IMMUNITY TO PARASITIC INFECTION

这一建议将推进获得性抗性的研究 随时为我们提供帮助螺旋在模型系统中使用大鼠。 的重点 调查将是对T.螺旋， 被动地从一个特定免疫的母亲转移到她身上， 年轻 目标是评估不同的 获得性抗感染抗体的亚类; 阐明入侵肌肉幼虫成为 捕获在粘液中;表征靶向于 免疫反应;确定自然史， 调节保护性抗体分泌B细胞;并评估 断奶对抗体被动免疫能力的影响 保护大鼠免受T.螺旋形的 已知亚类的多克隆抗体和单克隆抗体 而特异性则进一步表现为被动的 保护实验 产生抗体的杂交瘤变体 具有与替代性重金属相关的保护性结合部位， 将选择链以确定同种型在 确定抗体的保护功能。 这个问题将是 通过将抗体酶促切割成 F（ab ′ 2片段。 另外的单克隆抗体将是 为了证实我们的观察，IgG 2c抗体 可以高度保护。 保护性抗体与粘液的相互作用 批判性地审视。 粘液的作用将被研究， 确定粘蛋白的释放是否是由抗原触发的， 抗体的存在;它是否与抗体结合以形成 抗原特异性陷阱或粘液完全被动作用 而且事实上，并不需要快速驱逐 我们会评估 抗体诱导物质释放的潜力 其抑制幼虫在粘液中的移动或抑制这种移动 直接. 保护性单克隆抗体将用于研究 其靶抗原在肌幼虫中的分布和功能。 核心问题是相关的寄生虫抗原是否 因为它在幼虫的表面表达， 因为它在功能上对寄生虫很重要， 它侵入上皮细胞的能力。 表位作图， 保护性和非保护性单克隆抗体将 以鉴定靶抗原上的活性位点。 另一个目标是确定保护性的自然历史 抗体生成细胞。 特异性B细胞对相关 感染期间的寄生虫抗原将在两种情况下进行比较。 粘膜和非粘膜淋巴组织。 帮助者的影响 来自不同组织的T细胞对B细胞反应性和同种型的影响 表达将被检查。 这些实验将解决 一个由单一抗体控制的抗体反应 同种型在复杂感染期间形成。 最后，我们将评估断奶对表达的影响， 快速驱逐。 特别是，我们将评估保护性 保护性单克隆抗体的成人潜力 对于幼鼠来说。 我们会研究是否需要辅助细胞 以及IgE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.