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
what does ICOS do
binds ICOSL on APC to induce cytokines
CTLA-4
is highly related to CD28, and shows stronger binding to B7.1/2 than CD28
what does CTLA-4 do
antagonizes CD28 blocking signal 2
what does the presence of non functioning CTLA-4 result in
autoimmune conditions
how can anti CTLA-4 help in cancer treatment
can enhance the immune response to the tumour
what happens when APCs encounter pathogens
APCs are activated and co stimulatory molecules are expressed
what does APC activation lead to
APC upregulation of MHC and co-stimulatory molecules
What are high endothelial venules
specialized vascular pathways into secondary lymphoid tissues from the blood
List 3 types of cells that a T cell might interact with via a CAM
HEVs, APCs, and infected cells
what does B7 on an APC bind to on a T cell
CD28 and CTLA-4
what types of cytokines result in which type of T cells
IL-4 = TH2 cells
IL-12 and IFN-γ = TH1 cells
TGF-β and IL-6 = TH17 cells
IL-6 = TFH cells
TGF-β = Treg cells
what is the function of dendritic cells in the secondary lymphoid organs
only present Ag to activate naive T cells
what is the function of macrophages and B cells in the secondary lymphoid organs
present antigen in order to receive help from effector T cells
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