Allergy and Hypersensitivity Flashcards

1
Q

Define allergy

A
  • an altered capacity of the body to react to a foreign substance
  • more specifically: disease following a response by the immune system to an otherwise unharmful antigen
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2
Q

What is the immune reactant, antigen, effector mechanism and example of a type 1 hypersensitivity reaction?

A
  • immune reactant: IgE
  • antigen: soluble
  • effector mechanism: mast cell activation
  • example: allergy, asthma
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3
Q

What is the immune reactant, antigen, effector mechanism and example of a type 2 hypersensitivity reaction?

A
  • immune reactant: IgG
  • antigen: cell/matrix associated complement or cell surface receptor
  • effector mechanism:
  • FcR+ cells (if complement)
  • Ab alters signalling (if cell surface receptor)
  • example:
  • drugs (if FcR+)
  • chronic urticaria (if Ab)
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4
Q

What is the immune reactant, antigen, effector mechanism and example of a type 3 hypersensitivity reaction?

A
  • immune reactant: IgG
  • antigen: soluble
  • effector mechanism: complement, phagocytes
  • example: arthus reaction, dermatitis
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5
Q

What is the immune reactant, antigen, effector mechanism and example of a type 4 hypersensitivity reaction?

A
  • immune reactant: Th1 cells
  • antigen: soluble
  • effector mechanism: macrophage activation
  • example: contact dermatisis or tuberculin reaction
  • immune reactant: Th2 cells
  • antigen: soluble
  • effector mechanism: eosinophil activation
  • example: chronic asthma or allergic rhinitis
  • immune reactant CTL
  • antigen: cell-antigen
  • effector mechanism: cytotoxicity
  • example: contact
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6
Q

Where is IgE produced and located?

A
  • by plasma B cells in lymph nodes
  • locally at site of inflammation
  • located mostly in tissue bound to mast cell surface through high affinity IgE receptor FceRI
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7
Q

What are the instances that favour IgE production?

A
  • CD4+ T cells of Th2 phenotype produce IL4 cytokines favour IgE responses
  • Th2 T cells also force B cells to switch the isotype of the Ig they secrete from IgM to IgE
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8
Q

Describe the features of inhaled allergens

A
  • protein: induce T cell responses
  • enzymatically active: often proteases
  • low dose: favours IL4 producing CD4 T cells
  • small size: allergens can diffuse out of particle
  • highly soluble: elutes readily from particle
  • stable: allergen can survive dessication
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9
Q

Describe the host defence against enzymatic allergens

A

IgE is the host defence against parasites, many of which gain access by secreting proteolytic enzymes

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10
Q

Describe what response the different effector T cells bring about

A
  • CD8 (cytotoxic): secrete IFNy, TNFa to target cell lysis
  • CD4 (Th1): secrete IFNy, GM-CSF, TNFa to cause activation of macrophages
  • CD4 (Th2): secrete IL4 and IL5 to activate B cells
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11
Q

What is an important factor in how symptoms of an allergen manifest?

A

location and distribution of the antigen

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12
Q

Describe how different routes of allergen delivery affect symptoms

A
  • inhaled antigens will affect nasal epithelium causing allergic rhinitis (hayfever) due to seasonal pollens
  • allergen induced degranulation further down airway results in allergic asthma
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13
Q

What occurs in allergic asthma?

A
  • bronchial constriction
  • increased secretion of fluid and mucus, trapping inhaled air
  • chronic inflammation may ensue with continued presence of Th2 T cells,
    eosinophils and neutrophils
  • chronic asthma driven by specific allergen can then result in hyperreactive airways to other irritants (eg. smoke/pollutants)
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14
Q

Describe what happens in skin allergies

A
  • Wheal and Flare (swelling and redness of the skin), first appears within a few minutes as a result of vasodilation after mast cell degranulation
  • around 8 hours later, diffuse edema at site due to influx of lymphocytes and other leukocytes attracted by chemokines
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15
Q

Describe what happens if you have ingested an allergen

A

2 main symptoms:

  • activation of GI mast cells causing transepithelial fluid loss and smooth muscle contraction: diarrhoea and vomiting
  • if allergen enters bloodstream, generalised disseminated rash (urticaria - hives)
  • if severe case (nuts/shellfish), life-threatening generalised anaphylaxis and CV collapse can occur
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16
Q

What are the chemical mediators of allergic responses?

A
  • mast cell granules
  • lipids
  • toxic mediators
  • cytokines
  • enzymes
17
Q

Describe lipids response to allergic reaction

A
  • prostaglandins:
  • increase vascular permeability
  • increase body temperature
  • platelet activating factor: increased adhesion between endothelium and neutrophils
  • leukotrienes:
  • attract and activate neutrophils
  • increase vascular permeability
18
Q

Describe toxic mediators response to allergic reaction

A
  • histamine:
  • increase vascular permeability
  • promotes movement of fluid from vasculature by constricting vascular smooth muscle
  • heparin: inhibits coagulation
19
Q

Describe cytokines response to allergic reaction

A
  • IL4, IL13: amplify Th2 response
  • IL3, IL5, GM-CSF: promote eosinophil activation and production
  • TNF-a: pro-inflammatory, activates endothelium
  • chemokine MIP-1a: attracts macrophages and neutrophils
20
Q

Describe enzymes response to allergic reaction

A
  • tryptase
  • chymase
  • cathepsin G
  • carbopeptidase
  • remodel connective tissue matrix
21
Q

What is the treatment of allergies?

A
  • desensitisation treatment
  • blockage of effector pathways
  • shift response from IgE dominated to IgG dominated
  • patient injected with escalating doses of allergen to cause a gradual shift from Th2 to Th1 T cells
    (potential risk of anaphylaxis)
  • anti-histamines for H1 receptor blocking
  • topica/systemic corticosteroids to suppress chronic inflammation in asthma and rhinitis