1.2.2 Type I HSRs Mechanism of Reaction

Question 1

Outline the immune mechanism of allergic reaction

Answer 1

1. Allergen 1st exposure, TH2 response
2. Antigen specific IgE produced, binds to mast cell
3. In second exposure, antigen binds to two IgE on the mast cell and causes IgE crosslinking
4. Mast cell degranulation leads to:
5. Increased vascular permeability, vasodilation and bronchial constriction

Question 2

What happens when there is mast cell activation wtihin the epidermis?

Answer 2

Urticaria-hives

Prolonged and chronic exposure can lead to atopic dermatitis and eczema

Question 3

What mediators are involved in allergic reactions of the epidermis?

Answer 3

Histamine
Leukotrienes (made from arachidonic acid)/ cytokines

Question 4

What manifestations of the face can occur due to mast cell activation in deep dermis?

Answer 4

Angioedema- Emergency as can block airways

Swelling of lips, eyes, tongue and upper respiratory tract

Mediators: Histamine and bradykinin

Question 5

What is anaphylaxis?

Answer 5

Systemic activation of mast cells

Question 6

What happens in anaphylaxis?

Answer 6

• Hypotension
• Cardiovascular collapse
• Generalised urticaria
• Angioedema
• Breathing problems

Need to run ABC assessment, airways, breathing, circulation

Can result in 35% drop in blood pressure within minutes

Question 7

What are the signs and symptoms of anaphylaxis?

Answer 7

Confusion, loss of consciousness

Shortness of breath, wheezes or stridor

Pain with swallowing

Fast or slow heart rate
Low BP

Skin- hives etc

Question 8

How do you treat anaphylactic shock?

Answer 8

IM adrenaline, lateral thigh

Question 9

What is the mechanism of treatment when using adrenaline for anaphylaxis?

Answer 9

• At concentrations above physiological concentration of adrenaline, adrenaline has increased affinity for A1 receptors which causes peripheral vasoconstriction, reducing oedema and alleviating hypotension
• Reverses airway bronchospasm, B2 receptors
• Increases ionotropy, B1 receptors
• Inhibits mast cell activation

DO NOT DELAY TREATMENT
Monitor pulse, BP, ECG and oximetry

Question 10

What are 4 key points about adrenaline therapy?

Answer 10

• Timesaver vs lifesaver-can have biphasic reaction
• IM
• Multiple doses may be required
• Need to use epipen properly, need to educate

Question 11

Give 5 examples of IgE-mediated allergic reactions

Answer 11

• Systemic anaphylaxis
• Acute urticaria (wheal and flare)
• Allergic rhinitis- hay fever
• Asthma
• Food allergy

Question 12

What therapy is avaiable against abnormal adaptive immune response against allergens T1HSRs?

Answer 12

TH2 response- Allergen desensitisation (oral immunotherapy)

Omalizumab- Anti-IgE monoclonal antibody

Mepolizumab- Anti-IL5 monoclonal antibody

Question 13

What therapy is available for mast cell activation?

Answer 13

Anti-histamines
Leukotriene receptor antagonists
Corticosteroids

Question 14

What is allergen desensitisation?

Answer 14

Administration of increasing doses of allergen extracts over a period of years, given to patients by injections or drops/tablets under tongue

90% effective in patients with bee and wasp venom anaphylaxis

Highly effective in kids with certain allergies

Idea is to prevent future anaphylaxis/ reactions to allergens

Question 15

How does allergen densensitisation work

Answer 15

Shift from TH2 to TH1
Change from IgE mediated reaction to IgG