Evolutionary Principles and Host Defense

The principles of evolution are uniquely relevant to understanding and reliably manipulating mechanisms of host immunity, pathogen behavior, and the interaction between host and pathogen in the service of promoting the health and well-being of individual patients and populations. In this chapter, I use examples of immune system function and interactions between pathogens and human hosts to illustrate some of the ways that evolution-related insights are exploited to advance the aims of clinicians and public health officers. I first focus on the coevolutionary processes by which human immunodeficiency virus-1 (HIV-1) evades neutralizing antibodies synthesized by host B-lymphocytes and B-lymphocytes evolve such that the antibodies they secrete can bind better to HIV-1 variants. In particular, I address the critical roles of somatic hypermutation of antibody variable domain genes and selection of Blymphocytes in the production of potent and broadly neutralizing antibodies which are regarded as necessary for a highly efficacious vaccine intended to control the spread of a highly variable pathogen such as HIV-1. I also use other examples to illustrate the contributions of evolutionary thinking in immunology and infectious disease, including determining the paths of transmission of methicillin-resistant Staphylococcus aureus, the effects of vaccines and antibiotics on pneumococcal epidemiology, and the patterns of antibiotic resistance in selected pathogens.