Title: Lecture 20 Hypersensitivity Reactions
1Lecture 20Hypersensitivity Reactions
- Immune responses that result in tissue injury
2Immune-mediated hypersensitivity reactions
- Type I - Anaphylactic/Atopic
- Type II - Cytotoxic
- Type III - Toxic Complex
- Type IV - T-cell mediated
3Immune-Mediated Hypersensitivities
4Anaphylactic/Atopic Hypersensitivity(Type I )
5Atopy
- Describes the clinical features of individuals
who develop Type I hypersensitivity - increased vascular permeability
- local edema
- itching
- Strong hereditary linkages
- Mediated by a serum factor termed "reagin"
- "Wheal and flare" reaction
6Immediate and Late-Phase Reactions
Wheal-and-flare reaction (lasts up to 30 min post
injection)
Late-phase reaction (develops approximately eight
hours later and persists several hours)
7IgE response is a local event
- site of allergen entry
- local synthesis results in sensitization of local
mast cells - spillover of IgE enters circulation and
sensitizes mast cells and basophils systemically
8Characteristics of IgE
- Heat labile
- Fc binding destroyed by heating at 56C for 30
min - antigen binding is not lost
- Half-life
- serum half-life is 2 1/2 days (IgG is 21 days)
- mast cell bound half-life is 12 weeks
9IgE Levels in Disease
- Normal levels do not preclude atopy
- 30 of random population allergic to at least one
common allergen - Genetic background puts individual at risk
- family history indicates predisposition for atopy
- cannot predict specific reactions(s)
- higher level of IgE associated with increased
risk of atopy
10Mast Cell Activation/Degranulation
Antigen
IgE
Fc Receptor
11Contents of the Mast Cell Granules
- Active agent Activity
- Histamine Increases vascular permeability
elevates level of cyclic AMP - Heparin Anticoagulation
- Serotonin Increases vascular permeability
- SRS-A Increases vascular permeability causes
contraction of human broncholes - Chymase Proteolysis
- Hyaluronidase Increases vasuclar permeability
- Eos. Chem. Factor Chemoattraction of eosinophils
- Neut. Chem. Factor Chemoattraction of neutrophils
- Platelet Agg. Factor Aggregates platelets
12Comparison of IgE and IgG1 Structure
- heavy chain domains 5 vs. 4
- mol. wt. 188,000 vs. 146,000
- carbohydrate 12 vs. 2-3
- half-life (serum) 2 1/2 vs. 21d
13Risk of allergy Family
50
40
percent of children with atopy
30
20
10
0
none
one
both
number of parents with history of allergy
14Risk of allergy IgE Levels
100
Percent of subjects
80
60
40
20
0
lt60
60-200
200-450
gt450
of population with given IgE concentration
of subjects with that IgE concentration who are
atopic
15T Cell Control of the IgE Response
antigen
Ts cells
Thymectomy
8
6
specific IgE (arbitrary units)
4
2
control
0
5
4
3
2
1
-1
0
Weeks
16Hyposensitization
Allergen injections
Symptoms
IgG
Activity
Lymph. Trans.
IgE
Time
17Clinical Tests for Allergy
- Skin Tests
- Immediate Response (wheal flare reaction 20
min) - increased vascular permeability
- local edema
- itching
- Late Reactions (5-24 hr)
- RAST (Radio Allergo Sorbant Test)