Fig. 7. Early and late phase reactions in AR. (A) Early phase reaction: Ligation of allergen-specific IgE-FcεRI complexes by the corresponding allergen on mast cells activates mast cells to secrete preformed mediators (e.g. histamine and tryptase) and lipid-derived mediators (e.g. PGD2, LTB4 and PAF), which increase vascular permeability, mucus secretion, and blood vessel dilation. This results in watery rhinorrhea, mucosal edema, and nasal congestion. Stimulation of sensory nerves in the nose results in sneezing and sensations of nasal itch and congestion (adapted from Galli and colleagues [142]). (B) Late phase reaction: Ligation of IgE-FcεRI complexes by allergen on mast cells results in release of newly synthesized cytokines, chemokines and growth factors, which contribute to the late phase reaction. Mast cells promote the influx and activation of inflammatory leukocytes (such as neutrophils, eosinophils and T cells) by producing TNF-α, LTB4, IL-5, IL-8, and CCL2. T cells that recognize allergen-derived peptides also release products (e.g. IL-4, IL-13, and IL-9) and contribute to late-phase reactions. IL-4 and IL-13 released by Th2 cells can stimulate mast cells to produce more IgE and induce goblet cell hyperplasia, which results in excess mucus production. The recruited immune cells have some downstream effects. For example, elastase released by neutrophils promotes activation of matrix metalloproteinases and degradation of type III collagen. Basic proteins released by eosinophils can cause epithelial cell damage (adapted from Galli and colleagues [142]).