Asthma Pathway

Inhaled allergens encounter antigen presenting cells (APC) that line the airway. Upon recognition of the antigen and activation by APC, naive T cells differentiate into Th2 cells, a process that is promoted by interleukin 4 (IL-4). Activated Th2 cells stimulate B cells to produce IgE antibodies in response to IL-4 and IL-13. IgE binds the high affinity IgE receptor at the surface of mast cells, the proliferation and differentiation of which is promoted by IL-9.The crosslinking of mast-cell-bound IgE by allergens leads to the release of biologically active mediators (histamine, leukotrienes) by means of degranulation and, so, to the immediate symptoms of allergy. Activated mast cells and Th2 cells also induce the production of IL-5. IL-5 travels to the bone marrow and regulates the differentiation and egress of eosinophils from the bone marrow into the blood. Moreover activated mast cells and Th2 cells in the lung generate the cytokines interleukin IL-4, IL-13 and tumour necrosis factor (TNF)-alpha. These cytokines stimulate the generation of eotaxin by lung epithelial cells, fibroblasts and smooth muscle cells. Eotaxin then stimulates the selective recruitment of eosinophils from the airway microvessels into the lung tissue. The activation of eosinophils leads to release of toxic granules and oxygen free radicals that lead to tissue damage and promote the development of chronic inflammation. (NCI Thesaurus/KEGG)

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