1. T Cell Mediated Immunity Flashcards
What chemokine draws naive T Cells to the lymph nodes?
How does it accomplish this?
CCR7, L-Selectin, Integrin
Lymph node chemokines bind and increase integrin dependent adhesion as well as migration through the High Endothelial Venules (HEV).
What is the intermediate between DAG and NF-κB in the T Cell receptor pathway?
PKC (Protein Kinase C)
What is an ITAM?
One of the regions on the signaling proteins of immune cells that are phosphorylated, and that are docking sites for other tyrosine kinases
slide 12
What is the primary factor in T Cell contraction after infection?
What pathway clears T Cells that are no longer useful?
IL-2 starvation
Intrinsic apoptotic pathway
What drives a T Cell progeny to become an effector CD4 T Cell?
What promotes a T Cell progeny to become a T Memory Cell?
T-bet
BLIMP-1
What is the most abundant lymphocyte population in the body over a lifetime?
Memory T Cells
What interleukin is produced by naive T Cells after contact with an antigen, which stimulates them to proliferate through autocrine signaling?
IL-2 (and “other cytokines”)
pg 106
What signals production of the PD1 ligand? (PD1L)
IFN-y (gamma)
What are the three steps of differentiation into Treg cells?
TGFß
SMAD2-SMAD4
FOXP3
Treg
slide 25
What are the three steps of differentiation into Th2 cells?
IL-4
STAT 6
GATA-3
Th2
slide 25
What is the function of CD28 and CTLA-4?
What is their ligand?
CD 28 Functions as a costimulator for CD4+ T Cells
CTLA-4 “shuts off” T Cell response
Both bind to B7-1 (CD80) and B7-2 (CD86) on antigen presenting cells
pg 108
What is the function of CD40?
When it binds to CD40L on the T Cell, CD40 on APCs triggers production of more B7 (CD80/CD86) costimulators, and cytokine secretion to stimulate B Cells.
How long does it take a Naive T Cell to respond to an infection?
What about a Memory T Cell?
5-7 days
1-3 days
(memory cells respond much faster)
What does IP3 do in the T Cell receptor pathway?
Increases intracellular Ca+ and activates NFAT
What transcriptional factor is produced first after CD4+ T Cell activation?
c-Fos
What are the three steps of differentiation into Th17 Cells?
IL-6
STAT3
RORyt (gamma tau)
Th17
slide 25
What does PLC-1 produce in the T Cell receptor pathway?
IP3 and DAG
What keeps T Cells from leaving the lymph nodes before they are activated?
What changes after activation to allow them to leave?
Lymph nodes have less sphingosine 1 phosphate than peripheral tissues, and naive T Cells have their S1P receptors (S1PR1) downregulated by CD69 once they arrive in the lymph nodes.
CD 69 expression decreases after division, so the activated T Cells start to express S1PR1 again, and are encouraged to exit the lymph nodes.
How do T Cells in the peripheral tissues that encounter their antigen stay in the area, where T Cells that don’t encounter their antigen are sent on their way?
T Cells produce VLA integrins when they meet their antigen, and the VLA complex sticks to extracellular matrix. This means the T Cells that become activated are less likely to be pulled away from the site.
Even if a naive T Cell finds its antigen, it won’t be activated if the APC presenting the antigen isn’t “activated,” and will instead become anergic. What about the APC changes during APC activation to allow activation of naive T Cell?
What is the advantage to this additional balance?
Activated APCs produce B7-1 (CD-80) and B7-2 (CD-86); coreceptors that bind to CD28 and are necessary for naive T Cell activation. “Resting” APCs do not produce B7-1 and B7-2.
T Cells are less likely to be activated by harmless antigens.
What is the function of T-bet?
Regulates transcription of genes encoding perforin, granzymes, and IFN-γ
Vital in differentiation of CD8+ T Cells and Th1 Cells
What T Cell antigen does not get processed into a peptide before activating a T Cell?
Superantigens
What does GRB2 phosphorylate in the T Cell receptor pathway?
