Department of Bioengineering, Rice University, Houston, Texas, United States of America.
PLoS One. 2011;6(8):e23910. doi: 10.1371/journal.pone.0023910. Epub 2011 Aug 29.
Original antigenic sin is the phenomenon in which prior exposure to an antigen leads to a subsequent suboptimal immune response to a related antigen. Immune memory normally allows for an improved and rapid response to antigens previously seen and is the mechanism by which vaccination works. I here develop a dynamical system model of the mechanism of original antigenic sin in influenza, clarifying and explaining the detailed spin-glass treatment of original antigenic sin. The dynamical system describes the viral load, the quantities of healthy and infected epithelial cells, the concentrations of naïve and memory antibodies, and the affinities of naïve and memory antibodies. I give explicit correspondences between the microscopic variables of the spin-glass model and those of the present dynamical system model. The dynamical system model reproduces the phenomenon of original antigenic sin and describes how a competition between different types of B cells compromises the overall effect of immune response. I illustrate the competition between the naïve and the memory antibodies as a function of the antigenic distance between the initial and subsequent antigens. The suboptimal immune response caused by original antigenic sin is observed when the host is exposed to an antigen which has intermediate antigenic distance to a second antigen previously recognized by the host's immune system.
原始抗原性错误是指先前接触抗原会导致对相关抗原的后续免疫反应不佳的现象。免疫记忆通常允许对以前见过的抗原进行改善和快速反应,这是疫苗接种起作用的机制。我在这里开发了流感中原发性抗原性错误的动力学系统模型,阐明并解释了原始抗原性错误的详细自旋玻璃处理。该动力学系统描述了病毒载量、健康和感染上皮细胞的数量、幼稚和记忆抗体的浓度以及幼稚和记忆抗体的亲和力。我给出了自旋玻璃模型的微观变量与当前动力学系统模型的微观变量之间的明确对应关系。动力学系统模型再现了原始抗原性错误的现象,并描述了不同类型的 B 细胞之间的竞争如何影响免疫反应的整体效果。我将幼稚抗体和记忆抗体之间的竞争作为初始抗原和后续抗原之间的抗原距离的函数进行了说明。当宿主暴露于与宿主免疫系统先前识别的第二种抗原具有中等抗原距离的抗原时,会观察到原始抗原性错误引起的免疫反应不佳。