29-privlege

• Privileged Sites


  Transplants to some sites do not result in immune responses
• Privileged Sites


  • Tissues are non-living so don't mount a response
  • Some living tissues don't respond
• Examples of Privileged Sites

  • Brain
  • Eye
  • Testis
  • Uterus
  • Hamster Cheek pouch
• Destroying the germ line is bad because you can't really reproduce that: the immune system won't respond
• Privileged sites include cartilage and cornea
• Brain and Eye

  • Important to not have inflammation (from immune response) because of squishing/exploding. Also bad if any ROS because can't really replace these tissues if they are damaged
• Privileged Sites

  • No lymphatic drainage
  • Surrounded by tissue barrier that has no lymphocytes
  • Antigens can still leave via blood or diffusion through tissues
  • Cytokines are produced and leave with the antigens (TG-6)
  • Allows for non-inflammatory, non-destructive responses (Th2)
  • Tissues express Fas ligand-induces apoptosis in Fas bearing lymphocytes that do enter
• Common Mechanisms of Privileged Sites

  • Lack of lymphatic drainage
  • Local production of immunosuppressive cytokines (TGF-B)
  • Constitutive (always an) expression of Fas Ligand that controls entry of Fas lymphoid cells
  • Low MHC expression
  • Surface molecules that inhibit complement activation
  • Neuropeptides present: can be immunosuppressant
• Pregnant Uterus


  • Even though fetus is only 50% self it is still not rejected due to strict barriers by placenta
  • Tregs are more present when pregnant
  • IL-10 and TGF B are secreted which keep immune responses under control
• Testis


  • Macrophages are present but with low levels of MHC II (no response)
  • IL-10 higher concentration of macrophages than other places
  • Macrophages are less responsive: Produce less IL 1B, INFa, IL-6 and GM-CSF but more TGFB
• Microglial Cells


  • Specialized immune cells: like macrophages for the brain
  • Clean up any dead cells but don't cause inflammation
  • Most remain quiescent
  • Tight regulation
  • Inactive: lack MHC and CD 45, IFN Y
  • Active: proliferate quickly solve issue quickly then shut down again
• Brain

  • Cannot regenerate neurons- need to keep inflammatory reactions to a minimum
• Eye


  • Blood brain barrier keeps many cells and antibodies out
  • Privilege varies in different regions
  • White matter: most privilege, no dendritic cells, few microglia
  • Cerebrospinal dendritic cells go straight to cervical lymph nodes and B follicles to completely avoid T cells
  • Goal is to induce humoral TH2 response
  • Neurons express Fas Ligand binds to Fas on I cells which causes apoptosis
  • Neurons express CD47 which is an antiphagocytic signal
  • Neurons express CB1 (cannabinoid) receptor: Decrease release of inflammatory cytokines, induces dendritic cell apoptosis
  • TGFB1: expressed by neurons (shuts things down)
  • Neurons express MHC I heavy chain but no beta 2 microglobulin
  • Neurons have no antigen presentation
  • When neurons think they are dying: turn on B2m gene, upregulate MHC and ask at cell to come kill them
  • If they think they are infected: want to get taken out quickly so infection doesn't spread
• Privileged Sites in the Eye

  • Anterior chamber and vitreous chamber (blood/ocular barrier)
  • AIRE: transcription factor that eliminates self-reactive T cells
  • Thick fibrous acellular connective tissue around iris vasculature and retinal endothelium made of tight junctions keep things out
  • If something does sneak through, vitreous humor has TGF-B, cortisol and NK inhibitory factor
  • Tregs are present
  • ACAID: if antigen are in anterior chamber you get a TH 12 response NOT TH1 inflammatory response
• Thymus


  • Artificial Privilege
  • Site where T cells learn so can generate privilege like mechanism
  • T cells are developing but not fully active so would not get a response if things were injected here
  • T cells will learn something is self if enough antigen is injected here