Hypersensitivity and Anaphylaxis

Question 1

Define hypersensitivity

Answer 1

An inappropriate and excessive immunological reaction to an external antigen due to dysfunctional control of the immune system

Allergy= local reaction

Anaphylaxis = systemic reaction

Question 2

Define allergen

Answer 2

An antigen capable of producing a hypersensitivity reaction

Question 3

Give an example of type 1 hypersensitivity reactions.

What are type 1 reactions mediated by?

Answer 3

Anaphylaxis, allergies, asthma, atopy.

Mediated by IgE and mast cells

Question 4

Describe the pathology of type 1 hypersensitivity reactions

Answer 4

• First exposure:
  
  • ​Antigen activation of T_H2 cells and stimulation of B cell IgE class switching.
  • IgE production from B cells
  • IgE binds to mast cells
• Second exposures:
  
  • Activation and degranulation of mast cells (release of mediators)
    
    • Vasoactive amines and lipid mediators → immediate hypersensitivity reaction
    • Cytokines → late phase reaction

Question 5

Describe the process of mast cell degranulation: which substances are released and what effects do they have?

Answer 5

Second exposure of antigen = activation of mast cells = release of mediators (degranulation):

• Exocytosis of granules with pre-formed mediators:
  
  • Vasoactive amines → vascular dilation, smooth muscle contraction
  • Proteases → tissue damage
• Lipid mediators (secretion)
  
  • Prostaglandins → vascular dilation
  • Leukotrienes → smooth muscle contraction
• Cytokines (secretion)
  
  • E.g. TNF → inflammation, leukocyte recruitment

Question 6

Describe the clinical features of a type 1 hypersensitivity reaction

Answer 6

• Airway and eye mucous membranes →pruritis and sneezing, rhinorrhoea and lacrimation.
• Skin →pruritis and urticaria
• Oral and GI mucous membranes → pruritis and angioedema
• Systemic hypersensitivity →
  
  • Local swelling
  • Vasodilation
  • Flushed skin
  • Dizziness
  • Dyspnoea
  • Wheeze
  • Chest-tightness
  • Peri-oral paraesthesia (esp. food)
  • Pale
  • Sweating
  • Hypotension
  • Low GCS

Question 7

Give examples of type IV hypersensitivity reactions. What are they mediated by?

What may be seen clinically?

Answer 7

Normal cytotoxic T cell response (slow and specific) but excessive and inappropriate. More localised than type I

e.g. contact dermatitis from nickel and other metals, latex

Clinical features: slowly developing, localised reactions

Question 8

What investigations can be carried out to prove type I hypersensitivity reactions?

What investigations can be carried out to identify the specific allergen (for type I and IV reactions)?

Answer 8

To confirm type I: measurement of blood markers such as tryptase, IgE, eosinophils.

To identify specific allergen: skin prick testing; +ve result = lesion >3mm larger than negative control.

Question 9

How can hypersensitivity reactions be treated?

Answer 9

• Avoidance
• Mast-cell stabilisers
• Anti-histamines (blockage of histamine receptors)
• Steroids (anti-inflammatory)
• Leukotriene receptor antagonists
• De-sensitisation (exposure)

Question 10

How should anaphylaxis be treated?

Answer 10

• Airway, breathing, circulation
• Lie pt down
• High flow O₂
• IV fluids
• Adrenaline
• IV chlorphenamine
• IV hydrocortisone
• Salbutamol nebs
• Rpt adrenaline if no effect after 5 mins