  The immune system is a real-time example of an evolving system that navigates
the essentially infinite complexity of protein sequence space. How this system
responds to disease and vaccination is discussed. Of particular focus is the
case when vaccination leads to increased susceptibility to disease, a
phenomenon termed original antigenic sin. A physical theory of protein
evolution to explain limitations in the immune system response to vaccination
and disease is discussed, and original antigenic sin is explained as stemming
from localization of the immune system response in antibody sequence space.
This localization is a result of the roughness in sequence space of the evolved
antibody affinity constant for antigen and is observed for diseases with high
year-to-year mutation rates, such as influenza.
