ACCESSORY CELL ACTIVATION IN THE IMMUNE RESPONSE

免疫反应中的辅助细胞激活

• 批准号: 3142127
• 负责人: PHILIP E AURON
• 金额: $ 30.82万
• 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/3142127
• 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; peptidases; radioimmunoassay; secretory immune system; tissue /cell culture

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分化中发挥着核心作用 通过其在抗原摄取中的作用传播免疫应答， 加工和呈递T细胞特异性功能。 在 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， 通过分泌可溶性蛋白因子 例如单核因子、水解酶和酶抑制剂。 的 本文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 activation. 实验将侧重于具体的表征 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沿着的试剂 用亚细胞分离的方法， 参与单核细胞活化。 另外，转录后， 翻译后分泌调节和表面参与 T细胞活化将得到解决。 初步研究将 关注四种不同的标志物：白细胞介素1 α（IL-1 α）; 白细胞介素1 β（IL-1 β）;肿瘤坏死因子-α（TNF-α） α）;和蛋白水解酶抑制剂， 在实体瘤遏制中（纤溶酶原激活物抑制剂， 派-2）。 这些蛋白质代表了充分表征的因子， 在某些情况下似乎是协调一致的。 的 这些研究的总体目标是阐明 支持单核细胞活化所需的过程， 免疫力和肿瘤抑制