The PSIIM Program in Systems Immunology and Infectious Disease Modeling represents a new multidisciplinary research initiative focused on the immune system, with an emphasis on quantitative, computer-based, microscopic and macroscopic modeling of immune functions, integration of these modeling efforts with data sets derived from global analyses of cell components, and the development and application of advanced imaging methods to the analysis of immune responses in vivo in models systems, and ultimately, man. The program is designed to deal with the existing lack of any large-scale effort to understand the engineering of the immune system from the biochemical through the organismal levels and to generate predictive models based on such understanding.? ? The overall goal of the PSIIM will be the development of a new level of integrated understanding of how the immune system functions and how it interacts with pathogens. The primary imperative would be accumulation of the specific information necessary to devise robust quantitative, predictive models of immune behavior in various circumstances, including exposure to infectious agents, following vaccine administration, or in autoimmune diseases. A key effort will be the implementation of the type of measurement rigor needed for effective modeling at all levels of immune organization, from the biochemical to the whole animal. ? ? During the past year, the Immunology Team has undertaken a major project involving a top-down analysis of the immune and non-immune tissue response of mice to various strains of influenza virus. Highly standardized preparations of both mildly pathogenic (Tx91) and highly pathogenic (PR8) viruses have been used at varying infectious doses in a single inbred strain of mouse and microarray transcriptional analyses have been conducted with RNA isolated from diverse tissues of these infected animals at varying time points post-inoculation, including lung (hematopoietic cells and non-hematopoiteic cells), draining and non-draining lymph nodes, and spleen. More than 100 arrays have been generated and data are now being collected from these arrays, with preliminary results indicating extremely high biological and technical replicate agreement. These latter findings indicate that we will have an extremely high quality data set for eventual informatic analysis. Early findings suggest marked differences in the types of immune cells and immune factors present at the site of infection at early time points in mice given the Tx91 vs. the PR8 viruses, with some of the data pointing to possible explanations for the marked differences in pathogenicity of the two infectious agents.
