Immunology: Allergy

Question 1

Provide an overview of the immune mechanisms of allergic disorders.

Answer 1

• Allergy is defined as immediate hypersensitivity mediated by IgE (In minutes)
  
  • Usually involves IgE type 1 hypersensitivity reaction. Ie Ex excess IgE production.
• Adaptive immune response is made of Th1, Th2 and Th17 reactions. Allergies occur when T helper cells are skewed towards excessive Th2 reactions
• Allergies begin with disruption of epithelial cells (they are the ‘sensor’). The cells release ‘signalling’ cytokines. The cytokines act on Th2 lymphocytes, which in turn release ‘effector’ cytokines. Effector Cytokines act on effector cells (Such as eosinophils or basophils). This leads to allergen expulsion and mucous secretion.
• The lymphocytes, once activated by signalling cytokines, can activate B cells to generate IgE.
• IgE then binds to mast cells and eosinophils that have migrated into tissues
• If allergen crossreacts with IgE, the mast cells begin to degranulate and release histamine
• Type 2 immune response
  
  • Stressed epithelium
• Dedritic cell moves from periphery to local lymph node and presents antigen to Naïve T cell.
  
  • Sensitisation (Presence of IgE) can occur but doesn’t always lead to allergic disease
• This is caused by Th2 immune response (Th2 cells secreted IL-4 and make B cells secrete IgE)
  
  • Treatment depends on the type of reaction
  • T regulatory cells don’t regulate Th2 responses properly

Question 2

Examples of allergic diseases/disorders

Answer 2

• Anaphylaxis (Systemic)
  
  • Angioedema
  • Urticaria
  • Rhinitis
  • Asthma
  • Dermatitis/eczema

Question 3

Provide an overview of the epidemiology of allergic disorders.

Answer 3

• Atopic eczema: typically presents in the infant
  
  • Food allergies: usually 12-36 months (Toddler)
  • Allergic rhinitis and asthma: develop around 6-14 years
  • allergy affects 40% of the population in the developed world
  • Risk of allergy is inherited
  • Prevalence has increased in the developed world

Question 4

Outline the clinical features for suspected allergic disorders.

Answer 4

• Anaphylaxis
• Asthma/Rhinitis
• Urticaria
• Angioedema
• Atopic eczema
• Low blood pressure.
• Erythema

Question 5

Outline the diagnostic investigations for suspected allergic disorders.

Answer 5

• Skin prick testing: Pricking skin with known allergen.
• Blood testing: For presence of mast cell tryptase or specific IgE antibodies.
• Mast cell tryptase indicates mast cell degranulation

Question 6

Describe skin prick testing:

Answer 6

• Allergen is pricked into the dermis. It binds to specific IgE molecules or mast cells
  
  • Cross-linked IgE activates mast cells, which release mediators (eg histamine)
  • mediators cause vasodilation and opening of gaps between endothelial cells.
• Characteristic erythema (flare) and dermal swelling (Wheal) indicates a positive skin-prick test

Question 7

What are the clinical features of anaphylaxis?

Answer 7

• Hypotension
• Angioedema
• Airway obstruction
• Allergy to nuts, antibiotics

Question 8

What investigations are required in suspected anaphylaxis?

Answer 8

• Mast cell tryptase

- Specific IgE antibodies for specific allergens

Question 9

What are the treatments for anaphylaxis?

Answer 9

• Identification and avoidance of allergen
• Intramuscular adrenaline
  
  • 150mcg: paediatric dose
• Beta 2 agonist for airway dilation
• Sodium Cromoglycate: stabilises mast cells and prevents degranulation.

Question 10

What are the clinical features of food allergy?

Answer 10

• Upon exposure to allergen, a type I immune response can cause a number of allergic syndromes
• Anaphylaxis (Systemic reaction): Hypotension, angioedema, airway obstruction, urticaria (Skin rash).
• Or Angioedma, airway obstruction or urticarial can occur separately (Local reaction)

Question 11

What investigations are required in food allergy?

Answer 11

• Skin prick testing
• Mast cell tryptase
  
  • Presence of specific IgE antibodies using ELISA

Question 12

What are the treatments for food allergy?

Answer 12

• Identification and avoidance of allergen
• Beta 2 agonists to prevent airway constriction
• Adrenaline, intramuscular, to raise blood pressure and dilate airways
• Inducing T regulatory cells to stop Th2 hypersensitivity reactions(Allergen Immunotherapy)
• Antihistamines (eg chlorphenamine): slow acting
• Specific receptor blockers (eg Montelukast blocks the effects of leukotrienes, reducing airway inflammation).
• Corticosteroids: long term prevention
• Sodium Cromoglycate: stabilises mast cells and prevents degranulation.