Immunology 6 - Allergy Flashcards
What is the difference in CD4 T cell response between microbial recognition and allergen recognition?
Microbe: PAMP is recognised –> Th1 and Th17 response
Allergen: functional change caused by release of proteolytic enzymes by the allergen is recognised (eg tissue damage) –> Th2 response
How does Th2 activation cause mast cell degranulation?
Th2 secretes IL4
IL4 activates B cells to produce IgE and IgG4
IgE and IgG4 binds to high affinity Fc receptor on mast cells–>causes mast cells to degranulate and secrete:
- prostaglandins
- leukotrienes
- histamines
- proteases
Why does atopic dermatitis predispose to allergic sensitisation?
Skin exposure more likely to lead to IgE response than oral exposure
Which interleukin is most important in Th2 cell responses?
IL4
formation is only induced following peptide-MHC presentation to naïve/memory Th2 cells
Why do filagrin mutations increase risk of allergic disease?
Increase risk of atopic dermatitis which increases allergen exposure
What represents a positive result in a skin-prick allergy test?
Wheal >3mm (path lecture)/ >2mm (path guide) bigger than control
Recall 2 limitations of skin prick allergy testing
- Necessary for diagnosis but is insufficient alone
- Result does not predict severity of reaction
- not as good for some fruit and vegetables
What can component/ molecular allergy testing be useful for?
For nuts, detection of storage protein is indicative of a stronger reaction
For wheat, detection of omega-5-gliadin is indicative of a stronger reaction
**this is where you test for IgE against specific components of an allergen
**helps to distinguish between sensitisation and allergy
What is a measurement of mast cell tryptase used for?
Biomarker for anaphylaxis that peaks 1-2 hours following a reaction
Useful if diagnosis of anaphylaxis is not clear
What is the gold standard method of food and drug allergy testing?
Challenge tests
but can be difficult to interpret mild symptoms and there is a risk of causing anaphylaxis
How should an allergy challenge test be performed?
Increase volume of allergen and measure response - it is the gold standard for food allergy diagnosis (done as a double blind)
Describe the symptoms of the oral allergy syndrome
Symptoms of allergy limited to mouth
Very low chance of progression to anaphylaxis
Pre-existing pollen allergy
Cross-reactive IgE - binds to certain stone fruit (apple, pear), vegetables (carrots), and nuts (peanut, hazlenut)
**adults > children
Recall some foods that may trigger the Latex Food Syndrome?
Chestnut
Avocado
Banana
Potato
Tomato
Papaya
Kiwi
Aubergine
Mango
Wheat
Melon
Latex
What are the positive and negative controls used in skin prick testing?
Positive: histamine
Negative: diluent
Recall the management of anaphylaxis in adults
Elevate legs
100% oxygen
IM adrenaline 500 mcg
Inhaled bronchodilators
Hydrocortisone 200mg IV
Chlorphenamine 20mg IV
IV fluids
Seek help
What cytokines are secreted by Th2 cells?
Which transcription factors do they express?
IL-4 → helps B cells to produce IgE and IgG4
IL-5 → expands and activates eosinophils
IL-13 → stimulates mucous secretion
TF:
STAT6
GATA3
What are the two types of mast cells?
MC (Tryptase T) in skin
MC (Chromotryptase CT) in airways
Key mast cell receptors
High affinity receptor
Low afifnity receptor
MRGPRX1
Rapid vs delayed symptoms of allergy
Rapid onset of symptoms:
- within 2-3 hours
- caused by the release of inflammatory mediators following:
- allergen cross-linking of IgE on surface of mast cells and basophils
Delayed symptoms:result in:
- T2 cell (IL-4, IL-5, IL-13) immune responses
- and eosinophil related tissue damage
Trend in allergic diseases over time
Environmental rather than genetic is the most likely driver for increased incidence of allergic disorders
- hygiene hypothesis
- more childhood vaccination and exposure to broad spectrum antibiotics
- alteration in intestinal microbiome
- dietary factors