymeric, mainly IgA dimers (pIgA) - produced by local plasma cells stimulated by antigens that target the mucosae. SIgA was early shown to be complexed with an epithelial glycoprotein - the secretory component (SC). In 1974, a common SC-dependent transport of pIgA and pentameric IgM was proposed. From the basolateral surface, pIg-SC complexes are taken up by endocytosis and finally extruded into the lumen. Membrane SC is now referred to as polymeric Ig receptor (pIgR). In 1980, it was shown to be synthesized as a larger transmembrane protein - first cloned from rabbit and then from human. Mice deficient for pIgR showed that this is the only receptor responsible for epithelial transport of IgA and IgM. In the gut, induction of B cells occurs in gut-associated lymphoid tissue, particularly the Peyer's patches, but also in mesenteric lymph nodes. Plasma cell differentiation is accomplished in the lamina propria to which the memory/effector cells home. The airways also receive such cells from nasopharynx-associated lymphoid tissue - but by different homing receptors. Such compartmentalization is a challenge for development of mucosal vaccines.
通过接种疫苗预防感染仍然是改善公众健康的一个极具吸引力的目标。大多数感染都涉及黏膜，但针对许多此类病原体的疫苗开发尚未成功。黏膜疫苗将使免疫程序更简便，更适合大规模接种，并且能最有效地诱导免疫排斥——这一术语用于描述由分泌型免疫球蛋白A（SIgA）介导的对体内表面的非炎性抗体保护。输出的抗体是聚合体，主要是IgA二聚体（pIgA）——由靶向黏膜的抗原刺激局部浆细胞产生。早期研究表明，SIgA与一种上皮糖蛋白——分泌成分（SC）结合。1974年，有人提出pIgA和五聚体IgM存在一种共同的依赖SC的转运方式。从基底外侧表面开始，pIg-SC复合物通过内吞作用被摄取，最终被挤出到管腔中。膜SC现在被称为聚合免疫球蛋白受体（pIgR）。1980年，研究表明它是作为一种更大的跨膜蛋白合成的——首先从兔子身上克隆，然后从人类身上克隆。缺乏pIgR的小鼠表明，这是负责IgA和IgM上皮转运的唯一受体。在肠道中，B细胞在肠道相关淋巴组织，特别是派尔集合淋巴结中诱导产生，但也在肠系膜淋巴结中诱导产生。浆细胞分化在固有层完成，记忆/效应细胞归巢于此。气道也从鼻咽相关淋巴组织接收此类细胞——但通过不同的归巢受体。这种分隔对黏膜疫苗的开发来说是一个挑战。
