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20 Cards in this Set

  • Front
  • Back

TH cell + Ag will stimulate...

T cells to enter the cell cycle==>IL2R & secretion of IL2

Receptor crosslinking

Ab + TcR = activation of T cell directly

To activate a T cell you need

Ag, processedand sitting in the MHC and the TcR

IP3

-mediates release of intracellular Ca++


-an intracellular kinase adds additional phosphate to IP3 → IP4 = opens Ca++ channels on membrane to let in additional Ca++



DAG

-activates PKC (protein kinase C)


-increase affinity for PKC Ca++-->


-change in intracellular H+ therefore increases pH/PKC catalysis the phosphorylation of many signaling proteins


-CD4,IL-2R, NF-κB, etc

PTK-->PLCγ1-->cleaves PIP2-->IP3/DAG

-------

Immediate genes

NF-κB

Early genes

IL-2, IL-2R,IL-6,IFNy

Late genes

various adhesion molecules

use Ca++ ionophores (A23187 or ionomycin) to...

activate cells w/o TcR


-Open Ca++ channels and induce influx of Ca++


-A23187 stimulates IL-2 secretion

use PKC activators (i.e., phorbol myristateacetate; PMA) to...

-Directly activate PKC and initiate the events


-PMA stimulates IL-2R expression

Ca++ is from...

intracellular pools, but forsustained levels you do need extracellular Ca++

EGTA

Gets rid of extracellular Ca++

Ab to TcR

Found an increase in intracellular Ca++, just like controls

PTK

Interact with the ITAM sequences of CD3 cytoplasmictail


-lck, associated with the cytoplasmic tails of CD4 and CD8


-fyn associated with the cytoplasmic tail of the CD3 protein ζ (zeta)

activation ofTH cells requires...

co-stimulatory signalprovided by the APC = surface molecule B7(CD80/CD86)

Stimulus needed for full TH cell activation...

Interaction between TcR and MHC & B7

Signal # 1 (Activation)

Interaction of a peptide and MHC molecule with aspecific TcR-CD3 complex

Signal #2 (Survival)

Subsequent Ag non-specific co-stimulatory signal byinteractions between CD28 (or CTLA-4) on T cells andB7 (CD80/CD86) on APC

Signal #3 (Proliferation &/or Differentiation)

Directing T-cell differentiation into different subsets ofeffector T cells