hypersensitivity reactions lászló l. tornóci semmelweis university institute of pathophysiology
TRANSCRIPT
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Hypersensitivity reactions
László L. Tornóci
Semmelweis University
Institute of Pathophysiology
http://xenia.sote.hu/depts/pathophysiology
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Classification
Type Name
1 Immediate hypersensitivity
2 Antibody-mediated cytotoxicity (sometimes without tissue damage)
3 Immune complex reaction
4 Delayed type hypersensitivity
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Type 1 hypersensitivity reaction
Hypersensitivity of immediate type
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Terminology
• Hypersensitivity of immediate type
fastest reaction of all four
• Allergy
rare, tissue damage
• Anaphylaxy
generalized, severe reaction
• Atopy
an umbrella term for genetic susceptibility
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Clinical significance
• Very common, increasing trend– 30-40% of the population in developed countries– gets more and more common since 1800– very great (10-15-times) geographical difference
• The anaphylactic reaction is rare, but sever (may cause death)
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Diseases
• urticaria
• allergic rhinitis
• atopic eczema
• asthma
• food allergy
• anaphylaxy
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Bee sting
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Food allergy
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Common allergens
• pollen (grass, tree, flower)
• household dust (mite: Dermatophagoides pteronyssinus)
• animal hair (cat, dog)
Airways:
Enteral/parenteral (anaphylactic reaction):• drug (e.g. penicillin)
• food (milk, fish, shellfish, peanut)
• sting (bee, wasp)
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Dermatophagoides mite
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Type 1: pathomechanism
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Activation of mast cells
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Activation of Th1 and Th2 cells
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Factors involved in Th1/Th2 activation
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Heredity
• MHC class II
• FcRI ( subunit)
• IL-4 cytokine cluster
• IL-4 receptor ( subunit)
A few genes causing atopy
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Diagnostics, total IgE
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Diagnostics, skin prick test
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The advantage of type 1 reaction
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Type 2 hypersensitivity reaction
Antibody-mediated cytotoxicity
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Diseases
• Incompatible blood transfusion
• Autoimmune hemolytic anamia (AIHA)
• Goodpasture syndrome
• Pemphigus vulgaris (Ag: desmoglein)
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Mechanisms
• complement activation MAC cytolysis
• complement activation, chemotaxis
• ADCC reaction
• „frustrated phagocytosis”
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“Frustrated phagocytosis”
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Symptoms of the transfusion reaction
• fever
• BP drop
• lumbar pain
• chest pain
• nausea, vomiting
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Maternal-fetal Rh incompatibility
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Erythroblastosis fetalis
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Autoimmune hemolysisThe “innocent bystander”
mechanism
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Diagnostics: indirect Coombs’ test
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Type 2 reaction without tissue damage
Blocking antibodies
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Type 3 hypersensitivity reaction
Immune complex reaction
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Circulating immune complexes
Cause AntigenPlace of
deposition
chronic infection microbial Agsite of infection,
kidneys
autoimmunity autoantigenkidneys, joints,
vessels, skin
external environmental Ag lungs
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Diseases
• classic serum sickness
• serum sickness-like reaction caused by drugs
• immune complex reaction caused by infections
• systemic autoimmune diseases
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The time course of serum sickness
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Occurrance of immune complexes
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Pathomechanism
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Type 4 hypersensitivity reaction
Delayed type hypersensitivity reaction
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Types of delayed hypersensitivity reaction
Type of reaction Time of maximal reaction
Jones-Mote 1 day
contact 2-3 days
tuberculin 2-3 days
granulomatous at least 2 weeks
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Contact allergy
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Contact eczema
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Tuberculin test
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Leprosy