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 Preface

Since early 2020, the field of immunology has moved to an unexpectedly prominent place in daily life. As SARS-CoV-2 spread around the globe, basic questions about how the immune system combats viruses moved into the forefront of public attention. Why were individual responses to the virus so variable? Why were outcomes in older patients so much more dire than in younger infected individuals? And, most important, how quickly would a vaccine be available, would it provide adequate protection, and for how long? While some questions have been answered, notably observing the most rapid vaccine development in human history, many other questions remain outstanding. Clearly, the need for continued research into basic mechanisms controlling human immunity is undeniable. Though somewhat overshadowed during the COVID-19 pandemic, there has been a dramatic rise in the use of various other immunotherapies in the years since the last edition of Janeway’s Immunobiology.

 Multiple methods for manipulating immune responses have significantly altered the practice of clinical medicine, benefiting patients who present with a diagnosis of cancer, autoimmune disease, or chronic inflammatory disorder. In large part, these clinical advances arose from decades of basic research aimed at uncovering the molecules and pathways that regulate immune cells at steady-state conditions or during infection, inflammation, or autoimmunity. This Tenth Edition of Janeway’s Immunobiology strives to carry on Charlie Janeway’s legacy of providing a comprehensive, up-to-date textbook focused on the mechanisms underlying the responses to infection. In keeping with this mission, this edition’s text and figures have been updated throughout. The immune response to SARS-CoV-2 and the multiple vaccine strategies utilized against this infection are introduced in Chapter 1 and further discussed in Chapters 12, 16, and Appendix I. Chapter 3 now includes a detailed explanation of the mechanism by which mutations in innate sensors of infection can lead to autoimmunity .

New developments in the identification of ligands for γδ T cells are highlighted in Chapter 4, and the new cryo-electron microscopy (cryo-EM) structure of the RAG-1:RAG-2 complex bound to DNA is described in Chapter 5. Recently discovered structural features of the peptide-loading machinery for antigen presentation to T cells are included in Chapter 6. The treatment of antigen receptor signaling in Chapter 7 now includes discussion of lymphocyte metabolism, a topic also revisited in the revised Chapters 9 and 11. Additionally, new information in Chapter 7 highlights the pathways targeted by checkpoint blockade immunotherapy and describes the signaling modules used to engineer chimeric antigen receptors (CARs) for cell-based therapies, a topic also elaborated in Chapter 16. The latest findings on T-cell localization and dynamics during priming interactions with dendritic cells are covered in Chapter 9, while Chapter 11 describes new insights into the development and functions of tissue-resident memory T cells.

 Chapter 12, which focuses on immunity at the barrier surfaces, has undergone a major overhaul and includes an expanded discussion of immune interactions with commensal microorganisms and a detailed discussion of the roles of diverse epithelial cell types in the intestine, respiratory tract, and the skin. Chapter 12 also includes a new section on respiratory virus infections, including influenza and SARS-CoV-2. Chapter 16 brings vaccines to the forefront and includes a detailed discussion of the new vaccine approaches used for SARS-CoV-2 and poliovirus vaccines. The Immunologist’s Toolbox (Appendix I) has been updated with new sections on single-cell technologies such as single-cell RNA-seq and lineage-tracing approaches, antigen tetramers for identifying antigen-specific B cells, and parabiosis used to determine lymphocyte tissue residency.

 Also included in Appendix I is a new description of an analytic technique used to measure antibody responses to SARS-CoV-2 in infected or vaccinated individuals. End-of-chapter study questions have been reworked in the Tenth Edition, and an online learning platform for student self-assessment, InQuizitive, has been created. We have benefited greatly from the major contribution of Gregory Barton, an expert in innate immune signaling, who has revised and updated Chapter 3. Many additional people deserve special thanks, including our thoughtful colleagues who reviewed the Ninth Edition and provided insights that helped direct revisions in this new edition. We benefited from the eagle-eyed accuracy reviewers who provided feedback on Tenth Edition chapters. All of these individuals are cited in the Acknowledgments section, and we express our gratitude for their efforts. We have the good fortune to work with an outstanding editorial group at W. W. Norton. We thank Denise Schanck, our editorial advisor, who coordinated the entire project, guiding us gently but firmly back on track throughout the process.

 We thank Betsy Twitchell, our editor, who contributed her guidance, support, and wisdom. Sincere thanks also go to Judith Kromm, our developmental editor, and Christopher Curioli, our copyeditor, for their insights and attention to detail. As in all previous editions, Matt McClements has contributed his genius—and patience—reinterpreting the authors’ sketches into elegant illustrations. Our editing, production, and permissions teams provided their expertise throughout; they are Maggie Stephens, David Bradley, Ben Reynolds, Stephanie Romeo, and Patricia Wong. Our media experts, Kate Brayton, Jasmine Ribeaux, Alexandra Malakhoff, and Kara Zaborowsky, created our excellent supplements package. The authors wish to thank their most important partners—Theresa, Cindy Lou, and Charles—colleagues in life who have supported this effort with their generosity of time, their own editorial insights, and their infinite patience.