hyper and granule

• Types of hypersensitivity reactions

  • Type 1
  • Type 2
  • Type 3
  • Type 4
• Type 1 hypersensitivity


  Immediate, antibody-mediated (IgE), mast cell degranulation, release of histamine and other mediators
• Type 2 hypersensitivity


  Cytotoxic, antibody-antigen complexes on cell surface, can activate complement or recruit effector cells
• Type 3 hypersensitivity


  Immune complex-mediated, antibody-antigen complexes in circulation, can deposit in tissues and activate complement
• Type 4 hypersensitivity


  Cell-mediated, T cell-mediated, no antibodies involved, delayed reaction
• Reaction speed


  Type 1 is fastest, Type 4 is slowest
• Type 1 hypersensitivity involves IgE antibodies, mast cell degranulation, and release of histamine and other mediators
• Type 2 hypersensitivity involves antibody-antigen complexes on cell surfaces, can activate complement or recruit effector cells like eosinophils or neutrophils
• Type 3 hypersensitivity involves antibody-antigen complexes in circulation that can deposit in tissues and activate complement, leading to inflammation
• Type 4 hypersensitivity is cell-mediated, involving T cells, with no antibodies, and a delayed reaction
• Type 2 hypersensitivity can either inhibit or stimulate the target cell, with stimulation being an unusual case (previously called type 5 hypersensitivity)
• Rheumatoid factor is an IgM antibody against the Fc portion of IgG, an example of type 3 hypersensitivity
• Antigen-antibody complexes in type 3 hypersensitivity can deposit in vessel walls, joints, and kidneys, causing vasculitis, arthritis, and nephritis
• The complement system is involved in both type 2 and type 3 hypersensitivity reactions
• Antigen-antibody complex


  When the antigen and antibody are floating freely in the circulation, it is called a type 3 hypersensitivity reaction
• Antigen-antibody complex deposited into tissues

  Causes vasculitis, immune complex mediated arthritis, immune complex mediated nephritis
• Antigen-antibody complex deposited into vessel walls

  Causes fibrinoid necrosis
• Type 3 hypersensitivity reaction


  Antigen-antibody complex floating freely in the circulation
• Types of type 3 hypersensitivity reaction

  • Generalized reaction
  • Localized reaction (e.g. arthus reaction)
• Serum sickness reaction


  Generalized, acute type 3 hypersensitivity reaction caused by injection of foreign antibodies
• Arthus reaction


  Localized, subacute type 3 hypersensitivity reaction caused by subcutaneous or intradermal exposure to an antigen in a previously sensitized individual
• Serum sickness like reaction is caused by infections or drugs, not foreign antibodies
• Type 4 hypersensitivity


  Cell-mediated immunity, not antibody-mediated
• Type 4 hypersensitivity reaction

  1. Antigen presenting cells present antigen to CD4 T cells

  2. CD4 T cells secrete interferon-gamma to activate macrophages

  3. Macrophages form granulomas around persistent, virulent organisms
• Granulomas


  • Surround and imprison persistent, virulent organisms like tuberculosis
  • Contain epithelioid histiocytes, multinucleated giant cells, fibroblasts
  • Develop caseous necrosis in the center
• Sarcoidosis has non-caseating granulomas with no identifiable organism
• Treatments for asthma (type 1 hypersensitivity)

  • Leukotriene inhibitors
  • Mast cell stabilizers
  • Monoclonal antibodies against IL-5, IgE
  • Inhaled corticosteroids
  • Beta-2 agonists
  • Muscarinic antagonists
• Asthma involves bronchoconstriction and increased bronchial secretions
• Examples of type 2 hypersensitivity

  • Rheumatic fever
  • Goodpasture's syndrome
  • Hyperacute transplant rejection
  • Autoimmune hemolytic anemia
  • Immune thrombocytopenia
  • Myasthenia gravis
  • Graves' disease
• Type 3 hypersensitivity can be generalized (serum sickness) or localized (arthus reaction)
• Type 4 hypersensitivity involves cell-mediated immunity, not antibodies
• Type 4 hypersensitivity reactions

  • Tuberculin skin test
  • Contact dermatitis (e.g. poison ivy, nickel allergy, new makeup)
  • Graft-versus-host disease