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PATH30001 - Mechanisms of Disease > Lecture 22 - Food Allergy > Flashcards

Lecture 22 - Food Allergy Flashcards

1
Q

Characterise the prevalence of immune disorders

A 
Since 1950:
 • Exponential increase in immune disorders
- MS
- Type I diabetes
- Asthma
- Crohn's disease
- Food allergy & anaphylaxis

The increase is seen across all age groups, but children 0-4 in particular

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2
Q

What is anaphylaxis?

A

Most severe form of allergic reaction
Rapid onset
May cause death

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3
Q

What are the determinants of allergic disease?

A
  1. Genes
  2. Early life environment:
    • Microbial exposure (most important)
    • Vit D
    • UV light
    • Diet
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4
Q

Describe the effect of genetics and environment leading to disease

A
  1. Genes & environment
  2. Epigenetic modification
  3. Gene expression
  4. Altered immune tolerance
  5. Disease
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5
Q

Describe the observations from studies of mice in germ free conditions

A

“Fail to develop oral tolerance”:
• Underdeveloped Peyer’s patches lacking GCs
• Few IgA plasma cells and CD4+ T cells in LP
• Reduced n° of IELs
• Fail to develop oral tolerance
• Persistent Th2 responses

Window of opportunity:
• These abnormalities can be reversed, but only in the neonatal period

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6
Q

Compare intestinal microbiota in allergic and non-allergic children

A

Allergic:
In general:
• Decreased levels of probiotic bacteria
• Increased levels of pathogenic bacteria

  • ‘Good’ Bifidobacterium levels reduced and less adherent to intestinal mucous
  • Microbiota induce less IL-10 production
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7
Q

Which bacteria are probiotic?

Which bacteria are pathogenic?

A

Probiotic:
• Lactobacillus
• Bifidobacteria

Pathogenic:
• C. difficile
• S. aureus

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8
Q

When is abnormal microbiota seen in children?

A

Preceding the development of allergic disease

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9
Q

Describe the changes to microbiota over the first 12 months of life in children who will develop allergic disease

A

1 month:
• decreased bifidobacteria
• decreased colonisation of Enterococci
• increased Clostridia

6 months:
• increased Staphylococcus

12 months:
• decreased Bacteroides

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10
Q

Why is microflora important for disease?

A

Intestinal microflora plays a vital role in:
• Immune system maturation
• Development of tolerance

Which are required to avert allergic responses

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11
Q

What is the prevalence of food allergy?

A

2% - 5% of population

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12
Q

Which group of people most common experience food allergy?

A

Children: 6-10%

Compared to
Adults: 2%

Food allergies resolve with age

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13
Q

What are the major food groups that cause allergy?

A 
In order of increasing prevalence:
 • Peanuts
 • Tree nuts & seeds
 • Fish
 • Crustaceans
 • Eggs
 • Milk products
 • Fruit & veg
 • Food additives
 • Wheat

8 major food groups cause > 90% of food allergy

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14
Q

What are the common food allergies in children?

Compare this with adults

A

Children:
• Egg, milk, peanut
• Soy, wheat, fish

Adults:
• Peanut, tree nuts, fish, shellfish

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15
Q

What are the various clinical symptoms caused by the IgE mediated allergic reaction?

A
  • Urticaria

* Angioedema

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16
Q

What is urticaria?

A

Hives:
• IgE mediated allergic reaction
• Red bumps on skin
• Similar to angioedema, but only occurs in the upper dermis

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17
Q

What is angioedema?

A

Rapid swelling of dermis, subcutaneous tissue, mucosa & submucosa

Around eye

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18
Q

What are the symptoms in the following regions due to the IgE mediated allergic reaction?
• Airway
• Cardiovascular system

A 
1. Airway
 • Hoarse voice
 • Difficultly swallowing & breathing
 • Feeling of tightness in throat
 • Coughing
 • Wheeze
  1. Cardiovascular
    • Drowsy
    • Collapse
    • Pale and floppy
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19
Q

How is food allergy managed?

A

• Allergen avoidance

• Education:
- management of allergic reactions - preparation for anaphylaxis

• Adrenaline auto-injector

20
Q

Is allergen avoidance successful?

A

No, it’s difficult

  • 50% of children have accidental ingestion within 1 yr
  • In fatal cases most were aware of the allergy but failed to avoid the food
  • 40-100% of fatal reactions were from food prepared outside the home
21
Q

Is the EpiPen widely used?

A
  • 75% carried it
  • 10% were expired
  • 32% could use it correctly

Requires regular training

  • Even when used, person can die:
  • In 12-14% of fatal cases there were early, repeated doses of adrenaline
22
Q

Describe the mechanism for loss of tolerance to food

A
  • Increased Th2, decreased Th1
  • Reduced Treg numbers & activity
  1. Allergen in gut
  2. Allergen taken up by DCs
  3. Allergen presentation to Th2
  4. Stimulation of B-cells to produce IgE
    → Food allergy
23
Q

What was observed in the immune response in resolution of food allergy?

