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These receptors are expressed on mast cells, basophils, eosinophils, monoctyes, macrophages, T-cells, basophils, and DCs.31,35 H4 receptors mediate the recruitment of mast cells, eosinophils, and T-lymphocytes to the site of allergen-induced inflammation.35,38 This further amplifies the histamine-mediated immunopathological response in the conjunctiva.33 In ocular allergy, histamine binding to H4 receptors on eosinophils primes eosinophils to respond to eotaxin, a chemokine for eosinophils.31 Immunopathological mechanisms Exposure of the MEK inhibitor review conjunctiva to allergens is associated with an immunopathological response that occurs in three phases �C sensitization, early phase, and late phase. Sensitization phase The sensitization phase of allergic conjunctivitis occurs on initial exposure of the conjunctiva to airborne allergens such as pollen. When the allergens are deposited on the conjunctiva, the allergen via action of their proteolytic enzymes degrade the tight junction of the conjunctiva epithelial cells in order to gain access to immune cells such as macrophages, DCs, and mast cells. The immature DCs will engulf the allergen, process it, and undergo biochemical changes that lead to the upregulation of major histocompatibility complex (MHC) class II molecules. The processed allergen is displayed as a peptide in association with MHC class II molecules on the DCs. The mature DC will migrate to the regional lymph node where they activate na?ve T-cells to proliferate and differentiate into Th2-lymphocytes.39 The Th2-lymphocytes secrete cytokines such as IL-4, IL-5, and IL-13.5,13 Additionally, the na?ve B-lymphocyte interacts with the same allergen, processing the allergen into peptides that are presented in association with MHC class II molecules as a peptide:MHC class II complex on the B-cell receptors. Interaction between T-cell receptors of the allergen-specific Th2-lymphocytes and B-cell receptors of the allergen-activated B-lymphocytes in conjunction with CD40�CCD40L interactions in the presence of IL-4 will trigger the proliferation and differentiation of the B-lymphocyte into IgE-secreting plasma cells.40,41 Additionally, allergens in contact with the conjunctiva can trigger conjunctival epithelial cells to produce thymic stromal lymphopoietin (TSLP), which in turn activates DCs through TSLP�CTSLPR receptor interaction to induce the activation of na?ve T-cells via OX40L�COX40 signaling pathways42,43 and their subsequent differentiation into Th2 cells that produce IL-4 that induce B-cells to produce IgE-secreting plasma cells.44 TSLP is capable of causing ocular itch via activation of TSLP receptors on sensory neurons and/or immune cells that release mediators that interact with their respective sensory receptors.45 Thus, TSLP also participates in the initiation of the sensitization process and the exacerbation of allergic eye diseases.