SCHISTOSOMIASIS AND CHAGAS DISEASE IN BRAZIL

我们建议建立一个跨学科研究计划，以 巴西米纳斯格雷亚斯的曼氏血吸虫病和恰加斯病。 这些学科将包括免疫学、分子生物学、生物化学、 病理学、流行病学和临床医学。该计划植根于 血吸虫免疫调节方面的合作研究 这项申请的三名高级调查员。我们的目标是 了解这些疾病的发病机制，并开发疫苗或 控制这些疾病发病率和死亡率的其他方式 感染。血吸虫病免疫调节的研究进展 不同疾病患者T细胞克隆/杂交瘤的比较 临床表现及其在体外诱导/调节肉芽肿的能力 多克隆/单克隆抗血吸虫独特型(ID)的比较 来自临床组的患者。血吸虫致病能力 患者刺激/调节纤维化形成，并产生纤维化 细胞外基质蛋白，在蛋白质和基因激活水平上。 恰加斯病的免疫学研究：细胞免疫反应 不同临床类型查加斯病患者的临床表现及调控 疾病；患者抗T.克隆氏抗体和 母婴免疫影响的回顾性和纵向研究 关于随后的反应性、发病率和死亡率；自身免疫研究 人类白细胞抗原分型，并与临床分型进行相关性分析。 曼氏血吸虫分子生物学研究：鉴定、克隆 和生产寄生虫编码的抗原，这对诊断和 血吸虫病的免疫调节研究。关于分子的研究 克氏原虫生物学：寄生虫的鉴定、克隆和生产 与患者细胞免疫相关的编码抗原，在 查加斯病的诊断，并可能与交叉反应有关 以及与宿主组织的自身免疫反应。

We propose to build a research program of interdisciplinary studies on human schistosomiasis mansoni and Chagas' disease in Minas Gerias, Brazil. The disciplines will include immunology, molecular biology, biochemistry, pathology, epidemiology and clinical medicine. This program is rooted in the collaborative research being pursued in schistosomal immunoregulation by 3 of the senior investigators on this application. Our goals are to understand the pathogenesis of these diseases, and develop vaccines or other modalities to control the morbidity and mortality of these infections. Studies on the immunoregulation of schistosomiasis: comparisons of T cell clones/hybridomas from patients with different clinical forms, and their abilities to induce/regulate in vitro granuloma formation; comparisons of multi/monoclonal anti-schistosome idiotypes (Ids) from patients in clinical groups. Schistosomal pathogenesis: ability of patients to stimulate/regulate fibrogenesis, and to produce fibrogenic extracellular matrix proteins, at the protein and gene activation levels. Studies on the immunology of Chagas' disease: cellular immune responses and regulation in patients with different clinical forms of Chagas' disease; Id analysis of patients' anti-T. cruzi antibodies and retrospective and longitudinal studies of maternal/perinatal immune effects on subsequent responsiveness, morbidity and mortality; autoimmune studies and HLA-typing, with analysis in relationship to clinical patterns. Studies of the Molecular Biology of S. mansoni: identification, cloning and production of parasite encoded antigens useful in both diagnosis and immunoregulatory studies of schistosomiasis. Studies of the Molecular Biology of T cruzi: identification, cloning and production of parasite encoded antigens related to patients' cellular immunity and useful in diagnosis of Chagas' disease, and potentially involved in cross-reactivity and autoimmune reactions with host tissues.