1. Hypersensitivity Reactions

2. Hypersensitivity reactions: Inflammatory immune responses induced by repeated antigen (allergen) exposure resulting in host tissue damage. Allergen: o A nonparasitic antigen capable of stimulating hypersensitivity reactions. o An antigen that produces a vigorous immune response in which the immune system fights a threat that is harmless to the body.

3. Examples of Allergen:  Exogenous: Animal products: fur and dander, cockroach calyx, wool, dust mite excretion Drugs ( penicillin, sulfonamides) Food : egg albumen, corn, legumes (peanuts, soybeans), milk, and seafood. Insect venom. Mold spores. Plant pollens ( hay fever)  Endogenous: Self antigen.

4. Types of Hypersensitivity: Four groups: according to mechanism of action into Type I (Immediate hypersensitivity). Type II (Cytotoxic hypersensitivity). Type III (Immune complex hypersensitivity). Type IV (Cell-mediated hypersensitivity) (delayed hypersensitivity).

5. Type I Hypersensitivity: Known as allergic or immediate hypersensitivity. The reaction takes 15-30 minutes to appear. It could appear as a delayed response (10-12 hours later). Examples: eczema, urticaria, hay fever, asthma.

6. Tow types according to the site of reaction:  Localized reaction: Skin, eye, nasopharynx, bronchopulmonary or GIT.  Systemic reaction: In bloodstream: venom or toxin. Lethal effect.

7. Mechanism of Type I Hypersensitivity: o Sensitization phase: Exposure to allergen. IL4, IL13: isotype switching; IgE production Sensitization of mast cell by IgE (FcεRI). o Effector phase: Exposure to the same allergen. IgE cross-linking. Mast cell degranulation and release of vasoactive amines, lipids and cytokines and attraction of eosinophils.

10. Mast cell inflammatory mediators:  Biogenic amines ( histamines): Bronchiole constriction, and mucus secretion from goblet cell. Vasoconstriction and capillary endothelial vasodilation ; increased vascular permeability (fluid loss and shock).  Lipid mediators: Leukotriene; similar to histamine effect. PAF (platelet aggregation): micro thrombosis Prostaglandins D 2 : edema and pain.  Cytokines: TNF.

11. Localized reaction in Skin: Urticaria Eczema

12. Type II Hypersensitivity: Known as cytotoxic hypersensitivity. Allergen could be:  Endogenous: Cell surface proteins  Exogenous: Drugs adsorbed onto cell membrane.

13. Sites of occurrence of Type II reactions: – On cell surface (Example: RBCs). – Within extracellular matrix (Example: Basement membrane). Mechanism of inflammation in Hypersensitivity Type II: IgG, IgM, complement, and cytotoxic cells are involved in this type of inflammation.

16. Examples on Type II Hypersensitivity: o Alloimmune hemolytic anemia: Alloimmune hemolytic anemia: blood transfusion reaction (recipient IgM against donor RBCs) Erythroblastosis fetalis (fetus anaemia): maternal IgG X fetal RBCs in Rh – ve mothers. o Goodpasture’s syndrome (kidneys & lungs). o Graves Disease ( Antibodies against TSH receptors) leading to activation.

17. Recipient

18. Type III Hypersensitivity: Soluble immune Complex hypersensitivity IgG-antigen-IgG. Lead to inflammation at the site of their deposition. Types of Allergen: o Exogenous: e.g. animal sera, drugs…. o Endogenous: soluble self antigens.

19. Mechanism of type III hypersensitivity reaction: Ag-Ab (IgG) complexes accumulate and deposit (usually in the endothelium) leading to complement activation and neutrophil attraction (C3a, C4a, C5a). This will lead to inflammation (necrotizing vasculitis).

21. Types and clinical examples:  Localized (Arthus reaction): example: -Necrotizing vasculitis: in the skin: intradermal injection of antigen. -Rheumatoid arthritis (self antigens).  Systemic: wide dissemination of immune complexes. – Serum sickness disease associated with: some types of food allergy and prophylactic vaccine (animal antisera). Symptoms develop after 7-10 days and is self- limiting after clearance of the antigen. – Systemic lupus erythematosus (self antigens)

22. Type IV Hypersensitivity:  Known as cell mediated (CD4 or CD8) or delayed type hypersensitivity.  The reaction occurs 24-72 hours after exposure.  The classical example of this hypersensitivity is tuberculin reaction (Mantoux) which peaks 48 hours after the injection of antigen (tuberculin).

23.  Three types: Contact dermatitis: toxic sensitizer absorbed through epidermis, bind self proteins & form neoantigen. Delayed type hypersensitivity(DTH): Granulomatous inflammation, not limited to the dermis. Usually due to intracellular pathogens e.g. M. tuberculosis. T cell mediated cytotoxicity: caused by CD8 T lymphocytes. reactive chemicals (haptens) pass through the cell membrane, bind to cytoplasmic proteins to produce neoantigen which will be presented by MHC class I

24. Contact dermatitis

25. Clinical example: Tuberculin (Mantoux) test (DTH)

27. Erythema induratum (Bazin disease): nodules in the legs due to sensitivity to some pathogens e.g. M.tuberculosis