HOST IMMUNE RESPONSES TO ORAL PATHOGENS IN HIV INFECTION

对口腔病原体的免疫反应是粘膜和中枢免疫系统协调分工的结果。虽然很明显，这些免疫反应的部分是分开的，但令人惊讶的是，关于它们相互作用的调节信息却很少。事实上，甚至粘膜免疫系统在控制或预防口腔中的机会性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。我们将检查对白色念珠菌、爱泼斯坦·巴尔病毒和人乳头瘤病毒的全身反应和原位粘膜反应，这三种病原体是导致hiv感染者口腔最常见的机会性感染的原因：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和强大的技术，可以第一次提供关于这些病原体的精确免疫反应的详细信息，无论是对血液中的细胞（一种全身免疫反应的测量）还是对病变本身的细胞（一种局部免疫反应的测量）。我们希望在HAART的背景下，确定与口腔疾病的存在或进展相关的特定缺陷。从更大的意义上说，这些研究将首次提供口腔疾病水平上免疫反应协调的详细视图，即使是在HAART的背景下。从更大的意义上说，这些研究将提供口腔病变水平上免疫反应协调的第一个详细视图，各种免疫细胞对感染作出反应的拓扑结构和功能组织。这些研究将大大扩展我们对粘膜免疫学的认识。

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.