1. ALLERGIC REACTIONS

2. HYPERSENSITIVITY State of heightened immune reactivity What causes the problems Multistep Dormant Reaction (either or both) Antibody – within minutes Cell-mediated – 2-3 days There are 4 types of hypersensitivity – we’ll talk about Type I IgE-mediated Hypersensitivity today

3. TYPE I I G E-MEDIATED HYPERSENSITIVITY Varies in severity Can mean systemic anaphylaxis (vigorous contractions of smooth muscle) Characteristic of Humoral Immune Response

4. STEPS OF TYPE I -- SENSITIZATION 1.Entry of antigen into body (antigen=allergen) 1 st dose = sensitizing dose 2.Immune system response (B lymphocytes  plasma  IgE antibodies) 3.IgE circulates and attaches to mast cells and basophils 4.Increasing amounts of IgE on mast cells and basophils Person becomes sensitized

5. STEPS AFTER SENSITIZATION 5. Allergen binds with IgE on mast cells or basophils Cross-linking occurs

6. STEPS CONTINUED 6.Cross-linking triggers degranulation Release of granule contents Inflow of Ca2+ Stimulation of adenylyl cyclase ATP  cyclic AMP Granules swell and repress adenylyl cyclase Decreased cAMP means degranulation occurs! Role of epinephrine 7.Release of histamine 8.Release of leukotrienes, prostaglandins, and cytokines

7. SYSTEMIC ANAPHYLAXIS Degranulation through out body! Contract smooth muscles Edema Rash and itching/burning GI tract Bronchial muscles Death within 10-15 minutes

8. ALLERGIC REACTIONS Localized Anaphylaxis

9. ATOPIC DISEASES Localized anaphylaxis (common allergy) ~20% of US population Limited production of IgE (in comparison to systemic anaphylaxis) and sensitization of mast cells in localized areas (Still more IgE than normal individuals) Ex: Allergic rhinitis

10. LATE-PHASE ANAPHYLAXIS Takes several hours for inflammation to show Mast cells release chemotactic factors Eosinophils Neutrophils Helper T Cells

11. ASTHMA Triggers 2 parts Early response – mast cells in lower respiratory tract Late response – eosinophils and neutrophils Treatments

12. FOOD ALLERGIES GI tract reaction Hives = wheal and flare

13. ECZEMA Atopic dermatitis IgE levels elevated Rash and itching Increased eosinophils and helper T cells Allergen unknown

14. WHY HYPERSENSITIVITY? B cells that produce IgA vs. B cells that produce IgE Atopic individuals have lower levels of IgA Suppressor T lymphocytes stop production of IgE – defective in atopic individuals

15. ALLERGIES POSITIVE? Sneezing GI contractions Resistance to pathogens Hygiene hypothesis

16. TREATMENT OF ALLERGIES Desensitization types Tiny but increasing doses of allergens Series of injections of allergens over weeks -- blocking antibodies Monoclonal antibodies – anti-IgE antibodies