Lecture 20 Hypersensitivity Reactions

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Lecture 20Hypersensitivity Reactions

• Immune responses that result in tissue injury

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Immune-mediated hypersensitivity reactions

• Type I - Anaphylactic/Atopic
• Type II - Cytotoxic
• Type III - Toxic Complex
• Type IV - T-cell mediated

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Immune-Mediated Hypersensitivities
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Anaphylactic/Atopic Hypersensitivity(Type I )
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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

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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)
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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

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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

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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

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Mast Cell Activation/Degranulation
Antigen


IgE
Fc Receptor
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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

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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

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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

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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
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T Cell Control of the IgE Response
antigen
Ts cells
Thymectomy
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6
specific IgE (arbitrary units)

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2
control
0
5
4
3
2
1
-1
0
Weeks
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Hyposensitization
Allergen injections
Symptoms
IgG
Activity
Lymph. Trans.
IgE
Time
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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)