Hypersensitivity Reactions

Injurious, patologic immune reactions causing tissue injury and disease

Excessive or aberrant immune response to:

Foreign antigens (non-self)- non-infectious (environmental)- infectious

Self (autologous) antigens failure of self-tolerance (autoimmunity, autoimmune diseases)

Types of Hypersensitivity Reactions

Type I

Type II

Type III

Type IV

Antibodymediated

T cellmediated

Type I(Immediate hypersensitivity)

(Allergy)

Atopy – inherited propensity of an individual to produce high levels of IgE to various environmental antigens

Alergen – an antigen that induces immediate hypersensitivity in atopic people

"in recognition of his work on anaphylaxis"

Charles Richet

1913Nobel Prize of Medicine and

Physiology

Common allergens

Common allergens

Food allergens (“the big eight”)

The sequence of events

The sequence of events

Type I hypersensitivity

Biochemical events in mast cell activation

High level IgE production is determined by:

• Genetic factors(MHC II, cytokines, cytokine receptors...)

• Nature of allergen(mass, glycosylation, charge, stability)

• Environmental factors(exposure to microbes, polution, smoking...)

Clinical manifestasions

• Alergic conjuctivitis• Alergic rhinitis (hay fever)• Alergic (bronchial) asthma• Hives (Urticaria)• Atopic dermatitis• Food allergy• Anaphylaxis (systemic)

Testing for type I hypersensitivityin vivo

Skin tests Prick testing Intradermal testing

Provokativni testoviBronchoprovocative tests (metacholin chloride or alergen)DBPCFC (Double-Blind Placebo-Controlled Food Challenge)

15 min.

Prick testing

Swelling

2mm › negative control – positive

≥ 5mm – clinically relevant

5-10 mm weak sensitivity10-15 mm moderate

sensitivity › 15 mm strong sensitivity

Swelling and redness

Testing for type I hypersensitivityin vitro

Total IgE nephelometry ...

Alergen specific IgE

RAST (RadioAllergoSorbent Test) EIA (PHADIA ImmunoCap ...)

Therapy

• Inhibition of mast cell degranulation (cromolyn)

• Blocking of mast cell mediator effects (antihistamines)

• Reduction of inflammation (corticosteroids)

• Bronchial smooth muscle relaxation (phosphodiesterase inhibitors)

• “Desensitization” – repeated administration of allergen

• Epinephrine - anaphylaxis