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Immunology > Allergy > Flashcards

Allergy Flashcards

1
Q

Define allergic disorder

A

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

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2
Q

Define allergen

A

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

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3
Q

Define sensitisation

A

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

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4
Q

Summarise the immune response to pathogens

A

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

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5
Q

Summarise the Th2 immune response

A
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6
Q

Summarise the Th2 immune memory response

A
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7
Q

Describe innate lymphoid cells

A
  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
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8
Q

Describe CD4 Th2 cells.

A
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9
Q

Describe eosinophils

A
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10
Q

Describe IgE

A
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11
Q

Describe mast cells

A
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12
Q

Describe the process of Mast cell/basophil degranulation

A
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13
Q

What factors promote IgE production?

A
  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
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14
Q

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

A
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15
Q

Summarise the Th2 immune responses.

A
  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
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16
Q

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

A

C: IL-4 promotes Th2 immune responses

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17
Q

Define the hygiene hypothesis.

A

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

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18
Q

Why have allergic disorders risen over the last 150 yrs?

A
  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
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19
Q

Describe allergic rhinitis

A
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20
Q

Describe the amish and Hutterite study.

A
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21
Q

Describe food allergies.

A
22
Q
A

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

23
Q

How do we diagnose allergic diseases?

A
24
Q

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

A
25
Q

What are the clinical features of IgE allergic responses?

A

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
25
Q

What are the clinical features of IgE allergic responses?

A

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
26
Q

What are symptoms that are not associated with IgE allergic reactions

A
27
Q

Describe the use off sensitisation tests in diagnosing allergies.

A
28
Q

Describe the process of skin-prick test.

A
  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
29
Q

What are the advantages and disadvantages of skin prick tests?

A
30
Q

Describe intradermal tests.

A
31
Q

Describe sensitisation (IgE antibody) blood tests.

A
32
Q

Describe the risk profile of specific IgE blood tests.

A
33
Q

What are the indications for blood sensitisation tests?

A
34
Q

Describe component resolved/molecular allergen testing.

A
35
Q

Describe food components allergen tests.

A
36
Q

Describe the use of mast cell tryptase

A

a biomarker for anaphylaxis

37
Q

Describe the use of basophil activation tests.

A
38
Q

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

A
39
Q
A

Skin prick test

40
Q
A

Serial mast cell tryptase

41
Q

Define food allergy.

A

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

42
Q

Define food intolerance

A

non immune reactions which include metabolic, pharmacological and unknown mechanisms

43
Q

What are adverse reactions to food?

A
44
Q

How do food allergy prevalence differ in children to adults?

A
  1. Milk and egg - children
  2. Fish and Shellfish in adults.
45
Q

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

A
46
Q

What are the ix for food allergies?

A

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.

47
Q

What is the management of food allergies?

A
48
Q

What are the IgE mediated food allergy syndromes

A

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
49
Q

Describe allergic reactions to red meat.

A
50
Q
A

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

Immunology (10 decks)

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