Hypersensitivity reactions László L. Tornóci Semmelweis University Institute of Pathophysiology http://xenia.sote.hu/depts/pathophysiology
Jan 19, 2016
Hypersensitivity reactions
László L. Tornóci
Semmelweis University
Institute of Pathophysiology
http://xenia.sote.hu/depts/pathophysiology
Classification
Type Name
1 Immediate hypersensitivity
2 Antibody-mediated cytotoxicity (sometimes without tissue damage)
3 Immune complex reaction
4 Delayed type hypersensitivity
Type 1 hypersensitivity reaction
Hypersensitivity of immediate type
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
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)
Diseases
• urticaria
• allergic rhinitis
• atopic eczema
• asthma
• food allergy
• anaphylaxy
Bee sting
Food allergy
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)
Dermatophagoides mite
Type 1: pathomechanism
Activation of mast cells
Activation of Th1 and Th2 cells
Factors involved in Th1/Th2 activation
Heredity
• MHC class II
• FcRI ( subunit)
• IL-4 cytokine cluster
• IL-4 receptor ( subunit)
A few genes causing atopy
Diagnostics, total IgE
Diagnostics, skin prick test
The advantage of type 1 reaction
Type 2 hypersensitivity reaction
Antibody-mediated cytotoxicity
Diseases
• Incompatible blood transfusion
• Autoimmune hemolytic anamia (AIHA)
• Goodpasture syndrome
• Pemphigus vulgaris (Ag: desmoglein)
Mechanisms
• complement activation MAC cytolysis
• complement activation, chemotaxis
• ADCC reaction
• „frustrated phagocytosis”
“Frustrated phagocytosis”
Symptoms of the transfusion reaction
• fever
• BP drop
• lumbar pain
• chest pain
• nausea, vomiting
Maternal-fetal Rh incompatibility
Erythroblastosis fetalis
Autoimmune hemolysisThe “innocent bystander”
mechanism
Diagnostics: indirect Coombs’ test
Type 2 reaction without tissue damage
Blocking antibodies
Type 3 hypersensitivity reaction
Immune complex reaction
Circulating immune complexes
Cause AntigenPlace of
deposition
chronic infection microbial Agsite of infection,
kidneys
autoimmunity autoantigenkidneys, joints,
vessels, skin
external environmental Ag lungs
Diseases
• classic serum sickness
• serum sickness-like reaction caused by drugs
• immune complex reaction caused by infections
• systemic autoimmune diseases
The time course of serum sickness
Occurrance of immune complexes
Pathomechanism
Type 4 hypersensitivity reaction
Delayed type hypersensitivity reaction
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
Contact allergy
Contact eczema
Tuberculin test
Leprosy