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Hypersensitivity Reactions
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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)
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Types of Hypersensitivity Reactions
Type I
Type II
Type III
Type IV
Antibodymediated
T cellmediated
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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
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"in recognition of his work on anaphylaxis"
Charles Richet
1913Nobel Prize of Medicine and
Physiology
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Common allergens
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Common allergens
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Food allergens (“the big eight”)
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The sequence of events
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The sequence of events
Type I hypersensitivity
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Biochemical events in mast cell activation
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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...)
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Clinical manifestasions
• Alergic conjuctivitis• Alergic rhinitis (hay fever)• Alergic (bronchial) asthma• Hives (Urticaria)• Atopic dermatitis• Food allergy• Anaphylaxis (systemic)
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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)
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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
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Testing for type I hypersensitivityin vitro
Total IgE nephelometry ...
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Alergen specific IgE
RAST (RadioAllergoSorbent Test) EIA (PHADIA ImmunoCap ...)
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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