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具有抗体动力学的凯莱树免疫网络模型。

A Cayley tree immune network model with antibody dynamics.

作者信息

Anderson R W, Neumann A U, Perelson A S

机构信息

Theoretical Biology and Biophysics, Los Alamos National Laboratory, NM 87545.

出版信息

Bull Math Biol. 1993 Nov;55(6):1091-131. doi: 10.1007/BF02460701.

Abstract

A Cayley tree model of idiotypic networks that includes both B cell and antibody dynamics is formulated and analysed. As in models with B cells only, localized states exist in the network with limited numbers of activated clones surrounded by virgin or near-virgin clones. The existence and stability of these localized network states are explored as a function of model parameters. As in previous models that have included antibody, the stability of immune and tolerant localized states are shown to depend on the ratio of antibody to B cell lifetimes as well as the rate of antibody complex removal. As model parameters are varied, localized steady-states can break down via two routes: dynamically, into chaotic attractors, or structurally into percolation attractors. For a given set of parameters percolation and chaotic attractors can coexist with localized attractors, and thus there do not exist clear cut boundaries in parameter space that separate regions of localized attractors from regions of percolation and chaotic attractors. Stable limit cycles, which are frequent in the two-clone antibody B cell (AB) model, are only observed in highly connected networks. Also found in highly connected networks are localized chaotic attractors. As in experiments by Lundkvist et al. (1989. Proc. natn. Acad. Sci. U.S.A. 86, 5074-5078), injection of Ab1 antibodies into a system operating in the chaotic regime can cause a cessation of fluctuations of Ab1 and Ab2 antibodies, a phenomenon already observed in the two-clone AB model. Interestingly, chaotic fluctuations continue at higher levels of the tree, a phenomenon observed by Lundkvist et al. but not accounted for previously.

摘要

构建并分析了一个包含B细胞和抗体动力学的独特型网络的凯莱树模型。与仅包含B细胞的模型一样,网络中存在局部状态,其中有限数量的活化克隆被未活化或接近未活化的克隆包围。研究了这些局部网络状态的存在性和稳定性与模型参数的关系。与之前包含抗体的模型一样,免疫和耐受局部状态的稳定性取决于抗体与B细胞寿命的比率以及抗体复合物的清除率。随着模型参数的变化,局部稳态可以通过两条途径瓦解:动态地转变为混沌吸引子,或者结构上转变为渗流吸引子。对于给定的一组参数,渗流吸引子和混沌吸引子可以与局部吸引子共存,因此在参数空间中不存在将局部吸引子区域与渗流吸引子和混沌吸引子区域分开的明确边界。稳定极限环在双克隆抗体B细胞(AB)模型中很常见,仅在高度连接的网络中观察到。在高度连接的网络中还发现了局部混沌吸引子。正如伦德奎斯特等人(1989年。美国国家科学院院刊86,5074 - 5078)的实验所示,向处于混沌状态的系统中注入Ab1抗体可导致Ab1和Ab2抗体波动停止,这一现象在双克隆AB模型中已被观察到。有趣的是,在树的更高层次上混沌波动仍在继续,这是伦德奎斯特等人观察到的现象,但之前未得到解释。

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