A
  • Shift to Th1 responses

* Increased allergen specific Tregs

24
Q

Compare Desensitisation & tolerance

How are they measured?

A

Desensitisation: the ability to tolerate a food while ingesting regular doses of the food
• Rapidly reversible
• Mediated by changes in effector cells (mast cells, basophils)

Tolerance: Ability to tolerate a food after a period of time has elapsed since ingesting the food
Expected to last for months-years after stopping therapy

Measured by:
Desensitisation: oral food challenge whilst still on treatment
Tolerance: oral food challenge after stopping therapy

25
Q

What immunological changes occur in tolerance?

A

• Induction of allergen-specific Tregs

Less common:
• Allergen specific anergy / clonal deletion

26
Q

Describe the mechanism of immunotherapy

A
  1. Injected allergen taken up by APC
  2. Presented to Treg
  3. Treg produces suppressive cytokines (IL-10, TGF-beta)
  4. Suppression of Th2, stimulation of Th1
    → Reduced IgE
    → Incresed IgA & IgG4
27
Q

What was seen in immunotherapy for peanut allergy?

A
  • Desensitisation: threshold for allergen increased from 178mg to 2805mg
  • High rate (39%) of serious systemic reactions
28
Q

Describe efficacy of oral immunotherapy

What are the immunological changes?

What are the drawbacks?

A

• Majority of patients successfully desensitised
- i.e., whilst still receiving OIT they were tolerant of cow’s milk

• Yet to achieve tolerance

Immunological changes:
• Decreased milk IgE
• Increased milk IgA & IgG4
• Increased IFN-gamma

Draw backs:
• Limited ability to induce tolerance
• Allergic reactions during treatment are common
• Severe reactions (10-20%)

29
Q

Describe the study of high dose Egg OIT

A

Aiming to induce tolerance

  • Placebo group: 0% tolerance
  • Treatment group: 28% tolerance
30
Q

What was observed in long term follow up of OIT?

A
  • Milk OIT for 4.5 years
  • Well tolerated (desensitised)
  • Regular ingestion of milk
  • No evidence of tolerance
  • Recurrence of allergy in subjects who discontinued OIT for period of a few weeks
31
Q

How could OIT be improved?

A
  • Higher maintenance dose

* Adjuvant

32
Q

Describe the use of adjuvants in OIT

Give examples

A

Immune response modifiers:
• Target TLRs with ligands linked to allergens
• Aims to resolve Th1 / Th2 imbalance

Examples:
1. CpG-containing-DNA-allergen complexes
• Increased in allergen-specific Th1 responses

2. Monophosphoryl lipid A
 • Bacterial cell wall component
 • Binds TLR4
 • Decreased IgE
 • Increased IgG4
33
Q

What is the PPOIT study?

A

Probiotic and Peanut OIT study

• Two groups:

  1. Probiotic (LGG) + Peanut OIT
  2. Placebo
  • Many samples taken at various points in time
  • Oral food challenge at end of treatment course

Preliminary results:
• Skin prick tests:
• Desensitisation observed in treatment group

34
Q

What is the most important environmental feature in regards to allergy?

A

Microbial exposure during fist few weeks and months of life

35
Q

Is dysbiosis reversible?

A

Yes, but only in the neonatal period

36
Q

How can microflora be targeted to help allergic disease?

A

Probiotics & diet to resolve dysbiosis

37
Q

What is observed in terms of IL-10 in the MALT of people with allergic disease?

A

Microbiota of individuals with allergic disease induce less IL-10 production

38
Q

Why are adults less commonly affected by food allergy?

A

Allergies can resolve over time

39
Q

Which food allergies tend to resolve with age?

Which do not?

A

Resolve with age:
• Cow’s milk
• Egg
• Wheat

Do not resolve with age:
• Peanut
• Shellfish

40
Q

What is the time frame for IgE mediated allergic reaction?

A

30 mins - 1 hr

41
Q

Describe multi-system involvement in the IgE mediated allergic reaction

A

Skin:
• Urticaria
• Angioedema
• Eczema

Gastrointestinal:
• Vomiting
• Diarrhoea
• Cramps

Respiratory:
• Coughing
• Wheezing

Cardiovascular:
• Hypotension

42
Q

What is the first clinical sign of the IgE mediated immune response?

A

Urticaria

43
Q

What is the biggest treatment strategy for allergy?

A

Management:
• Allergen avoidance
• Having an action plan for anaphylaxis

EpiPen

44
Q

Which cytokines released by Th2 are involved in skewing towards B cell IgE production?

A

IL-4
IL-5
IL-13

45
Q

What are the two types of immunotherapy?

A

Earlier: Subcutaneous immunotherapy

Now: Oral immunotherapy (OIT)

46
Q

What were the results of the RCT of OIT for peanut allergy?

A

(RCT: randomised controlled trial)

No effect observed, i.e. same rates of tolerance observed in both the ‘OIT’ and ‘avoid’ groups

47
Q

What were the results of the high dose OIT for egg allergy?

A

Considerable result:
28% tolerance in OIT group
0% tolerance in control group

PATH30001 - Mechanisms of Disease (34 decks)

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