Hypersensitivity Flashcards
What is Type I Hypersensitivity?
Immediate (anaphylactic) hypersensitivity. IgE mediated reaction to a substance that occurs minutes after contact to antigen
Describe general characteristics of Type I Hypersensitivity antigens
Low MW, highly soluble, stable proteins. Peptides can be expressed on MHCII and are effective at activating Th2-type cytokines (especially IL-4) and stimulate IgE response
Describe the molecular process of initial and subsequent exposure of allergen
Sensitization: allergen exposed causing activation of TH2 cells and class switching to IgE in B cells. Plasma cells secrete IgE which binds to FcR(epsilon) on mast cells, basophils, and eosinophils. Subsequent Exposure: Bound IgE-FCR(ep) crosslinks with antigen causing mast cell degranulation. Immediate hypersens. and Late phase rxns occur.
What are the effects of mast cell degranulation in a Type I Hypersensitivity rxn?
Vascular leak (histamine), bronchoconstriction, intestinal hypermotility, inflamm, tissue remodeling (enzymes [tryptase])
What are the terms used to describe the early and late phases of a Type I Hyper. Rxn?
Wheal and Flare
What causes hypermotility in a Type I Hyper. Rxn?
Eosinophils - their original purpose is to increase motility and mucous production to expel parasites
Describe the response of subcutaneous allergen Type I Hyper. Rxn.
Antigen activates mast cells which causes an increase in vascular permeability and localized swelling
Describe the response to inhaled allergens in Type I Hyper. Rxn.
Exposure: Inhaled allergen ingested by APC which activates T cells. Causes T cell secretion of IL-4 and IgE class switching. Subsequent exposure: Antigen activates mast cells which increase vascular permeability and activation of epithelium. Eosinophils enter nasal passages.
Describe the allergic asthma response
(Acute) Mucosal mast cells capture antigen which expel inflammatory mediators that contract smooth muscle, increase mucus secretion, and increase vascular permeability. (Chronic) TH2 cells produce IL-13 without allergen stimulation. Eosinophils also mediate. Chronic inflamm results in tissue remodeling
Describe reaction to food allergies
Sensitized mast cells release histamine which acts on epithelium, blood vessels, and smooth muscle resulting in urticaria, muscle contractions, vomiting, diarrhea, fluid outflow
Describe the response to systemic allergens
Most severe Type I rxn. Increased capillary permeability, swelling of tissues, loss of blood pressure, hypoxia, irregular heartbeat, anaphylactic shock, smooth muscle contraction of lungs, contraction of GI smooth muscle, N/V/D
Two hypotheses accounting for increased hypersensitivity
Hygiene hypothesis: poor hygeine -> exposure to TH1 infections which protect against allergy. Counter Regulation Hypothesis: Infections that lead to IL-10 and TGF(Beta) production downregulate both TH1 and 2 so less hypersensitivity
Tx of allergies
Avoid allergen, drugs (antihistamines, corticosteroids, montelukast), Desensitization via controlled exposure with allergy shots (increase IgG and A to block IgE), Allenergic peptide caccination to anergize allergen specific T cells
Describe type II Hypersensitivity Rxns. Examples?
Ab-mediated Cytotoxic Hypersensitivity. Mediated by IgG. Abs bind to antigen and cause lysis via complement or complement induced phagocytosis of cell-antigen-Ab complex. Mismatched blood transfusions or drug-modified surface antigens.
Describe type III Hypersensitvity Rxns.
Immune complex-mediated hypersensitivity. Large quantities of soluble antigen and their Abs form large latticed immune complexes that can deposit systemically in any of a variety of tissue sites causing occlusions
