Degeneracy and Complexity in the Immune System

免疫系统的简并性和复杂性

基本信息

  • 批准号:
    7059192
  • 负责人:
  • 金额:
    $ 0.75万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2006
  • 资助国家:
    美国
  • 起止时间:
    2006-01-01 至 2006-12-31
  • 项目状态:
    已结题

项目摘要

There has been an increasing realization within the past decade that lymphocyte recognition is degenerate. Even more recent is the further knowledge that degeneracy is a ubiquitous property of biological systems, appearing in gene networks, neural networks and other levels of biologic organization. As Edelman and Gaily have pointed out, degeneracy is almost invariably accompanied by complexity. Degeneracy, in contemporary immunological usage, describes the ability of a single receptor to recognize and react to a heterogeneous assortment of ligands, with each lymphocyte clone having its own pattern of degeneracy (i.e. its own set of stimulatory ligands). For example, a single T cell receptor on the surface of the T lymphocyte can bind to a large variety of molecular structures and in that sense; the T cell has a degenerate recognition for antigen. Such a degenerate system is quite adaptable and it can be argued that evolution itself depends heavily on extensive degeneracy in a set of complex systems. Actually, most of the crucial receptor elements in the immune system, aside from lymphocyte antigen receptors, are degenerate to a great extent, e.g. a single major histocompatibility complex (MHC) molecule can bind a very large and diverse set of peptides, and cytokine/chemokine receptors also have familial relationships owing to shared components. It is time to reevaluate and consider the role of degeneracy in the immune system as one of its most characteristic and distinctive attributes, rather than a peculiar and occasional oddity. The immune system, even more than the nervous system, functions to receive and process molecular information. It would be the major thrust of a workshop on this topic to question how the system, which cannot rely on the specificity of its receptors at the molecular level can behave with such marvelous specificity at the operational level. We believe that this topic, with a focus on the immune system, but including related aspects such as connectivity and synaptic plasticity, would be an excellent subject for the Santa Fe Institute, one whose focus is on complexity. This is the optimal location for this discussion, where there already exists a community of thinkers well schooled in problems of molecular recognition and interaction, at both an intricate and a global level. We are not aware that a previous conference or workshop has been held on the subject of degenerate receptor recognition. There are many threads in the study of molecular recognition that would be brought together in this context. A first question is the structural basis for the degeneracy. Second is the broad concept of degeneracy in immune reactivity at all levels?at the T and B cell recognition of antigen, but also with cytokines and their interactions with receptors, as well as recent studies of the innate immune receptors ("toll-like receptors") whose recognition units are intertwined. Another set of findings relate to "molecular mimicry" in the immune system, between the antigens on infectious organisms and self-antigens in the human or animal host. Such mimicry can lead to autoimmunity and there is a burgeoning literature on the subject. Finally, some of the most basic aspects of immune development and physiology, such as positive selection of T cells in the thymus, involve a degenerate recognition event at their essence. The pattern of degenerate recognition in the immune system provides a major source of its robustness and flexibility, its ability to adjust to perturbations, which were previously never experienced. It is hoped that through the agency of this workshop, the wide-ranging ability of the immune system to develop outputs by different strategies can be rationalized with the clear lack of specificity of its elements, and that the emergent properties of the system operating as a whole can serve as a subject for mathematical treatment.
在过去的十年中,人们越来越认识到淋巴细胞识别是退化的。更近的是进一步的知识,简并是生物系统的普遍属性,出现在基因网络,神经网络和其他层次的生物组织。正如Edelman和Gyndham所指出的,简并几乎总是伴随着复杂性。在当代免疫学用法中,简并性描述了单个受体识别配体的异质分类并与之反应的能力,其中每个淋巴细胞克隆具有其自身的简并性模式(即其自身的刺激配体组)。例如,T淋巴细胞表面上的单个T细胞受体可以结合多种分子结构,并且在这个意义上,T细胞具有对抗原的简并识别。这样的简并系统是相当适应性的,可以说进化本身在很大程度上取决于一组复杂系统中的广泛简并。事实上,除了淋巴细胞抗原受体之外,免疫系统中的大多数关键受体元件在很大程度上是简并的,例如单个主要组织相容性复合物(MHC)分子可以结合非常大且多样的肽组,并且细胞因子/趋化因子受体也由于共享组分而具有家族关系。现在是时候重新评估和考虑退化在免疫系统中的作用,将其视为其最具特征和独特的属性之一,而不是一种特殊和偶尔的古怪。免疫系统比神经系统更能接收和处理分子信息。这将是一个研讨会上关于这个主题的主要推力,质疑系统,它不能依赖于其受体在分子水平上的特异性,如何能够在操作水平上表现出如此惊人的特异性。我们认为,这个主题,重点是免疫系统,但包括相关的 连接性和突触可塑性等方面,将是圣达菲研究所的一个很好的课题,该研究所的重点是复杂性。这是进行讨论的最佳地点,在这里已经存在一个思想家社区,他们在分子识别和相互作用的问题上受过良好的教育,无论是在复杂的还是全球的层面上。我们不知道以前的会议或研讨会已经举行了关于简并受体识别的主题。在分子识别的研究中,有许多线索将在此背景下汇集在一起。第一个问题是简并的结构基础。第二个是广义的概念,在所有水平的免疫反应性退化?在T和B细胞识别 除了抗原的研究外,还包括细胞因子及其与受体的相互作用,以及最近对识别单位相互交织的先天免疫受体(“Toll样受体”)的研究。另一组发现涉及免疫系统中的“分子模拟”,即感染性生物体上的抗原与人类或动物宿主中的自身抗原之间的分子模拟。这种模仿会导致自身免疫,关于这个主题的文献正在蓬勃发展。最后,免疫发育和生理学的一些最基本的方面,例如胸腺中T细胞的阳性选择,在其本质上涉及简并识别事件。免疫系统中的简并识别模式提供了其鲁棒性和灵活性的主要来源,以及其适应扰动的能力,这是以前从未经历过的。我们希望,通过这个研讨会的机构,免疫系统通过不同的策略开发输出的广泛能力可以合理化,其元素明显缺乏特异性,并且作为一个整体运行的系统的涌现特性可以作为数学处理的主题。

