Atopy, allergy and delayed type hypersensitivity 2 Flashcards

1
Q

Skin prick testing

  • Purpose
  • Method
  • Realiability
A

Method of detecting sensitivity to allergens in vivo
- Uses Type 1 hypersensitivity reaction

Method

  • Allergen is applied as drops to skin
  • Control is there: histamine, no histamine
  • Epidermis is punctured with lancet
  • Wait for 15 mins to observe a wheel and flare reaction

Test is not diagnostic as there can be many false positives and false negatives

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2
Q

Detection of allergen specific IgE in vitro

A

More reliable that skin prick test.

ELISA

  • The well is coated with specific allergen
  • Patient serum is added, if it contains IgE ab sensitised to allergen, it will bind.
  • Polyclonal anti-IgR detection Ab is added to detect immobilised IgE bound to allergen
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3
Q

Nasal decongestant

  • Mechanism
  • Example
  • Use
A

Treats symptom of allergy
- Stimulates a1 adrenoreceptors= vasoconstriction

Example
- Oxymetazoline

Use
- short term topical and systemic use

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4
Q

B2 agonist

  • Mechanism
  • Example
  • Use
A

Acts of B2 adrenoreceptors
= smooth muscle relaxation in airway

Example
- Salbutamol

Use
- Inhaler

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5
Q

Epinephrine

  • Mechanism
  • Example
  • Use
A

Stimulates adrenergic receptors in the sympathetic system, inhibits=

  • Vasoconstriction
  • Bronchodilation

Use
- 0.5mg injected intramuscularly.

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6
Q

Drugs that act on early phase mediators

A

Inhibits the effects action of histamine and leukotrienes or prevents mast cell degranulation

Examples

  • H1 anti-histamines
  • Leukotriene receptor antagonists
  • Mast cell stabilisers
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7
Q

Mast cell stabilisers

  • Mechanism
  • Example
  • Use
A

Reduces mast cell degranulation
- Unknown mechanism

Example
- Sodium cromoglycate

Use

  • Topical use [i.e eye drops]
  • Frequent dosing due to short half-life= poor efficacy
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8
Q

H1 antihistamines

  • Mechanism
  • Example
  • Use
A

Inverse agonist of H1 receptors
- Prevents the inflammatory effects of histamines, by inhibiting its actions on cells

Example
1st generation
- Chlorpheniramine

2nd generation

  • Cerizine
  • Lortidine
  • Desloratidine
  • Fexofenadine
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9
Q

1st generation H1 antihistamines

A

Chlorpheniramine

  • Causes sedation
  • Drug interactions
  • Adverse psychological effects [tardive dyskinesia]

2nd generation drugs better, no/minimal sedation

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10
Q

Leukotriene receptor antagonists

  • Mechanism
  • Example
  • Use
A

Inhibits the effects of leukotriene, so inhibits
- Bronchoconstriction

Example
- Montelukast

Inferior to H1 antihistamines
- Usually used for those with chronic asthma

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11
Q

Mechanism of corticosteroids

A

Alters gene expression in leucocytes

  • lymphocytes
  • Innate immune cells

Steroid receptors are usually bound to Hsp90 but corticosteroids displaces it and binds instead
- Steroid-receptor complex crosses nuclear membrane than binds to regulatory gene sequences to initiate transcription

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12
Q

Corticosteroids examples

  • Inhaled
  • Nasal
  • Topical
A

Inhaled

  • Beclamathosome
  • Fluticasone

Nasal

  • Beclamathosome
  • Mometasone
  • Fluticasone

Topical
- Hydrocortisone

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13
Q

Omalizumab

A

Monoclonal antibody against IgE
- Indicated for atopic asthma

Binds to IgE, occupying their antigen binding site, preventing them from binding to allergens
- Decreases the expression of high affinity IgE receptors on mast cells= less mediator release

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14
Q

Type 4 delayed type hypersensitivity

A

Reaction mediated by antigen specific effector T cels
- Reaction does not develop until at least 24 hours as it takes time to process and present antigens, and for T cells to recognise them

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15
Q

Contact dermatitis

- Mechanism

A

Type 4 hypersensitivity reaction.

Mechanism:

  • Reactive small molecules
    (hapten) [sensitising agent] penetrates the skin
  • Small molecules for protein-hapten complex
  • Protein-hapten are taken up by langerhan cells, processed via MHC 2—> migrate to lymph nodes
  • Recognised by T cell cells as foreign= activation of T cells
  • T cells migrate to dermis and stimulate inflammatory reaction
  • Chemokines stimulate migration of macrophage= Th1 releases IFN-g to activate macrophage and increase vascular adhesion molecules

TNF-a/b= local inflammation

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16
Q

Poison ivy

A

Causes contact dermatitis

  • Due to release of pentadecacathechol lipid that crosses into skin= modifies intracellular proteins
  • Not everyone is susceptible

Proteins are processed and presented via MHC1 to CD8 T cells

17
Q

Patch testing

A

Uses Type 4 hypersensitivity

Patch with specific antigen is placed on the back
- e.g nickels, chrome, cobalt, epoxy resin etc

Wait 2 days to look for inflammation

18
Q

Compare contact dermatitis to type 1 allergy

  • Clinical features
  • Temporal
  • Causative agents
  • Effector mechanism
  • Assessment
  • Management
A

Clinical features

  • Type 1= features of mast cell degranulation
  • Type 4= eczematous skin reaction

Temporal

  • Type 1= rapid, within minutes, after exposure
  • Type 4= delay between exposure and symptoms

Causative agents

  • Type 1= naturally occurring protein/ closet related one
  • Type 2= Many causes, usually synthetic

Effector mechanism

  • Type 1= Allegern-specific IgE, mast cell degranulation
  • Type 2= Antigen-specific effector Th1 cells

Assessment

  • Type 1= allergy clinic, skin prick, serology for allergen specific IgE
  • Type 2= dermatology, skin patch testing

Management

  • Type 1= avoid allergen, pharmacotherapy, immunotherapy
  • Type 2= avoidance
19
Q

Skin prick vs skin patch testing

  • Indication
  • Test format
  • Positive result
  • Immunology
A

Indication

  • Skin prick= history of IgE allergy
  • Patch= history of contact dermatitis

Test format

  • Prick= allergen drops, puncture, read after 15 mins
  • Patch= Allergen under occlusive dressing, read after 48 hours

Positive result

  • Prick= wheal and flare
  • Patch= Eczematous reaction

Immunology

  • Prick= type 1 hypersensitivity, IgE, mast cell degranulation
  • Patch- Type 4, T cell mediated
20
Q

Tuberculin skin test

A

Type 4 reaction

  • Tests previous exposure to TB (later TB)
  • Allows chemoprophylaxis to reduce chance of reactivation

Method

  • Tuberculin [complex of antigens from MTB] injected intradermally
  • Wait for 24-72 hours to observe local inflammation

Mechanism

  • Injected antigen is processed by APCs in skin
  • Th1 (previously exposed to TB antigen) recognises the antigen and stimulates cytokines release
  • Phagocytes and plasma into site of injection= lesion

Reliability
- Poor for active TB (esp if lungs)

21
Q

Allergen-specific immunotherapy

A

Method of providing long-term protection for resistance allergies.
- Especially venom and rhinitis

Method:
- Small does of allergen is injected subcutaneous or sublingually.

Effects:

  • T cell responses to allergens
  • Reduces Th2 responses
  • Allergen-specific IgG an
  • Decreases mast cell responseiveness
  • Decreases allergen-specific IgE levels