T Cell-Mediated Immunity: Activation of T cells by Cell-Associated Antigens Flashcards
Where do resident tissue memory T cells reside?
What do they do?
in epithelial barrier tissue
produce INF gamma and TNF and are specific for pathogens and Ags that have been through barrier before
What is VLA-4 and what does it bind?
What does this cause?
VLA-4 and LFA-1 = homing receptor on activated T cell –> ICAM-1 or VCAM-1 on endothelium –> stable arrest of T cell on endothelium at site of infection
How do activated CTLs kill infected cells?
w/ perforin and granzymes –> apoptosis and eaten by macrophages = CLEAN KILL so viruses don’t escape to infect other cells
What is LFA-1 (beta2 integrin) and what does it bind to?
What does this do?
LFA-1 = receptor on naive T cell –> binds ICAM-1 on HEV
causes stable arrest on HEV
does same binding on activated T cell and endothelium at site of infection
What is CCR7 and what does it bind to?
What does this do?
CCR7 = receptor on naive T cell --> binds CCL19 or CCL21 on HEV effect = activation of integrins and chemotaxis
What are the costimulatory receptors on T cells?
CD28
ICOS
What cells are CD80 and CD86 on?
DCs, macrophages, B cells
When is PD1 expressed/bound during immune response?
PD1 is always expressed on T cell; activation increases expression –> inflammation in tissue causes PD1-L to be expressed –> binds PD1-L –> limits tissue damage
Where do central memory T cells (Tcm) hang out?
What do they do?
in LNs, spleen, and blood
produce IL-2 and proliferate to make a lot of effector cells
What does blimp-1 do?
promotes generation of memory T cells (transcription factor)
Where do effector memory T cells reside?
What do they do?
circulate in blood
do NOT proliferate; produce IFN gamma and TNF or become cytotoxic
What cells is CD28 on?
T lymphocytes
What does TGF beta induce in T cells?
SMAD2/SMAD4 –> FOXP3 –> Treg cell –> tissue remodeling/anti-inflammatory
What does IL-12R induce in T cells?
STAT4 –> Tbet–> Th1 cell
What are the inhibitory receptors on t cells?
PD-1
CTLA-4
What type of T cell is IL-2 super important for, and research has shown it can’t live without it?
T regulatory cells
What is the anti-apoptosis signal that IL-2 stimulates in Ag-stimulated T cells?
BcI-2
How does IL-2 specifically stimulate cell cycle progression in T cells?
degrades the cell-cycle inhibitor p27
What is ICOS and what is its function?
receptor on T cells
when it binds ICOS-L from APC –> costimulation of effector and Tregs; generation of follicular helper T cells
Once T cells are activated, where do they go?
either in the lymphoid organs to help B cells or migrate to sites of infection to help activate macrophages
What does Tbet induce in a CD4+ T cell?
drives differentiation into an effector cell
What is the effect of CD80/86 binding to CD28 on a T cell?
positive costimulation –> generation of regulatory T cells
In general, what is IL-2 important for?
autocrine growth factor for all T cells
signals NK cells and CTLs to kill
induces death later
Where is ICOS-L (CD275) found?
DCs, macrophages, B cells, other cells
When does CD40L expression peak in T cells?
24-48 hours after activation
What does IL-4R induce in T cells?
STAT6 –> GATA3 –> Th2 cell
Where is CTLA-4 stored in T cells?
When is it activated?
stored in vesicles –> activated at time of naive T cell activation
the more TCR signaling –> the more CTLA-4 put on surface = maintains consistent level of T cell activation in body
What does IL-6R induce in T cells?
STAT3 –> RORgammaT –> Th17 cell
What are the 3 T cell homing receptors on naive T cells discussed?
L-selectin
LFA-1 (beta 2 integrin)
CCR7
What is a superantigen and how does it work?
most powerful T cell mitogens ever discovered bind MHC class II molecules and the V region of beta subunit of the TCR --> stuck together too long --> too many proinflammatory cytokines
Genetically, how do T memory cells relate to effector T cells?
memory cells are generated from effector cells through epigenetic modification
(have similar DNA methylation patterns)
What is CXCR3 and what does it bind?
What does this cause?
CXCR3 = homing receptor on activated T cell –> binds CXCL10 –> activation of integrins and chemotaxis
Once an Ag is eliminated from the body, what happens to the number of effector T cells?
number declines leaving only memory T cells
Where do naive CD8 t cells recognize Ags? from what cells specifically?
in lymph nodes
from DCs
What are ITIMs?
immunoreceptor tyrosine-based inhibitory motifs
sites for tyrosine phosphatases that counteract actions of ITAMs
How is IL-2R alpha expression induced and what does it do?
IL-2 –> IL-2Ralpha expression –> high affinity IL-2R alpha beta gamma c complex –> t cell proliferation
Where are E/P selectin ligands and what do they bind? What does this cause?
on activated T cell –> bind E/P selectin on endothelial cells –> initial weak adhesion to endothelium at site of infection
How do we think memory cells survive in a quiescent state without an Ag?
memory cells express increased levels of anti-apoptotic proteins
What is CTLA-4 and what is its function?
receptor on T cells
when it binds CD80/86 –> inhibition of immune responses
What is the best known inducer of PD1-L expression?
interferon gamma from Th-1 cells
What cells can activate naive T cells?
only dendritic cells
What is the CD40L pathway?
Ag recognition in T cell –> CD40L expression –> binds CD40 on APCs –> APCs secrete cytokines and make more B7 –> activate T cells
How do the number of memory T cells for a specific Ag compare to the number of naive T cells for the same Ag?
10 to 100 fold more memory cells
Ag recognition by naive T cells induces secretion of what cytokine?
What occurs after that?
IL-2 –> clonal expansion
How does CD69 signaling affect T cells?
T cell activated –> CD69+CD69L –> S1PR1 expression decreases –> T cell stays in LN –> receives signals for proliferation and differentiation into Effector and Memory cells –> CD69 decreases –> S1PR1 goes back up –> cell leaves LN
What cytokines do superantigens induce?
TNF, IL-1, and IL-2
What are the 2 phenotypes of T helper cells?
What determines their function?
Th1 and Th2
cytokines they are able to produce
What is PD-1 and what is its function?
receptor on T cells
when it binds PD-L1 or PD-L2 –> negative regulation of T cells
What are the 3 homing receptors on activated T cells discussed?
E and P selectin ligand
LFA-1 or VLA-4
CXCR3
When is IL-2R alpha at peak expression in T cells?
24 hrs after activation
What signal do CTLs release to activate macrophages to digest the cells they apoptose?
IFN-gamma
What cytokines induce the expression of anti-apoptotic proteins and stimulate low-level proliferation in memory T cells?
IL-7 and IL-15
What cells can effector T cells recognize Ags from?
macrophages and B cells
What are the 3 signals required for the proliferation and differentiation of T lymphocytes into effector and memory cells?
- Ag recognition
- costimulation
- cytokines
Where does activation of naive T cells occur?
in the central part of lymph nodes
What cytokines does IL-2 costimulate T cells to secrete?
IL-4
Il-5
IFN-gamma
What are adjuvants and how do they work?
substances that must be administered with vaccines to elicit T cell-dependent immune responses
induce expression of costimulators on APCs and cytokines that activate T cells
What can activated dendritic cells release to help T lymphocytes develop into Th1 effector cells?
IL-12
What is the maintenance of memory cells dependent on?
cytokines
but not Ags!
