Generals die in friendly fire, or modeling immune response to HIV
Generals die in friendly fire, or modeling immune response to HIV
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将军死于误伤，或模拟艾滋病毒免疫反应
DOI：
10.1016/j.cam.2004.08.018
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发表时间：
2005
影响因子：
2.4
通讯作者：
R. Ahmed
中科院分区：
文献类型：
--
作者：
I. M. Rouzine;K. Murali;R. Ahmed
我们开发了一个动力学模型的CD8 T淋巴细胞（CTL），其目的是杀死感染病毒和细胞内寄生虫的细胞。使用一组一阶非线性微分方程，该模型预测参与CTL应答的不同细胞类型的数量如何依赖于时间。该模型假设CTL应答需要由巨噬细胞和树突状细胞组成的专职抗原呈递细胞（APC）的持续存在。它假设任何超过阈值水平的病毒都会激活APC，APC反过来又激活CTL，CTL在数量上扩增并成为武装的“效应”细胞。最后，APC在病毒被清除后被停用。缺乏来自APC的信号导致效应细胞默认分化为“暂时性细胞”，这些细胞要么死亡，要么在一小部分中成为长寿的记忆细胞。能够感染APC的病毒将导致效应CTL的过早退休。如果暂时性细胞遇到病毒，这发生在过早耗尽之后，CTL变得无反应性（对外部刺激无反应）。该模型的设计，以适应最近的实验主要CTL反应猿免疫缺陷病毒密切相关的艾滋病毒和淋巴细胞性脉络丛脑膜炎病毒。已知这两种病毒感染APC并使它们成为它们应该控制的CTL的靶。这两种病毒都引起CTL的过早消耗和无反应性，并在宿主体内持续存在。
We develop a kinetic model for CD8 T lymphocytes (CTL) whose purpose is to kill cells infected with viruses and intracellular parasites. Using a set of first-order nonlinear differential equations, the model predicts how numbers of different cell types involved in CTL response depend on time. The model postulates that CTL response requires continuous presence of professional antigen-presenting cells (APC) comprised of macrophages and dendritic cells. It assumes that any virus present in excess of a threshold level activates APC that, in turn, activate CTL that expand in number and become armed “effector” cells. In the end, APC are deactivated after virus is cleared. The lack of signal from APC causes effector cells to differentiate, by default, into “transitory cells” that either die, or, in a small part, become long-lived memory cells. Viruses capable of infecting APC will cause premature retirement of effector CTL. If transitory cells encounter virus, which takes place after the premature depletion, CTL become anergic (unresponsive to external stimuli). The model is designed to fit recent experiments on primary CTL response to simian immunodeficiency virus closely related to HIV and lymphocytic choriomeningitis virus. The two viruses are known to infect APC and make them targets for CTL they are supposed to control. Both viruses cause premature depletion and anergy of CTL and persist in the host for life.
影响因子：
56.9
作者：
Mohri, H;Bonhoeffer, S;Ho, DD
通讯作者：
Ho, DD
影响因子：
32.4
作者：
Murali-Krishna, K;Altman, JD;Ahmed, R
通讯作者：
Ahmed, R