The role of delays in innate and adaptive immunity to intracellular bacterial infection.
The role of delays in innate and adaptive immunity to intracellular bacterial infection.
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DOI：
10.3934/mbe.2007.4.261
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发表时间：
2007-02
期刊：
影响因子：
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通讯作者：
Simeone Marino;E. Beretta;D. Kirschner
中科院分区：
文献类型：
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作者：
Simeone Marino;E. Beretta;D. Kirschner
人类的免疫反应是复杂和多重的。最初，先天反应试图清除任何微生物的入侵。如果它不能清除或遏制病原体，那么就会产生适应性反应，这种反应对微生物是特异性的，在大多数情况下，它能成功地消除病原体。在以前的工作中，我们开发了一个延迟微分方程（DDE）模型的先天性和适应性免疫反应的细胞内细菌感染。我们通过探索不同的内核和延迟函数来解决这些响应中已知延迟的相关性，并测试了每种受影响的感染是如何产生的。我们的研究结果表明，如何局部稳定性的两个感染的结果，即边界平衡和内部正平衡，是完全依赖于先天免疫的延迟和独立的延迟适应性免疫。在目前的工作中，我们有三个目标。第一个是扩展以前的模型，以解释适应性免疫的直接细菌杀伤。例如，这反映了一类称为巨噬细胞的细胞的主动杀伤，并将使我们能够确定适应性免疫延迟的相关性。我们目前的分析结果在这种情况下。其次，我们实现了一个启发式的论点，调查的存在性稳定开关的正平衡在流形上定义的两个延迟。第三，我们应用一种新的分析，在设置的DDE称为不确定性和敏感性分析。这使我们能够完全评估模型中所有参数的作用。这包括确定稳定性转换参数对感染结果的影响。
The immune response in humans is complex and multi-fold. Initially an innate response attempts to clear any invasion by microbes. If it fails to clear or contain the pathogen, an adaptive response follows that is specific for the microbe and in most cases is successful at eliminating the pathogen. In previous work we developed a delay differential equations (DDEs) model of the innate and adaptive immune response to intracellular bacteria infection. We addressed the relevance of known delays in each of these responses by exploring different kernel and delay functions and tested how each affected infection out come. Our results indicated how local stability properties for the two infection outcomes, namely a boundary equilibrium and an interior positive equilibrium, were completely dependent on the delays for innate immunity and independent of the delays for adaptive immunity. In the present work we have three goals. The first is to extend the previous model to account for direct bacterial killing by adaptive immunity. This reflects, for example, active killing by a class of cells known as macrophages, and will allow us to determine the relevance of delays for adaptive immunity. We present analytical results in this setting. Second, we implement a heuristic argument to investigate the existence of stability switches for the positive equilibrium in the manifold defined by the two delays. Third, we apply a novel analysis in the setting of DDEs knows as uncertainty and sensitivity analysis. This allows us to evaluate completely the role of all parameters in the model. This includes identifying effects of stability switch parameters on infection outcome.