Immune Hypersensitivity Chapter 18

1. Immune Hypersensitivity Chapter 18 Self-Test Questions: Intro: all A1-2: all A3: 1, 3, 5 A4: all B: 1, 2, 4, 5 C: 1 - 4 D: 1 - 4 Hypersensitivities

2. What characteristics are shared by all hypersensitivies? Immune responses: Primary (sensitization) response Secondary (activation) response Abnormal (hyper-) response to antigens (allergens) Symptoms: localized or systemic Onset can be: Early, Late or Chronic Hypersensitivities

3. What are hypersensitivities? 4 types of hypersensitivities (Gel and Combs classification) Immune Namesystem involvedEffectorsEffectsOnset Type 1 “Atopic” Humoral (IgE) mast cells inflammation seconds eosinophils (anaphylaxsis) Type II “Cytotoxic” Humoral/ macrophages cell destruction hours Complement complement (hemolysis) Type III “Im. Complex” Humoral/ granulocytes inflammation hours Complement Type IV “Delayed type” Cell-mediated macrophages inflammation days -- TH1 Hypersensitivities

4. IgE is linked to common allergies Initial exposure -- “sensitization” Humoral response and IgE production Later exposure -- antigen binds to IgE -- mast cell degranulation later Hypersensitivities

5. Early phase responses Molecular Mediators: Primary– in granules -- histamine -- serotonins, etc. Secondary– synthesized later (w/in 1- few minutes) Localized clinical response (Atopy) atopic asthma: urticaria (hives) eczema (skin lesions) atopic rhinitis food allergies Systemic clinical response (anaphylaxis) anaphylatic shock Hypersensitivities

6. Late phase responses -- 4-6 hours later e.g., Erythema, etc “peak flow rate” measurements Due to: -- Cytokines from mast cells -- Recruited eosinophils & TH2 -- degranulation Chronic Type I -- eosinophilia -- inflammation: damaged airways & mucous membranes Early phase Late phase Hypersensitivities

7. What factors affect predisposition toward Type I hypersensitivities? Genetic factors Environmental factors Hygiene hypothesis Hypersensitivities

8. Treatment Skin testing -- carries some risk Drugs therapies -- Theophylline (blocks degranulation) -- antihistamines (block histamine receptors) -- epinephrine (reverses trachael & bronchiole SM and contracts arteriole SM) Desensitization Desensitization Therapy Hypersensitivities

9. Type II hypersensitivity -- “Cytotoxic” Ig binding to AG on cells -- triggers cell lysis Complement mediated Macrophage mediated Various types of “immunohemolytic anemia” e.g., Blood transfusion incompatibility {see section in chapter 17} Some penicillin rxs -- other drugs Various autoimmune disorders -- multiple sclerosis -- myasthenia gravis RBC being phagocytosed in fetal erythroblastosis 1967 Science 158: cover Hypersensitivities

10. Type III hypersensitivity • -- “immune complex” • Localized:(Arthus reaction) • -- could result from an insect bite • Ag-Ab complex • Excess AG  small complexes •  complement activation • 2) mast cell degranulation • 3) neutrophil recruitment • 4) Triggering of inflammation • Systemic: • Serum sickness • Vasculitis C3a, C5a Hypersensity pneumonitis -- Pigeon breeders disease (pigeon feces dust) -- Farmers lung (Actinomycetes) -- Mushroom picker’s… -- Cheese washer’s… -- Chicken plucker’s… -- etc., … disease Adapted from Majno and Joris, 2004, Cells, Tissues and Disease Type III Hyper Hypersensitivities

11. Type IV hypersensitivity “Delayed-type” -- slow onset ~day(s) (if sensitized) TH1-cell mediated Sensitization phase-- week(s) onset -- TH1 expansion Effector stage– day(s) onset -- TH1 & macrophage activation -- inflammation Latex type IV hypersensitivity Hypersensitivities

12. Type IV, cont. Contact Dermatis is a different type of allergic response -- T-cell / macrophage -- involves hapten production -- hair sprays, plant toxins, turpentine, etc. Hypersensitivities Latex type IV hypersensitivity

13. Tuberculosis (see Chapter 14 pp 212-213) -- Persistent Mycobacterium tuberculosis Granuloma (tubercule) formation TH1cells and activated macrophages ‘caseous’ regions extended tissue destruction Hypersensitivities