Early and late phases of an allergic reaction in the nasal tissues

This schematic shows pathways (including significant cells and cytokines) underlying early (left) and late (right) phase nasal reactions. This is a simplified overview of what is known about the immunopathogenesis of allergic rhinitis. However, the complexity of the process is appreciated in greater detail, providing information which may ultimately result in new therapies. First, proteases from inhaled allergens promote penetration of the nasal epithelial barrier and release of epithelial cytokines to include thymic stromal lymphopoietin, IL-25, and IL-33. These cytokines polarize dendritic cells to interact with lymphocytes promoting a Th2-type cascade of events as dendritic cells then process allergen and present it to naive T-cells and B-cells in lymph nodes. Allergen specific T-follicular helper cells and Th2 lymphocytes; and, type 2 innate lymphoid cells (with no T-cell receptor) respond by producing IL-4, IL-5, and IL-13 that facilitate B-lymphocyte isotype switches to IgE production and the resulting plasma cells produce allergen-specific IgE. That IgE binds to FceR1 on nasal mast cells. With repeat allergen exposure, nasal mucosal mast cells are activated and release mediators of immediate hypersensitivity. Nasal symptoms begin with mast cell mediator release of vasoactive amines and lipid mediators that produce the immediate allergic response. Cytokines are also released that subsequently produce the late phase allergic response. Those cytokines promote in-migration of activated neutrophils, eosinophils, basophils and helper T- cells with increased IL-4, IL-5, IL-9 and IL-13 release that produces the nasal inflammation of the late phase response.