25- Allergy and Hypersensitivity

• Hypersensitivity


  A set of undesirable reactions by the normal immune system
• Hypersensitivity


  • Generally just an overreaction to an antigen that is not a threat
  • Usually require pre-sensitisation (prior exposure that provides immune status)
• Antigens that cause allergy

  • Contain PAMPS
  • Fail to elicit a strong innate response
  • Very low dose, low T cells reactivity, chronic exposure
  • Low second signal
• Enzyme activity

  • Proteases that affect cells and molecules of the immune system
  • Ex: house dust mite protease cleaves and activates complement
• Immediate Hypersensitivity: Type 1 Responses (Allergy)

  • IgE mediated
  • Basophils, eosinophils: circulating granulocytes with high affinity FCERS
  • Mast cells: tissue granulocytes with high affinity FCERS
  • FCER clustering causes activation
  • Signal transduction NF-KB, Map kinase
  • Granules contain mediators which cause bronchial constriction, smooth muscle contraction, vasodilation and local inflammation
• Mild form (local): allergy (atopy: over production of IgE)


  • Extreme form (systemic): anaphylaxis or anaphylactic shock
  • Asphyxiation &/or cardiovascular collapse
• Late Phase Reaction


  • Starts hours later, then subsides over several hours or days
  • TNF-a and IL-1B cause an influx of inflammatory leukocytes
  • Neutrophils, basophils, eosinophils, and CD4 (TH2)?
  • In tissues, more pronounced swelling due to influx of cytokine producing T cells and vascular permeability
• Allergens that enter the blood can cause anaphylactic shock within minutes


  Seafood, nuts, insect stings, drugs
• Testing For Allergies


  Expose skin to allergens then observe
• Allergy Treatments: Desensitization


  1. Injections of increasing doses of allergen with adjuvant to switch to Treg of IgG mediated response

  2. Inject large doses of peptides from common allergens without adjuvant to induce T cell anergy
• Allergy Treatments: Drugs


  • Antihistamines
  • Bronchodilators
  • Steroids
  • Leukotriene inhibitors
  • Anti-IgE antibodies
• Type 2 Hypersensitivity

  • Antibody dependent destruction of red blood cells or platelets (haemophilia)
  • Certain drugs (penicillin) bind to the surface of these cells, attract anti-drug lgG also causing hemolytic anaemia
  • Macrophages with Fcy receptors destroy and clear the cells
  • Only in minority of individuals
• Type 3 Hypersensitivity: Arthus Reaction

  • Antibody dependent destruction caused by soluble antigen
  • Complexed antibodies: again IgG in this case)
  • Can be complement of phagocytes
  • Antigen- Antibody complexes deposit and attract leukocytes with Fey receptors
  • Tissues: cleared by complement and macrophage
  • Blood vessels: causes tissue injury and problems
• Serum Sickness

  • Hypersensitivity reaction to large quantities of foreign antigen
  • Development of immune complexes throughout blood
  • Ex: injection of monoclonals
  • 7-10 day post injections patient develops chills, fever, rash, arthritis, nephritis
  • Immune complexes fix complement and attract leukocytes
  • These clear out the antigen, so its self limiting
  • Second time around it starts faster because it evokes a secondary response
• Type 4: Delayed Type Hypersensitivity (DTH)

  • Elicited by both CD4 (TH1, TH2) and CD8 t cells hours after exposure to antigen
  • Cytokine secretions attracts neutrophils and macrophage or eosinophils which cause damage
  • CD8 T cells lyse target cells (Self or foreign)
  • Prolonged DTH can cause granulomas
• IgE/TH2 mediated "allergies" are just 1 type
• Types I to III involve antibodies, Type IV (Delayed Type) involves cell