论文标题

免疫异质性的动态因果模型

Dynamic causal modelling of immune heterogeneity

论文作者

Parr, Thomas, Bhat, Anjali, Zeidman, Peter, Goel, Aimee, Billig, Alexander J., Moran, Rosalyn, Friston, Karl J.

论文摘要

一些共同的19个流行病学模型提出的一个有趣的推论是,即使在当前大流行开始时,也存在不易感染的人群的比例。本文引入了对病毒的免疫反应模型。这是基于与流行病学相同的平均场动力学。但是,我们考虑了流行病学模型中人们的位置,临床状况和其他属性,我们考虑了病毒,B和T淋巴细胞的状态以及它们产生的抗体。我们的目的是对抵抗机制的一些关键假设进行形式化。我们提供了一系列简单的模拟,说明了这些假设下免疫反应动力学的变化。其中包括减弱的病毒细胞进入,预先存在的交叉反应性体液(抗体介导的)免疫力以及增强的T细胞依赖性免疫力。最后,我们通过说明该模型的变异反转(使用模拟数据)来说明其在测试假设中的使用,从而说明了这种模型的潜在应用。原则上,这提供了基于顺序的血清学的快速有效的免疫学测定 - 它提供了(i)对潜在免疫学反应的定量度量,以及(ii)贝叶斯对不同种类的免疫学反应的最佳分类(C.F.,葡萄糖耐受性测试用于测试胰岛素抵抗测试)。这对于评估SARS-COV-2疫苗可能特别有用。

An interesting inference drawn by some Covid-19 epidemiological models is that there exists a proportion of the population who are not susceptible to infection -- even at the start of the current pandemic. This paper introduces a model of the immune response to a virus. This is based upon the same sort of mean-field dynamics as used in epidemiology. However, in place of the location, clinical status, and other attributes of people in an epidemiological model, we consider the state of a virus, B and T-lymphocytes, and the antibodies they generate. Our aim is to formalise some key hypotheses as to the mechanism of resistance. We present a series of simple simulations illustrating changes to the dynamics of the immune response under these hypotheses. These include attenuated viral cell entry, pre-existing cross-reactive humoral (antibody-mediated) immunity, and enhanced T-cell dependent immunity. Finally, we illustrate the potential application of this sort of model by illustrating variational inversion (using simulated data) of this model to illustrate its use in testing hypotheses. In principle, this furnishes a fast and efficient immunological assay--based on sequential serology--that provides a (i) quantitative measure of latent immunological responses and (ii) a Bayes optimal classification of the different kinds of immunological response (c.f., glucose tolerance tests used to test for insulin resistance). This may be especially useful in assessing SARS-CoV-2 vaccines.

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