PATHOGENESIS OF INTESTINAL CRYPTOSPORIDIOSIS IN AIDS

微小隐孢子虫是最常见的单一传染病 艾滋病患者腹泻的原因(艾滋病相关性腹泻)。 不幸的是，这种感染对一种 多种治疗方案，可能的例外情况是 对螺旋霉素的有限反应和有争议的效应 部分患者出现牛乳抗体。基础生物学和 致病机制中涉及的相互作用 寄生虫和肠道上皮了解甚少，而且 腹泻本身的机制尚不清楚，因此它 不可能制定合理的干预或预防措施 战略。不太可能取得重大进展。 在没有基础研究的情况下， 这一最重要的肠道表现的发病机制 艾滋病。在这个项目中，我们打算通过检查 微小隐孢子虫卵囊和子孢子表面的存在 可以对分离株进行分类的抗原决定簇 根据宿主中的抗原和临床毒力分为亚组， 以确定可能涉及寄生虫的表面成分 对肠道细胞的识别及其在入侵过程中的作用 肠上皮细胞，以确定多克隆或单克隆的影响 针对生物体特定表面成分的抗体 附着和/或侵入肠细胞，以寻找糖 这种相互作用中的特定结合机制，以研究 囊壁的化学性质，并获得线索 包囊的生物化学，并测定分泌物 对有机体的免疫反应。生物体将会被获得 来自患有慢性细小弧菌感染的人类艾滋病患者， 通过传播给年轻的牛犊来提供库存 以卵囊为研究对象，将单抗和多克隆抗体 用粗提物和纯品免疫小鼠和兔 抗原，附着物侵袭的检测将建立或 为此目的而开发的，以及致病特性 生物体将使用体内小动物模型和 体外系统的设计，以揭示特定的特征 相关的细胞间相互作用。最终目标是确定 主动或被动疫苗中使用的免疫原 免疫接种。

Cryptosporidium parvum is the most common single infectious cause of diarrhea in AIDS patients (AIDS-associated diarrhea). Unfortunately, the infection has failed to respond to a large variety of treatment regimens, with the possible exception of a limited response to spiramycin and a controversial effect of bovine milk antibody in some patients. The basic biology and pathogenic mechanisms involved in the interaction between the parasite and the intestinal epithelium is poorly understood, and the mechanism of the diarrhea itself is unknown, hence it has been impossible to develop rational intervention or prevention strategies. It is unlikely that significant progress can be made without basic studies to understand the mechanisms of pathogenesis of this most important intestinal manifestation of AIDS. In this project we intend to do just this, by examining the surface of oocysts and sporozoites of C. parvum for the presence of antigenic determinants that may allow classification of isolates into subgroups based on antigens and clinical virulence in the host, to identify surface components that may be involved in parasite recognition of the intestinal cell and in the invasion of the enterocyte, to determine the impact of polyclonal or monoclonal antibody to specific surface constituents of the organism on attachment and/or invasion of the enterocyte, to search for sugar specific binding mechanisms in this interaction, to investigate the chemical nature of the cyst wall and to obtain clues to the biochemistry of encystation, and to determine the secretory immune response to the organism. Organisms will be obtained from human AIDS patients with chronic C. parvum infection, amplified by transmission to young calves to supply stocks of oocysts for study, monoclonal and polyclonal antibodies will be developed in mice and rabbits immunized with crude and purified antigens, assays for attachment invasion will be set up or developed for the purpose, and pathogenic properties of the organism will be evaluated using in vivo small animal models and in vitro systems designed to reveal specific characteristics of the relevant cell-cell interactions. The ultimate goal is to determine the immunogens to be used in a vaccine for active or passive immunization.