Grebennikov D S, Donets D O, Orlova O G, Argilaguet J, Meyerhans A, Bocharov G A
Moscow Institute of Physics and Technology (National Research University), Dolgoprudny, Moscow Region, 141701 Russia.
Marchuk Institute of Numerical Mathematics, Russian Academy of Sciences, Moscow, 119333 Russia.
Mol Biol (Mosk). 2019 Sep-Oct;53(5):815-829. doi: 10.1134/S0026898419050082.
The modern era of research in immunology is characterized by an unprecedented level of detail about structural characteristics of the immune system and the regulation of activities of its numerous components, which function together as a whole distributed-parameter system. Mathematical modeling provides an analytical tool to describe, analyze, and predict the dynamics of immune responses by applying a reductionist approach. In modern systems immunology and mathematical immunology as a new interdisciplinary field, a great challenge is to formulate the mathematical models of the human immune system that reflect the level achieved in understanding its structure and describe the processes that sustain its function. To this end, a systematic development of multiscale mathematical models has to be advanced. An appropriate methodology should consider (1) the intracellular processes of immune cell fate regulation, (2) the population dynamics of immune cells in various organs, and (3) systemic immunophysiological processes in the whole host organism. Main studies aimed at modeling the intracellular regulatory networks are reviewed in the context of multiscale mathematical modelling. The processes considered determine the regulation of the immune cell fate, including activation, division, differentiation, apoptosis, and migration. Because of the complexity and high dimensionality of the regulatory networks, identifying the parsimonious descriptions of signaling pathways and regulatory loops is a pressing problem of modern mathematical immunology.
现代免疫学研究时代的特点是，人们对免疫系统的结构特征及其众多组成部分活动的调节有了前所未有的详细了解，这些组成部分作为一个整体的分布参数系统共同发挥作用。数学建模提供了一种分析工具，通过应用还原论方法来描述、分析和预测免疫反应的动态过程。在现代系统免疫学和作为一个新的跨学科领域的数学免疫学中，一个巨大的挑战是建立能够反映人类免疫系统结构理解水平并描述维持其功能过程的数学模型。为此，必须推进多尺度数学模型的系统开发。一种合适的方法应该考虑：（1）免疫细胞命运调控的细胞内过程；（2）各种器官中免疫细胞的群体动态；（3）整个宿主生物体中的系统免疫生理过程。本文在多尺度数学建模的背景下，对旨在模拟细胞内调控网络的主要研究进行了综述。所考虑的过程决定了免疫细胞命运的调控，包括激活、分裂、分化、凋亡和迁移。由于调控网络的复杂性和高维度性，确定信号通路和调控回路的简约描述是现代数学免疫学中一个紧迫的问题。
