De Boer R J, Perelson A S, Kevrekidis I G
Utrecht University, The Netherlands.
Bull Math Biol. 1993;55(4):781-816. doi: 10.1007/BF02460673.
Two types of behavior have been previously reported in models of immune networks. The typical behavior of simple models, which involve B cells only, is stationary behavior involving several steady states. Finite amplitude perturbations may cause the model to switch between different equilibria. The typical behavior of more realistic models, which involve both B cells and antibody, consists of autonomous oscillations and/or chaos. While stationary behavior leads to easy interpretations in terms of idiotypic memory, oscillatory behavior seems to be in better agreement with experimental data obtained in unimmunized animals. Here we study a series of models of the idiotypic interaction between two B cell clones. The models differ with respect to the incorporation of antibodies, B cell maturation and compartmentalization. The most complicated model in the series has two realistic parameter regimes in which the behavior is respectively stationary and chaotic. The stability of the equilibrium states and the structure and interactions of the stable and unstable manifolds of the saddle-type equilibria turn out to be factors influencing the model's behavior. Whether or not the model is able to attain any form of sustained oscillatory behavior, i.e. limit cycles or chaos, seems to be determined by (global) bifurcations involving the stable and unstable manifolds of the equilibrium states. We attempt to determine whether such behavior should be expected to be attained from reasonable initial conditions by incorporating an immune response to an antigen in the model. A comparison of the behavior of the model with experimental data from the literature provides suggestions for the parameter regime in which the immune system is operating.
先前在免疫网络模型中已报道了两种行为类型。仅涉及B细胞的简单模型的典型行为是包含多个稳态的静止行为。有限幅度的扰动可能会导致模型在不同平衡之间切换。更现实的模型(涉及B细胞和抗体两者)的典型行为包括自主振荡和/或混沌。虽然静止行为在独特型记忆方面易于解释,但振荡行为似乎与在未免疫动物中获得的实验数据更相符。在此,我们研究了两个B细胞克隆之间独特型相互作用的一系列模型。这些模型在抗体的纳入、B细胞成熟和区室化方面存在差异。该系列中最复杂的模型有两个现实的参数区域,其行为分别是静止的和混沌的。平衡态的稳定性以及鞍型平衡态的稳定和不稳定流形的结构与相互作用结果是影响模型行为的因素。模型是否能够达到任何形式的持续振荡行为,即极限环或混沌,似乎由涉及平衡态稳定和不稳定流形的(全局)分岔决定。我们试图通过在模型中纳入对抗原的免疫反应来确定从合理的初始条件是否应预期会达到这种行为。将模型的行为与文献中的实验数据进行比较,为免疫系统运行的参数区域提供了建议。