Lecture 20 Hypersensitivity Reactions - PowerPoint PPT Presentation

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Lecture 20 Hypersensitivity Reactions

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Lecture 20 Hypersensitivity Reactions Immune responses that result in tissue injury – PowerPoint PPT presentation

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Title: Lecture 20 Hypersensitivity Reactions


1
Lecture 20Hypersensitivity 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

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

8
Characteristics 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

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

10
Mast Cell Activation/Degranulation
Antigen


IgE
Fc Receptor
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

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

13
Risk of allergy Family
50
40
percent of children with atopy
30
20
10
0
none
one
both
number of parents with history of allergy

14
Risk 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
15
T 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
16
Hyposensitization
Allergen injections
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)
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