Hypersensitivity reactions http://xenia.sote.hu/depts/pathophysiology László L. Tornóci Semmelweis University Institute of Pathophysiology
Classification
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 Airways: Enteral/parenteral (anaphylactic reaction): pollen (grass, tree, flower) household dust (mite: Dermatophagoides pteronyssinus) animal hair (cat, dog) 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 A few genes causing atopy MHC class II FcRI ( subunit) IL-4 cytokine cluster IL-4 receptor ( subunit)
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 hemolysis The “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 Antigen Place of deposition chronic infection microbial Ag site of infection, kidneys autoimmunity autoantigen kidneys, 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 granulomatous at least 2 weeks
Contact allergy
Contact eczema
Tuberculin test
Leprosy