Practice question

Severe persistent allergic asthma pathophysiology centers on Th2 polarization with interleukin-4 and interleukin-13 driving class switch recombination from IgM to IgE mediated by AID and germline ε transcription in B cells within bronchial associated lymphoid tissue. Secreted IgE circulates at low concentration 150 ng per ml but binds extremely high affinity FcεRI alpha chain Kd 10^-10 M on mast cells and basophils through Cε3 domain interaction, sensitizing them for months despite short serum half-life two days. Upon re-exposure to perennial aeroallergen such as Dermatophagoides pteronyssinus Der p1, multivalent allergen crosslinks receptor-bound IgE triggering Lyn and SYK tyrosine kinase activation, phospholipase Cγ mediated calcium rise, degranulation releasing preformed histamine causing bronchial smooth muscle contraction, mucus hypersecretion, vascular permeability, plus newly synthesized leukotriene C4, prostaglandin D2, and cytokines IL-5 recruiting eosinophils. Omalizumab humanized IgG1 binds Cε3 domain of free IgE at site overlapping FcεRI binding interface forming small biologically inert trimers cleared by hepatic reticuloendothelial Kupffer cells.