Immunity to Parasitic Infection

描述（由申请人提供）：肠上皮屏障对生存至关重要。肠道线虫部署新的工具生活在这个网站。反过来，对寄生线虫的免疫力有一组新的参数。我们的目的是阐明保护性肠道免疫对寄生线虫的机制。快速排出是一种有效的免疫现象，可保护大鼠免受旋毛虫继发感染。我们已经表明，特异性针对幼虫排泄分泌产物上的泰维洛糖加帽聚糖的IgG抗体，可从乳鼠体内排出幼虫。成年大鼠的排出也依赖于抗泰维糖IgG，但需要与未鉴定的先天组分合作。有证据表明，固有的基本成分是粘膜肥大细胞。免疫机制尚不清楚。我们复制T.螺旋体在体外为我们提供了一个独特的机会，研究合作，保护活动的细胞和抗体。我们的具体目标将测试以下假设：1。免疫复合物对粘膜肥大细胞的激活具有同种型依赖性。将检测单克隆抗泰维糖IgG形成的免疫复合物与大鼠粘膜肥大细胞的受体结合、脱粒和细胞因子诱导。肥大细胞将用感染期间局部产生的细胞因子处理，以诱导可能有助于肠道免疫的细胞特性。2.粘膜肥大细胞的活化破坏了T.螺旋形的T.为了剖析促进寄生虫排出的肥大细胞活性，将在体外对螺旋体进行建模。特异性和非特异性介质的工作，损害T。螺旋将被定义。3.肥大细胞和抗泰维糖IgG介导体内快速排出。将感染肥大细胞缺陷大鼠以测试肥大细胞对体内快速排出的贡献。我们将通过诱发大鼠肥大细胞增多症来重建免疫肠，而不依赖于肠T细胞。螺旋体，然后用泰维糖特异性抗体被动免疫大鼠。我们提出的工作将阐明肠道免疫的有效机制，并将提高我们开发新型肠道病原体疫苗的能力。

DESCRIPTION (provided by the applicant): The epithelial barrier in the intestine is crucial to survival. Intestinal nematodes deploy novel tools to live in this site. In turn, immunity to parasitic nematodes has a set of novel parameters. Our objective is to elucidate mechanisms of protective, intestinal immunity against parasitic nematodes. Rapid expulsion is a potent immune phenomenon that protects rats against secondary infection by Trichinella spiralis. We have shown that IgG antibodies, specific for tyvelose-capped glycans on larval excretory-secretory products, expel larvae from suckling rats. Expulsion by adult rats is also dependent upon anti-tyvelose IgG but requires cooperation with an unidentified innate component. Evidence suggests that the essential innate constituent is the mucosal mast cell. The mechanism of immunity is unknown. Our ability to reproduce the epithelial habitat of T. spiralis in vitro affords us a unique opportunity to investigate the cooperative, protective activities of cells and antibodies. Our specific aims will test the following hypotheses: 1. Activation of mucosal mast cells by immune complexes is isotype dependent. Immune complexes formed with monoclonal anti-tyvelose IgGs will be tested for receptor binding, degranulation and cytokine induction with rat mucosal mast cells. Mast cells will be treated with cytokines that are produced locally during infection in order to induce cellular properties that may contribute to intestinal immunity. 2. Activation of mucosal mast cells disrupts the epithelial habitat of T. spiralis. The intestinal habitat of T. spiralis will be modeled in vitro in order to dissect mast cell activities that promote parasite expulsion. The workings of specific and non-specific mediators that compromise the epithelial habitat of T. spiralis will be defined. 3. Mast cells and anti-tyvelose IgG mediate rapid expulsion in vivo. Mast cell deficient rats will be infected to test the contribution of mast cells to rapid expulsion in vivo. We will recreate the immune intestine by eliciting mastocytosis in rats independently of intestinal T. spiralis, and then passively immunizing rats with tyvelose specific antibodies. The work we propose will elucidate a potent mechanism of intestinal immunity and will improve our ability to develop novel vaccines for intestinal pathogens.