**6. Immune signaling mechanism of IgE-mediated hypersensitivity (allergy)**

Mast cells and basophils degranulation process is considered to be a prime signaling event for the development of allergic disease. Cross bridging of mast cell bound IgE molecules by allergen is thought to initiate the activation through Fc epsilon R1 receptor bound G protein coupled GTPase. This in turn causes the activation of phospholipase C and release phosphatidyl inositol bisphosphate (PIP2) and diacyl glycerol (DAG) from membrane lipids. The Inositol triphosphate (IP3) produced induce the release of calcium (Ca2+) from endoplasmic reticulum and increase intracellular calcium levels [27, 28]. Increased Ca2+ in cytoplasm activates certain enzymes such as myosin light chain kinase and calmodulin. Calcium combined with DAG activates protein kinase C (PKC), these intracellular events trigger the migration of preformed granules in mast cells and basophils to their periphery. The preformed granules fuse with plasma membrane and release granular contents through exocytosis process [29]. In the same time these events also promote generation of lipid mediators like prostaglandins and leukotrienes resulting in the induction of allergic inflammation (**Figure 3**).
