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亲和力如何影响独特型网络中的耐受性。

How affinity influences tolerance in an idiotypic network.

作者信息

Hart Emma, Bersini Hugues, Santos Francisco C

机构信息

School of Computing, Napier University, Edinburgh, Scotland, UK.

出版信息

J Theor Biol. 2007 Dec 7;249(3):422-36. doi: 10.1016/j.jtbi.2007.07.019. Epub 2007 Aug 8.

Abstract

Idiotypic network models give one possible justification for the appearance of tolerance for a certain category of cells while maintaining immunization for the others. In this paper, we provide new evidence that the manner in which affinity is defined in an idiotypic network model imposes a definite topology on the connectivity of the potential idiotypic network that can emerge. The resulting topology is responsible for very different qualitative behaviour of the network. We show that using a 2D shape-space model with affinity based on complementary regions, a cluster-free topology results that clearly divides the space into distinct zones; if antigens fall into a zone in which there are no available antibodies to bind to, they are tolerated. On the other hand, if they fall into a zone in which there are highly concentrated antibodies available for binding, then they will be eliminated. On the contrary, using a 2D shape space with an affinity function based on cell similarity, a highly clustered topology emerges in which there is no separation of the space into isolated tolerant and non-tolerant zones. Using a bit-string shape space, both similar and complementary affinity measures also result in highly clustered networks. In the networks whose topologies exhibit high clustering, the tolerant and intolerant zones are so intertwined that the networks either reject all antigen or tolerate all antigen. We show that the distribution and topology of the antibody network defined by the complete set of nodes and links-an autonomous feature of the system-therefore selects which antigens are tolerated and which are eliminated.

摘要

独特型网络模型为某类细胞出现耐受性而同时对其他细胞保持免疫状态提供了一种可能的解释。在本文中,我们提供了新的证据,表明独特型网络模型中亲和力的定义方式会在可能出现的潜在独特型网络的连通性上强加一种确定的拓扑结构。由此产生的拓扑结构导致网络具有非常不同的定性行为。我们表明,使用基于互补区域的亲和力的二维形状空间模型,会产生一种无簇拓扑结构,该结构将空间清晰地划分为不同的区域;如果抗原落入没有可用抗体与之结合的区域,它们就会被耐受。另一方面,如果它们落入有高度集中的可用抗体进行结合的区域,那么它们将被清除。相反,使用基于细胞相似性的亲和力函数的二维形状空间,会出现一种高度聚类的拓扑结构,其中空间不会被分隔为孤立的耐受区和非耐受区。使用位串形状空间,相似和互补的亲和力度量也会导致高度聚类的网络。在拓扑结构表现出高聚类性的网络中,耐受区和非耐受区相互交织,以至于网络要么排斥所有抗原,要么耐受所有抗原。我们表明,由完整的节点和链接集定义的抗体网络的分布和拓扑结构——系统的一个自主特征——因此决定了哪些抗原被耐受,哪些被清除。

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