Biomedical Engineering Reference
In-Depth Information
4.2
MICROSIMULATION OF INDUCIBLE
REORGANIZATION IN IMMUNITY
Thomas B. Kepler
Department of Biostatistics and Bioinformatics and Department of Immunology,
Duke University, Durham, North Carolina
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 bal-
anced between unicellular autonomy—both physiological and genetic—and multicellular
cooperation. Transitions between these two modes of operation are induced when the ap-
propriate 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 inde-
pendently 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 organi-
zation 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 di-
rect contact and via soluble factors. These soluble factors, including host cytokines as
well as bacterial chemoattractants and toxins, are represented as continuous fields gov-
erned by reaction diffusion partial differential equations. I illustrate the use of the model
with an examination of microlocal inflammation.
1.
INTRODUCTION
Somewhere around a billion years ago, the differentiated multicellular life-
style had its debut. This strategy requires that cells abdicate their ability to pro-
liferate unchecked and pass along to progeny the changes accumulating uniquely
Address correspondence to: Thomas B. Kepler, 101A North Building, Research Drive, Durham, NC
27708 (kepler@duke.edu).
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