1. Lecture 20 Hypersensitivity Reactions
Immune responses that result in tissue injury

2. Immune-mediated hypersensitivity reactions
Type I - Anaphylactic/Atopic
Type II - Cytotoxic
Type III - Toxic Complex
Type IV - T-cell mediated

3. Immune-Mediated Hypersensitivities

4. Anaphylactic/Atopic Hypersensitivity (Type I )

5. Atopy
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
Study Guide
Who develops Type I hypersensitivity?

6. Immediate 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)

7. IgE 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
Study Guide
Why is the Type I reaction usually a local event?

8. Characteristics of IgE
Heat labile
Fc binding destroyed by heating at 56°C 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
Study Guide
What does tissue-fixing mean?
Why is antigen binding not lost when the tissue-fixing ability is lost?
What is the significance of thelong half-life of IgE when bound to the mast cell?

9. IgE 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
Study Guide
What does your genetic backgroung put you at risk for?

10. Mast Cell Activation/Degranulation
Antigen
IgE
Fc Receptor
Study Guide
What causes mast cell degranulation?

11. Contents 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
Study Guide
What are the activities of the contents of the mast cell granules?

12. Comparison 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
Study Guide
What is the difference between IgG and IgE?

13. Risk of allergy: Family50 40
percent of children with atopy 30 20 10
Study Guide
Is there a genetic predisposition to be atopic?
none
one
both
number of parents with history of allergy

14. Risk of allergy: IgE Levels
100
Percent of subjects 80 60 40 20
<60
60-200
>450
Study Guide
What does the level of circulating IgE tell you?
% of population with given IgE concentration
% of subjects with that IgE concentration who are atopic

15. T Cell Control of the IgE Response
Thymectomy
antigen
Ts cells 8 6
specific IgE (arbitrary units) 4 2
Study Guide
What is the role of the T-suppressor cell in atopy?
control -1 1 2 3 4 5
Weeks

16. Hyposensitization Allergen injections IgG Activity Lymph. Trans. IgE
Symptoms
IgG
Activity
Lymph. Trans.
IgE
Time

17. Clinical 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)