Type I Hypersensitivity Flashcards
What is the sensitization phase in type I hypersensitivity?
Primary exposure causes patient to be sensitized to allergen - allergen activation of Th2 cells and stimulation of IgE class switching in B-cells w/production of IgE. IgE Ab bind to mast cells
What is the process by which individuals prone to allergies produce IgE antibody?
Encounter with allergen results in activation of Th2 cells that secrete IL-4 and IL-13 that stimulate B-cells to class switch from IgG to IgE. IgE Ab binds to the Fce receptor on mast cells.
What is the effector phase in type I hypersensitivity?
Secondary exposure to an allergen results in immediate activation of mast cells - degranulation of inflammatory mediators. Late phase rxn 6-24h post exposure, eosinophils, leukotrienes and prostaglandins are mainly responsible for prolonged inflammation
What are the primary mediators and cytokines released by mast cells and basophils in type I hypersensitivity rxn?
Histamine, eosinophil chemotactic factor, neutrophil chemotactic factor, IL-4, IL-5, IL-6, TNF-a. Basophils triggered by IgG1 release PAF instead of histamine.
What are the secondary mediators released by mast cells and basophils in type I hypersensitivity rxn?
Leukotrienes and prostaglandins are released and synthesized de novo within minutes of mast cell or basophil degranulation.
What are the clinical manifestations of immediate hypersensitivity rxns (type I)?
1) allergic rhinitis, sinusitis, hay fever
2) food allergies
3) bronchial asthma
4) anaphylaxis
What are diagnostic tests for type I hypersensitivity?
1) patch test - erythema (vascular dilation) and edema (vascular permeability)
2) RAST test - checks for presence of IgE in serum (measures amt of IgE bound to radiolabeled anti-IgE antibody)
What are clinical interventions for type I hypersensitivity?
1) allergen-specific immunotherapy (hyposensitization)
2) acute desensitization
3) mast cell stabilization - cromolyn
4) immunosuppressants - corticosteroids
5) anti-IgE monoclonal Abs - omalizumab
6) anti-histamines - H1 receptor blockers
What is allergen-specific immunotherapy (hyposensitization)?
Administration of low doses of allergen and gradually increasing the dose over months to induce production of IgG instead of IgE. Th2 responses change to Th1 responses.
Aka grass shots, allergy shots
What is acute desensitization?
Administration of very low doses of allergen q 10-15m to slowly trigger all mast cells via IgE (done in the ICU)
What is omalizumab and what is its action?
Omalizumab is an anti-IgE monoclonal Ab that binds to the Fc portion of IgE blocking IgE from binding with the Fce receptor on mast cells
Why do we have IgE antibodies?
Eosinophils and mast cells provide the best protection against worms and parasites via release of granule contents
What is the mechanism of cromolyn?
Inhibits mast cell degranulation