Protective immune mechanisms of Mongolian jirds (Meriones unguiculatus) against infectious diseases with a special reference to the mucosal defense mediated by IgA

为了评估IgA抗体在从肠道驱逐线虫中的潜在作用，从口服接种辐照的布氏旋毛虫肌幼虫的BALB/c小鼠的肠系膜淋巴结产生一组IgA单克隆抗体（mAb）。一种IgA单抗HUSM-Tb1在活肌幼虫表面形成免疫沉淀，并通过免疫组织化学与其肌间细胞和表皮表面反应。当给予小鼠每20 g体重2.0 mg特异性IgA时，在攻击前5小时腹腔注射该mAb的BALB/c小鼠赋予了高水平（超过95%）的抗旋毛虫感染的保护。同样的处理在SCID小鼠和大鼠中产生了类似的效果，但在蒙古沙鼠（长爪沙鼠）中没有。小鼠和沙鼠腹腔注射IgA mAb的体内清除率不同。在小鼠中，超过一半的可检测到的粪便IgA在注射后5小时内排出， ...更多信息 n几乎在12小时内完成。相反，沙鼠在注射后5至12小时内排出一半以上的可检测粪便IgA，并在24小时内完成排泄。与此相关的是，沙鼠血液中IgA的滞留时间比小鼠长。因此，我们推测沙鼠在免疫系统中可能存在一定的缺陷，对沙鼠特有的免疫系统的研究还有待进一步深入。沿着上述工作，我们进行了以下观察，以阐明沙鼠免疫系统的特点：1）使用补体依赖性抗Thy-1肾小球肾炎模型的补体活性，2）肠绦虫的T细胞依赖性消除（粗头绦虫）感染与血锥虫使用抗沙鼠T细胞mAb，通过使用T细胞耗竭的沙鼠感染（巨锥虫）（HUSM-M.g.15），3）沙鼠皮肤树突状细胞与穿皮寄生虫的体内相互作用（Schistosoma mansoni）的免疫应答的时间变化;（4）沙鼠中两种IgG亚类的表征和T细胞耗尽的曼氏血吸虫T.被感染的沙鼠这些工作增加了我们对蒙古沙鼠独特的免疫防御系统的了解，这些免疫防御系统作为各种具有医学重要性的传染病的实验室模型非常有用。少

To assess the potential role of IgA antibody in expulsion of the nematode from the intestine, a panel of IgA monoclonal antibodies (mAbs) were produced from the mesenteric lymph nodes of BALB/c mice orally vaccinated with irradiated muscle larvae of Trichinella britovi. One IgA mAb, HUSM-Tb1, formed immunoprecipitates on the surface of live muscle larvae, and by immunohistochemistry reacted with their stichocytes and cuticular surface. Intraperitoneal injection of BALB/c mice with this mAb 5 hours before challenge conferred a high level of protection (more than 95%) against Trichinella infection, when 2.0 mg of specific IgA per 20 g body weight was given to a mouse. The same treatment produced a similar effect in SCID mice and rats, but not in Mongolian jirds (Meriones unguiculatus). In vivo clearance of intraperitoneally-injected IgA mAb was different between mice and jirds. In mice, more than a half of detectable fecal IgA was excreted within 5 hours after injection, and the excretio … More n was almost completed within 12 hours. In contrast, jirds excreted more then a half of detectable fecal IgA between 5 and 12 hours after injection, and completed its excretion by 24 hours. Correlating with it, prolonged retention of more IgA in the blood was noticed in jirds than mice. It is speculated that jirds might have some defect(s) in mucosal transportation of murine IgA, and it is needed to explore more on the mucosal IgA defense system unique to jirds.Along with the works mentioned above, we have performed the following observations to clarify the characteristics of jird immune systems; 1) complement activity using the complement-dependent anti-Thy-1 glomerulonephritis model, 2) T-cell dependent elimination of intestinal cestode (Taenia crassiceps) infection and blood trypanosome (Trypanosoma grosi) infection, by use of T-cell-depleted jirds using anti-jird T-cell mAb (HUSM-M.g.15), 3) In vivo interaction of jird cutaneous dendritic cells with skin-penetrating parasites (Schistosoma mansoni) by use of anti-jird MHC class II mAb (HUSM-M.g.30), and 4) characterization of two IgG subclasses in jirds and temporal changes in humoral immune responses of T-cell-depleted, T. grosi-infected jirds. These works increase our knowledge on the unique immune defense system of Mongolian jirds that are highly useful as a laboratory model of various infectious diseases of medical importance. Less