CORE--CLINICAL LABORATORY CORE

这个临床研究核心机构的目标是及早发现 发生DHF风险增加的免疫学和病毒学标志物 (项目1)。 该核心将测量患者的免疫激活的血浆标志物 参加项目1研究：细胞因子水平，如IL-Ibeta、TNF-Alpha、 IL-2、IL-6；T细胞活化产物水平，如可溶性CD8 (SCD8)、可溶性CD_4(SCD_4)；以及休克和血浆介质水平 渗漏，如血小板激活因子(PAF)和补体成分。 该中心将评估选定患者的细胞免疫反应。 参与项目1：IL-2等T淋巴细胞标志物的表达 受体，人类白细胞抗原DR；单核/巨噬细胞激活，如Fc上调 受体；以及登革热特异性细胞毒T淋巴细胞活性水平 在急性感染期间。(d和dhf)。这个核心将会量化 中和和增强人单核细胞中的登革病毒抗体 化验。 该核心还将进行诊断和定量病毒学研究 对于项目1，例如在蚊子中分离登革热病毒，测量登革热 抗体反应与免疫细胞化学检测登革热抗原 急诊患者外周血单核细胞培养技术。 核心将分析I类和II类之间的相关性 在项目1中登记的D和 DHF。核心还将评估长期中和和增强 项目1中D或DHF患者的抗体和T细胞记忆。这些 结果将表征与登革热相关的人类白细胞抗原免疫反应，以及 评估长期有益(中和)和有害(增强) 这些抗体对疫苗的开发很重要。 泰国的这个设施将处理、冷冻保存和运送病人 用于分子免疫学研究的项目1的样本(血浆和PBMC) 项目2(UMMC)和中国病毒株的分子特征 项目3(雅鲁县)。

The goal of this Clinical Research Core Facility is to identify early immunologic and virologic markers of increased risk of developing DHF (Project 1). This core will measure plasma markers of immune activation in patients enrolled in Project 1 studies: cytokine levels, e.g. IL-Ibeta, tnf-ALPHA, il-2, il-6; levels of products of T cell activation, e.g. soluble CD8 (sCD8), soluble CD4 (sCD4); and levels of mediators of shock and plasma leakage, e.g. platelet activating factor (PAF), and complement components. The core will assess cellular immune responses in selected patients enrolled in Project 1: expression of T lymphocyte markers e.g. IL-2 receptors, HLA DR; monocyte/macrophage activation e.g. upregulation of Fc receptors; and the level of dengue-specific cytotoxic T lymphocyte activity during acute infections. (D and DHF). This core will quantitate neutralizing and enhancing antibodies to dengue virus in a human monocyte assay. The core will also perform diagnostic and quantitative virologic studies for Project 1, e.g. dengue virus isolation in mosquitoes, measure dengue antibody responses and detect dengue antigens by immunocytochemical techniques in PBMC of acutely ill patients. The core will analyze correlations between Class I and Class II histocompatibility (HLA) types of patients enrolled in Project 1 with D vs. DHF. The core will also assess the long term neutralizing and enhancing antibodies and T cell memory in patients in Project 1 with D or DHF. These results will characterize HLA-associated immune responses to dengue, and assess long-term beneficial (neutralizing) and detrimental (enhancing) antibodies which are important for vaccine development. This facility in Thailand will process, cryopreserve and ship patient samples (plasma and PBMC) from Project #1 for molecular immunologic studies in Project 2 (UMMC) and molecular characterization of virus strains in Project 3 (YARU).