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.

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).

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.

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.

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 IgE (FcεRI). Effector phase:

1-IgE Cross-linking.

2-Mast cell degranulation.

3-Release of vasoactive amines, Lipids, and cytokines.

Type I Hypersensitivity (sensitization phase):N

Type I Hypersensitivity (Effector phase):N

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 vasoconstriction.

2 -Lipid mediators :

A-Leukotriene C4,and D4 ; similar to histamine effect.

B-PAF (platelet aggregation: microthrombosis)

C-Prostaglandins D2 : edema and pain .

3-Cytokines: TNF .

Clinical examples on Type I Hypersensitivity:

1-Localized reaction in Skin: Urticaria Eczema

2-Systemic Anaphylaxis: In bloodstream. Lethal effect.

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).

Mechanism of inflammation in Hypersensitivity Type II:

-IgG , IgM , Complement, and Cytotoxic cells are involved in this type of inflammation.

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 .

Type III Hypersensitivity: -Immune Complex hypersensitivity. -Soluble Immune complexes: (IgG- short peptide-IgG) or (IgG-Animal sera-IgG). -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.

Mechanism of Inflammation in Type III Hypersensitivity:

-Immune complex (IgG), complement, and Neutrophils are involved.

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 .

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 .

Mechanism of inflammation in type IV :

-DTH cell,and toxin or neoantigen are involved.

Clinical example:

Tuberculin test: