L05 Flashcards
what do naive T cells do after exiting the thymus
recirculate via blood/lymphatics through secondary lymphoid tissue
what are the secondary lymphoid tissue
lymph nodes, spleen
what causes clonal proliferation and
differentiation of T cells
Contact with specific Ag and APC
what do naive T cells develop into
cytotoxic effector T cells (CD8+)- kill infected cells
helper effector T cells (CD4+) -secrete cytokines
what happens in the lymphoid tissue
T cells recognize Ag/MHC on antigen presenting cells (APC)
array of APC are found, some specialised, trap and present Ag
-lymph nodes
-spleen
Following activation, T cell ”effectors” leave these areas and migrate to sites of infection
how do T cells get to where they need to be?
enter lymph node from blood via high endothelial venules (HEV)
move into T cell area which is rich in dendritic cells and macrophages (APC)
APC present antigen and deliver other activation signals e.g. cytokines
what happens to T cells that are not activated (i.e. don’t see p/MHC)
they leave lymph node via cortical sinuses into the lymphatics; re-enter circulation
-> recycled for another day
how do T cells communicate
they express molecules on the surface (chemokine receptors)
bind ligands (chemokines) released by other cells
once close to other cells different molecular sets of CAMs mediate cell/cell interactions
list examples of cell/cell interactions through CAMs
naïve T cell with HEV
T cell with APC
effector T cell and target cell
what are the steps of T cell communications
1) T cells contact APCs using CAMs
2) TCR scans APC peptide/MHC complexes
what happens when a T cell does not recognize an Ag
it disengages
what happens when a T cell recognizes an Ag
starts a signal from TCR complex (CD3)
what does CD3 signal result in
increases affinity of CAM interactions
T cell divides
progeny differentiate to effector cells, exit LN
-> T cell-mediated response
how does the binding of TCR to the Ag affect LFA-1 and ICAM-1
T cells bind APC through low-affinity LFA-1:ICAM-1 interactions
subsequent binding of T cell receptors signals LFA-1
conformational change in LFA-1 increases affinity and prolongs cell-cell contant
how many signals do naive T cells need for activation
3
what is signal 1 in naive T cells
signal from TCR contacting MHC/peptide on APC involving CD3 (zeta) chain
what is signal 2 in naive T cells
signal delivered by CD28 when it interacts with co stimulatory molecules (B7.1 and B7.2) expressed by APC
what is signal 3 in naive T cells
cytokines (IL-6,IL-12, TGF-beta, IL4) bind cytokine receptors on naive T cells delivering the signal
what does signal 1
activation
what does signal 2 do
survival
what does signal 3 do
differentiation
what happens to a naive T cell after receiving the 3 signals
turns into an effector T cell
does the effector T cell require the same levels and types of signals as the naive T cells to function
NO
it can function with lower co stim and cytokine
what do activated T cells express
ICOS and CTLA-4
