Immunology 6 - Allergy

Question 1

What is the difference in CD4 T cell response between microbial recognition and allergen recognition?

Answer 1

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

Question 2

How does Th2 activation cause mast cell degranulation?

Answer 2

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

Question 3

Why does atopic dermatitis predispose to allergic sensitisation?

Answer 3

Skin exposure more likely to lead to IgE response than oral exposure

Question 4

Which interleukin is most important in Th2 cell responses?

Answer 4

IL4

formation is only induced following peptide-MHC presentation to naïve/memory Th2 cells

Question 5

Why do filagrin mutations increase risk of allergic disease?

Answer 5

Increase risk of atopic dermatitis which increases allergen exposure

Question 6

What represents a positive result in a skin-prick allergy test?

Answer 6

Wheal >3mm (path lecture)/ >2mm (path guide) bigger than control

Question 7

Recall 2 limitations of skin prick allergy testing

Answer 7

1. Necessary for diagnosis but is insufficient alone
2. Result does not predict severity of reaction
3. not as good for some fruit and vegetables

Question 8

What can component/ molecular allergy testing be useful for?

Answer 8

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

Question 9

What is a measurement of mast cell tryptase used for?

Answer 9

Biomarker for anaphylaxis that peaks 1-2 hours following a reaction
Useful if diagnosis of anaphylaxis is not clear

Question 10

What is the gold standard method of food and drug allergy testing?

Answer 10

Challenge tests

but can be difficult to interpret mild symptoms and there is a risk of causing anaphylaxis

Question 11

How should an allergy challenge test be performed?

Answer 11

Increase volume of allergen and measure response - it is the gold standard for food allergy diagnosis (done as a double blind)

Question 12

Describe the symptoms of the oral allergy syndrome

Answer 12

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

Question 13

Recall some foods that may trigger the Latex Food Syndrome?

Answer 13

Chestnut
Avocado
Banana
Potato
Tomato
Papaya
Kiwi
Aubergine
Mango
Wheat
Melon
Latex

Question 14

What are the positive and negative controls used in skin prick testing?

Answer 14

Positive: histamine
Negative: diluent

Question 15

Recall the management of anaphylaxis in adults

Answer 15

Elevate legs
100% oxygen
IM adrenaline 500 mcg
Inhaled bronchodilators
Hydrocortisone 200mg IV
Chlorphenamine 20mg IV
IV fluids
Seek help

Question 16

What cytokines are secreted by Th2 cells?

Which transcription factors do they express?

Answer 16

IL-4 → helps B cells to produce IgE and IgG4

IL-5 → expands and activates eosinophils

IL-13 → stimulates mucous secretion

TF:

STAT6

GATA3

Question 18

What are the two types of mast cells?

Answer 18

MC (Tryptase T) in skin

MC (Chromotryptase CT) in airways

Question 19

Key mast cell receptors

Answer 19

High affinity receptor

Low afifnity receptor

MRGPRX1

Question 20

Rapid vs delayed symptoms of allergy

Answer 20

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

Question 21

Trend in allergic diseases over time

Answer 21

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

Question 22

Age of onset of allergic diseases

Question 23

What is oral allergy syndrome?

Answer 23

allergy antibodies mistaking certain proteins in fresh fruits, nuts or vegetables for pollen

→ itchiness of mouth

Question 25

Prevalence of asthma in Amish vs Hutterites

Answer 25

Lower in amish communities

Question 26

Factors influencing development of peanut allergy

Answer 26

* 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)

Question 27

Recall 3 allergen specific tests that exist

Answer 27

* Skin prick * intradermal test * IgE blood tests

Question 28

Examples of functional tests

Answer 28

* In vitro tests * Basophil activation * Serial mast cell tryptase * Ex vitro tests * Open or blinded allergen challenge

Question 29

When does an IgE allergic response occur?

Answer 29

Occurs within minutes or up to 3-4 hours after exposure to allergen

Question 30

Symptoms of IgE allergic response

Answer 30

**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

Question 31

How many organ systems must be involved in IgE mediated response?

Answer 31

At least 2

Question 32

What is a key feature of IgE response?

Answer 32

Must be reproducible

Question 33

What are some cofactors that can trigger allergic response

Answer 33

exercise, alcohol, NSAID and in children viral infection

Question 34

Senistisation vs allergy

Answer 34

Sensitisation is necessary but not sufficient for allergy

Question 36

What are the positive and negatvie controls used in skin prick testing?

Answer 36

Positive: histamine Negative: diluent

Question 37

WHat must be discontinued prior to skin prick testing?

Answer 37

Antihistamines and some antidepressants \*\*for 48 hours

Question 38

When do you use intradermal skin tests?

Answer 38

* 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

Question 39

Disadvantages of intradermal skin tests

Answer 39

Labour intensive, greater risks of anaphylaxis

Question 41

Which factors in IgE blood tests are important to predict allergic symptoms?

Answer 41

* antibody concentration: higher risk * antibody affinity: higher risk

Question 42

Indications for IgE blood test

Answer 42

Question 43

If mast cell tryptase fails to return to baseline following 6-12 hours what is suggested?

Answer 43

•systemic mastocytosis

Question 44

What is the basophil activation test?

Answer 44

* used as surrogate marker for challenge tests * to reduce need for challenge tests * measure expression of markers of activated basophils

Question 45

4 categories of food allergies

Answer 45

Question 46

Link between atopic dermantitis and food allergy

Answer 46

Moderate/severe Atoptic dermatitis is a risk factor for food allergy - indication for testing even in absence of clinical history

Question 47

Incidence of food allergy in children

Answer 47

Most children outgrow milk and egg allergy but rarely outgrow peanut and tree nut allergy

Question 49

Breastfeeding and food allergy

Answer 49

•Breast feeding: strong family of allergy

Question 50

Common food allergens that induce anaphylaxis

Answer 50

Peanut, tree nut shellfish, fish, milk and eggs

Question 51

What is Food associated exercise induced anaphylaxis

Answer 51

Food induces anaphylaxis if individual exercises within 4-6 hours of ingestion Common food triggers are wheat, shellfish, celery

Question 52

Allergy to beef, pork, lamb

Answer 52

Delayed anaphylaxis 3-6 hours after ingestion Induced by tick bites which should be avoided

Question 54

how does allergen desensitisation work?

Answer 54

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.