Immune Digital Twin Blueprint: A Comprehensive Mechanistic Model of the Human Immune System

Abstract

The human immune system, which protects against pathogens and diseases, is a complex network of cells and molecules. The effects of complex dynamical interactions of pathogens and immune cells on the immune response can be studied using computational models. However, a model of the entire immune system is still lacking. Here, we developed a comprehensive computational model that integrates innate and adaptive immune cells, cytokines, immunoglobulins, and nine common pathogens from different classes of virus, bacteria, parasites, and fungi. This model was used to investigate the dynamics of the immune system under two scenarios: (1) single infection with pathogens, and (2) various medically relevant pathogen coinfections. In coinfections, we found that the order of infecting pathogens has a significant impact on the dynamics of cytokines and immunoglobulins. Thus, our model provides a tool to simulate immune responses under different dosage of pathogens and their combinations, which can be further extended and used as a tool for drug discovery and immunotherapy. Furthermore, the model provides a comprehensive and simulatable blueprint of the human immune system as a result of the synthesis of the vast knowledge about the network-like interactions of various components of the system.

Toward mechanistic medical digital twins: some use cases in immunology

“…The Digital Twin Innovation Hub ( 17 ), established in August, 2022, is leading the development of a generic immune digital twin platform that will be contextualizable and applicable to many, and eventually any, immune-related pathology. A comprehensive cellular-level model and map of the immune system, consisting of nearly 30 cell types, over 30 cytokines and immunoglobulins spanning both innate and adaptive immunity has been developed to form a “blueprint” of the general purpose immune digital twin ( 18 ). Detailed sub-cellular models of signal transduction and genome-scale metabolism for each of the 30 cell types have also been developed (e.g., dendritic cells, CD4+ T cells ( 19 , 20 ).…”