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