Immunology 6 - Allergy Flashcards

1
Q

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

A

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

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2
Q

How does Th2 activation cause mast cell degranulation?

A

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

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3
Q

Why does atopic dermatitis predispose to allergic sensitisation?

A

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

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4
Q

Which interleukin is most important in Th2 cell responses?

A

IL4

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

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5
Q

Why do filagrin mutations increase risk of allergic disease?

A

Increase risk of atopic dermatitis which increases allergen exposure

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6
Q

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

A

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

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7
Q

Recall 2 limitations of skin prick allergy testing

A
  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
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8
Q

What can component/ molecular allergy testing be useful for?

A

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

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9
Q

What is a measurement of mast cell tryptase used for?

A

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

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10
Q

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

A

Challenge tests

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

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11
Q

How should an allergy challenge test be performed?

A

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

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12
Q

Describe the symptoms of the oral allergy syndrome

A

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

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13
Q

Recall some foods that may trigger the Latex Food Syndrome?

A

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

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14
Q

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

A

Positive: histamine
Negative: diluent

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15
Q

Recall the management of anaphylaxis in adults

A

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

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16
Q

What cytokines are secreted by Th2 cells?

Which transcription factors do they express?

A

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

IL-5 → expands and activates eosinophils

IL-13 → stimulates mucous secretion

TF:

STAT6

GATA3

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17
Q
A
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18
Q

What are the two types of mast cells?

A

MC (Tryptase T) in skin

MC (Chromotryptase CT) in airways

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19
Q

Key mast cell receptors

A

High affinity receptor

Low afifnity receptor

MRGPRX1

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20
Q

Rapid vs delayed symptoms of allergy

A

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
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21
Q

Trend in allergic diseases over time

A

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
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22
Q

Age of onset of allergic diseases

A
23
Q

What is oral allergy syndrome?

A

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

→ itchiness of mouth

24
Q
A
25
Q

Prevalence of asthma in Amish vs Hutterites

A

Lower in amish communities

26
Q

Factors influencing development of peanut allergy

A
  • 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)
27
Q

Recall 3 allergen specific tests that exist

A
  • Skin prick
  • intradermal test
  • IgE blood tests
28
Q

Examples of functional tests

A
  • In vitro tests
  • Basophil activation
  • Serial mast cell tryptase
  • Ex vitro tests
  • Open or blinded allergen challenge
29
Q

When does an IgE allergic response occur?

A

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

30
Q

Symptoms of IgE allergic response

A

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

31
Q

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

A

At least 2

32
Q

What is a key feature of IgE response?

A

Must be reproducible

33
Q

What are some cofactors that can trigger allergic response

A

exercise, alcohol, NSAID and in children viral infection

34
Q

Senistisation vs allergy

A

Sensitisation is necessary but not sufficient for allergy

35
Q
A
36
Q

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

A

Positive: histamine

Negative: diluent

37
Q

WHat must be discontinued prior to skin prick testing?

A

Antihistamines and some antidepressants

**for 48 hours

38
Q

When do you use intradermal skin tests?

A
  • 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
39
Q

Disadvantages of intradermal skin tests

A

Labour intensive, greater risks of anaphylaxis

40
Q
A
41
Q

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

A
  • antibody concentration: higher risk
  • antibody affinity: higher risk
42
Q

Indications for IgE blood test

A
43
Q

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

A

•systemic mastocytosis

44
Q

What is the basophil activation test?

A
  • used as surrogate marker for challenge tests
  • to reduce need for challenge tests
  • measure expression of markers of activated basophils
45
Q

4 categories of food allergies

A
46
Q

Link between atopic dermantitis and food allergy

A

Moderate/severe Atoptic dermatitis is a risk factor for food allergy

  • indication for testing even in absence of clinical history
47
Q

Incidence of food allergy in children

A

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

48
Q
A
49
Q

Breastfeeding and food allergy

A

•Breast feeding: strong family of allergy

50
Q

Common food allergens that induce anaphylaxis

A

Peanut, tree nut shellfish, fish, milk and eggs

51
Q

What is Food associated exercise induced anaphylaxis

A

Food induces anaphylaxis if individual exercises within 4-6 hours of ingestion

Common food triggers are wheat, shellfish, celery

52
Q

Allergy to beef, pork, lamb

A

Delayed anaphylaxis 3-6 hours after ingestion

Induced by tick bites which should be avoided

53
Q
A
54
Q

how does allergen desensitisation work?

A

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.