Multicellular Heritage, Unicellular Attitude: Computational Studies of the Leukocyte Lifestyle

Thomas B. Kepler

Chief, Division of Computational Biology, Duke University

The cells of the vertebrate immune system spend part of their lives as effectively autonomous entities, circulating in the blood or wandering through the tissues, surveying them for misplaced microbes or host damage.  When evidence for such occurrences is encountered, however, these cells begin to communicate with each other via diffusive signaling molecules, called cytokines, and surface receptor-ligand pairs and thus coordinate their activities and organize themselves spatially.

We have developed a simulation model to study these phenomena.  The simulation is based on the individual cell, behaving in continuous time and continuous 3-dimensional space.  The cells have non-trivial internal dynamics coupled to their external behaviors, such as the secretion of any of several cytokines.  They respond to these cytokines and other soluble factors both internally and chemotactically.  The cytokines, for their part, diffuse through the tissue and interact with each other. I will describe this system in detail and illustrate it with the simulation of a simple inflammatory process, describing how the immune response changes qualitatively as the strength and duration of the stimulus increase.  The simulation further embodies a hypothesized mechanism for the resolution of simple inflammation and thereby provides insight into a possible cause of the periodic fever syndromes.