Development of a Dynamic Cumulative Dose-Response Model

Principal Investigator

Joseph Eisenberg

Co-Principal Investigator

James Koopman

Co-Investigator

Charles Haas

Additional Personnel

Josep Pujol

Funding Sources

Michigan State University - Center for Advancing Microbial Risk Assessment (CAMRA)

About this Project

We develop a simple model that illustrates the need to generate new data that can describe dose-timing effects while at the same time providing a base upon which to build more realistic models that incorporate more data and theory on immunity. Our model addresses immune control of pathogens between the time pathogens arrive at a host and the time they are either eliminated or have multiplied enough so that an acquired immune response will be needed for control.

We make our model general enough to capture dynamics of pathogen control that might arise from established antibodies and T-cells, macrophages, polymorphonuclear leukocytes, plasma cells, dendritic cells, complement cascades, chemokines, interleukins, interferons, toll like receptors, and other diverse elements affecting immunity. But we lump all these mediators of pathogen control into a highly abstract entity we label as immune effectors. We assume that the dynamic effects of limited immune effector numbers are similar whether the limitation arises from immune effectors being occupied with previously arrived pathogens or from prior consumption of immune effectors in their process of killing pathogens. Therefore we only model the latter source of immune effector limitations. The resulting model is one where any single pathogen always has some chance of initiating an infection but the risk of infection associated with each additional pathogen exposure can markedly increase a higher pathogen doses given over short temporal windows. The exact dynamics of our model will vary as realistic details are added to it. Our goal here is simply to illustrate the importance and inevitability of immune mediated dose-timing effects so as to stimulate further empirical and theoretical work.