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CLASSIFICATION OF IMMUNE-MEDIATEDINJURY (HYPERSENSITIVITY)

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19.4 CLASSIFICATION OF IMMUNE-MEDIATEDINJURY (HYPERSENSITIVITY)

Under certain circumstances immune responses can produce tissue damage. These deleterious reactions are collectively known as hypersensitivity or allergy. Hypersensitivity reactions have been divided into four types (originally proposed by Gell and Coombs) based on mechanism (Table 19.5). In all cases the adverse effects of hypersensitivity develop in two stages: (1) Induction (sensitization) requires a sufficient or cumulative exposure dose of the sensitizing agent to induce immune responses that cause no obvious symptoms. (2) Elicitation occurs in sensitized individuals upon subsequent exposure to the antigen and results in adverse antigen-specificresponses that include inflammation.

Type I hypersensitivity (sometimes referred to as atopy) is mediated by an antigenspecific cytophilic antibody (usually IgE) that binds to mast cells and basophils. On subsequent exposure, the allergen binds to these cell-boundantibodies andcross-linksIgE molecules, causing the release of mediators such as histamine andslow-reactingsubstance of anaphylaxis(SRS-A).These mediators cause vasodilation and leakage of fluid into the tissues, plus sensory nerve stimulation (leading to itching, sneezing, and cough). Type I is also calledimmediate-typehypersensitivity because reactions occur within minutes after exposure of a previously sensitized individual to the offending

Table 19.5 Classification of Hypersensitivity Reactions

 

Mechanisms

 

 

 

 

 

 

Induction (Initial

Elicitation (Re-exposure

 

Type

Exposure to Antigen)

to Antigen)

Example

 

 

 

 

I

Clonal expansion of B

Antigen binds to cell

Anaphylactic response to

(immediate)

cells; Cytophilic

bound antibody,

bee sting

 

antibody (IgE)

cross-linksreceptors,

 

 

generated; binds to

causing release of

 

 

mast cells

mediators

 

II

Clonal expansion of B

Anamnestica Ig

Rh factor

(cytolytic)

cells; IgM, IgG

response; binds to cell

incompatibility,

 

generated. Antigen

bound antigen and in

Hemolytic anemia in

 

binds to cell

the presence of

reaction to drug

 

membrane

complement or

treatment

 

 

activated macrophages

 

 

 

cell lysis occurs

 

III

Clonal expansion of B

Anamnestic Ig response;

glomerular nephritis,

(Arthrus)

cells; IgM, IgG

antigen antibody

rheumatic heart

 

generated

complexes form in

disease, farmers lung

 

 

some tissues leading

 

 

 

to inflammation

 

IV

Clonal expansion of

T cells activated, release

contact dermatitis

(delayed)

antigen-specificT

cytokines, activate

 

 

cells occurs

macrophages,

 

 

 

inflammation

 

a Heightened response onre-exposureto antigen.