Microsimulation of Inducible Reorganization in Immunity

Abstract

The immune system is the key interface between the multicellular host and its unicellular microbial commensals and pathogens. The cells of the immune system live a life balanced between unicellular autonomy—both physiological and genetic—and multicellular cooperation. Transitions between these two modes of operation are induced when the appropriate combination of events occurs and an immune response is triggered. These events may be the detection of tissue damage or of conserved microbial molecular motifs, and the detection of “non-self” epitopes. The transition is mediated by soluble and cell-surface bound signaling molecules, and involves the reorganization of cells from independently moving agents to functional aggregates. I have developed a model to study the properties of such transitions and to inform our thinking about the role of spatial organization in the immune response. It is an agent-based model evolving in continuous time and space, with its agents, representing cells of both microbe and host, interacting via direct contact and via soluble factors. These soluble factors, including host cytokines as well as bacterial chemoattractants and toxins, are represented as continuous fields governed by reaction diffusion partial differential equations. I illustrate the use of the model with an examination of microlocal inflammation.