DEVELOPMENTAL IMMUNOLOGY RESEARCH

RFA-NIH-92-AI-14组件C的主要目标是“提供 有资源回答临床相关问题的研究者， 强调利用ACTG方案产生的标本”。 的 本提案将通过提供人力和 用于患者免疫功能评价的后勤资源 参加了梅哈里医学院的艾滋病临床试验 艾滋病病毒以两种主要方式损害免疫系统： CD 4 + T细胞和辅助性T细胞功能下降。 cd 4+细胞 计数是最常用的免疫学参数， 对艾滋病毒/艾滋病患者的评估。 但Th细胞的丢失 功能先于并且独立于CD 4+细胞计数的下降。 由于Th细胞功能受损与 和艾滋病毒/艾滋病的临床演变，我们建议早期 特异性和非特异性免疫的表征和评价 作为诊断和监测医疗状况的必要工具 艾滋病毒/艾滋病干预。 本部分的目标是 加强现有的人力和实验室资源， 用于艾滋病免疫学研究并开发和提供更少 常用的研究工具来观察功能性免疫参数， 在梅哈里参与ACTU协议的人类受试者。 这些功能 参数是：1）特异性免疫功能（记忆反应）。 a）、 细胞免疫：淋巴细胞对回忆抗原（即HIV）的反应 抗原和有丝分裂原），人细胞毒性淋巴细胞的杀伤能力 表达或携带HIV抗原的靶细胞，B）抗体应答： 人类产生针对HIV抗原的特异性抗体同种型，或 其他相关抗原，并评估T辅助细胞活性， 体内破伤风类毒素特异性抗体应答。 2)非特异性 免疫反应。 （a）吞噬细胞功能：代谢研究 化学发光法测定吞噬细胞活性，B）淋巴细胞 活化：流式细胞术分析表达和分布 淋巴细胞标记物的活化和识别 与HIV感染/AIDS进展相关的亚群，c）体液免疫 细胞和体液免疫功能的参数： 细胞因子（即IL-1 α和β、IL-2、IL-4、IL-6、TNF α和TNF β） β，γ IFN），补体组分，新蝶呤，β 2-微球蛋白和 其他可能与艾滋病毒感染有关。

The primary objective of component C of RFA-NIH-92-AI-14 is to "provide investigators with resources to answer clinically relevant questions with emphasis on utilizing specimens generated from ACTG protocols". The present proposal will address this objective by providing human and logistic resources for the evaluation of immune functions in patients enrolled in AIDS clinical trials at Meharry Medical College. HIV compromises the immune system in two major ways: Severe depletion of CD4+ T-cells and decline in T-helper (th) cell functions. CD4+ cell counts are the most commonly used immunological parameter for the evaluation of patients with HIV/AIDS. However, the loss of Th cell functions precedes and is independent of the decline in CD4+ cell counts. Since there is a connection between the impairment of Th cell functions and the clinical evolution of HIV/AIDS, we propose the early characterization and evaluation of specific and non-specific immune responses as necessary tools for diagnosis and for monitoring medical intervention in HIV/AIDS. The objective of this component is the strengthen our existing human and laboratory resources to provide support for research in immunology of AIDS and to develop and provide less commonly used research tools to look at functional immune parameters in human subjects involved in ACTU protocols at Meharry. These functional parameters are: 1) Specific immune functions (memory responses). a) cellular immunity: lymphocyte responses to recall antigens (i.e. HIV antigens and mitogens), capacity of human cytotoxic lymphocytes to kill target cells expressing or carrying HIV antigens, b) antibody responses: human production of specific antibody isotypes against HIV antigens, or other relevant antigens, and evaluation of T-helper activity in the specific antibody response to Tetanus toxoid in vivo. 2) Non-specific immune responses. a) phagocytic cell function: study of the metabolic activity of phagocytic cells by chemiluminescence, b) lymphocyte activation: flowcytometry analyses of the expression and distribution of lymphocyte markers for activation and identification of lymphocyte subsets associated with the progression of HIV infection/AIDS, c) Humoral parameters for cellular and humoral immune functions: quantitation of cytokines (i.e. IL-1 alpha and beta, IL-2, IL-4, IL-6, TNF alpha and beta, gammaIFN), complement fractions, neopterin, beta2-microglobulin and others which may become relevant in HIV infection.