14- Signal Transduction

• First signal turns on apoptosis signal


  Need the second signal to turn that off
• TCR Complex Signal Transduction

  TCR signals activate biochemical pathways
• Antigen recognition


  • Causes clustering of TCR complexes: important for reaching threshold for response
• Immunoreceptor Tyrosine-based Activation Motif (ITAM)


  • Present on cytoplasmic tail of many cell surface receptors that pass signals
  • 2 tyrosines separated by 9-12 AA
• T cell Receptors


  • Need Co receptors
  • Short cytoplasmic tail
  • 2 CD3
  • CD3 and zeta chains have ITAMS
  • Ionic charges hold all the co-receptors to the TCR
• TCR Signal Transduction

  1. TCR first signal activates RAS/MAP kinase pathway

  2. Produces ELK-1: a transcription factor for Fos

  3. FOS forms dimer with Jun when phosphorylated

  4. Jun comes from Second signal pathway: B7/CD28

  5. To get full activation NEED to have both of these signals
• Clustering

  • ~50 MHC/TCR interactions needed to reach threshold
• TCR Signal Transduction

  1. CD 28 and 45: 45 phosphorylates Ys on ITAMS so Zap binds

  2. LAT brings everything to one place for Zap to phosphorylate

  3. Produces first signal only (Fos)

  4. Signals are passed
• Activation

  • Includes cytokine production: IL-2, IFN-y or IL4
• Functions of T cells

  • TC
  • Th
• TC

  • Activation leads to effector cytotoxic T lymphocytes
  • Release contents of granules to destroy targets
  • Target cells within intracellular pathogen, foreign tissue, tumor
• Th

  Provide help to other cells in form of soluble messages to activate cells
• B Cell Transduction

  • BCR is a membrane bound immunoglobulin molecule
  • Requires a signalling partner: Iga/IgB heterodimer
  • Process is similar to TCR
  • Syk instead of Zap70
  • BLNK instead of LAT
  • Get NFAT: Nuclear factor of activated T cells even though they are BCR
• Second Signal For B cells

  • Can come from: CD21 binding to C3d, with CD81 and CD19 (T cell independent)
  • Can also come from cytokines ( T cell dependent)