Allergy

Question 1

Define allergic disorder

Answer 1

Immunological process that results in immediate and reproducible symptoms after exposure to an allergen.

In clinical practice immunological process usually involves an IgEmediated type 1 hypersensitivity reaction

Question 2

Define allergen

Answer 2

Allergen is usually a harmless substance that can trigger an IgE mediated immune response and may result in clinical symptoms

Question 3

Define sensitisation

Answer 3

Sensitisation is the detection of specific IgE either by skin prick testing or in vitro blood tests: OCCURS MORE OFTEN THAN ALLERGIC DISEASE

Question 4

Summarise the immune response to pathogens

Answer 4

In contrast to immune responses to bacteria, virus and fungi, immune responses to worms, venoms and allergens tend to react to tissue damage caused by these agents rather then relying on direct recognition of the pathogen

Worms, venoms and allergens are far more diverse than bacteria

Question 5

Summarise the Th2 immune response

Answer 5

Question 6

Summarise the Th2 immune memory response

Answer 6

Question 7

Describe innate lymphoid cells

Answer 7

1. Innate lymphoid cells found at mucosal barriers (skin, respiratory and the gastrointestinal tract) which lack antigen specific receptors
2. Respond to a number of inflammatory cytokines (IL-33, TSLP, IL-25) IL-1 and IL-12 family cytokines member
3. CD4 ILC classified into ILC1, ILC2, ILC3, based on their cytokine production and transcriptional profiles with ILC1s, ILC2s, and ILC3s resembling CD4⁺ T helper (Th)1, Th2 and Th17/22 cells, respectively.
4. ILC2 secrete IL-4, IL-5, IL-9, IL-13 and amphiregulin (AREG)

• Secretion of type 2 cytokines by ILC2 implicated in allergic asthma, allergic rhinitis AD, food allergy and eosinophilic oesophagitis
• Amphiregulin paly an important role in epithelial barrier repair in skin and respiratory tract
• In allergic disease overcome steady state inhibition exerted by tissue CD4 T regulatory cells

Question 8

Describe CD4 Th2 cells.

Answer 8

Question 9

Describe eosinophils

Answer 9

Question 10

Describe IgE

Answer 10

Question 11

Describe mast cells

Answer 11

Question 12

Describe the process of Mast cell/basophil degranulation

Answer 12

Question 13

What factors promote IgE production?

Answer 13

1. Antigen dose
2. Length of exposure
3. Physical properties of allergen•Source•Small water soluble proteins•Carbohydrate•Resistance to heat, digestive enzymes•
4. Route of exposure

Question 14

What type of exposure promotes tolerance and which ones induce IgE sensitisation?

Answer 14

Question 15

Summarise the Th2 immune responses.

Answer 15

1. Not fully understood in humans
2. Defects in skin epithelial barrier (atopic dermatitis) are a significant risk factor for development of IgE antibodies
3. Stressed or damage epithelial cells secrete IL-25, IL-33, GM-CSF and TSLP which act on tissue immune cells (DC, basophils, type 2 innate lymphoid cells) and neurons to induce Th2 cells immune responses (IL-4, IL-5, IL-9, IL-13)
4. IL-4 plays a crucial role in development of Th2 immune responses and is only induced following peptide-MHC presentation to naïve/memory Th2 cells
5. IL-4 secretion is only induced following peptide-MHC presentation to TCR to either naïve and/or memory Th2 cells
6. IgE is the characteristic antibody of allergic sensitisation
7. Rapid onset of symptoms within 2-3 hours caused by release of inflammatory mediators following allergen cross linking of IgE on surface of mast cells and basophils
8. Delayed symptoms result from T2 cell (IL-4, IL-5, IL-13) immune responses and eosinophil related tissue damage
9. Th2 cytokines secreted by tissue lymphocytes act on effector cells (eosinophils, basophils, epithelial cells, B cells, sensory neurons endothelium and smooth muscle cells) to eliminate and expel pathogens allergens, and repair tissue damage

Question 16

Allergic disorder: Choose the most correct answer

A. Cutaneous exposure to allergen promote immune tolerance

B. IgE degranulation of mast cells promotes a delayed clinical response

C. IL-4 plays a crucial role in development of Th2 immune responses

D. Targeted drug therapy against IgE has not been useful in the treatment of atopic asthma

E. Secretion of IL-22 by epithelial cells induces Th2 immune responses

Answer 16

C: IL-4 promotes Th2 immune responses

Question 17

Define the hygiene hypothesis.

Answer 17

lack of childhood exposure to infectious agents increases susceptibility to allergic diseases by supressing natural development of immune system.

Question 18

Why have allergic disorders risen over the last 150 yrs?

Answer 18

1. Hygiene hypothesis
2. Increase in epithelial-damaging agents linked to industrialisation, urbanisation and modern lifestyle.
3. Loss of symbiotic relationship with bacteria with reduction in biodiversity and alteration in composition of composition of gut skin and respiratory bacteria
4. Dietary factors:

• Change in food processing and preparation
• Delayed introduction of peanuts in children with egg allergy and atopic dermatitis
• Lack of Vitamin D and dietary fatty acid

Question 19

Describe allergic rhinitis

Answer 19

Question 20

Describe the amish and Hutterite study.

Answer 20

Question 21

Describe food allergies.

