A major question in influenza infection pathology is whether viruses of varying virulence invoke distinct immune responses. While efforts have attempted to mathematically characterize the host immune response to influenza virus infection, there has been no previous exploration of strain-specific infection dynamics. Here, a mechanism-based mathematical model is developed and used to compare the immune dynamics invoked by deadly H5N1 and moderately pathogenic H1N1 viruses. Results suggest that the kinetics of the immune response, specifically those related to the virus as well as those involved in interferon production, differ between H1N1 and H5N1 infections. The ability to predict strain differences could aid in clinical understanding of infection severity and take a step towards future application of patient-specific treatment profiles.