Hematolymphatic and nonhematolymphatic cells in the pathogenesis of allergic airway disease. The left half of the figure focuses on the role of hematolymphatic cells (1-6) and the right half on the role of nonhematolymphatic cells (eg, airway epithelial cells and smooth muscle cells; 7-10). Dendritic cells (1) present peptides from the allergen to allergen-specific CD4 T cells (2). CD4 T cells secrete cytokines like IL-4, IL-5, and IL-13 (3). IL-4 and IL-13 stimulate the differentiation of B cells into IgE-plasma cells. IL-5 recruits eosinophils and stimulates their differentiation (4). IgE binds to FcεRI on the mast cells or basophils (5). Mast cells, basophils, and eosinophils release vasoactive, chemotactic, and other inflammatory mediators (histamine, leukotrines, etc) (6) resulting in edema, smooth muscle hyperresponsiveness and hypertrophy, basal membrane thickening, and mucus secretion. Perhaps due to the influence of the hematolymphatic cells (?) epithelial cells do the following. Epithelial cells release TARC and IL-16 that activate CD4 T cells (via CCR4 receptor), leading to release of cytokines like IL-4, IL-5, and IL-13 (7). Epithelial cells release GM-CSF and chemokines like RANTES and Eotaxin that lead to recruitment and activation of eosinophils (via CCR3 receptors)(8). Epithelial cells release growth factors like PDGF and EGF that stimulate smooth muscle cells to proliferate and secrete histamine (9). Smooth muscle cells are also activated by mast cells. Epithelial cells release proinflammatory cytokines like TNF-α (stimulates macrophages and dendritic cells) and IL-8 (recruits neutrophils; 10).