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具有免疫反应的慢性丙型肝炎病毒感染模型的动力学分析

Dynamical analysis on a chronic hepatitis C virus infection model with immune response.

作者信息

Li Jianquan, Men Ke, Yang Yali, Li Duan

机构信息

Science College, Air Force Engineering University, Xi׳an 710051, China.

The Department of Epidemiology, The Fourth Military Medical University, Xi'an 710032, China.

出版信息

J Theor Biol. 2015 Jan 21;365:337-46. doi: 10.1016/j.jtbi.2014.10.039. Epub 2014 Nov 7.

Abstract

A mathematical model for HCV infection is established, in which the effect of dendritic cells (DC) and cytotoxic T lymphocytes (CTL) on HCV infection is considered. The basic reproduction numbers of chronic HCV infection and immune control are found. The obtained results show that the infection dies out finally as the basic reproduction number of HCV infection is less than unity, and the infection becomes chronic as it is greater than unity. In the presence of chronic infection, the existence of immune control equilibrium is discussed completely, which illustrates that the backward bifurcation may occur under certain conditions, and that the two quantities, the sizes of the activated DC and the removed CTL during their average life-terms, play a critical role in controlling chronic HCV infection and immune response. The occurrence of backward bifurcation implies that there may be bistability for the model, i.e., the outcome of infection depends on the initial situation. By choosing the activated rate of non-activated DC or the cross-representation rate of activated DC as bifurcation number, Hopf bifurcation for certain condition shows the existence of periodic solution of the model. Again, numerical simulations suggest the dynamical complexity of the model including the instability of immune control equilibrium and the existence of stable periodic solution.

摘要

建立了一个丙型肝炎病毒(HCV)感染的数学模型,其中考虑了树突状细胞(DC)和细胞毒性T淋巴细胞(CTL)对HCV感染的影响。求出了慢性HCV感染和免疫控制的基本再生数。所得结果表明,当HCV感染的基本再生数小于1时,感染最终会消失;当大于1时,感染会变为慢性。在存在慢性感染的情况下,全面讨论了免疫控制平衡点的存在性,这表明在某些条件下可能会出现反向分岔,并且活化DC的数量以及其平均寿命期间被清除的CTL数量在控制慢性HCV感染和免疫反应中起着关键作用。反向分岔的出现意味着模型可能存在双稳性,即感染的结果取决于初始情况。通过选择未活化DC的活化率或活化DC的交叉呈递率作为分岔参数,在一定条件下的霍普夫分岔表明模型存在周期解。同样,数值模拟表明了该模型的动力学复杂性,包括免疫控制平衡点的不稳定性和稳定周期解的存在。

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