20- T cell Mediated Immunity

• CD8


  Cytotoxic T cells kill infected cells
• CD4


  TH1 cells activate macrophages
• How do Naïve T Cells get to Peripheral Lymphoid Organs

  Continually circulating due to chemokine gradients

  • Blood-spleen-blood-lymph nodes-blood...Ensure that it will eventually come into contact with AG

  4. Migrate to lymph node cortex through HEV attracted by chemokines from lymph node
• Entry into Lymph Node

  • Adhesion molecules are important to guide them there
  • CCR7 is a chemokine receptor on naïve T cells that bind to the chemokines that attract them to the lymph nodes
  • Once bound: diapedesis (blood cells pass through capillary walls)
  • Get into paracortical spaces and tissues
• Once in the node paracortex

  1. T cells interact with Ag presented by dendritic cells

  2. If not activated: they leave (always circulating)

  3. If activated: proliferation, can no longer leave node

  4. They differentiate into effector T cells and leave
• How do APCs get to Peripheral Lymphoid Organs

  1. CCR7 again!

  2. Once dendritic cell is activated it increase CCR7 receptor so it can be attracted by chemokines and will migrate to lymph node
• Activation of T cells

  Proliferation, turn into effector T cells, no longer respond to chemokines
• No activation

  • No co stimulatory signal (CD80/86): Anergy
  • Not all APCs can provide co-stimulation well
  • Would need T helper to help (CD4 T cells will induce more co stimulatory molecules on APC with CD40L)
• When T cells are primed


  1. Up regulates IL2R and IL-2

  2. T cells proliferate/ clonal expansion

  3. Differentiate into effector T cells, CD8 will no longer need a 2nd signal
• When T cells Activates

  • CTLA-4 is expressed
  • Binds to B7 (CD80/86)
  • Acts to limit T cells proliferative response to antigen and IL-2
• Steps to CD8 Killing


  1. CTL finds cell presenting antigen in MHC I groove

  2. Cytoskeleton rearrangements form SMAC (immunological synapse)

  3. Release of granules in the synapse

  4. Perforin and granzymes (all completely contained in the SMAC)

  5. Apoptosis neat and tidy
• Effector CD8 cells


  • Only kill specific cells
  • One T cell will kill multiple targets before it apoptoses
• CD4 TH1 Killing

  1. Killing through macrophage that has phagocytosed pathogen

  2. Releases many dangerous chemicals: proteases, NO, ROS

  3. Damages self cells as well
• Some bacteria can avoid macrophage activation
• If immune system cannot deal with the infection

  It creates a wall around it to stop it from reacting
• Central core of infected macrophages are surrounded by CD4 T cells
• Granulomas

  Hard bone-like mass