Atopy and allergy 1

Question 1

Early phase allergic reaction

Answer 1

Exposure to allergens in sensitised individuals leads to rapid development of symptoms.

Mechanism

• Allergens specific to IgE bind to IgE on mast cells
• IgE are bound to FceR1 on mast cells.
• Binding of allergen triggers degranulation of mast cells to release histamines and other inflammatory mediators.

Question 2

Leukotrienes

Answer 2

Delayed mediator that triggers inflammation

Can be released as a result of mast cell activation
- Through the release of phospholipase A2 (to arachidonic acid)

Question 3

Pharmacological effects of mast cell mediators and leukotrienes

• skin
• nose
• eyes
• lungs

Answer 3

Skin= wheal and flare

Nose

• Increased mucus production
• Sneezing

Eyes
- Conjunctivitis

Lung
- Wheeze

Question 4

Effects of mast cell activation of

• GI
• Airway
• Blood vessels

Answer 4

GI
- Increased fluid secretion and peristalsis= vomiting and diarrhoea.

Airway
- Bronchoconstriction and increased mucus= wheeze, cough, swelling.

Blood vessels
- Increases blood flow and permeability= oedema, lymph enlargement, increase of effector response in tissues.

Question 5

Common allergen sources

Answer 5

Pollen [hayfever]

House dust mite faeces

Stinging insect venom

Question 6

Characteristics of allergens

Answer 6

Mainly proteins
- Because that is what T cells recognise

Can cross mucus membranes [soluble, LMW]
- Allows it to activate immunity

Biologically active

Moderate homology with self-antigens
- Enough to bind to MHC without getting deleted during negative selection

Question 7

Anaphylasxis

Answer 7

Generalised allergic reaction
- Release of histamine causes generated vasodilator and fluid entry into tissue.

Causes:

• Food allergens
• Drugs
• Insect venom

Presents:

• Hives
• Angioedema
• Laryngeal oedema
• Bronchoconstriction

Question 8

Oral allergy syndrome

Answer 8

Food allergy
- IgE against pollen [mainly birch] cross reacts with homologous proteins in plant foods [rosaceae fruits].

Secondary exposure to food after allergen exposure= oral itching with raw fruits, nuts, vegetables.

Question 9

Airway disease

Answer 9

Exposure to allergen causes lower airway obstruction/ rhinitis

Can be:

• Seasonal [hayfever]
• Episodic [occupational, animal]

Question 10

Allergic march

Answer 10

Progression of disease from infancy that typically leads to asthma.

1. Eczema
2. Food allergy
3. Rhinitis
4. Asthma
   - Eczema and food allergies usually outgrown

Question 11

Chronic allergic inflammation in asthma

Answer 11

Airway undergoes remodelling due to constant exposure of airborne allergens

• Inflammatory infiltrates
• Thickened basement membrane and smooth muscle
• due to late phase allergic reaction

Question 12

Late phase allergic reaction

Answer 12

Follows early phase

• Less rapid response
• Involves infiltration of inflammatory cells: CD4, eosinophils, mast cells

Question 13

Th1

Answer 13

Releases IFN-gamma, IL-2

- Stimulates inflammation

Question 14

Th2 cells

Answer 14

Releases IL-4, 5, 9, 13.

• Acts eosinophils, basophils, and mast cells, B cells.
• Important in the production of IgE and activation of mast cells

Overactivation against autoantigen will cause Type1 IgE-mediated allergy and hypersensitivity

Question 15

Th17 cells

Answer 15

Produces IL-17= proinflammatory

Question 16

Th2 and allergy

Answer 16

Important in allergic inflammation, by releasing IL 4, 5, 9, 13.

IL-4

• B cell class switching to IgE
• [w/ IL-3] Mucus hyper secretion

IL-5
- Required for eosinophil survival

IL-9
- Recruits mast cells

IL-13
- Bronchial hyper-responsivemenss

Question 17

Hygiene hypothesis

Answer 17

States that lack of early childhood exposure to infectious agents, leads to the increased susceptibility into developing allergies.

Environments less likely to develop allergic diseases (but more likely to develop infectious disease)
- low hygiene levels
- High pathogen load
- High helminth infection load
= skews immunity from th2 to Th1
- induces Treg cells