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2011-05-18 19:54:09
Immunology Lecture MS1

Immunology Lecture 10 syllabus and mp3 complete
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  1. 3 signal model of activating T cells
    • A. TCR bind to MHC-peptide
    • B. costimulator (CD28, ICOS)
    • C. cytokine-cytokine receptor induce cell differentiation
  2. Naive T cells develop into 4 activated T cell populations
    • A. CD4+ à Th: secrete cytokines
    • B. CD8+ à CTL: lyse target cells
    • C. NK T à secrete cytokines
    • D. NK à lyse target cells
  3. 3 naïve T cell surface molecules target to lymph node
    L -selectin, CXCR4, CCR7 target to HEV of lymph node
  4. 4 Molecular adhesion bonds allow T cell sampling of APC surface
    • LFA 1 (CD11/CD18) to ICAM1 (CD54)
    • ICAM1 (CD54) to LFA 1 (CD11/CD18)
    • VLA4 to VCAM
    • CD2 to LFA3
  5. Key components of T cell—APC interactions
    • A. APC presents peptide-MHC Class 1 to CD8+ T cells
    • B. APC presents peptide-MHC Class 2 to CD4+ T cells
    • C. 3-5 agonist peptide-MHC on APC surface is sufficient for activation of T cell
    • D. TCR amplifies signal via endocytosis recycling and serial engagement of new TCR with peptide-MHCs
    • E. T cell CD28 binds to B7.1/B7.1, which is expressed on activated APCs only
  6. steps in Signal 1 of T cell activation: TCR binding to peptide-MHC
    • A. TCR conformation change upon binding with antigen-MHC
    • B. CD3 activate Lck (Src kinase)
    • C. Lck phosphorylate ITAMs (immunoreceptor tyrosine-based activation motifs)
    • D. Biphosphorylated ITAMs bind to ZAP70/Syk
    • E. ZAP70 phosphorylation activate LAT
    • F. Phosphorylated LAT binds and activates SLP76, vav, PLCγ1
    • G.PLCγ1 hydrolyzes PI3Pà IP3 + DAG
    • H. IP3à increase Ca2+ à activate calciuneurin à activate NFAT (nuclear factor of activated T-cells)
    • I. DAGà MAP kinase cascade
  7. 5 variations of ITAM signaling pathway
    • Receptor: receptor component
    • TCR: CD3 γε, δε, ζζ
    • BCR: Igα, Igβ
    • NK activating receptors: DAP12
    • Fc receptors: FcγRIII
    • Neuronal receptors: CD3 ζ, ε
  8. Signal 2 of T cell activation: CD28 mediated
    • A. APC B7.1/B7.2 binding activate CD28 pathway
    • B. CD28 tyrosine residues are phosphorylated
    • C. PI3K and other proteins associate with CD28-Pi
    • D. PI3K facilitate NFκb activation
    • E. Increase mRNA stability of cytokines produced by T cells
    • F. Slow activation CTLA-4, which competes with CD28 for B7.1/B7.2 binding; prevents T cell from activating out of control
  9. Signal 1 alone leads to...
    anergy, cell is rendered inactive to prevent autoimmunity
  10. 2 Secreted factors mediating T cell activation
    • IL2 autocrine growth factor
    • IL4 mediates T cell activation of B cell antibody response
  11. 3 surface molecules expressed after CD4+ T cell activation
    • IL-2R=CD25: receive IL2 growth signal
    • S1P1: allows egress from lymph node and thymus to infected tissue
    • CD154=CD40L: interact with CD40 on B cell to promote isotype switching
  12. Digeorge syndrome
    • 22.q11.2 deletion
    • no T cell in thymus
  13. Chronic variable immunodeficiency disease (CVID)
    CD19, ICOS, TACI mutation
  14. hyper IgM syndrome
    • CD40, CD40L, AID, UNG mutation
    • no isotype switching in B cells
  15. X linked agammaglob or auto recessive ARA
    Btk/mu, λ5, Igα, Igβ, BLNK
  16. FTY720 targets ___
    S1P1, which allows activated T cells to egress form LN/thymus to infection site
  17. Rapamycin targets ___
    • IL2, IL2R
    • which is the growth factor signal for T cells
  18. cyclosporin and FK506 targets ___
    calcineurin, which is a phosphatase that activates NFAT
  19. normal WBC cell count
    • WBC=4400-8100
    • Myeloid= 2/3
    • Lymphocyte= 1/3 (1400-3300)
    • neutrophil= majority of myelocyte 1800-7700
    • Monocytes<800
    • Eosinophils<450
    • Basophils <200
    • B cells (CD19+)1100-1570
    • T cells (CD3+) 1000-2200
    • CD4+ T cells 530-1300
    • CD8+ T cells 330-920
    • NK cells 70-480