title: The cup runneth over: lessons from the ever-expanding pool of primary immunodeficiency diseases.
abstract: A recent surge in newly described primary immunodeficiencies (PIDs) has highlighted new physiological and pathophysiological pathways that affect the immune system. Furthermore, the study of individuals with PIDs has substantially improved our understanding of basic cellular and signalling pathways in host defence and immune regulation. Single-gene defects can lead to disease manifestations that range from extremely narrow infectious phenotypes to remarkably broad multisystem effects. Hypomorphic or hypermorphic gene mutations often occur in human diseases; when coupled with the fact that humans are exposed to naturally encountered antigens and pathogens, this helps to make the case that the study of immunological diseases in humans should be at the forefront of basic immunological research.
authors.affiliation: Allergic Inflammation Unit, Laboratory of Allergic Diseases, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, 9000 Rockville Pike, Bethesda, Maryland 20892, USA. jdmilner@niaid.nih.gov
authors.forename: Joshua D
authors.initials: JD
authors.lastname: Milner
authors.forename: Steven M
authors.initials: SM
authors.lastname: Holland
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D016207:Cytokines / Q000276:immunology; D006801:Humans; D056724:Immunity, Humoral / Q000235:genetics / Q000276:immunology; D007113:Immunity, Innate / Q000235:genetics / Q000276:immunology; D007153:Immunologic Deficiency Syndromes / Q000235:genetics / Q000276:immunology*; D009154:Mutation
chemical_list: D016207:Cytokines