ACCESSORY CELL ACTIVATION IN THE IMMUNE RESPONSE

免疫反应中的辅助细胞激活

• 批准号: 3142130
• 负责人: PHILIP E AURON
• 金额: $ 34.67万
• 依托单位: IMMUNE DISEASE INSTITUTE, INC.
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-04-01 至 1994-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3142130
• 关键词: DNA binding protein; antibody formation; antifibrinolytic agents; cellular immunity; chloramphenicol; complementary DNA; disease /disorder model; enzyme inhibitors; gene expression; genetic translation; human tissue; immune response genes; immunogenetics; immunomodulators; interleukin 1; leukocyte activation /transformation; major histocompatibility complex; membrane proteins; messenger RNA; monocyte; neoplasm /cancer immunology; nucleic acid hybridization; nucleic acid probes; nucleic acid sequence; peptidases; posttranscriptional RNA processing; radioimmunoassay; secretory immune system; tissue /cell culture; transcription factor

The human monocyte plays a central role in the initiation and propagation of the immune response via its role in antigen uptake, processing, and presentation for T cell specific functions. In addition to antigen-specific functions, the monocyte supports the T cell response, as well as other immunologic processes, in a generalized fashion by the secretion of soluble protein factors such as monokines, hydrolytic enzymes, and enzyme inhibitors. The research proposed herein will utilize such de novo synthesized agents as markers for studying the earliest stages of immunity activation. Experiments will focus on specific characterization of the monocyte response to chemical and biological induction agents using antibodies and nucleic acid hybridization probes along with subcellular fractionation, in order to determine the events involved in monocyte activation. Also, posttranscriptional, posttranslational secretory regulation, and surface involvement in T cell activation will be addressed. The initial studies will focus on four different markers: interleukin 1alpha (IL-1alpha); interleukin 1beta (IL-1beta); tumor necrosis factor-alpha (TNF- alpha); and a proteolytic enzyme inhibitor which may play a role in solid tumor containment (the plasminogen activator inhibitor, PAI-2). These proteins represent well characterized factors which appear to be coordinately regulated under some circumstances. The overall goal of these studies will be to elucidate the specific processes needed to support monocyte activation which is required for immunity and tumor containment.

人类单核细胞在启动和释放过程中起着核心作用 免疫反应通过其在抗原摄取中的作用而传播， T细胞特定功能的处理和呈现。在……里面 除了抗原特异性功能外，单核细胞还支持 T细胞反应以及其他免疫过程，在一个 通过分泌可溶性蛋白因子而产生的广义时尚 如单因子、水解酶和酶抑制剂。这个 这里提出的研究将利用这种从头合成的 作为研究免疫早期阶段的标志物的试剂 激活。实验将重点放在具体的特性上 单核细胞对化学和生物诱导的反应 使用抗体和核酸杂交探针的试剂 通过亚细胞分离，以确定事件 参与单核细胞的激活。另外，转录后， 翻译后分泌调节和表面参与 将解决T细胞激活问题。初步研究将 关注四种不同的标记物：白介素1α(IL-1α)； 白介素1β(IL-1β)；肿瘤坏死因子-α Alpha)；以及一种蛋白水解酶抑制剂，它可能起到 在实体肿瘤遏制中(纤溶酶原激活物抑制物， PAI-2)。这些蛋白质代表了具有良好特性的因子 在某些情况下似乎受到协调监管。这个 这些研究的总体目标将是阐明具体的 支持单核细胞激活所需的过程 用于免疫力和肿瘤抑制。