Secretory IgA: Designed for Anti-Microbial Defense.
Secretory IgA: Designed for Anti-Microbial Defense.
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DOI：
10.3389/fimmu.2013.00222
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发表时间：
2013
影响因子：
7.3
通讯作者：
Brandtzaeg P
中科院分区：
文献类型：
--
作者：
Brandtzaeg P
通过接种疫苗预防感染仍然是改善公共卫生的一个紧迫目标。黏蛋白疫苗将使免疫程序更容易，更适合于大规模管理，最有效地诱导免疫排斥-一个术语创造的非炎症抗体屏蔽内部身体表面，主要由分泌型免疫球蛋白A（SIgA）介导。输出的抗体是聚合的，主要是伊加二聚体（pIgA），由靶向粘膜的抗原刺激的局部浆细胞（PC）产生。SIgA早期显示与上皮糖蛋白-分泌组分（SC）复合。然后提出了pIgA和五聚体IgM的共同SC依赖性转运机制，这意味着膜SC作为受体，现在通常称为聚合物IG受体（pIgR）。从基底外侧表面，pIg-pIgR复合物通过内吞作用被摄取，然后在分泌抗体中具有稳定和先天功能的受体结合SC的顶端切割后被挤出到管腔中。缺乏pIgR的小鼠表明，这是负责伊加和IgM上皮输出的唯一受体。这些基因敲除小鼠在其粘膜防御和肠道微生物群的变化中表现出各种缺陷。在肠道中，B细胞的诱导发生在肠道相关的淋巴组织中，特别是派尔集合淋巴结和孤立的淋巴滤泡，但也发生在肠系膜淋巴结中。PC分化在固有层中完成，激活的记忆/效应B细胞归巢于该固有层。气道也接受来自鼻咽相关淋巴组织的此类细胞，但通过不同的归巢受体。这种区室化对粘膜接种是一个挑战，粘膜免疫系统用于区分肠道共生体（互利共生）、致病菌和明显病原体（消除）的机制也是如此。
Prevention of infections by vaccination remains a compelling goal to improve public health. 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 (PCs) stimulated by antigens that target the mucose. SIgA was early shown to be complexed with an epithelial glycoprotein – the secretory component (SC). A common SC-dependent transport mechanism for pIgA and pentameric IgM was then proposed, implying that membrane SC acts as a receptor, now usually called the polymeric Ig receptor (pIgR). From the basolateral surface, pIg-pIgR complexes are taken up by endocytosis and then extruded into the lumen after apical cleavage of the receptor – bound SC having stabilizing and innate functions in the secretory antibodies. Mice deficient for pIgR show that this is the only receptor responsible for epithelial export of IgA and IgM. These knockout mice show a variety of defects in their mucosal defense and changes in their intestinal microbiota. In the gut, induction of B-cells occurs in gut-associated lymphoid tissue, particularly the Peyer’s patches and isolated lymphoid follicles, but also in mesenteric lymph nodes. PC differentiation is accomplished in the lamina propria to which the activated memory/effector B-cells home. The airways also receive such cells from nasopharynx-associated lymphoid tissue but by different homing receptors. This compartmentalization is a challenge for mucosal vaccination, as are the mechanisms used by the mucosal immune system to discriminate between commensal symbionts (mutualism), pathobionts, and overt pathogens (elimination).
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影响因子：
4.4
作者：
Beisner, DR;Ch'en, IL;Hedrick, SM
通讯作者：
Hedrick, SM
影响因子：
3.1
作者：
BIESBROCK, AR;REDDY, MS;LEVINE, MJ
通讯作者：
LEVINE, MJ
影响因子：
5.4
作者：
Brandtzaeg, P.
通讯作者：
Brandtzaeg, P.
DOI：
10.1007/bf01002902
发表时间：
1977-01-01
期刊：
HISTOCHEMICAL JOURNAL
影响因子：
--
作者：
BRANDTZAEG, P
通讯作者：
BRANDTZAEG, P
影响因子：
4.4
作者：
Agnello, Davide;Denimal, Damien;Pothier, Pierre
通讯作者：
Pothier, Pierre