Modeling Innate Immunity Causing Chronic Inflammation and Tissue Damage

Abstract

Mathematical models of immune responses have traditionally focused on adaptive immunity and pathogen-immune dynamics. However, recent advances in immunology have highlighted the critical role of innate immunity. In response to physical damage or pathogen attacks, innate immune cells circulating throughout the body rapidly migrate from blood vessels and accumulate at the site of injury, triggering inflammation. These cells engulf, break down, and eliminate pathogens. This innate immune response occurs much faster than adaptive immune responses, which require time for cell activation and proliferation. While inflammation helps eliminate pathogens, it can sometimes lead to chronic inflammation by triggering excessive immune responses, ultimately causing tissue damage. In this study, we examine a simple dynamical model of innate immunity. The analysis indicates that when an infection occurs, it triggers inflammation, which activates the innate immune system and initiates the activation cycle. Consequently, pathogens may be eradicated, leaving behind persistent chronic inflammation. Alternatively, the pathogens may not be eradicated, with their abundance either stabilizing at a positive level or oscillating indefinitely. The dynamics exhibit both transcritical and Hopf bifurcations. When innate immunity is activated in the absence of inflammation, pathogens are eradicated more easily, and the likelihood of oscillations in inflammation, immune responses, and pathogen abundance is reduced.