Hypersensitivity

Hypersensitivity

An immune response that causes damage to host tissue

Gell and Coombs classification

System dividing hypersensitivity reactions into Types I–IV

Type I hypersensitivity

IgE-mediated immediate allergic reaction involving mast cell degranulation

Type I antigen

Heterologous antigens known as allergens or atopic antigens

Type I mediator

IgE

Type I complement involvement

1-Complement is not involved

Type I time course

Seconds to minutes with a late-phase reaction at 6–8 hours

Type I first exposure

Sensitization phase where IgE is produced and binds mast cells without symptoms

Type I second exposure

Allergen crosslinks IgE on mast cells causing degranulation and symptoms

Reason two exposures are needed in Type I

Mast cells must be sensitized with IgE before degranulation can occur

Type I preformed mediators

Histamine, proteases, chemotactic factors

Type I newly synthesized mediators

Cytokines and prostaglandins

Clinically relevant cells in Type I

Mast cells, basophils, CD4 T cells, B cells

Examples of Type I hypersensitivity

Anaphylaxis, hay fever, food allergies, asthma

Atopy

Inherited predisposition to develop IgE-mediated allergic reactions

Inherited factors in atopy

Genetic tendency toward increased IgE production and Th2 responses

General treatment of Type I hypersensitivity

Allergen avoidance, antihistamines, corticosteroids, epinephrine, immunotherapy

Type I diagnostic methods

Specific IgE blood testing, skin testing, clinical symptoms

Specific IgE testing

Direct measurement of allergen-specific IgE, Phadia assay is gold standard

RAST test

Older solid-phase IgE assay that is becoming obsolete

Type II hypersensitivity

Antibody-mediated cytotoxic reaction targeting cell surface antigens

Type II mediator

IgG primarily or IgM

Type II complement involvement

2-Complement is involved

Type II time course

Minutes to hours

Type II immune mechanism

Antibody binds cell surface antigen leading to complement-mediated cytolysis

Examples of Type II hypersensitivity

Transfusion reactions, autoimmune hemolytic anemia, HDN, autoimmune organ destruction

Warm autoantibodies

IgG autoantibodies associated with viruses, drugs, or idiopathic causes

Cold autoantibodies

IgM autoantibodies often associated with bacterial antigens

Type III hypersensitivity

hyper- Immune complex-mediated reaction causing tissue damage via complement activation

Type III mediator

IgG or IgM immune complexes

Type III complement involvement

3-Complement is involved

Type III time course

Hours to days

Type III immune mechanism

mech- Immune complex deposition triggers inflammation and tissue injury

Examples of Type III hypersensitivity

SLE, rheumatoid arthritis, serum sickness, Arthus reaction

Type III order of events

Immune complex formation, deposition, complement activation, tissue damage

Complement levels in Type III disease

Decreased during active disease due to consumption

Type IV hypersensitivity

Delayed T-cell–mediated hypersensitivity reaction

Type IV mediator

Sensitized T cells and cytokines

Type IV complement involvement

4-Complement is not involved

Type IV time course

Weeks after first exposure, hours to days after re-exposure

Type IV immune mechanism

T cells release cytokines that recruit macrophages and cause inflammation

Examples of Type IV hypersensitivity

Contact dermatitis, tuberculin skin test, pneumonitis

TB skin test

Delayed hypersensitivity reaction read at 72 hours

Normal immune response

Protective immune reaction that eliminates pathogens without host damage

Hypersensitivity response

Exaggerated immune reaction resulting in host tissue injury