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Antigen Recognition by Lymphocytes

淋巴细胞识别抗原

基本信息

批准号：
8134395
负责人：
Philippa C. Marrack
金额：
$ 132.24万
依托单位：
NATIONAL JEWISH HEALTH
依托单位国家：
美国
项目类别：
财政年份：
1997
资助国家：
美国
起止时间：
1997-12-01 至 2014-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8134395
关键词：
Antigen Recognition Lymphocytes

项目摘要

DESCRIPTION (provided by applicant): The specificities and numbers of lymphocytes in animals are tightly controlled to avoid autoimmunity and to avoid accumulation of lymphocytes generated during previous infections. This control can be achieved through the death of autoreactive lymphocytes as consequence of selection events. Similarly, many lymphocytes that are generated in response to infections die when the infectious agent disappears. The lymphocyte repertoire is also influenced by the ability of lymphocytes to alter their antigen receptor. For example, the antigen receptor expressed by some autoreactive lymphocytes can be modified either by deletion of the genes encoding the offending receptor, or by silencing the action of the autoreactive receptor. The numbers, specificities and activities of lymphocytes in animals are controlled, to avoid accumulation of the huge numbers of lymphocytes which are generated in each successive response to infection and to prevent autoimmunity. Several processes are used to achieve this control. Many of the lymphocytes which are generated in response to infections die when the infectious agent disappears. Some autoreactive lymphocytes die, others modify their receptors for antigen, either by deleting genes coding for the offending receptor, or by somehow silencing the action of the autoreactive receptor. Other autoreactive lymphocytes survive for a while as anergic cells and do not respond productively to antigen and have a shortened half life. The Projects in this Program will examine the ways in which lymphocytes are controlled, comparing the mechanisms used in different types of lymphocytes under different circumstances, with the goal of understanding how the immune system generates a useful but innocuous collection of antigen specific lymphocytes. The individual Projects will focus as follows: 1. On the role of bystander, non autoreactive receptors on B cells, and their ability to rescue cells bearing, in addition, autoreactive receptors from death. 2. On the generation and maintenance of anergic B cells, their specificities and the ability of infectious agents to allow these cells to escape anergy. 3. On the role of Bcl-2 related proteins in the death of activated T, and B cells. The Program has 4 Cores, all essential to the work on all Projects. The subjects of the Cores are: Flow Cytometry; Microscopy; Genetics and Administration.

性状（由申请方提供）：严格控制动物中淋巴细胞的特异性和数量，以避免自身免疫和避免既往感染期间产生的淋巴细胞蓄积。这种控制可以通过选择事件导致自身反应性淋巴细胞死亡来实现。类似地，许多因感染而产生的淋巴细胞在感染因子消失时死亡。淋巴细胞库也受到淋巴细胞改变其抗原受体的能力的影响。例如，由一些自身反应性淋巴细胞表达的抗原受体可以通过缺失编码攻击性受体的基因或通过沉默自身反应性受体的作用来修饰。控制动物中淋巴细胞的数量、特异性和活性，以避免在对感染的每次连续反应中产生的大量淋巴细胞的积累，并防止自身免疫。几个过程被用来实现这种控制。当感染原消失时，许多因感染而产生的淋巴细胞就会死亡。一些自身反应性淋巴细胞死亡，另一些则通过删除编码攻击性受体的基因或以某种方式沉默自身反应性受体的作用来修改其抗原受体。其他自身反应性淋巴细胞作为无反应性细胞存活一段时间，对抗原没有产生有效反应，并且半衰期缩短。该计划中的项目将研究淋巴细胞的控制方式，比较不同情况下不同类型淋巴细胞的机制，目的是了解免疫系统如何产生有用但无害的抗原特异性淋巴细胞。各个项目的重点如下： 1.旁观者的作用，B细胞上的非自身反应性受体，以及它们拯救携带自身反应性受体的细胞免于死亡的能力。 2.关于无反应性B细胞的产生和维持，它们的特异性和感染因子使这些细胞逃避无反应性的能力。 3. Bcl-2相关蛋白在活化T、B细胞死亡中的作用该计划有4个核心，对所有项目的工作都至关重要。核心的主题是：流动细胞计数;显微镜检查;遗传学和管理。