Allergy and Hypersensitivity Flashcards
Define allergy
- 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
What is the immune reactant, antigen, effector mechanism and example of a type 1 hypersensitivity reaction?
- immune reactant: IgE
- antigen: soluble
- effector mechanism: mast cell activation
- example: allergy, asthma
What is the immune reactant, antigen, effector mechanism and example of a type 2 hypersensitivity reaction?
- 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)
What is the immune reactant, antigen, effector mechanism and example of a type 3 hypersensitivity reaction?
- immune reactant: IgG
- antigen: soluble
- effector mechanism: complement, phagocytes
- example: arthus reaction, dermatitis
What is the immune reactant, antigen, effector mechanism and example of a type 4 hypersensitivity reaction?
- 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
Where is IgE produced and located?
- 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
What are the instances that favour IgE production?
- 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
Describe the features of inhaled allergens
- 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
Describe the host defence against enzymatic allergens
IgE is the host defence against parasites, many of which gain access by secreting proteolytic enzymes
Describe what response the different effector T cells bring about
- 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
What is an important factor in how symptoms of an allergen manifest?
location and distribution of the antigen
Describe how different routes of allergen delivery affect symptoms
- inhaled antigens will affect nasal epithelium causing allergic rhinitis (hayfever) due to seasonal pollens
- allergen induced degranulation further down airway results in allergic asthma
What occurs in allergic asthma?
- 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)
Describe what happens in skin allergies
- 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
Describe what happens if you have ingested an allergen
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
What are the chemical mediators of allergic responses?
- mast cell granules
- lipids
- toxic mediators
- cytokines
- enzymes
Describe lipids response to allergic reaction
- prostaglandins:
- increase vascular permeability
- increase body temperature
- platelet activating factor: increased adhesion between endothelium and neutrophils
- leukotrienes:
- attract and activate neutrophils
- increase vascular permeability
Describe toxic mediators response to allergic reaction
- histamine:
- increase vascular permeability
- promotes movement of fluid from vasculature by constricting vascular smooth muscle
- heparin: inhibits coagulation
Describe cytokines response to allergic reaction
- 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
Describe enzymes response to allergic reaction
- tryptase
- chymase
- cathepsin G
- carbopeptidase
- remodel connective tissue matrix
What is the treatment of allergies?
- 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