项目成果

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ELI E SERCARZ其他文献

ELI E SERCARZ的其他文献

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{{ truncateString('ELI E SERCARZ', 18)}}的其他基金

B cell regulation of diabetogenic activity
B 细胞对糖尿病活性的调节
  • 批准号:
    7196856
  • 财政年份:
    2007
  • 资助金额:
    $ 0.75万
  • 项目类别:
B cell regulation of diabetogenic activity
B 细胞对糖尿病活性的调节
  • 批准号:
    7385968
  • 财政年份:
    2007
  • 资助金额:
    $ 0.75万
  • 项目类别:
PATHOGENIC AND REGULATORY AUTOIMMUNE T CELL REPERTOIRES
致病性和调节性自身免疫 T 细胞库
  • 批准号:
    6606941
  • 财政年份:
    2000
  • 资助金额:
    $ 0.75万
  • 项目类别:
PATHOGENIC AND REGULATORY AUTOIMMUNE T CELL REPERTOIRES
致病性和调节性自身免疫 T 细胞库
  • 批准号:
    6374611
  • 财政年份:
    2000
  • 资助金额:
    $ 0.75万
  • 项目类别:
PATHOGENIC AND REGULATORY AUTOIMMUNE T CELL REPERTOIRES
致病性和调节性自身免疫 T 细胞库
  • 批准号:
    6511557
  • 财政年份:
    2000
  • 资助金额:
    $ 0.75万
  • 项目类别:
PATHOGENIC AND REGULATORY AUTOIMMUNE T CELL REPERTOIRES
致病性和调节性自身免疫 T 细胞库
  • 批准号:
    6191305
  • 财政年份:
    2000
  • 资助金额:
    $ 0.75万
  • 项目类别:
Competition Among Pathogenic or Protective T Cell Clones
致病性或保护性 T 细胞克隆之间的竞争
  • 批准号:
    6828690
  • 财政年份:
    1999
  • 资助金额:
    $ 0.75万
  • 项目类别:
T CELL MATURATION AND LIGAND QUALITY
T 细胞成熟和配体质量
  • 批准号:
    6137246
  • 财政年份:
    1999
  • 资助金额:
    $ 0.75万
  • 项目类别:
Competition Among Pathogenic or Protective T Cell Clones
致病性或保护性 T 细胞克隆之间的竞争
  • 批准号:
    6891332
  • 财政年份:
    1999
  • 资助金额:
    $ 0.75万
  • 项目类别:
Competition Among Pathogenic or Protective T Cell Clones
致病性或保护性 T 细胞克隆之间的竞争
  • 批准号:
    6726358
  • 财政年份:
    1999
  • 资助金额:
    $ 0.75万
  • 项目类别:

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  • 批准号:
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CENTER FOR DEVELOPMENTAL IMMUNOLOGY AND HOST DEFENSE
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