IMMUNITY TO PARASITIC INFECTION

这项提议将推进获得性抵抗力的研究 在使用老鼠的模型系统中传播到旋毛虫。这次会议的重点是 调查将是关于对旋毛虫的抗性，即 被动地从特定免疫的母亲身上转移到她身上 年青的。目标是评估不同角色(S)的作用 获得性感染抵抗力中的抗体亚类 阐明入侵肌幼虫成为 困在粘液中；鉴定靶向寄生虫抗原 免疫反应；以确定自然历史和 调节保护性的、分泌抗体的B细胞；并评估 断奶对抗体被动免疫能力的影响 保护老鼠免受旋毛虫的侵袭。 已知亚类的多克隆抗体和单抗 而专一性将进一步被描述为被动 保护实验。产生抗体的杂交瘤变种 具有与替代重质相关的保护性结合部位 将选择链来确定同种异型在 确定抗体的保护功能。这个问题应该是 进一步分析是通过将抗体酶切成 F(Ab)‘2片段。其他单抗将是 是为了证实我们观察到的IgG2c抗体 可以起到高度的保护作用。 保护性抗体与粘液的相互作用将是 经过严格的审查。粘液的作用将被调查以 确定粘蛋白释放是否是由 抗体的存在；它是否与抗体结合形成 抗原特异性陷阱或粘液完全被动起作用 而且，事实上，快速驱逐并不是必需的。我们会评估 抗体诱导物质释放的潜力 它们抑制幼虫在粘液中的活动或抑制这种活动 直接去吧。 保护性的单抗将被用于研究 它们的靶抗原在肌幼虫中的分布和功能。 中心问题是相关的寄生虫抗原是否 靶标是因为它表达在幼虫的表面或 因为它在功能上对寄生虫很重要，特别是 其侵入上皮细胞的能力。表位映射 保护性和非保护性单抗将是 进行靶抗原鉴定和活性部位(S)的研究。 另一个目标是确定保护性的自然历史 抗体产生细胞。特异性B细胞对相关基因的反应性 感染期间的寄生虫抗原将在两者中进行比较 粘膜和非粘膜淋巴组织。帮手的影响力 不同组织T细胞对B细胞反应性及亚型的影响 表达将被检查。这些实验将解决 一种抗体反应是如何由单一的 同型病毒在复杂的感染过程中发生。 最后，我们将评估断奶对表情的影响 被迅速驱逐出境。特别是，我们将评估保护性 具有保护性的单抗对成人的潜在作用 对于幼年老鼠来说。我们将调查辅助细胞的需求 以及免疫球蛋白E抗体以促进快速表达 被成年人驱逐。

This proposal would carry forward studies of acquired resistance to T. spiralis in a model system using rats. The focus of the inquiry would be on the resistance to T. spiralis that is transferred passively from a specifically immunized mother to her young. The objectives are to evaluate the role(s) of different subclasses of antibody in acquired resistance to infection; to elucidate the mechanism by which invading muscle larvae become entrapped in mucus; to characterize parasite antigens targeted in the immune response; to ascertain the natural history and regulation of protective, antibody secreting B cells; and to assess the effect of weaning on the ability of antibody to passively protect rats against T. spiralis. Polyclonal antibodies and monoclonal antibodies of known subclass and specificity would be further characterized in passive protection experiments. Hybridoma variants producing antibodies with a protective combining site associated with alternative heavy chains would be selected to determine the importance of isotype in defining the antibody's protect function. This question would be further analyzed by enzymatically cleaving the antibody into F(ab)'2 fragments. Additional monoclonal antibodies would be produced in order to confirm our observation that IgG2c antibodies can be highly protective. The interaction of protective antibodies with mucus would be critically examined. The role of mucus would be investigated to determine whether mucin release is triggered by antigen in the presence of antibody; whether it binds to antibody to form an antigen specific trap or if mucus is entirely passive in action and, in fact, not required for rapid expulsion. We would evaluate the potential of antibodies to induce the release of substances which inhibit larval mobility in mucus or to inhibit such mobility directly. Protective monoclonal antibodies would be used to investigate the distribution and function of their target antigen in muscle larvae. The central question is whether the relevant parasite antigen is targeted because it is expressed on the surfaces of larvae or because it is functionally important to the parasite, particularly to its capacity to invade the epithelium. Epitope mapping with protective and non-protective monoclonal antibodies would be conducted to identify and active site(s) on the target antigen. Another objective is to determine the natural history of protective antibody producing cells. Specific B cell reactivity to relevant parasite antigens during infection would be compared in both mucosal and non-mucosal lymphoid tissues. The influence of helper T cells from various tissues on B cell reactivity and isotype expression would be examined. These experiments would address the question of how an antibody response that is dominated by a single isotype develops during a complex infection. Finally we would assess the effects of weaning on the expression of rapid expulsion. In particular we would evaluate the protective potential for adult of monoclonal antibodies which are protective for infant rats. We would investigate the need for ancillary cells as well as IgE antibodies to facilitate expression of rapid expulsion by the adult.