In 1964, Gell and Coombs classified four types of immunologically mediated hypersensitivity states. The majority of disease states encountered in the clinical practice of allergy are related to type I, or immediate type hypersensitivity. In this model, an allergen interacts with preformed IgE on the surface of a mast cell or basophil. This interaction causes cross-linking of the FceRI receptor and release of multiple mediators, including histamine, leukotriens, and various interleukins. Depending on the relative localization of release, clinical states such as allergic asthma, allergic rhinitis, or systemic anaphylaxis occur. Of the remaining clinical allergy hypersensitivity states, type IV, or delayed-type hypersensitivity, is most common. In this type, T-cell antigen receptors on TH1 or TH2 lymphocytes bind to tissue antigens, causing clonal expansion of lymphocytes and release of pro-inflammatory lymphokines. Distinc clinical entities such as contact dermatitis (eg, poison ivy) or tuberculin skin test sensitivity in pulmonary tuberculosis may occur relative to the site of the tissue antigen.