During the past decade, there has been a dramatic expansion in our understanding of the mechanistic underpinnings of innate and adaptive immune responses, yielding important insights into the pathophysiology of infectious and autoimmune diseases. In addition, a series of new respiratory viruses have been discovered, and drug-resistant microbes, such as community-acquired methicillin-resistant Staphylococcus aureus and broadly resistant plasmodium species, have become common foes. The contributions to this special issue were selected to provide to the readership of Pediatric Research a broad and insightful overview of these topics.

Reviews by Notarangelo and coworkers, Bonilla and Geha, and Su and Anderson (1–3), grouped under the heading of “Inheritable Disorders of the Immune System,” summarize how examination of monogenic immunodeficiency and autoimmunity disorders and genome-wide association studies have helped reveal novel pathways of innate and adaptive immunity and of mechanisms involved in immunologic tolerance. At a higher level of complexity, Eisenstein and Williams (4) detail the relationship between two recently described T cell subsets that serve opposing functions: regulatory T cells, which play an essential role in peripheral tolerance, and T helper type 17 (Th17) cells, which promote inflammatory responses. As detailed by Freeman and Holland (5), the recently described mutations in STAT3 in the hyper IgE (Job's) syndrome are associated with failed development of Th17 cells. Accordingly, this disease has proven highly informative in understanding the role of Th17 cells in immunity to specific pathogens including S. aureus and Candida species. Additionally, fundamental breakthroughs in our understanding of triggering and effector mechanisms involved in innate immunity came from the genetic and functional characterization of autoinflammatory disorders, detailed in the review by McGonagle et al. (6). As discussed by Walker and Modlin and Philbin and Levy (7,8), we may be able to exploit our understanding of the developmental differences in innate immune responses to enhance or focus the efficacy of immunomodulators and vaccines.

Other contributions to this special issue focus on the pathogens themselves. A survey by Liu (9) broadly reviews the molecular and clinical peculiarities of the so-called community-acquired methicillin S. aureus strains that contribute to the recent worldwide rise in life-threatening staphylococcal disease. Travassos and Laufer (10) tackle the issue of antimalarial drug resistance, a problem fundamental to the resurgence of malaria as a global threat. The discovery of the human bocavirus and human metapneumovirus, reviewed by Milder and Arnold (11), has broadened the list of suspects for both mild and severe respiratory disease in children.

In some cases, the balance between the virulence of microbes and genetic properties of the host determine the outcome of infection. This theme is central to the review by Singh and Spector (12), which examines the impact of host genetic determinants on the outcome of HIV infection in children, the article by Viscardi and Hasday (13), which examines the immunopathology of ureaplasma infections and their putative link to chronic lung disease in infants, and the analysis of biomarkers of necrotizing enterocolitis in neonates as clues to pathogenesis by Young et al. (14). On a related note, Onouchi (15) provides a review of the recent studies of molecular genetics of Kawasaki disease, which may help explain the well-described ethnic predisposition of this disorder seen in certain populations.

Thus, we hope that the articles in this special edition will assist readers by providing a broad conceptual overview of the recent developments in our understanding of the interplay between infection and immunity, and the basis for well-known, but often poorly understood, immunodeficiency, autoimmunity, and inflammatory disorders.