Understanding the human innate immune system In-silico studies

The human innate immune system (HIIS) is the body’s first line of defence. HIIS is a complex yet delicate network of highly specialized cells and molecules that work together to generate a calculated response to noxious stimuli such as inflammation triggering moieties (ITMs). The aim of this work is to understand the underpinning mechanisms of HIIS using ordinary differential equations, evolutionary game theory, cellular automata and concepts on critical transitions. By developing a robust model of HIIS, deeper insights on how HIIS is activated and suppressed and how it reacts to various levels of stimuli are brought to light. By incorporating Alkaline Phosphatase (AP) in modelling HIIS, I show that AP has a pivotal role in neutralizing inflammation in patients undergoing cardiac surgery. Adding ITMs in-silico in various regimes reveals that HIIS undergoes critical transitions from health to death when challenged with a specific concentration of ITMs. This transition between states of health and death is also investigated in neutrophils, which are immune cells known to induce “overreaction” in HIIS when the stimuli is too intense. By using evolutionary game theory, I pinpoint and quantify the driving mechanisms on how neutrophils pick a death pathway in response to various levels of ITMs. I hope that this work paves the way into gaining a deeper understanding of the intricate details and mechanisms that are driving the immunological response of HIIS that is not only limited to cardiac surgery but also to oxidative stress mediated inflammation.