Hara Akane, Iwasa Yoh
Department of Biology, Faculty of Science, Kyushu University, Motooka 744, Nishi-ku, Fukuoka 819-0395, Japan.
Department of Bioscience, School of Science and Technology, Kwansei Gakuin University, Gakuen 2-1. Sanda-shi, Hyogo 669-1337, Japan.
J Theor Biol. 2020 Aug 7;498:110296. doi: 10.1016/j.jtbi.2020.110296. Epub 2020 May 1.
Many incurable diseases in humans are related to autoimmunity and are initially induced by a viral infection. Presumably, the virus has antigens with epitopes similar to those found in components of the host's body, thus allowing it to evade immune surveillance. Viral infection activates the immune system, which results in viral clearance. After infection, the enhanced immune system may begin to attack the host's cells, tissues, and organs. In this study, we developed a simple mathematical model in which we identify the conditions needed to trigger an autoimmune response. This model considers the dynamics of T helper (Th) cells, viruses, self-antigens, and memory T cells. Viral infection results in a temporal increase in viral abundance, which is suppressed by an increase in the number of Th cells. For the virus to be eliminated from the body, the level of Th cells must be maintained above a certain threshold to prevent viral replication, even in the absence of virus in the body. This role is realized by memory T cells produced during temporal viral infections. Thus, we investigated the conditions needed for the immune response to be enhanced after viral infection and concluded that cross-immunity must be weak for negative selection and T-cell activation but strong for antigen-suppressing reactions. We also discuss alternative models of cross-immunity and possible extensions of the model.
人类的许多不治之症都与自身免疫有关，最初是由病毒感染引发的。据推测，该病毒具有与宿主身体成分中发现的表位相似的抗原，从而使其能够逃避免疫监视。病毒感染激活免疫系统，导致病毒清除。感染后，增强的免疫系统可能开始攻击宿主的细胞、组织和器官。在本研究中，我们开发了一个简单的数学模型，在该模型中我们确定了引发自身免疫反应所需的条件。该模型考虑了辅助性T（Th）细胞、病毒、自身抗原和记忆T细胞的动态变化。病毒感染导致病毒丰度随时间增加，而Th细胞数量的增加会抑制这种增加。为了将病毒从体内清除，即使体内没有病毒，Th细胞水平也必须维持在一定阈值以上以防止病毒复制。这一作用由暂时性病毒感染期间产生的记忆T细胞实现。因此，我们研究了病毒感染后增强免疫反应所需的条件，并得出结论，交叉免疫对于阴性选择和T细胞激活必须较弱，但对于抗原抑制反应必须较强。我们还讨论了交叉免疫的替代模型以及该模型可能的扩展。
