About the Cover
Dendritic cells (DC; large cells with dendrites) are master regulators of immune responses: They are the principle antigen-presenting cells for adaptive immune responses, and they have receptors for sensing pathogens and danger signals for innate immune responses. The competency of a DC to activate a robust immune response, particularly against weak antigens such as tumor antigens, depends on the countervailing effects of pathogen-sensing and regulatory T cells (Treg; salmon color cells). In the absence of Tregs, a naïve, conventional CD4 T cell (Tconv; sky blue cells), interacting with a DC presenting an antigen in an MHC complex (blue spikes from DC) for which the TCR of the Tconv is specific and binds with high affinity, induces the reciprocal activation of the Tconv and DC and the subsequent immune responses. In the presence of Tregs that also recognize peptide/MHC complexes on the same DC, the DC is prevented from becoming activated, thus restraining T-cell activation. If the DC receives a signal through its pathogen-sensing receptors, shown here as endotoxin bacterial lipopolysaccharide (LPS; dark green) stimulating the pathogen-sensing Toll-like receptor 4 (TLR-4; yellow receptor), it will then become activated even in the presence of Tregs. The activated DC will then stimulate the specific conventional CD4 T cell to undergo its full range of responses. For details of the proposed model of pathogen-sensing and Tregs as integrated regulators of immune responses, see the Masters of Immunology primer by William E. Paul and Zvi Grossman on page 503 of this issue. [Cover image adapted from Paul et al. Cold Spring Harb Symp Quant Biol 2013 Oct 15. Epub ahead of print.]

About the Master
William E. Paul, MD, is an NIH Distinguished Investigator, and chief of the National Institute of Allergy and Infectious Diseases (NIAID) Laboratory of Immunology. Dr. Paul is best known for his path-breaking work on cytokine biology, including the discovery of interleukin-4, and its role as the key regulator of allergic inflammatory diseases. He delineated the mechanisms of differentiation of naïve CD4 T cells into T-helper effector cells, a subject that remains one of the dominant themes of contemporary immunology.
Dr. Paul was born in Brooklyn, NY. He received his BA degree, summa cum laude, from Brooklyn College, and his MD, cum laude, from the State University of New York Downstate Medical Center.He served his internship and residency in medicine at the Boston Medical Center. He was a research fellow in the laboratory of Nobel laureate Dr. Baruj Benacerraf at the New York University School of Medicine. In 1968, Dr. Paul joined the NIAID, where he became chief of the Laboratory of Immunology in 1970. From 1994 to 1997, during his tenure as Assistant Surgeon General of the United States, he served as the director of the NIH Office of AIDS Research (OAR) and the associate NIH director for AIDS. As OAR director, Dr. Paul was responsible for, at that time, a new emphasis on HIV vaccine research and development and the creation of the Vaccine Research Center on the NIH campus.
Dr. Paul has been elected to the U.S. National Academy of Sciences, the Institute of Medicine, and the American Academy of Arts and Sciences. He has served as president of the American Association of Immunologists (AAI) and of the American Society of Clinical Investigation. Dr. Paul has received numerous honorary degrees, awards, and recognitions, including the 1980 Founder's Prize of the Texas Instruments Foundation, the 1988 Life Sciences Award from the Federation of American Societies for Experimental Biology, the Tovi Comet-Wallerstein Prize of Bar-Ilan University, Lifetime Achievement Awards from the AAI and the International Cytokine Society, the 2008 Max Delbruck Medal, and the 2009 Clemens von Pirquet Medal. He is a Raymond and Beverly Sackler Senior Professor by Special Appointment at Tel Aviv University and an Adjunct Professor of Pathology and Laboratory Medicine at the University of Pennsylvania Medical School. Dr. Paul is a prolific researcher and educator. He has authored more than 600 scientific articles and has edited two of the most influential immunology text and reference books. He served as founding editor-in-chief of the Annual Review of Immunology for its first 31 editions. He is the editor of the advanced textbook, Fundamental Immunology, now in its seventh edition. He has mentored many prominent immunologists, including the late Charles Janeway Jr, Ron Schwartz, Laurie Glimcher, Mark Davis, and Tony DeFranco.