Lecture 5 Flashcards
What do plasmacytoid dendritic cells do?
- Produce lots of type 1 IFNs
- May act as helper cells for Ag presentation by conventional DCs
What guides lymphocytes from secondary lymphoid tissue to where they’re needed?
A chemokine gradient
How do lymphocytes enter lymph nodes?
via high endothelial venules
What chemokine is secreted by stromal cells in LN to attract DCs?
CCL21
Receptor for CCL21
CCR7 (expressed on DCs)
What chemokine do DCs secrete to attract T cells to LN?
CCL19
What chemokine do follicular DCs secrete to attract B cells to LN?
CXCL13
Lymphocyte rolling is mediated by __
Selectins
e.g. binding of L-selectin on lymphocyte to GlyCAM-1 and CD34 on cells of HEV allows rolling interaction
Adhesion of lymphocytes to cell surfaces in secondary lymphoid tissues is mediated by __
integrins e.g. LFA-1
Name of the process by which lymphocytes pass through blood vessels (mediated by CCL21 & CXCL12)
diapedesis
CCL21-CCR7 binding activates which signalling molecule?
LFA-1
The exit of T cells from LNs is controlled by which chemotactic lipid?
Sphingosine-1 phosphate (S1P)
How does S1P control the exit of T cells from lymph nodes?
S1P binds S1PR1 on naive T cell, causing receptor internalisation. S1P-S1PR1 signalling guides T cells out of LNs, and T cells balance the pull of S1P with retention cues from chemokines within the LNs. Upregulation of CD69 on surface of activated T cell causes downregulation of S1PR1, so the T cell cannot follow S1P gradient from LN to blood. Downregulation of CD69 leads to recovery of S1PR1 on T cells, allowing the T cells to respond to the S1P conc gradient i.e. leave LN
What is Fingolimod (Gilenya)?
An FDA immunomodulatory drug used to treat MS by inhibiting lymphocyte egress from lymphoid tissues by downregulating S1PR
Interaction of which chemokines with CCR7 on DCs is required for their homing to local LNs?
CCL19 and CCL21
