Systems approaches to dissecting immunity.

Systems biology is the comprehensive and quantitative analysis of the interactions between all of the components of biological systems over time. Cells of the innate immune system are the first line of defense against invading pathogens and orchestrate the ensuing adaptive response, which is critical to the establishment of long-term protective immunity. Innate immunity is well suited for systems analysis, because the relevant cells can be isolated in various functional states and many of their interactions can be reconstituted in a biologically meaningful manner. Application of the tools of systems biology to the innate immune system will enable comprehensive analysis of the complex interactions that maintain the fine balance between host defense and inflammatory disease. In this review, we discuss innate immunity in the context of the systems biology concepts, emergence, robustness, and modularity. We also describe recent efforts to apply these approaches to enable rational vaccine design and accelerate the pace of clinical vaccine trials.