The role of delays in innate and adaptive immunity to intracellular bacterial infection

被引:26
作者
Marino, Simeone
Beretta, Edoardo
Kirschner, Denise E.
机构
[1] Univ Michigan, Sch Med, Dept Immunol & Microbiol, Ann Arbor, MI 48109 USA
[2] Univ Urbino, Inst Biomath, I-61029 Urbino, Italy
关键词
delay differential equations model; bacterial infections; innate and adaptive immunity; uncertainty and sensitivity analysis;
D O I
10.3934/mbe.2007.4.261
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
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 have addressed the relevance of known delays in each of these responses by exploring different kernel and delay functions and tested how each affected infection outcome. Our results indicated how local stability properties for 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 known 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.
引用
收藏
页码:261 / 286
页数:26
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