CUTANEOUS IMMUNE RESPONSE IN SECONDARY SYPHILIS

性病梅毒是一种慢性炎症性疾病， 其病原体梅毒螺旋体的持续存在。 虽然 局部密螺旋体感染部位免疫/炎症反应可能 最终奠定了保护性免疫援助 临床表现，这些局部细胞过程尚未被发现。 在人类中使用当代细胞和 分子免疫学T.苍白球诱发这些 潜在有害的炎症过程也很少 表征了我们对梅毒细胞免疫的理解是 由于我们目前对这一问题的了解有限， 梅毒和HIV感染之间的相互作用。 因此 研究有三个具体目标。具体目标1： 对皮肤活检和流式细胞术进行免疫细胞化学分析 分析抽吸水泡中的白细胞以表征皮肤 HIV-和HIV+患者的细胞免疫过程 梅毒 这些研究的数据将与我们的体外研究结果相关联。 研究涉及T.苍白球和 密螺旋体脂蛋白在具体目标2中，我们将使用相同的 免疫细胞化学和流式细胞术方法来表征 对T的合成类似物（脂肽）的皮肤炎症反应 苍白球脂蛋白这些实验是我们 假设T.苍白球脂蛋白是主要的炎症介质 在梅毒感染期间。根据我们的观察，苍白球T 脂蛋白类似物在体外诱导HIV基因表达， 在具体目标3中，将阐明这一点的机制， 现象 这项研究的一个主要长期目标是阐明 梅毒感染期间的免疫/炎症事件， 临床表现和保护性免疫。 一个同样重要 目的是获得细胞和分子数据， 我们对梅毒和艾滋病病毒之间相互作用的新认识 感染，包括梅毒作为辅助因素的可能性 艾滋病毒传播和艾滋病毒感染，以改变临床进程， 梅毒

Venereal syphilis is a chronic inflammatory disorder driven by the persistence of its etiologic agent Treponema pallidum. Though the immune/inflammatory response at sites of local treponemal infection may ultimately underlie the development of both protective immunity aid clinical manifestations, these local cellular processes have yet to be characterized in humans using the tools of contemporary cellular and molecular immunology. The components of T. pallidum that induce these potentially deleterious inflammatory processes also remain poorly characterized. Our understanding of cellular immunity in syphilis is further compromised by our currently limited knowledge concerning the interactions between syphilis and HIV infection. Accordingly, the proposed research has three Specific Aims. In Specific Aim 1, we will perform immunocytochemical analysis of skin biopsies and flow cytometry analysis of leukocytes in suction blisters to characterize cutaneous cellular immune processes in HIV- and HIV+ patients with secondary syphilis. Data from these studies will be correlated with our in vitro research involving immune effector cell activation by T. pallidum and treponemal lipoproteins. In Specific Aim 2, we will use the same immunocytochemical and flow cytometric approaches to characterize the cutaneous inflammatory response to synthetic analogs (lipopeptides) of T pallidum lipoproteins. These experiments are an outgrowth of our hypothesis that T. pallidum lipoproteins are major inflammatory mediators during syphilitic infection. Building upon our observation that T pallidum lipoprotein analogs induce HIV gene expression in vitro, the experiments in Specific Aim 3 will elucidate the mechanisms which underlie this phenomenon. A principal long-term objective of this research is to elucidate the immune/inflammatory events during syphilitic infection which engender both clinical manifestations and protective immunity. An equally important objective is to obtain cellular and molecular data which will complement our emerging understanding of the interactions between syphilis and HIV infection, including the potential for syphilis to serve as a co-factor for HIV transmission and for HIV infection to alter the clinical course of syphilis.