Evolutionary Principles and Host Defense

Abstract

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.

Glossary

Immunity-related GTPases

A family of proteins in humans, mice, and other mammals that are encoded by genes that can become active in response to the cytokine interferon-gamma. These proteins can catalyze the hydrolysis of guanosine triphosphate to guanosine diphosphate and orthophosphate and can be involved in immunity to vacuolar pathogens by triggering the process of autophagy, which also participates in normal cellular recycling of cellular components. Opsonization—the process by which molecules such as antibodies or proteolytically derived components of the serum proteins that are participants in the complement cascade facilitate the ingestion of bacteria, other microbial pathogens, or other particulates by phagocytes, such as neutrophils, monocytes, macrophages, or dendritic cells.

Pathogen

A microbe or macroscopic parasite that can infect host organisms and can cause cellular dysfunction, tissue damage, and fitness reduction in those hosts.

Phylogenetic relationship

A relationship between species, cells, or genes based on relative temporal proximity to shared common ancestors; thus if we consider three species or three genes, A, B, and C, if A and B shared a more recent common ancestor than either A or B shares with C, A and B are more closely related, phylogenetically, to one another than to C.

Somatic cell competition

A process in which survival and proliferation of non-germ cell body cells, such as Blymphocytes, depends on comparative abilities to acquire a limiting resource, such as critical signals from CD4+ T-cells (so-called helper T-cells) in the case of germinal center Bcells.

Somatic hypermutation

A process affecting Blymphocytes following their activation by antigens in which the portions of immunoglobulin encoding genes that determine the structures of the antibody domains responsible for directly binding to antigen are subjected to an increased rate of mutation. This process typically occurs in germinal centers within lymph nodes or other secondary lymphoid tissues.

Tropism

A characteristic of a virus or other pathogen that pertains to which cell types or tissues of which species can support the replication of that pathogen.

Virulence

Frequently regarded as an attribute of a pathogen pertaining to the extent of debilitation that follows infection; in evolutionary terms, virulence is a relational property attributable to a particular host–pathogen pair that measures the extent to which infection of that host with that pathogen reduces host reproductive fitness.