CRYPTOSPORIDIUM INTERACTION WITH MAMMALIAN CELLS

隐孢子虫是一种新发现的人类病原体，与 免疫功能低下的患者患有严重的持续性肠炎， 特别是那些患有获得性免疫缺陷综合征(艾滋病)和 免疫正常的重大疾病，尽管是自限性疾病 主持人。随着越来越多的医生寻找病原体， 免疫受损和正常人群中报告的隐孢子虫病病例 个人数量持续上升。目前还没有已知的有效方法 这种疾病的治疗方法。 人类宿主防御成功的关键因素 隐孢子虫的根除还没有被描述出来。几乎没有什么线索 是由临床和组织病理学特征的研究提供的 人类的疾病，主要是免疫功能低下的(艾滋病)患者和动物。 目前可获得的数据表明：A)T细胞和B细胞都介导 免疫在宿主防御这种病原体方面起作用，以及b) 免疫的细胞和体液成分与 靶细胞：肠道上皮，成功防御 这种寄生虫。 猪隐孢子虫致病机制的实验室研究 免疫病理发生受到以下因素的严重阻碍：a)缺乏体外培养 生物体的培养方法，b)小而复杂的生命 寄生虫的循环，以及c)缺乏有症状的小动物模型 这种疾病的危害。在过去的两年里，我们成功地开发了一种 隐孢子虫与细胞相互作用的体外研究模型 来自感染患者粪便标本的卵囊。我们还有 成功地将该模型应用于隐孢子虫的体外培养。 这个项目的目的是进一步完善我们的模型，并使用它来 探讨各种免疫和非免疫因素对血吸虫感染的影响。 隐孢子虫与宿主细胞--肠道细胞的相互作用 我们希望由此确定宿主防御的关键细胞和体液因素。 在完好的宿主中，哪些功能可以根除这种寄生虫，哪些是 在免疫功能受损的个体中缺失。这些研究应该进一步 我们对隐孢子虫病免疫发病机制的认识 形成了成功管理这一问题的新方法的基础 未来的疾病。

Cryptosporidium is a newly recognized human pathogen which is associated with severe, persistent enteritis in immunocompromised patients, particularly those with the acquired immunodeficiency syndrome (AIDS) and significant though self-limited illness in the immunologically normal host. As more physicians have looked for the pathogen, the number of reported cases of cryptosporidiosis in both immunocompromised and normal individuals has continued to rise. There is currently no known effective therapy for the disease. The factors of human host defense which are essential for successful eradication of Cryptosporidium have not been delineated. Few clues have been provided by study of the clinical and histopathologic features of the disease in man, primarily immunocompromised (AIDS) patients, and animals. Currently available data suggests that: a) both T and B-cell mediated immunity are functional in host defense against this pathogen, and b) cellular and humoral components of immunity act in close concert with the target cell: intestinal epithelium, to effect successful defense against this parasite. Laboratory investigation of cryptosporidial mechanisms of immunopathogenesis has been severely impeded by: a) lack of in vitro methods for cultivating the organism, b) the small size and complex life cycle of the parasite, and c) absence of a symptomatic small animal model of the disease. Over the past two years we have succeeded in developing a model for the study of Cryptosporidium-cellular interactions in vitro using oocysts derived from stool specimens of infected patients. We have also successfully adapted the model for cultivating Cryptosporidium in vitro. The intent of this project is to further refine our model and use it to investigate the effects of various immune and non-immune factors on the interaction of Cryptosporidium with its host target cell - the enterocyte. We hope thus to define key cellular and humoral factors of host defense which function to eradicate this parasite in the intact host and which are absent in the immunocompromised individual. These studies should further our understanding of the immunopathogenesis of cryptosporidiosis and also form the basis for novel approaches to successful management of this disease in the future.