Hypersensitivity Reactions Definitions Hypersensitivity reactions inflammatory immune responses

Hypersensitivity Reactions: Definitions: Hypersensitivity reactions: inflammatory immune responses induced by repeated antigen exposure resulting in host tissue damage. Allergen: is a nonparasitic antigen capable of stimulating hypersensitivity reactions. 1

Types of Hypersensitivity: Hypersensitivity reactions are divided according to mechanism of action into four groups: 1 -Type I (Immediate hypersensitivity). 2 -Type II (Cytotoxic hypersensitivity). 3 -Type III (Immune complex hypersensitivity). 4 -Type IV (Cell-mediated hypersensitivity). 2

Types of Allergen: Exogenous: 1 - Animal products. 2 - Drugs ( penicillin) 3 - Food : Egg albumen, Corn, legumes (peanuts, soybeans), milk, and seafood. 4 - Insect venom. 5 - Mold spores. 6 - Plant pollens. Endogenous: -Self antigen. 3

Type I Hypersensitivity: -Commonly known as allergic or immediate hypersensitivity. -Two types according to affected body sites: 1 -Localized reaction: Skin, eye, Nasopharynx, Bronchopulmonary, and GIT. 2 -Systemic reaction: In Bloodstream. -The reaction takes 15 -30 minutes to appear as inflammatory response. -It could appear as a delayed response (10 -12 hours later). -Examples: Eczema, Urticaria , Hay fever, Asthma. 4

Mechanism of inflammation in Hypersensitivity Type I: Sensitization phase: 1 -Exposure to allergen. 2 -Isotype switching (IL-4, IL-13 activity). 3 -Sensitization of Mast cell by Ig. E (FcεRI). Effector phase: 1 -Ig. E Cross-linking. 2 -Mast cell degranulation. 3 -Release of vasoactive amines, Lipids, and cytokines. 5

Type I Hypersensitivity (sensitization phase): N 6

Type I Hypersensitivity (Effector phase): N 7

Mast cell inflammatory mediators and their action: 1 - Biogenic amines ( histamines): A-Bronchiole constriction, and mucus secretion from Goblet cell. B- Endothelial vasodilation ; increased vascular permeability, and smooth muscle contractions. 2 - Lipid mediators: A-Leukotriene C 4, and D 4 ; similar to histamine effect. B-PAF (platelet aggregation: microthrombosis) C-Prostaglandins D 2 : edema and pain. 3 -Cytokines: TNF. 8

Clinical examples on Type I Hypersensitivity: 1 -Localized reaction in Skin: Urticaria Eczema 2 -Systemic Anaphylaxis: In bloodstream. Lethal effect. 9

Type II Hypersensitivity: -Known as Cytotoxic Hypersensitivity. -Allergen could be: 1 -Endogenous: Cell surface protein. 2 -Exogenous: Drug metabolite adsorbed onto cell membrane. -Sites of occurrence of Type II reactions: 1 -On cell surface (Example: RBCs). 2 -Within extracellular matrix (Example: Basement memb). 10

Mechanism of inflammation in Hypersensitivity Type II: -Ig. G , Ig. M , Complement, and Cytotoxic cells are involved in this type of inflammation. 11

Clinical Examples on Type II Hypersensitivity: 1 -Immune Hemolytic Anemia: A-Alloimmune hemolytic anemia. : Erythroblastosis fetalis B-Autoimmune hemolytic anemia. : Blood transfusion anemia. 2 -Goodpasture’s syndrome (nephritis). 3 -Graves Disease. 12

Type III Hypersensitivity: -Immune Complex hypersensitivity. -Soluble Immune complexes: (Ig. G- short peptide-Ig. G) or (Ig. G-Animal sera-Ig. G). -Two types: 1 -Localized in skin: Example: Arthus reaction. Intradermal injection of antigen in skin; necrotizing vasculitis. 2 -Systemic: Example: Serum sickness disease. -Types of Allergen: 1 -Exogenous. 2 -Endogenous: self antigen. 13

Mechanism of Inflammation in Type III Hypersensitivity: -Immune complex (Ig. G), complement, and Neutrophils are involved. 14

Clinical Examples on Type III Hypersensitivity: 1 -Serum sickness disease that associated with: -Some types of Food allergy. -The prophylactic Vaccine. 2 -Systemic lupus erythematosis. 3 -Rheumatoid arthritis. 15

Type IV Hypersensitivity: - known as cell mediated or delayed type hypersensitivity. - The classical example of this hypersensitivity is tuberculin (Montoux) reaction which peaks 48 hours after the injection of antigen (tuberculin). -Three types: 1 -Contact dermatitis: toxic sensitizer or neoantigen. 2 -Delayed type hypersensitivity(DTH): Granulomatous inf. 3 -T cell mediated cytotoxicity. 16

Mechanism of inflammation in type IV: -DTH cell, and toxin or neoantigen are involved. 17

Clinical example: Tuberculin test: 18