Immunology and Evolution of Infectious Disease

• Steven A. Frank
Princeton University Press: 2002. 352 pp. $75, £52 (hbk);$24.95, £17.95 (pbk)

It was Charles Darwin who observed: “It is not the strongest of the species that survive, nor the most intelligent, but the one most responsive to change.” In the ever-changing world of the immune system, neither size nor complexity of a parasite counts, but adaptability.

In Immunology and Evolution of Infectious Disease, Frank's multidisciplinary approach to infection dynamics brings together population ecology, immunology and evolution. He links evolutionary change of parasites to molecular details of immune recognition and to genetic variation of the host population. Newcomers are offered a comprehensive introduction to basic questions of immunology, as well as a synthesis that cuts across large areas of biology. Specialists will find detailed discussions of specific infectious agents from a highly original, evolutionary perspective, and inspiration for future research.

The structure of the book shows how different subjects must be integrated for comprehensive understanding of parasite variation. First, it gives a general introduction to vertebrate immunity and antigenic variation. There follows a discussion of molecular processes of immune recognition and parasite escape. Frank then focuses on the dynamics of a single infection and examines genetic variation within populations of hosts and parasites. Finally, he discusses methods to study the evolutionary dynamics of antigenic variation. As the book progresses, the complex issues of evolutionary change are related back to the structural and biochemical properties of molecular recognition introduced earlier in the book.

Antigenic variation benefits parasites by allowing a longer period of infection within an individual host and by facilitating re-infection of hosts with immune memory. It also increases the abundance of parasites within an infected individual and thereby enhances infectivity. The human immunodeficiency virus (HIV) is discussed as a primary example of a parasite that evolves within a single host. Antigenic variation of HIV leads to escape from cytotoxic T cells and neutralizing antibodies. It augments viral load and thus accelerates the destruction of CD4 cells. There is a highly dynamic balance of power between HIV and the immune system, which is slowly shifted as a consequence of virus evolution to allow the virus to escape from immune recognition and to reproduce more efficiently in a broader range of different cells. Thus, virus evolution within individual hosts may well be the cause of disease progression, as was first proposed some ten years ago.

Parasites in general have found an amazing diversity of processes by which they can escape immune recognition. Mechanisms of generating antigenic variation include baseline mutation during replication, hypermutation of antigenic loci, and switching between archival variants. The analysis of infection dynamics within individual hosts includes hepatitis C virus (HCV), human T-cell leukemia virus (HTLV), and the malaria parasite Plasmodium falciparum.

Frank examines variability in parasites and hosts across entire populations, discussing genetic differences among hosts in their immune responses and immune memory profiles. The overview of the methods for studying evolutionary change is exceptional. Immunological and phylogenetic classification of virus variants provides evidence for selection in genetic data of influenza A virus and HIV. Experimental evolution of foot-and-mouth disease virus is discussed, as well as selection for escape from cytotoxic T cells.

This book considers the natural history of antigenic variation at the molecular, population and evolutionary level. Through its novel way of integrating all factors that affect antigenic variation in pathogen biology, it provides new insights into the evolution of infectious disease. It is a rich source of ideas for scientists working in immunology and molecular biology as well as evolution. Frank defines the key problems for the future study of parasite variation and escape from host recognition. For example, he suggests studying experimentally the relations between infection length, parasite abundance and transmission success to learn how selection shapes antigenic variation within hosts.

To determine whether antigenic selection shapes phylogeny, mathematical models can clarify the relations between antigenic and phylogenetic classifications. Comparison of parasites in different hosts or geographical locations can reveal the effects of MHC diversity on antigenic variation.

The book brings home the point that the immunology of tomorrow will greatly benefit from making contact with structural, genomic, evolutionary and mathematical techniques. Academic institutions and granting agencies worldwide have started to predict such a multidisciplinary future for the whole of biology. Read this book and 90% of your multidisciplinary grant on any topic of infectious disease is already written.