Answer 21

Question 22

Answer 22

D. Increased secretion of pro-inflammatory innate cytokines by PBMC following exposure to environmental microbial products may protect against development of asthma

Question 23

How do we diagnose allergic diseases?

Answer 23

Question 24

What is the age of onset of allergic diseases:

Atopic dermatitis

Asthma (HDM, pets)

Allergic rhinitis (HDM, grass, tree pollens)

Drug allergy

Bee allergy

Food allergy (milk, egg, nuts)

Oral allergy syndrome

Occupational allergy

Answer 24

Question 25

What are the clinical features of IgE allergic responses?

Answer 25

At least 2 organ systems are usually involved. Reproducible: occurs after every exposure Allergic symptoms may be triggered by cofactors such as exercise, alcohol, NSAID and in children viral infection Link between exposure and onset symptoms may not be obvious * House Dust mite * Fungal skin colonisation•Red meat ingestion * **Clinical history is used to select what allergens should be tested by skin prick and/or blood tests**

Question 25

What are the clinical features of IgE allergic responses?

Answer 25

At least 2 organ systems are usually involved. Reproducible: occurs after every exposure Allergic symptoms may be triggered by cofactors such as exercise, alcohol, NSAID and in children viral infection Link between exposure and onset symptoms may not be obvious * House Dust mite * Fungal skin colonisation•Red meat ingestion * **Clinical history is used to select what allergens should be tested by skin prick and/or blood tests**

Question 26

What are symptoms that are not associated with IgE allergic reactions

Answer 26

Question 27

Describe the use off sensitisation tests in diagnosing allergies.

Answer 27

Question 28

Describe the process of skin-prick test.

Answer 28

1. A positive test is indicated by a wheal ≥ 3mm greater than the negative control. 2. High positive and negative predictive and positive skin for aero allergens 3. Allergen extracts labile for some fruit and vegetables: : prick-prick test: food and SPT 4. Antihistamines and some anti-depressants should be discontinued for at least 48 hours beforehand

Question 29

What are the advantages and disadvantages of skin prick tests?

Answer 29

Question 30

Describe intradermal tests.

Answer 30

Question 31

Describe sensitisation (IgE antibody) blood tests.

Answer 31

Question 32

Describe the risk profile of specific IgE blood tests.

Answer 32

Question 33

What are the indications for blood sensitisation tests?

Answer 33

Question 34

Describe component resolved/molecular allergen testing.

Answer 34

Question 35

Describe food components allergen tests.

Answer 35

Question 36

Describe the use of mast cell tryptase

Answer 36

a biomarker for anaphylaxis

Question 37

Describe the use of basophil activation tests.

Answer 37

Question 38

Describe the use of challenge tests: food and drug allergies.

Answer 38

Question 39

Answer 39

Skin prick test

Question 40

Answer 40

**Serial mast cell tryptase**

Question 41

Define food allergy.

Answer 41

adverse health effect arising from specific immune response that occurs reproducibly on exposure to a given food Food allergy likely affect up to 5% of adults and 8% of children

Question 42

Define food intolerance

Answer 42

non immune reactions which include metabolic, pharmacological and unknown mechanisms

Question 43

What are adverse reactions to food?

Answer 43

Question 44

How do food allergy prevalence differ in children to adults?

Answer 44

1. Milk and egg - children 2. Fish and Shellfish in adults.

Question 45

What type of clinical history would you expect in food allergy?

Answer 45

Question 46

What are the ix for food allergies?

Answer 46

A positive skin test or food specific IgE blood test indicates sensitisation but not necessarily allergy Increasing high food-specific IgE levels or larger skin tests wheal size indicate a higher chance of allergy Results can be followed over time to monitor for allergy persistence or resolution IgE concentrations and SPT wheal sizes to determine presence/absent allergic disease and/or disease persistence/resolution vary with age, hospital and different blood test assays Gold standard for the diagnosis of food allergy is a double blind oral food challenge**.**

Question 47

What is the management of food allergies?

Answer 47

Question 48

What are the IgE mediated food allergy syndromes

Answer 48

Anaphylaxis: * Peanut, tree nut shellfish, fish, milk and eggs are most common * Natural history dependent on food Food associated exercise induced anaphylaxis * Food induces anaphylaxis if individual exercises within 4-6 hours of ingestion• * Common food triggers are wheat, shellfish, celery Delayed food-induced anaphylaxis to beef, pork, lamb * Symptoms occur 3-6 hours after eating red meat and gelatin• * IgE antibody to oligosaccharide alpha-gal (α1, 3-galactose) found in gut bacteria• * Induced by tick bites which should be avoided Oral allergy syndrome * Limited to oral cavity, swelling and itch: only 1-2% cases progresses to anaphylaxis• * Sensitisation to inhalant pollen protein lead to cross reactive IgE to food• * Onset after pollen allergy established: affect adults \> young children• * Respiratory exposure to pollen (birch) results in IgE directed to homologous proteins in stone fruits (apple, pear) vegetables (carrot) and nuts (peanut, hazelnut)• * Cooked fruits, vegetables and nut cause no symptoms: heat labile allergens detected by component allergen tests

Question 49

Describe allergic reactions to red meat.

Answer 49

Question 50

Answer 50

**B: Cross reactive IgE sensitisation between hay fever and apple allergens**