Hypersensitivity reactions

• Hypersensitivity


  Immune system has reacted to something in such a way that it ends up damaging the person, as opposed to protecting them
• Type 1 hypersensitivity


  Reactions rely on Immunoglobulin E (IgE) antibody, which is a specific type of antibody
• IgE-mediated hypersensitivity


  Also called immediate hypersensitivity, because the reaction happens super fast—on the order of minutes
• Most allergic reactions are IgE-mediated, and therefore most allergies are type I hypersensitivity reactions
• Allergic reaction


  1. First exposure (sensitization)

  2. Subsequent exposure (more serious reaction)
• Genetic predisposition to allergies

  People have certain genes that cause their T-helper cells to be more hypersensitive to certain antigens
• Sensitization phase


  1. Antigen picked up by immune cells

  2. Antigen presented to T-helper cells in lymph nodes

  3. T-helper cells differentiate into TH2 cells

  4. B cells switch to producing IgE antibodies

  5. IgE antibodies bind to mast cells
• Allergic reaction (second exposure)

  1. Mast cells bind to antigen

  2. Mast cells degranulate and release mediators like histamine

  3. Early phase reactions occur within minutes

  4. Late phase reactions occur 8-12 hours later
• Effects of histamine


  • Smooth muscle contraction (airways get smaller)
  • Blood vessel dilation and increased permeability (fluid leaks out, causing edema and swelling)
• Other mediators released


  • Activate eosinophils
  • Proteases that break down proteins
• Early phase reactions


  Happen within minutes of second exposure
• Late phase reactions


  Happen 8-12 hours after second exposure, more immune cells recruited
• Mild allergy symptoms include hives, eczema, allergic rhinitis, and asthma
• Severe allergic reactions (anaphylactic shock) can be life-threatening due to increased vascular permeability and airway constriction
• Anaphylactic shock


  Condition where the body can't supply vital organs with enough oxygen-rich blood
• Allergy treatments


  • Antihistamines
  • Corticosteroids
  • Epinephrine
• It's important to get medical attention for serious type 1 hypersensitivity reactions, as they can get worse after initially improving
• Types of hypersensitivity


  • Type I
  • Type II
  • Type III
  • Type IV
• Type II hypersensitivity


  Also called cytotoxic hypersensitivity, involves antibody-mediated destruction of healthy cells
• Type II hypersensitivity


  • Tissue specific, meaning the antibodies are generally specific to one type of tissue or organ
  • Can also be systemic, which are generally Type III hypersensitivities
• Central tolerance


  Process where developing immune cells that are self-reactive get destroyed or inactivated, whereas immune cells that aren't are allowed to survive
• Central tolerance is not perfect and some self-reactive B and T cells will escape</b>
• Escaped self-reactive cells


  Can attack healthy tissue and result in autoimmune disease
• Type II hypersensitivity


  1. Escaped self-reactive B cells become activated

  2. Produce IgM or IgG antibodies

  3. Antibodies attach to antigens on host cells
• Antigens involved in type II hypersensitivity

  • Intrinsic (antigen the host cell normally makes)
  • Extrinsic (antigen from an infection or medication that gets attached to the host cell)
• Antigen-antibody complex formation


  IgG or IgM antibody binds to the extrinsic antigen (e.g. penicillin)
• Antigen-antibody complexes can happen in the course of a normal infection, but it's when an antibody is complexed to host tissue that it becomes a problem
• First cytotoxic mechanism of type II hypersensitivity

  1. Activation of the complement system

  2. IgG or IgM antibodies activate complement proteins

  3. Ultimately kills the red blood cell bound to the antigen-antibody complex
• Complement system


  • Family of small proteins that work in an enzymatic cascade to fight off bacterial infections
  • C3a, C4a, and C5a act as chemotactic factors, attracting neutrophils
  • Neutrophils degranulate and release enzymes and oxygen radicals that are cytotoxic
• Diseases involving type II hypersensitivity

  • Hemolytic anemia
  • Thrombocytopenia
  • Neutropenia
  • Goodpasture's syndrome
• Second cytotoxic mechanism of type II hypersensitivity

  1. Complement system forms the membrane attack complex (MAC)

  2. MAC inserts into the cell membrane, creating a channel that allows fluid and molecules to flow in and out

  3. Cell swells and bursts, causing cell lysis and death
• Direct Coombs test


  Used to detect antibodies on the surface of red blood cells in autoimmune hemolytic anemia
• Indirect Coombs test


  Used to check for blood group incompatibility by detecting antibodies in the patient's serum
• Third cytotoxic mechanism of type II hypersensitivity

  1. IgG antibodies coat a blood cell and are bound by C3b

  2. Cell is opsonized and targeted for phagocytosis by macrophages and neutrophils
• Fourth cytotoxic mechanism: Antibody-dependent cell-mediated cytotoxicity (ADCC)


  1. Bound antigen-antibody complex is recognized by natural killer cells

  2. Natural killer cells release toxic granules containing perforins and granzymes that cause cell death
• Non-cytotoxic type II hypersensitivity

  Antibody-mediated cellular dysfunction, where the antibody binding disrupts the normal function of the cell
• Diseases involving non-cytotoxic type II hypersensitivity

  • Myasthenia gravis (antibodies block acetylcholine receptors)
  • Graves' disease (antibodies activate thyroid hormone receptors)
• Type II hypersensitivity


  • Antibody mediated
  • Generally lead to cytotoxicity
  • Tissue specific
• Type III hypersensitivity


  Happens when antigen-antibody complexes deposit in blood vessel walls, causing inflammation and tissue damage
• Immune complexes


  Made of two parts - the antigen and the antibody