T Lymphocyte Mediated Immunity Flashcards
(57 cards)
general principle of T-cell activation and differentiation
antigen recognition - activation - clonal expansion - differentiation - effector functions
what are high endothelial venules
specialized blood vessels that bring naive B and T cells to the lymph nodes
- found in T cell zones (paracortical area)
formation and organization of secondary lymphoid organs are controlled by…
TNF family members
characteristics of the marginal sinus
- the marginal sinus separates white and red pulp
- circulating T and B cells are first delivered here when they get to the SLO
- enriched in marginal zome B cells
- T cells migrate from the marginal sinus to T-cell zones (PALS)
- B cells migrate from marginal sinus to B-cell follicles
what is the marginal sinus
area in SLO’s where circulating B and T cells are first delivered to - seperates red and white pulp
difference between marginal zone and follicular B cells
- marginal zone B cells do not recirculate, follicular do
- marginal zone = in marginal sinus
- follicular = in B cell follicle
what are Fibroblast reticular cells
stromal cells of the spleen which produce chemokines to attract T cells from the marginal sinus
what are follicular dendritic cells
lineage of dendritic cells concentrated mainly in the follicles of SLO’s - produce the chemokine CXCL13 to attract B cells
path of the antigen from delivery to SLO to when it is recognized
antigen is delivered to SLO via arterioles - antigen is taken up by dendritic cells - dendritic cell transports antigen into T-cell zones
what are MALT
mucosa-associated lymphoid tissue
- lymph node-like structures
- the epithelium overlying them contains M cells which adapt to channel antigens and pathogens directly from the gut lumen into the underlying lymphoid tissue
- e.g. peyer’s patches
what guides naive T-cell migration into the lymph node
cell adhesion molecules
what are the chemokines which attract T cells to secondary lymphoid organs
CCL19 and CCL21
how do naive T cells migrate into secondary lymphoid organs
- circulating lymphocyte enters an HEV in the lymph node
- L-selectin on T cell binds to glyCAM-1 and CD34 on endothelial cell to allow rolling
- CCR7 responds to chemokine CCL21 or 19 on endothelial surface which activates LFA-1
- LFA-1 binds to iCAM-1
- lymphocyte moves into lymph node via diapedesis
which molecules facilitate the movement of T cells from blood vessels into lymph nodes
selectins and integrins
what molecules do selectins and integrins bind to enter HEV’s
selectins: L-selectin binds CD34 or GlyCAM-1
integrins: LFA-1 binds iCAM-1
molecules do which selectins and integrins bind to enter the endothelium of mucosal lymphoid tissue or marginal sinus of spleen
selectins: L-selectin + MAdCAM-1
integrins: LPAM-1 + MAdCAM-1
what happens if T cells are activated vs not activated by APC in the secondary lymphoid organs
activated T cell: lose ability to exit the T-cell zone and begin to proliferate there over the next several days
non-activated T cell: exits from the lymph node via the cortical sinuses within hours
why can a T-cell not leave the lymph node for a few days after they recognize a pathogen?
the T cells need a few days to differentiate from naive to an effector in the SLO’s before they exit via the cortical sinus
T cells encountering properly presented antigens in circulation is very low because of their specificity. how is this resolved?
Traffic through SLO’s takes T cells past APC which are likely presenting foreign antigen since both antigen and leukocytes collect in SLO’s
trapping and activation of antigen-specific naive T cells in lymphoid tissue
- within 48 hours of antigen delivery most antigen-specific T cells can be trapped in the lymph fluid
- local inflammation stimulates an increase in influx/decrease in efflux of lymphocytes in and out of lymph node
- this is the basis for local lymph node swelling
Egress of lymphocytes from lymphoid tissue is mediated by…
Sphingosine 1-phosphate gradient
expression of the S1P receptor
antigen not encountered = increased expression
antigen encountered = decreased expression
* controlled by CD69 levels
important proteins involved in the S1P gradient
S1P lyase: degrades S1P
CD69: internalizes S1PR1 when T cells are activated
FTY720: an immunomodulatory molecule that inhibits T-cell aggression by down-modulating expression of S1PR1 by ligand-induced internalization in the lymph node
basis of the S1P gradient
- S1P levels in lymphoid tissues are low compared to blood and lymph
- S1PR1 is present at low levels on the surface of naive T cells as high levels of S1P in blood down-regulate it
- no antigen recognition = S1PR1 expression increases
- activated T cells up-regulate CD69 which down-regulates S1PR1 expression
- activated T cells eventually reexpress S1PR1 as CD69 expression decreases
