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Lecture 16 Allergy. Hay fever 20% Asthma ~5%. Figure 10-1. 4 types of hypersensitivity reactions. (hives). Allergies. Immune complex disease. Delayed-type hypersensitivity.
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Lecture 16 Allergy • Hay fever 20% • Asthma ~5%
4 types of hypersensitivity reactions (hives) Allergies
Immune complex disease Delayed-type hypersensitivity
Type I hypersensitivity-mediated by mast-cell degranulation. Preformed granules contain histamine, heparin, TNF, chondroitin sulfate, neutral proteases, and other. Mucosal mast cell/Connective tissue mast cell
Figure 10-5 In granules Produced after activation
Histamine Binds to histamine receptors: H1, H2, H3-cell-type specific Binding to H1 on: endothelial cells (increased permeability); smooth muscle (contraction); mucosal epithelium (mucus secretion)
Mediators Neutral proteases activate Metalloproteases - remodeling of the extracellular matrix TNF- inflammation Lipid Mediators (PGD2, LTC4) - inflammation Chemokines (MIP-1a) - chemotaxis of leukocytes Cytokines - Production of eosinophils, Th2 cells Proteoglycans, heparin and chondroitin - sequester mediators, and effect a timed release
Prostaglandins and leukotrienes PGD2- vessel dilation and permeability and chemoattractant for neutrophils LTC4- same as histamine, but 100x more potent - late response. Leukotrienes used to be called Slow Reacting Substance of Anaphylaxis - SRS-A
Biological effects of Eosinophil mediators Late stage of an allergic response includes the recruitment of eosinophils and Th2 cells contrast with a DTH (type IV) response which includes infiltration of macrophages and Th1 cells
Figure 10-9 part 1 of 2 Products released by eosinophils
Figure 10-16 FEV1 - the forced expiratory volume of air in one second
Use of adrenaline to counteract the effects of system anaphylaxis In anaphylactic shock, blood vessels leak, bronchial tissues swell and blood pressure drops, causing choking and collapse. Adrenaline (epinephrine) acts quickly to constrict blood vessels, relax smooth muscles in the lungs to improve breathing, stimulate the heartbeat and help to stop swelling around the face and lips (angioedema).
New therapy for asthma and allergy: blocking the Fc portion of IgE from binding to the FceR on mast cells
Skin test for allergy Ragweed Control Histamine
Type II hypersensitivityis caused by antibodies to altered cell-surface components
Type III hypersensitivity reactions (Arthus Reaction)Antibody-Antigen Complexes Critical mediators appear to be C5a-receptor and FcgRIII--probably present on mast cells
Figure 10-34 What is missing from this scheme? Also, note time scale