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YEAR 5: Immunopathology > Immuno: Allergy Pt.1 > Flashcards

Immuno: Allergy Pt.1 Flashcards

1
Q

Define allergic disorder.

A

Immunological process that results in immediate and reproducible symptoms after exposure to an allergen. Usually involves IgE-mediated type 1 hypersensitivity reaction.

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2
Q

Define sensitisation.

A

Detection of specific IgE either by skin prick testing or in vivo blood test

NOTE: this does NOT define allergic disease

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3
Q

Describe the difference between immune responses mediated by Th1 and Th2 cells.

A

Pathogens that have conserved structures (PAMPs) such as bacteria are recognised by Th1 and Th17 cells

Multicellular organisms (e.g. helminths) and allergens don’t have conserved structures but they release mediators that damage epithelial cells
* Disturbance of epithelial cells is recognised by the Th2 cells

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4
Q

Outline the Th2-mediated immune response.

A
  • Damaged epithelium releases signalling molecules (e.g. TSLP)
  • These cytokines will act on Th2, Th9 and ILC2 cells, which then produce IL4, IL5 and IL13
  • These cytokines act on basophils and eosinophils which play a major role in the expulsion of allergens and parasites
  • IL4 stimulates B cells to produce IgE and IgG4
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5
Q

What other allergic response can be initiated by parasites and allergens which is not mediated by Th2 cells?

A
  • Allergens can cross-link IgE leading to mast cell degranulation and the release of histamines, prostaglandins and leukotrienes
  • These mediators act on the epithelium causing increasing permeability, smooth muscle contraction and neuronal irritability (itching)
  • This response aims to expel the parasite/allergen and is implicated in asthma, eczema and hay fever
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6
Q

Describe the skin barrier and allergy

A

Skin defects (i.e. epithelial barrier issues) are a significant risk factor for the development of IgE antibodies via Th2 responses e.g. in atopic dermatitis

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7
Q

What induces the production of IL4?

A

Peptide presentation via MHC to TCR or Th2 cells

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8
Q

How is oral allergen exposure different from respiratory or skin exposure with regards to developing an allergic response?

A
  • Oral exposure promotes immune tolerance whereas skin and respiratory exposure promotes IgE sensitisation
  • When an allergen is ingested orally, Treg in the GI mucosa will inhibit IgE synthesis and promote tolerance
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9
Q

List some theories behind the increasing prevalence of allergic disorders.

A
  • Hygiene hypothesis - reduced childhood infection increases allergy susceptability
  • Lack of vitamin D and fatty acids in diet
  • Loss of symbosis with gut and respiratory bacteria due to altered composition and biodiversity
  • Increase in epithelium-damaging agents due to industrialisation
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10
Q

List the allergic diseases that present in the following age groups:

  1. Infants
  2. Children
  3. Adults
A
  1. Infants
    • Atopic dermatitis
    • Food allergy (milk, eggs, nuts)
  2. Children:
    • Asthma
    • Allergic rhinitis
  3. Adults:
    • Allergic rhinitis (MOST COMMON)
    • Drug allergy
    • Bee allergy
    • Occupational allergy
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11
Q

How is allergic disease diagnosed

A

History

Examination

Allergen specific IgE (sensitisation) tests

  • Skin prick
  • Serum IgE (RAST)

Functional allergen tests

  • Mast cell tryptase
  • Basophil activation test
  • Allergen challenge
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12
Q

List some clinical features of IgE-mediated allergic responses.

A

Symptoms are repoducible:

Skin
* Angioedema
* Urticaria
* Flushing
* Itching

Respiratory
* Cough
* SoB
* Wheeze

GI
* Nausea, diarrhoea, vomiting

Vascular and brain
* Hypotension, shock
* Sense of impending doom

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13
Q

State some examples of co-factors that could trigger an allergic response.

A
  • Exercise
  • Alcohol
  • NSAIDs - break GI tract
  • Viral infection - in children
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14
Q

List some investigations that may be conducted during an acute allergic episode.

A
  • Serial mast cell tryptase
  • Blood/urine histamine
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15
Q

Does a postive skin prick/specific IgE test demonstrate allergy?

A

No - it demonstrates sensitisation

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16
Q

What features of the specific IgE test are used to predict risk and likelihood of symptoms?

A
  • Concentration - higher levels means more symptoms
  • Affinity to the target - higher affinity means increased risk
  • Capacity of IgE antibody to induce mast cell degranulation
17
Q

Describe how skin prick tests are conducted.

A
  • Expose a patient to a standardised solution of allergen extract through a skin prick on the forearm
  • Use standard skin test solutions with a positive control (histamine) and negative control (dilutent)
  • Measure the local wheal and flare response
  • Positive result: wheal >3mm greater than the negative control
  • Antihistamines should be discontinued for at least 48 hours before the test
18
Q

What are the advantages and disadvantages of skin prick testing?

A

Advantages:

  • Rapid (15-20 mins)
  • Cheap
  • High negative predictive value
  • Increasing size of wheals correlates with higher probability of allergy

Disadvantages:

  • Operator-dependent
  • Risk of anaphylaxis
  • Poor positive predictive value (high false positive rate)
  • Limited value in patients with dermatographism or extensive eczema
19
Q

Describe the use of intradermal allergy tests

A

Direct injection of allergen and controls into skin

Used to follow up negative SPT

More sensitive but less specific that SPT

Greater risk of anaphylaxis

20
Q

Describe how specific IgE tests work.

A
  • Allergen is bound to a sponge and mixed with the patient’s serum
  • Specific IgE will bind to the allergens on the sponge (if present)
  • This is washed with anti-IgE antibody which is fluorescently labelled
  • Higher values are associated with allergic disorders

NOTE: good negative predictive value

21
Q

What is component resolved diagnostics?

A
  • A blood test to detect IgE to single protein components of whole allergens (useful for peanut and hazelnut allergy)
  • IgE sensitisaton to heat and proteolytic labile proteins = minor symptoms
  • IgE sensitisation to heat and protolytic stable protein = major symptoms
22
Q

List some indications for blood sensitisation tests

A
  • No access to SPT/IDT
  • Patients who cannot stop antihistamines
  • Patients with dermatographism/extensive eczema
  • History of anaphylaxis
  • Borderline skin prick results
  • Prediction for allergy resolution
  • Monitor response to anti-IgE therapy
23
Q

What is mast cell tryptase used for?

A
  • Tryptase is pre-formed protein found in mast cell granules
  • Systemic degranulation during anaphylaxis results in increased serum tryptase
  • Therefore, it is a biomarker for anaphylaxis
  • Retrospective diagnosis
  • Normal levels do not rule out anaphylaxis

YEAR 5: Immunopathology (25 decks)

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