CD4 T-Cell Activation Polarization and Memory

CD4 T-cell Activation/Polarization/Memory 3 signal hypothesis: TCR signaling dendritic cell presents antigen to helper T-cell at the TCR via MHC class 2 autocrine signal that tells T-cells to proliferate released by ND winds to the same cell one cell to many cells VERY quickly because each cell is secreting AND recieving IL-2 So A LOT of proliferation occurs the cells are identical so they can give each other IL-2 Costimulatory Interaction CD28 / CD86 not the same molecule BUT either could be expressed (and sometimes both are expressed) binds to CD28 on the T-cell their binding is known as "co stimulation" Cytokine Signaling release of cytokines from the dendritic cell to the naive cell known as "paracrine stimulation" because of their close proximity the molecule expressed is dependent on the nature of the PAMP Signal 2 in a crucial CHECKPOINT It's BAD! autoimmunity when a T cell with a self-reactive receptor recognizes self-antigen? Signal 2 is the checkpoint because it ONLY happens when PRR bind to PAMP when the dendritic cell phagocytoses antigen, some of it can bind to the DC PRR in the absence of PAMP/PRR Stimulation you ONLY have signal 1 without signal 2 the T-cell will NOT activate and becomes anergic anergy: sleepy/inactive component of peripheral tolerance mas/050 candra of las SOH IN Immunological Synapse "immunological Kiss" Naive T cell TCR signalling APC adhesion molecules make sure kiss goes on for a while BECAUSE if the kiss ends before the mokcular interactions con occur than nething happens Gen expression Costimulatory Intaraction Autocrine Paraczine (-2) (eg.-12) Cytokine signaling ceriral supramolecular activating complex (CSMAC) activation peripheral supramolecular activating complex (PSMAC): adhesion forms ring around CSMAC to make sure it stays together 50.40 located on the APC (NOT the T-cell) Signal transduction CD3: signal transduction element of TCR ceil aignaling surrounds TCR and allows signaling CD4 adhesion molecule that binds to MHC class 2 Signal transduction cell signaling results in: CD: adhesion malecule that binds to PMHC class 1. cell survival Signal transduction 2. cell probferation CD 28: receptor for co-stimulation on T-cell 3. cell differentiation CTLA-4 negative regulation of immune system Checkpoint inhibitor IpilibumabIppy CD23 and CTLA-4 are both released by the T-cell blocks CTLA-4 causing T-cells to remain activated CD23 binding to CD80/80 stimulation "gas pedal ne biras Semer concer cells -CTLA-4 binding to co50/se inhibition "break peaal" - both binding INHIBITION CTLA-4 wins