Type 1 Hypersensitivity

Question 1

Type I hypersensitivity

Answer 1

Trigger: exogenous antigens

Antibody: IgE

Mechanism: TH2 triggers IgE causing mast cells to release inflammatory mediators

Target: environmental, non infectious antigens

Outcome:
- local reaction - ingested or inhaled allergens
Systemic reactions- insect sting (in blood) or IV administration

Time: less than 30 mins

Question 2

Allergens

Answer 2

Seasonal exposure: tree and grass pollen

Perennial exposure:

• house dust mite
• animal dander
• fungal spores

Accidental exposure:

• animal venom
• drugs
• chemicals e.g. latex
• Foods

Question 3

Mechanism of type I hypersensitivity

Answer 3

Abnormal adaptive immune response against allergens

• TH2 response stimulating IL 4,5,13
• IgE production - activates mast cells

Question 4

Mast cell location

Answer 4

Skin - dermatitis
Lungs - asthma
Nose - hay fever

Question 5

Hygiene theory of allergy

Answer 5

• less infectious burden as child, more likely to develop inappropriate allergic response
• depends on environment I.e.
  > large families - share infectious burden with others
  > low antibiotic use
  > pets

Question 6

Western lifestyle

Answer 6

Alteration of the symbiotic relationship with parasites and bacteria leading to dysbiosis of the microbiome at mucosal surface e.g gut due to:

• stress
• pollution
• drugs
• C-section
• high fat diet

Question 7

Origin of mast cells

Answer 7

Produced by bone marrow
Mature in tissue due to stem cell factor and FCERI
Travels to mucous membranes and blood vessels

Question 8

FCER1

Answer 8

High affinity IgE receptor for the FC region of IgE

Question 9

Mast cell mediators

Answer 9

Tryptase - remodels connective tissue matrix

Histamine - toxic to parasites, increases vascular permeability, vasoconstriction

Leukotrienes: vasoconstriction, increases vascular permeability, increases mucus secretion

Platelet activating factor - attract leukocytes, activate neutrophils, platelets and eosinophils

Question 10

TH2 process

Answer 10

1. Atrophy alleles
2. Allergen stimulates TH2 response to produce IgE on first exposure
3. The antigen specific IgE binds to the cell surface of mast cell FCER1 systemically causing sensitisation
4. On second exposure, the allergen causes IgE cross linking
5. This stimulates mast cell degranulation
6. Histamines and chemokines are released and leukotrienes and prostaglandins and produced
7. Causes bronchoconstriction, increased cell permeability and vasodilation

Question 11

Urticaria

Answer 11

Itchy, erythematous rash with swelling

Caused by mast cell activation within the epidermis

Mediators: histamine and leukotrienes/ cytokines

Prolonged exposure can cause atopic dermatitis and eczema

Question 12

Angioedema

Answer 12

Caused by mast cell activation of the deep dermis
Affects lips, eyes, tongue and upper respiratory airways
Can also cause life threatening airway obstruction

Mediators: histamine and bradykinin

Question 13

Systemic allergic reaction

Answer 13

Allergen present in the blood circulation e.g bee venom
Causes systemic activation of mast cells causing:
- hypotension - vasodilation and loss of blood volume as increased vascular permeability
- generalised urticaria - superficial dermis
- angioedema - deep dermis
- breathing problems - bronchoconstriction

Question 14

Anaphylaxis

Answer 14

Acute onset
Rapidly progressive

Affects skin + another organ e.g.

• CVS
• Resp
• GI

Question 15

Known systemic anaphylaxis

Answer 15

No skin symptom required

• bronchoconstriction
• hypotension
• severe GI tract symptoms

Question 16

Treatment of anaphylactic shock

Answer 16

Intramuscular adrenaline ASAP

Beta 2 receptors - reverses bronchoconstriction and causes bronchodilator

Beta 1 receptors - increases the force of myocardial contraction- positive inotropy

Alpha 1 receptors - reverses peripheral vasodilation and causes vasoconstriction, alleviates hypotension

• reduced oedema
• reduced airway obstruction and bronchospasm
• inhibits mast cell activation

Question 17

Monitoring anaphylaxis

Answer 17

Monitor:
Pulse
Blood pressure 
ECG 
Oximetry

Question 18

Epinephrine therapy

Answer 18

Biphasic - require second dose
IM administration
Specific use of epipen but poorly known

Question 19

Type I hypersensitivity therapy

Answer 19

• Oral immunotherapy - allergen desensitisation against TH2 response
• Anti-IgE monoclonal antibody

Decreased mast cell activation:

• anti-histamine
• leukotriene receptor antagonist
• corticosteroid

Question 20

Allergen desensitisation

Answer 20

Administration of increasing doses of allergen extracts over a period of years, given via injection or sublingual tablets/ droplets