A Pox on You

Immunology of Infectious Diseases By S.H.E. Kaufmann, A. Sher, and R. Ahmed Washington, DC: ASM Press (2002). 495 pp. $115.95 Ring around the roses, A pocketful of posies, Ashes, ashes, We all fall down.—Childrens' rhyme in reference to the Black DeathThe Black Death of plague swept through Europe from 1347 to 1349, killing 20 million people, variably estimated at one-third to one-half of the population. Europe would not achieve similar population densities for over four centuries (N.F. Cantor, In the Wake of the Plague: The Black Death and the World It Made, Simon and Schuster, Inc., 2001). The dramatic selective forces imposed by infections of high mortality have undoubtedly driven genetic bottlenecking. Some have speculated that the high incidence of Δ32 CCR5 mutations in northern Europeans that, today, impact the progression of HIV, was established by the selective events of the 1350 plague. Similar bottlenecking has been invoked to account for the cruel selection for hemoglobin S in combating malaria or the cystic fibrosis gene in handling childhood diarrheal and/or respiratory syndromes. Our genomes are replete with the marks of evolutionary selection, baggage necessary to move past ancient scourges inflicted on isolated pockets of individuals.Perhaps nowhere does the impact of infectious disease play out as completely as the immune system. In both humans and mice, severe combined immunodeficiency results in early death from infectious diseases that are only delayed by antibiotics and isolation. Increasing life span, single birth pregnancies, and longer developmental periods in gestation and childhood may well represent the capacity achieved by the acquisition of the rudiments of adaptive immunity—the recombination-activating genes (RAG1 and RAG2)—by vertebrates some 450 million years ago (Litman et al., Annu. Rev. Immunol. 17, 109–147, 1999). Adaptive immunity, which underpins immunologic memory and thus the protection that is afforded by vaccination or survival of prior sickness-causing agents, underlies the capacity of genetically favorable selection after debilitating illness. In the absence of genetic selection and adaptive immunity, each subsequent wave of plague would have caused the same 30%–50% mortality, with the result that no Europeans would be alive today.Recent unfortunate events have forced reexamination of mechanisms by which organisms like Yersinia pestis, the agent of plague, and Bacillus anthracis, which may have contributed to plague, cause tissue destruction. Successes in identifying novel receptors and pathways involved in anthrax, for instance (Bradley et al., Nature 414, 225–229, 2001; Pannifer et al., Nature 414, 229–233, 2001), are related directly to the explosion of interest and research in microbial pathogenesis. The last decade has driven home the repeated message that pathogens are, in fact, different than non-pathogens or commensals, by virtue of acquisition of genes that enable them to overcome barriers and immune responses in the host. As more and more pathogen genomes become available, it is only natural to begin to examine them for the targets of protective immunity in order to develop better vaccines and drugs.Immunology of Infectious Diseases represents a timely treatise that addresses, as the authors note, “the dialogue between pathogen and the host immune system.” Although microbiology books traditionally discuss cell biology of invasion and dissemination, these areas increasingly involve uptake and evasion mediated by receptors of the innate and adaptive immune system. In response, standard immunology textbooks have increased their representation of chapters directed at the central role of infectious diseases in driving the evolution of the immune system. The gold standard textbook of immunology, Paul's Fundamental Immunology (4th Edition; Philadelphia: Lippincott and Raven; 1999), currently devotes 5 of 45 chapters to infectious diseases immunology (indeed, three of the strongest are organized by the editors of Immunology of Infectious Diseases, although the emphasis is different than that in the current text). The popular Immunobiology (edited by Janeway, Travers, Walport, and Shlomchik; 5th edition; New York: Garland Publishing, 2001) is structured to highlight infectious diseases examples throughout. None of the current immunology or microbiology textbooks, however, explores as thoroughly the central dialog that has shaped the evolution of not only the immune system, but the human genome, as does this book.The book has been organized in a linear manner reflecting the steps during activation of immunity. After a superb series of overviews of the major classes of pathogens—bacterial, fungal, viral, and parasitic—the chapters overview evolution, innate responses, adaptive responses, pathologic responses (including induction of autoimmunity and tissue damage), evasion and latency, immunogenetics, and vaccine strategies, using tuberculosis and HIV as examples. This book assumes the reader is familiar with the major cells and workings of the immune system, including cytokines and CD designations. The material is wonderfully comprehensive and some of the topics, particularly regarding fungal immunity and microbial persistence and latency, represent summaries that are simply unavailable elsewhere. One caveat regarding the organization is that readers attempting to familiarize themselves with measles immunity will need to look up measles references in the overview, the innate response, the adaptive response and the pathology chapters. Organizing the book around immunity makes sense for readers well versed in immunology, but filling in gaps in microbiology, virology, and parasitology involves substantial page turning. All the information is here, but not always in readily retrievable form.This is an admirable effort, and well worth a look by scientists from both microbiology and immunology backgrounds. Readers will need to be scientifically savvy —this is beyond most medical school microbiology or immunology courses—but investigators in or on the fringes of the fields will be rewarded by the immense collection of data. Highlights include the pithy microbial overviews—the overview of bacterial pathogens is an exceptional synthesis of material covering all major aspects found in much lengthier textbooks. The viral chapters, including an up-to-date and balanced discussion of therapeutic strategies against HIV, are particularly outstanding. The chapter on evolution, at a time when all the colliding genomes between human and microbes are becoming available, is disappointing. Some statements—“only TLR2 among mammals has been shown to play a role in immunity“—were not only wrong when the book was published, but could have been corrected had the author read some of the other chapters. More convincing evidence for the forces driving MHC diversity have been proposed (Flajnik and Kasahara, Cell 15, 351–362, 2001) and the extreme polymorphisms among the MHC-binding activating and inhibitory receptors should be addressed, particularly in light of recent evidence consistent with selective evolution driven by pathogens (Arase et al., Science 296, 1323–1326, 2002).What would make it better? Although some chapters are well illustrated, some suffer from a lack of figures or use figures better suited to other places in the text. Tightening the text with cross-references would cut down on redundancies and foster the switching about that this book invites. Few references to web-based resources exist, which, if included, could direct the reader to more in-depth databases. As an additional comment, infectious diseases are estimated to account for at least 15% of all cancers, although the figure is likely an underestimate. The intersection of microbes, immunity, tolerance and cancer would seem to make this a legitimate area for future consideration in the context of this book. Finally, a chapter devoted to the pathogenesis, immune response and vaccine approaches to agents of bioterrorism would certainly bring immediacy to the text and fill a much-needed void in the immunology literature. I'll look forward to the second edition.