Hypersensitivity Reactions:

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. An antigen that produces a vigorous immune response in which the immune system fights a threat that is harmless to the body.

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).

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.

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.

Tow types according to the site of reaction: Localized reaction: Skin, eye, Nasopharynx, Broncho pulmonary or GIT. Systemic reaction: In Bloodstream: venom or toxin. Lethal effect.

Mast cells Originate from the bone marrow and are scattered in the connective tissues of the body, especially skin, near blood vessels, respiratory system, and digestive tract). very similar to basophils (have granules that contains allergy mediators)

Mechanism of Type I Hypersensitivity: Sensitization phase: Exposure to allergen. Isotype switching to IgE Sensitization of Mast cell by IgE (FcεRI). Effector phase: IgE Cross-linking. Mast cell degranulation and release of vasoactive amines, lipids and cytokines and attraction of eosinophils.

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 D2: edema and pain. Cytokines: TNF.

Localized reaction in Skin: Urticaria Eczema

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

Within extracellular matrix (Example: Basement membrane). IgG , IgM , Complement, and Cytotoxic cells are involved in this type of inflammation. Sites of occurrence of Type II reactions: On cell surface (Example: RBCs). Within extracellular matrix (Example: Basement membrane).

Examples on Type II Hypersensitivity: Alloimmune hemolytic anemia: Erythroblastosis fetalis (maternal IgG X fetal RBCs) Alloimmune hemolytic anemia: Blood transfusion anemia (recipient IgM against donor RBCs) Goodpasture’s syndrome (kidneys & lungs). Graves Disease ( Antibodies against TSH receptors) leading to activation.

Recipient

Type III Hypersensitivity: Soluble immune Complex hypersensitivity. (IgG- short peptide or IgG- animal sera). Lead to inflammation at the site of their deposition. Types of Allergen: Exogenous: e.g. animal sera. Endogenous: soluble self antigens.

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).

Two types: Localized (Arthus reaction) example: in skin: Intradermal injection of antigen in skin; necrotizing vasculitis. Systemic (Serum sickness): Wide dissemination of immune complexes.

Clinical Examples: Serum sickness disease associated with: -Some types of food allergy. -Prophylactic vaccine (animal antisera). Symptoms develop after 7-10 days and is self-limiting after clearance of the antigen. Systemic lupus erythematosus (self antigens). Rheumatoid arthritis (self antigens).

Type IV Hypersensitivity: known as cell mediated (CD4 or CD8) or delayed type hypersensitivity. Antibodies are not involved. The classical example of this hypersensitivity is tuberculin (Mantoux) reaction which peaks 48 hours after the injection of antigen (tuberculin).

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 pathogens e.g. M. tuberculosis. T cell mediated cytotoxicity: caused by CD8 T lymphocytes.

Contact dermatitis

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

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