Hypersensitivity & Allergy

Cards (63)

  • What is a hypersensitivity reaction?
    Overreaction to a harmless substance(s) which results in an immune response that causes inflammation & tissue damage
  • What are the different types of hypersensitivity?
    Type I
    Type II
    Type III
    Type IV
  • All hypersensitivities involve components of the adaptive immune system.
  • What is the normal function of IgE?
    Binds to Fc receptors on the the surface of mast cells, eosinophils & basophils
    Induces responses to get rid of extracellular parasites (esp, multicellular ones that cannot be phagocytosed)
  • What are the cells involved in Type I hypersensitivity?
    Mast cells
    Eosinophils
    Basophils
  • Where are mast cells found?
    Tissue resident cell
    Predominantly in mucosal tissues near body surfaces & in connective tissue near blood vessels
  • How does IgE bind to mast cells?
    Binds to FcεR (type of Fc receptor) on mast cell
    1 mast cell can have surface pre-bound IgE that covers a range of specificities
  • What happens when pre-bound IgE on mast cells cross links?
    IgE is cross-linked -> mast cells degranulate & release histamine (+ prostaglandins, leukotrienes, cytokines & enzymes)
  • What is the hygiene hypothesis?
    Increased cleanliness (usually in 'Westernised' countries) leading to higher rates of allergies and autoimmune diseases.
    There is very little allergy in 'developing' countries
  • What is atopy?
    A genetic predisposition to develop allergic diseases.
  • Atopic individuals have higher levels of IgE & eosinophils in their blood.
    Strong genetic component to risk - polymorphisms of multiple genes on chromosomes 5, 6 & 11
  • What is the role of eosinophils in type I hypersensitivity?
    Have FcεRs for IgE on their surface
    Contain pre-formed toxic mediators in granules -> released on receptor crosslinking
    Also can secrete cytokines
  • Th2 cells regulate the eosinophil arm of the immune response
    • secrete cytokines (e.g. IL-5) -> promote development & survival of eosinophils
    • promote recruitment of eosinophils to sites of inflammation by stimulating release of chemokines by activated endothelial & epithelial cells
  • Where are eosinophils found?
    Present in small numbers in blood
    Resident in connective tissue under mucosal surfaces
  • Where are basophils found?
    A minor population in peripheral blood & not usually found in large numbers in peripheral tissues
    Recruited to sites of inflammation
  • What is the role of basophils in type I hypersensitivity?
    Have FcεR for IgE
    When activated, receptors crosslink -> release histamine & other mediators
    Cytokine production (IL-4 & IL-13) -> important in initiation of Th2 responses
  • What are the different ways that an allergen can enter the body?
    Intravenous
    Subcutaneous
    Inhalation
    Ingestion
  • What happens when an allergen is introduced by IV?
    Antigen is distributed widely across the body
    Release of histamine -> systemic increase in blood vessels permeability
    = Anaphylactic shock
  • What happens when an allergen is introduced subcutaneously?
    Local release of histamine -> oedema & reddening of the area
    = wheal & flare reaction
  • What happens when an allergen is introduced via inhalation?
    In upper airways
    -> nasal irritation & increased mucous production
    In lower airways
    -> contraction of smooth muscle & increased mucous production
    = runny nose & bronchoconstriction
  • When happens when an allergen is ingested?
    Contraction of smooth muscle
    Increased fluid loss
    = diarrhoea, urticaria, atopic eczema
    There is a risk of anaphylaxis, due to absorption of allergen into blood
  • What happens in a type I hypersensitivity?
    First exposure (sensitisation)
    • allergen is picked up by APC (usually at the mucosal surface) -> antigen presented to Th cells (Th2 response) -> Th cells then activate B cells -> B cells become plasma cells -> IgE production -> IgE 'sticks' to all of the local mast cells (FcεR), but allergen is gone
    Second exposure
    • allergen enters -> becomes bound to IgE pre-bound on mast cells -> cross-linking of IgE -> mast cells degranulate & release its granule contents -> vasodilation & increased permeability
  • Atopic individuals have haver levels of IgE & eosinophils in their blood.
  • What cytokines are involved in type I hypersensitivity?
    IL-4
    IL-5
    IL-13
    Histamine
  • What happens in a type II hypersensitivity?
    IgG antibodies bind to cell surfaces -> their destruction
    2 ways this can be initiated;
    • intrinsic -> antibodies to a self antigen
    • extrinsic -> antibodies to a neo- or foreign antigen (e.g. an infection or drug that attaches to a cell)
  • Give an example of a type II hypersensitivity.
    Response to an ABO- incompatible blood transfusion
  • What are preformed in mast cell granules?
    Enzymes (e.g. tryptase)
    Histamine
    Heparin
    Cytokines (TNF-a)
  • What happens in type III hypersensitivity?
    IgG binds to soluble antigen (not attached to cells) -> forms 'clumps' (immune complexes) -> small immune complexes circulate in the body & deposit in highly vascularised areas (as positively charged complexes are attracted to the negatively charged basement membrane) -> immune complexes activate & deposit complement -> vascular response & phagocytes are recruited -> inflammation is triggered, phagocytes take up immune complexes & ROS are produced -> can result in vasculitis
  • What is serum sickness?
    Systemic reaction to an injected foreign antigen
    Antigen is removed & is self-limiting
  • In type III hypersensitivity, a reaction to a self-antigen could cause autoimmunity (e.g. SLE).
  • What are the differences between the different types of hypersensitivities?
    Type I -> IgE, soluble antigen
    Type II -> IgG, cell-associated
    Type III -> IgG, soluble antigen
    Type IV -> cell mediated
  • Fill in the blanks
    A) IgE
    B) IgG
    C) IgG
    D) Cell mediated
    E) soluble
    F) cell-associated
    G) soluble
    H) soluble
    I) cell
    J) mast
    K) complement
    L) phagocytes
    M) complement
    N) phagocytes
    O) macrophage
    P) eosinohpil
    Q) cytotoxicity
  • Give 2 examples of type I hypersensitivity.
    Allergic asthma
    Eczema
  • Give an example of a type II hypersensitivity.
    Chronic urticaria
  • Given an example of a type III hypersensitivity.
    Serum sickness
  • Give 3 examples of type IV hypersensitivity.
    Allergic contact dermatitis
    Chronic asthma
    Graft rejection
  • What is the pathophysiology of allergic (acute) asthma (immediate phase)?
    Immediate phase
    • antigen enters -> taken up by APC -> mast cells activate & degranulate -> releases
    • …histamine -> smooth muscle contraction, increased vascular permeability, increased mucus production
    • …leukotrienes -> promote smooth muscle contraction & increased vascular permeability
    • …cytokines. IL-4 & IL-13 -> Th2 response & mucus production. IL-3 & IL-5 -> eosinophil production & recruitment
  • What is the pathophysiology of allergic (acute) asthma (late phase)?
    Late phase
    • Th2 cells -> stimulate mucus production, recruit eosinophils, trigger fibroblasts to synthesise collagen
    • Eosinophils -> produce type 2 cytokines, toxins, enzymes & leukotrienes -> damages airways
    • Smooth muscle cells -> constriction of airways, thickening of airways (chronic)
  • When is the immediate phase of allergic asthma?
    Within 30 mins
  • When is the late phase of allergic asthma?
    Begins within 12 hours