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
Age of onset of allergic diseases
What is oral allergy syndrome?
allergy antibodies mistaking certain proteins in fresh fruits, nuts or vegetables for pollen
→ itchiness of mouth
Prevalence of asthma in Amish vs Hutterites
Lower in amish communities
Factors influencing development of peanut allergy
- Early oral exposure will protect against development of peanut allergy
- Sensitisation to peanut and wheat can occur from exposure through the skin
- Differences in preparation of peanuts (roast promotes IgE whereas boiled IgG)
Recall 3 allergen specific tests that exist
- Skin prick
- intradermal test
- IgE blood tests
Examples of functional tests
- In vitro tests
- Basophil activation
- Serial mast cell tryptase
- Ex vitro tests
- Open or blinded allergen challenge
When does an IgE allergic response occur?
Occurs within minutes or up to 3-4 hours after exposure to allergen
Symptoms of IgE allergic response
Skin: angioedema (swelling of lips, tongues, eyelids) , urticaria ( wheals or ‘hives’), flushing and itch
Respiratory tract: cough, SOB wheeze, sneezing, nasal congestion and clear discharge, red itch watery eyes
Gastrointestinal tract: nausea, vomiting and diarrhoea
Blood vessels and Brain: symptoms of hypotension (faint, dizzy, blackout) and a sense of impending doom
How many organ systems must be involved in IgE mediated response?
At least 2
What is a key feature of IgE response?
Must be reproducible
What are some cofactors that can trigger allergic response
exercise, alcohol, NSAID and in children viral infection
Senistisation vs allergy
Sensitisation is necessary but not sufficient for allergy
What are the positive and negatvie controls used in skin prick testing?
Positive: histamine
Negative: diluent
WHat must be discontinued prior to skin prick testing?
Antihistamines and some antidepressants
**for 48 hours
When do you use intradermal skin tests?
- Moe sensitive but less specific than SPT
- Best used to follow up negative venom and drug allergy test (better than blood tests)
- Can be used if SPT to allergen is negative but convincing history
Disadvantages of intradermal skin tests
Labour intensive, greater risks of anaphylaxis
Which factors in IgE blood tests are important to predict allergic symptoms?
- antibody concentration: higher risk
- antibody affinity: higher risk
Indications for IgE blood test
If mast cell tryptase fails to return to baseline following 6-12 hours what is suggested?
•systemic mastocytosis
What is the basophil activation test?
- used as surrogate marker for challenge tests
- to reduce need for challenge tests
- measure expression of markers of activated basophils
4 categories of food allergies
Link between atopic dermantitis and food allergy
Moderate/severe Atoptic dermatitis is a risk factor for food allergy
- indication for testing even in absence of clinical history
Incidence of food allergy in children
Most children outgrow milk and egg allergy but rarely outgrow peanut and tree nut allergy
Breastfeeding and food allergy
•Breast feeding: strong family of allergy
Common food allergens that induce anaphylaxis
Peanut, tree nut shellfish, fish, milk and eggs
What is Food associated exercise induced anaphylaxis
Food induces anaphylaxis if individual exercises within 4-6 hours of ingestion
Common food triggers are wheat, shellfish, celery
Allergy to beef, pork, lamb
Delayed anaphylaxis 3-6 hours after ingestion
Induced by tick bites which should be avoided
how does allergen desensitisation work?
Supervised administration of an allergen 1. Start with tiny dose and escalate every week until maximal dose reached 2. Maintenance dose given monthly for 3-5 years
• Reduces clinical symptoms of monoallergic disorders
• Good for: Bee and wasp venom, grass pollen, house dust mite. NOT food, latex
• Costly, laborious and risk of severe adverse reaction
• However, only Tx that alters natural course of disease.
