Hypersensitivities

• Hypersensitivity


  Immune system has reacted in such a way that it ends up damaging, instead of protecting
• Type I reactions


  Rely on IgE
• IgE-mediated sensitivities or immediate hypersensitivities


  Reaction occurs within minutes
• Allergen


  Antigen that causes an allergic reaction
• Allergic reaction


  1. First exposure (sensitization)

  2. Subsequent exposure
• Allergic reaction process


  1. APC will present the antigen to T help cells in the lymph nodes

  2. Will also express co-stimulatory molecules- mount an effective immune response

  3. Becomes a primed T cell when it binds to the APC with co-stimulatory molecules

  4. Goes to a Th2 cell
• Interleukins


  IL-4, IL-5, and IL-10 sway the T-helper cell into turning into a Th2
• Interleukins


  1. IL-4 switches from IgM to IgE specific

  2. IL-5- stimulates production and activation of eosinophils
• Cytotropic antibodies


  Bind to cell surfaces
• Second exposure


  1. Mast cell will bind to the antigen

  2. Two or more bound antigens to cross-link the IgE antibodies signaling mast cell to degranulate and release a bunch of pr-inflammatory molecules
• Histamine


  1. Binds to H1 receptors and cause the smooth muscles around the bronchi to contract- airways get smaller, making it harder to breathe

  2. Causes blood vessel dilation and increased permeability of blood vessel walls- fluid is allowed more easily leak out the walls and get into the intersitium (spaces between the cells) causes edema (swelling) and urticaria (hives)
• Proteases


  Chop up large proteins into small peptides
• Early phase reactions


  Happen within minutes
• Late phase reactions


  Th2 cells, basophils, and eosinophils are recruited and IL-4, IL-5, and Il-10 cytokines along with leukotrienes released
• Leukotrienes


  Smaller molecules made out of fatty acids and facilitate communication between a local group of cells
• LTB-4 and LTC4

  • Cause smooth muscle contraction and damage to epithelium
  • Can attract immune cells (neutrophils, mast cells and eosinophils)
• Mild symptoms


  • Hives
  • Eczema
  • Allergic rhinitis- inflammation of the nose
  • Asthma
• Severe symptoms

  • Increase vascular permeability
  • Airways constriction
  • Anaphylactic shock
• Treatments


  • Antihistamines- block histamines, decreases vascular permeability, decrease bronchoconstriction
  • Corticosteroids- decrease inflammatory response
  • Epinephrine-constrict blood vessel, prevent anaphylactic shock
• Type 2 hypersensitivities


  • Antibody-mediated
  • Complement activity (MAC killing)
  • Antibodies can also create cellular dysfunction
  • Neutrophils
  • ADCC (NK cells)
  • Tissue specific
• Type 1,2,3 are all antibody mediated
• Antibody types


  • Type 1- IgE
  • Type 2- IgG
  • Type 3- IgG immune complex, Antibody- self antigen
• Small soluble antigens

  • Not great once bound by antibody to trigger engulfing
  • They circulate and group together
  • Complement will attach to antibody structures
• Anything that ends with itis is systemic specific
• Antigen-antibody complexes


  • Deposit in blood vessel walls, causing inflammation, and tissue damage
  • Mediated by immune complexes
• Antigen-antibody complex formation

  1. Antigen

  2. Antibody-produced by plasma cells (fully matured and differentiated B cells)
• B cell activation


  1. Initially make IgM

  2. When B cell undergoes cross-linking of two surface bound IgMs it then takes up the antigen and presents a piece to t helper cells via TCR to the MHC-2 molecule presenting the piece of antigen, along with costimulatory molecule CD4

  3. B cell's CD40 binds to the t cells CD40 ligand and then t cell releases cytokines

  4. B cells switch from making IgM to IgG
• Immune complexes with soluble antigens

  Systemic lupus erythematosus
• Tolerance


  • Only non-self reactive B and t cells allowed to mature
  • Self-reactive B and T cells are not
  • Cells that escape are self-antigens
• Autoimmune response


  1. A DNA autoantigen may get released from a damage cell where a circulating self-B cell can bind to it

  2. T helper cell will help to activate the B cell and enable it to differentiate into an IgG secreting machine
• Complement system activation

  1. C1 sets off chain reaction to activate C2-C9

  2. C3-5a are anaphylatoxins and increase vascular permeability

  3. Fluid can leak out more easily

  4. Edema or fluid buildup

  5. Act as chemokines, recruiting other cells like neutrophils to the site

  6. Neutrophils will degranulate- dump a bunch of lysosomal enzymes and reactive oxygen species causing inflammation and tissue necrosis
• Complement can be rapidly consumed in large amounts and can track disease progression in the blood overtime
• Immune complexes commonly take place in the areas where blood is being filtered (kidneys) and joints (arthritis)
• Type 4- T cell mediated killing


  • Inflammation
  • Delayed type hypersensitivity (DTH)
• TB skin test

  • Protein components of the bacteria injected into the skin and if there is a previous TB bacterium the immune system will attack the injected protein components
• Contact dermatitis


  • Metal allergies, latex
• Cytotoxic t cells


  Attack target cells directly
• Cytotoxic t cell targets


  • Insulin-secreting beta cells of the pancreas (type 1 diabetes)
  • Joint tissue (rheumatoid arthritis)
  • Thyroid hormone producing follicular cells (Hashimoto's disease)
  • Foreign grafted cells (graft rejection)
• Cytotoxic t cell killing


  1. Vesicle with perforins and granzymes that target cells take through endocytosis

  2. Granzymes indue apoptosis

  3. Can also bind to a FAS receptor expressed on target cell
• Type 1 diabetes, poison ivy, drug related reaction, Multiple sclerosis are not based on granules