Antigen Presenting Cells/T Cell Activation Flashcards
T cell activation occurs exclusively in ____
secondary lymphoid tissue (this is the only place where there’s enough contact between APCs and T cells)
Two signals required for T cell activation
- binding of TCR to it’s cognate determinant
binding of CD28 and B7 expressed by antigen presenting cells
Naive T cells can only be activated by ____
antigen binding cells (dendritic cells, macrophages, and B cells)
L-selectins
on the surface of naive T cells, interacts with addressins (CD34 and glycam-1) so that the T cells can diapedese into HEVs
glycam-1 and CD34
addressins on the surface of HEVs, bind L-selectins on T cells
glycam-1 also known as sulfonate sialyl-lewis
LFA-1
adhesion molecule expressed on naive and effector T cells (higher concentration of effectors)
binds iCAM on HEV’s
also binds iCAM on antigen presenting cells to allow close interaction between the T cells and APCs
VLA-4
adhesion molecule expressed on activated T cells, binds VCAM-1 in order to enter inflammatory tissues
B7 co-stimulator
expressed on the surface of APCs after encounter with a pathogen, needed for T cell activation, interacts with CD28
Dendritic cells only express B7 in _____
secondary lymphoid tissues
Macrophages and B cells express B7 in an _____
inducible manner
Dendritic cells are most important APCs for ___
presentation of viral determinants
Macrophages are most important APC’s for ____
presentation of bacterial deteminants
langerhans cells
immature dendrites
Where does T cell activation always occur?
secondary lymphoid tissues
T cell activation results in
- clonal expansion
- upregulation of IL-2
- upregulation of high affinity form of IL-2 receptor (CD25)
IL-2
autocrine growth factor that drives proliferation and activation of T cells
CD25
alpha chain of IL-2 receptor, important for high affinity form
(beta and gamma important for lower affinity receptor)
What happens to a T cell if there is no B7 activation?
becomes anergic and is inactivated
peripheral tolerance
because APCs only express B7 when they recognize a pathogen, and because without B7 co-stimulation a T cell undergoes apoptosis, if a naive T cell binds a MHC:self peptide complex it will be inactivated.
When are autoimmune disease most often initiated?
during infection with pathogen
3 ways for CD8 T cells to be activated
- dendritic APC’s express enough B7 to activate CD8 cells without any help
- macrophage- activate here CD4 cells which activate the APCs to produce more B7 and activate the CD8 T cell
- B cells or macrophage- activate CD4 to make IL-2 and CD8 cell to express the IL-2 receptor. IL-2 secreted by CD4 binds CD8 receptors-drives proliferation and activation
effector T cell
T cell that is fully differentiated to perform it’s effector function
Do effector T cells require B7 co-activation?
No
CD8 T cells
cytotoxic T cells, most suitable T cell for limiting virus infection
CD4 T cells
produce cytokines and cheekiness that activate other cell types
Th1 T cells
important for clearance of intracellular infections, supply second signals of B cell activation, activate macrophages
Th2 cells
important for clearance of extracellular infections, supply second signals of B cell activation, down-regulate macrophage activity
Two primary Th1 cytokines
IL-2-helps promote activation of CD8 cells
IFN-gamma-activate macrophages
Two primary Th2 cytokines
IL-4-initiates class switching to IgA Il-5initiates class switching to IgE
Cytokines that promotes Th0»>Th1
IL-12 and IFN-gamma
cytokines that promote Th0»>Th2
IL-4, 5, 6, 10 (4 most important, from a subset of NK cells)
NK T cells
produce IL-4 promoting differentiation of Th0»>Th2
Treg cells
if activated in the secondary lymphoid tissue by binding self-peptides they produce IL-10 and TGF-beta (anti-inflammatory) which down-regulates activation of other surrounding T cells in order to prevent autoimmune response
FoxP3
transcription factor that drives expression of IL-10 and TGF-beta
T-bet
transcription factor that drives expression of Th1 cytokines (IL-2 and IFN-gamma)
Gata-3
transcription factor that drives expression of Th2 cytokines (IL-4.5)
Th17
produces
IL-17-neutrophil chemotractant
IL-22-antimicrobial peptide production by epithelial cells
E-selectin upregulation stimulated by
TNF-alpha and IL-1, allows leukocytes like neutrophils to diapedese into inflammatory tissue
DC-CK
chemotactic signal on dendritic cells that acts as a chemotactant for naive T cells
T/F B7 binding CD28 in the absence of the first activation signal has no response
True
T/F Macrophages produce IL12 which stimulates NK cells to produce IFN-gamma which then activates Th0»Th1
true
