THE STRUCTURE AND DYNAMICS OF IMMUNE SIGNALING SYSTEMS AS A COEVOLVED STRATEGIC COUNTER AGAINST PARASITIC SABOTAGE

Abstract

The immune system of any host organism must translate the detection of invading parasites into the deployment of defenses that eradicate parasites and/or mitigate damage. This translation task requires signaling – the processing of information via cascades of molecular and/or cellular interactions. Immune signaling systems are often complex, without obvious organizational themes. And yet, parasites evolve mechanisms to sabotage immune signaling, decoupling detection from defense deployment and thereby escaping eradication. This presents a selection pressure on hosts to preempt or withstand targeted sabotage. Therefore, in this dissertation, I argue that studying how complex immune signaling systems function in the face of sabotage can reveal their underlying structure and dynamics. In Chapter One, I use coevolutionary simulation modeling to demonstrate how parasitic sabotage shapes the architecture of molecular signaling cascades observed in invertebrates. In Chapter Two, I argue that even the vastly more complex mammalian immune system may be organized to withstand parasitic sabotage, by deploying signaling cells as a swarm rather than a tightly-regulated hierarchy. In Chapter 3, I highlight one hallmark of swarming behavior in the vertebrate immune system, using a dynamical systems model to show that T-helper cells perform quorum sensing when choosing appropriate immune defenses. In Chapter 4, I present experiments designed to document the T-helper quorum sensing predicted by the mathematical model. These results suggest that swarming is a potent strategy for processing highly uncertain information across biological scales. Understanding the vertebrate immune system as a cellular swarm follows from examining signaling schemes that withstand sabotage, and it is poised to generate still more insight into the adaptive structure of immune systems.