HOST IMMUNE RESPONSES TO ORAL PATHOGENS IN HIV INFECTION

因为对口腔病原体的免疫反应是粘膜免疫系统和中枢免疫系统协调分工的结果。虽然免疫反应的这些部分显然是分开的，但令人惊讶的是，关于它们相互作用的调节信息很少，甚至粘膜免疫系统在控制或防止口腔中的条件病原体方面的作用也没有明确的定义。我们建议进行广泛的检测，以确定在HIV疾病背景下对口腔病原体的免疫反应中的特定缺陷。我们将检测对白色念珠菌、爱泼斯坦-巴尔病毒和人乳头状瘤病毒的全身反应和原位粘膜反应，这三种病原体导致艾滋病毒感染者最常见的口腔机会性感染：念珠菌病、毛状白斑和口腔疣。我们的研究是独一无二的，因为他们采用了新的强大的技术，可以第一次提供有关对这些病原体的精确免疫反应的详细信息，要么测量血液中的细胞(衡量全身免疫反应)，要么测量病变本身的细胞(作为局部免疫反应的衡量标准)。我们希望找出与口腔疾病的存在或进展相关的特定缺陷，即使在HAART的背景下也是如此。在更广泛的意义上，这些研究将提供第一个详细的观点，在口腔疾病的水平上的免疫反应的协调，即使在HAART的背景下。从更广泛的意义上说，这些研究将提供第一个详细的观点，在口腔损伤水平上的免疫反应的协调，各种免疫细胞的拓扑和功能组织，对感染作出反应。这些研究将极大地扩展我们对黏膜免疫学的总体认识。

For immune response to oral pathogens is the result of a coordinated division of labor between the mucosal and central immune systems. While it is clear that these parts of the immune response are compartmentalized, there is surprisingly little information about the regulation of their interaction In fact, even the role of the mucosal immune system in controlling or preventing opportunistic pathogens in the mouth is poorly defined. We propose to perform a wide range of assays to determine specific defects in the immune response to oral pathogens in the context of HIV disease. We will examine both the systemic response as well as the in situ mucosal response to Candida albicans, Epstein Barr virus, and human papillomavirus, -three pathogens responsible for the most common opportunistic infections of the oral cavity in HIV-infected people: candidiasis, hairy leukoplakia, and oral warts. Our studies are unique in that they employ new and powerful technologies that can, for the first time, provide detailed information about the precise immunological response to these pathogens, measured either for cells in the blood (a measure of the systemic immune response) or for cells in the lesions themselves (as a measure of the local immune response). We hope to identify specific defects that correlate with the presence or progression of oral diseases even in the context of HAART. In a larger sense, these studies will provide the first detailed view of the coordination of the immune response at the level of the oral diseases even in the context of HAART. In a larger sense, these studies will provide the first detailed view of the coordination of the immune response at the level of the oral lesion, the topological and functional organization of the various immune cells that respond to the infection. These studies will significantly extend our knowledge of mucosal immunology in general.