7- cytokines innate immunity

• TNF-a


  Produced by macrophages in response to bacteria
• IL-1B


  • Facilitates recruitment of neutrophils and macrophages and activates them
  • Causes endothelial cells to secrete chemokines
  • Dilate blood vessels (swelling)
• Release of IL-1B

  • Systemically: Liver /spleen
  • Locally: Blood clots, contains the pathogen, activates adaptive system
• Sepsis


  Vasodilation- plasma loss and shock, lots of clots through body BAD
• IL-1B


  • Produced by macrophages in response to TNF-a
  • Similar functions to TNF-a (activate immune cells)
  • Induce production of IL-6
• IL-6


  Same as above
• Chemokines


  Stimulate and regulate leukocyte movement
• Chemokine families

  • CXC: neutrophils
  • CC: monocytes, lymphocytes, eosinophils, dendritic cells
  • C: lymphocytes
  • CXXXC: lymphocytes
• Chemokines


  • Produced by macrophages, neutrophils, lymphocytes, epithelial and endothelial cells
  • In response to microbes, TNF-1 or IL-1
  • Bind to ECM and form chemical gradient- chemotaxis
• IL-12


  • Produced by macrophages, dendritic cells
  • In response to: viruses, intracellular bacteria
  • Receptor is T and NK cells
  • Activates NK cells; Kill with no MHC class 1
  • Produce IFN-gamma?, activates macrophage to enhance antigen presentation
  • Induces Th cells: Produce IFN-gamma?, activate macrophage, enhance antigen presentation (+feedback loop)
  • Produces IL-2 and IL-2R
• IFN a and B

  • Produced in response to dsRNA viruses
  • Alpha: by macrophage, dendritic cells
  • Beta: by many cells
  • Both bind to same receptor
  • Mediate early viral response: induces viral resistant state
  • Slow down mRNA production
  • Produce inhibitory proteins
  • Up regulate MHC class 1 deals with internal pathogens, activates T cells
  • Activates NK cells: kills cells with to MHC class I, produces IFN gammal activates macrophages, cleans up mess
• How NK cells Kill

  1. All of our own cells have MHC class 1- when NK cells comes in contact with that it shuts down

  2. Cytoxicity molecules: Perforin punches holes in cell membrane

  3. Granzyme can exit the vesicle

  4. Activates caspase-3

  5. Activate apoptosis
• Need thing to stay inside cell to not activate DAMPS