Lecture 16 Allergy Hay fever 20% Asthma ~5%

Figure 10-1

(hives) Allergies 4 types of hypersensitivity reactions

Delayed-type hypersensitivity Immune complex disease

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 10-4

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 (PGD 2, LTC 4 ) - inflammation Chemokines (MIP-1  ) - chemotaxis of leukocytes Cytokines - Production of eosinophils, Th2 cells Proteoglycans, heparin and chondroitin - sequester mediators, and effect a timed release

Prostaglandins and leukotrienes PGD 2 - vessel dilation and permeability and chemoattractant for neutrophils LTC 4 - same as histamine, but 100x more potent - late response. Leukotrienes used to be called Slow Reacting Substance of Anaphylaxis - SRS- A

Biologic effects of mediators

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

Eosinophils

Figure 10-9 part 1 of 2 Products released by eosinophils

Figure 10-10

Figure 10-12

Figure 10-14

Figure FEV1 - the forced expiratory volume of air in one second

Figure 10-18

Systemic anaphylaxis

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).

Asthma

Figure part 1 of 2

Figure part 2 of 2

Histopathology of bronchial asthma

Treatment of asthma

New therapy for asthma and allergy: blocking the Fc portion of IgE from binding to the Fc  R on mast cells

Ragweed Control Histamine Skin test for allergy

Food allergies

Type II hypersensitivity is caused by antibodies to altered cell-surface components

Figure 10-27

Type III hypersensitivity reactions (Arthus Reaction) Antibody-Antigen Complexes Critical mediators appear to be C5a-receptor and Fc  RIII--probably present on mast cells

Figure 10-31

Figure 10-29

Figure 10-32

Type IV hypersensitivity - Delayed-type hypersensitivity

Figure Also, note time scaleWhat is missing from this scheme?

Figure 10-35

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Figure 10-23