STUDIES OF THE IMMUNOLOGIC RESPONSES TO FILARIAL INFECTIONS

这个项目的目的是定义体液免疫和细胞免疫。 与免疫病理学、保护性免疫和 淋巴丝虫病和丝虫病患者的免疫诊断。 相当大的努力已被用于发展单克隆性 用于提高抗体敏感性/特异性的抗体试剂(McAbs) 实验室的几项重要化验结果。因此，免疫球蛋白的抗体 子类(它们在阻塞立即事件中显得尤为重要 超敏反应(IgG4)与淋巴管病变 病变(IgG3)可以通过具有很好的特征性和高度特异性来衡量 McAbs；嗜酸性粒细胞可由McAbs针对唯一的 表面抗原；其颗粒含量(MBP、EOP、EDN和ECP)现为 可与亲和纯化的多克隆和单抗进行鉴定； 而在感染患者中发现的200kD循环丝虫抗原可以 用针对它或它的McAbs更敏感地测量 免疫显性磷胆碱决定簇。 眼部盘尾丝虫病患者眼组织和眼液的研究 显示活跃的局部免疫球蛋白和免疫球蛋白E抗体的产生以及内皮 眼内存在微丝虫时的细胞激活(Ia+)。T细胞 然而，虹膜和结膜的渗透是一种 抑制子/细胞毒表型(Leu2a)，与大多数 葡萄膜炎综合征，但与一般寄生虫特有的， 原发性T细胞免疫抑制在两组患者中反复出现 盘尾丝虫病和淋巴丝虫病。

The purpose of this project is to define the humoral and cellular immune responses that relate to immunopathology, protective immunity and immunodiagnosis of patients with lymphatic filariasis and onchocerciasis. Considerable effort has been directed towards developing monoclonal antibody reagents (Mcabs) for improving the sensitivity/specificity of several of the laboratory's important assays. Thus, antibodies of the IgG subclasses (which appear differentially important in blocking immediate hypersensitivity reactions (IgG4) and in the pathogenesis of lymphatic lesions (IgG3) can be measured by well characterized and highly specific Mcabs; eosinophils can be identified by Mcabs directed against a unique surface antigen; their granule contents (MBP, EOP, EDN and ECP) are now assenssable with affinity purified polyclonal and monoclonal antibodies; and the 200 kD circulating filarial antigen seen in infected patients can be measured much more sensitively with Mcabs directed against it or its immunodominant phosphorylcholine determinant. Studies of eye tissue and fluid from patients which ocular onchocerciasis show active local IgG and IgE antibody production as well as endothelial cell activation (Ia+) in the presence of microfilariae in the eye. T-cell infiltration of the iris and conjunctiva, however, is of the suppressor/cytotoxic phenotype (Leu 2a), opposite to the findings in most uveitis syndromes but consistent with the general parasite-specific, primary T-cell immunosuppresstion repeatedly demonstrated in both onchocerciasis and lymphatic filariasis.