SCHISTOSOMIASIS AND CHAGAS DISEASE IN BRAZIL

我们建议建立一个跨学科研究的研究计划， 巴西米纳斯吉拉斯州人曼氏血吸虫病和恰加斯病。 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 在染色体免疫调节方面进行的合作研究 三名高级调查员的证词 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法 感染. 血吸虫病免疫调节的研究 来自不同患者的T细胞克隆/杂交瘤的比较 临床形式及其诱导/调节体外肉芽肿的能力 形成;多/单克隆抗人染色体独特型（Ids）的比较 从临床组的病人身上。 血吸虫病发病机制： 患者刺激/调节纤维化，并产生纤维化 细胞外基质蛋白，在蛋白质和基因活化水平。 南美锥虫病的免疫学研究：细胞免疫应答 不同临床形式的南美锥虫病患者的 疾病;患者抗T的Id分析。克氏抗体和 母体/围产期免疫影响的回顾性和纵向研究 对随后的反应性、发病率和死亡率的影响;自身免疫研究 和HLA分型，并分析与临床模式的关系。 S.的分子生物学研究。mansoni：鉴定，克隆 以及用于诊断和治疗的寄生虫编码抗原的制备， 血吸虫病的免疫调节研究。 分子生物学研究 克氏锥虫的生物学：鉴定、克隆和寄生虫的生产 编码与患者细胞免疫相关的抗原， 诊断恰加斯病，并可能涉及交叉反应性 和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.