CALCIUM IONS AND LYMPHOCYTE ACTIVATION

描述：除了调节神经中的电活动 系统中，离子通道在体内调节非常不同的细胞机制 免疫系统。最早发出抗原结合信号的事件 T淋巴细胞和肥大细胞的表面受体包括激活 离子通道和胞浆[Ca~(2+)]_i升高。 由开放的离子通道产生，并将膜受体连接到 基因表达、淋巴因子分泌和细胞增殖 免疫反应。由于强调的是单细胞方法， 研究人员提出了视频成像和膜片钳实验，以 阐明膜受体与效应器功能的联系机制，如 如细胞增殖、基因表达、细胞运动和分泌 免疫调节分子。关于T淋巴细胞的实验建议如下 分成两个部分，对应于以下事件的顺序 抗原刺激：(1)细胞内信号传递 [Ca~(2+)]_i信号的膜受体； 白细胞介素2基因等信号转导途径与细胞内钙离子浓度 本项目的目标是应用光学技术来研究[Ca~(2+)]i 刺激原代T细胞的信号、运动和基因表达 生理配体。调查人员将利用报告基因 动态可视化T细胞激活，以便将膜和 第二信使机制发挥效应器的作用。他们正在调查 在抗原呈递期间细胞之间的相互作用，以及 膜受体与基因联结的细胞内信号机制 表情。

DESCRIPTION: In addition to regulating electrical activity in the nervous system, ion channels mediate very different cellular mechanisms within the immune system. The earliest events signaling the binding of antigen to surface receptors in T lymphocytes and mast cells include the activation of ion channels and a rise in cytosolic [Ca2+]i. The "[Ca2+]i signal" is generated by the opening of ion channels, and links membrane receptors to gene expression, lymphokine secretion and cell proliferation essential to the immune response. With emphasis on a single-cell approach, the investigators are proposing video-imaging and patch-clamp experiments to clarify mechanisms which link membrane receptors to effector functions such as cell proliferation, gene expression, cell motility, and secretion of immunomodulatory molecules. The proposed experiments on T lymphocytes are divided into two sections corresponding to the sequence of events following antigen stimulation: (1) intracellular signaling from the engagement of membrane receptors to the [Ca2+]i signal; (2) activation of the interleukin-2 gene and other signaling pathways by the rise in [Ca2+]i. One goal of this project is to apply optical techniques to investigate [Ca2+]i signaling, motility, and gene expression in primary T-cells stimulated by physiological ligands. The investigators will use reporter genes to visualize T-cell activation dynamically in order to relate membrane and second-messenger mechanisms to effector function. They are investigating interactions between cells during antigen presentation, as well as intracellular signaling mechanisms that link membrane receptors with gene expression.