Lecture # 17 Naive T Cell/DC entry into LN Flashcards
Primary Cell mediated immune response
Activation of naive T cells in response to Ag
Priming
The activation of T cells upon initial encounter with Ag; occurs in Lymph nodes
How many signals prime naive cells? What are they?
3 signals; Signal 1: TCR recognition of MHC:peptide
Signal 2: costimulatory molecules on APC Signal 3:cytokines that promote different types of
effectors
What are the four steps of T cell migration into the lymph node? (RAAD)
Four steps: Rolling (L-selectin), Activation(CCL21), Adhesion (LFA-1), and Diapedesis (CCL21, CXCL12)
CD62L
L-selectin expressed on naive T Cell guides their exit
from the blood into LN by initiating attachment to HEV; ligand PNad on epithelial cells; weak interaction
T Cell homing receptors
L-Selectin (PNAd and Gly-CAM ligands); CCR7( CCL19 and CCL21 ligands) ; LFA-1 (ICAM-1 ligand)
LFA-1
Receptor on T Cells, binds to ICAM-1 on HEV with high stability
VLA-4
expressed on effector cells-binds to VCAM-1 on endothelial cells directing activated cells to inflamed tissue
CCL21
(SLC secondary lymphoid chemokine) stimulates chemokine R on the T cell to activate LFA-1
Process of Lymphocyte migration
1) L-selectin binds glycam-1 and CD34 with weak affinity/rolling 2) LFA-1 is activated by chemokines CCL21 on the endothelium (higher affinity) 3) LFA-1 binds to ICAM-1 4) lymphocyte migrates into the lymph node (diapedesis)
Immature DC
In tissues first, uptake soluble and particulate antigens at the site of infection and transport to the draining LN
Conventional DC
Mostly responsible for Ag presentation and activation of naive T cells (TLRs 2, 3, 4, 5, 8, 9)
Plasmacytoid DC
generate large amounts of IFN a and b in response to viral infection (TLRs 7,9 at high level) do not have CCR7 and do not migrate into lymph nodes
Licensing
DCs recognize PAMPS expressed by different pathogens, bind to PRR-DCs, allows different chemokine R expression and change in DC morphology and function; DC becomes activated, induces CCR7 and enhances processing of pathogen derived Ag immunoproteosome
Langerhans Cells
Specialized immature DC in skin, transfer antigens to resident dendritic cells; derived from embryonic tissue precursor.