PLC-1
What is the function of Central Memory T Cells (TCM)?
Where are they located?
Proliferation of memory T Cells
Mainly in the lymph nodes and spleen, do circulate in the blood though.
Where will you find naive T Cells?
Circulating from lymph node to lymph node looking for their antigen.
Why is it that the T Cells that are activated by an antigen are signaled by IL-2 to proliferate, but the nearby naive T Cells that have IL-2 bind to their receptors are not signaled to proliferate?
Because when a T Cell is activated by an antigen, it produces IL-α (CD 25), making the IL-αβγ complex. Non activated cells have only the IL-βγ complex, which does not have high enough affinity to signal proliferation.
What is recruited by phosphorylated LAT in the T Cell activation pathway?
GADS and GRB2
What do Resident Tissue Memory Cells do (TRM)?
Sit in the epithelial barrier and wait for their pathogen to come by.
Produce IFN-γ and TNF
When is CD40L increased in activated T Cells?
24-48 hours after antigen exposure
What may be responsible for the longevity of memory T Cells over other T Cells?
Increased amounts of anti-apoptotic proteins
Slow self renewal of the pool
What is the function of LFA - 1?
What is its ligand?
Adhesion and signal transduction on CD4+ T Cells
ICAM-1
pg 108
What is the primary role of CTLA4 over PD1?
CTLA is a signal dampener, in charge of maintaining consistency in T Cell activation.
PD1 regulates inflammatory response in tissues by inactivating T Cells in areas of high inflammation.
After phosphorylation of ZAP by LCK, what two things does ZAP turn around and phosphorylate?
What is the function of these two proteins?
LAT and SLP-76
They serve as a scaffold to recruit other signaling molecules
What two HEV endothelial cell proteins bind to CCR7 on the T Cell to activate chemotaxis?
CCL19 and CCL21
What is bound by superantigens?
MHC Class II and the V region of the Beta subunit of the TCR, locking them together and causing activation.
What two cytokines stimulate anti-apoptotic proteins and low-level proliferation in memory T Cells?
IL-7
IL-15
What are the three steps of differentiation into Th1 cells?
IL-12
STAT4
T-bet
Th1
slide 25
What is the function of LCK?
Sits on the cytoplasmic side of either CD8 or CD4 and provides initial phosphorylation to the ITAMS of the ζ chains, allowing them to dock ZAP-70.
What type of cell can present and activate naive T Cells?
Only dendritic cells
After it binds to its ITAM, what phosphorylates ZAP-70?
LCK
LCK phosphorylates the ITAM, allowing ZAP to bind to it - then it turns around and phosphorylates ZAP itself.
What is the function of Effector Memory T Cells (TEM)?
Circulate in the blood and produce IFN-γ / TNF or become cytotoxic
What are phytohemaglutinin and Staphylococcal enterotoxins?
Superantigens that can activate any T Cell regardless of its variable region.
Why are adhesion molecules (like integrins and LFA-1) necessary for a T Cell response to an antigen?
The TCR must contact the MHC long enough to elicit a response
What are the 6 major functions of IL-2
Makes CD8 cells cytotoxic
Stimulates production of IL-4, IL-5, and IFN-γ
Develops and sustains Tregs (only cytokine that does)
Can produce activation induced death
Induces anti apoptosis protein Bcl-2
Stimulates cell cycle progression by degradation of the cell cycle inhibitor p27
slide 39
What is different about the LFA-1 in a naive T Cell and an effector T Cell?
The LFA-1 of a naive T Cell is in a low affinity state compared to an effector T Cell
pg 110
What is the function of PD-1?
What is its ligand?
Inhibitory receptor on the surface of CD4+ T Cells
PD-L1 / PD-L2
pg 108
Out of all the necessary signals for normal T Cell activation, which one is always first?
Response to the antigen.
What is the intermediate between DAG and the MAPK pathway?
Ras
Other than IL-2 starvation, what three regulatory mechanisms are mentioned to contribute to immune response contraction?
CTLA4 and PD-1 activity
Apoptosis induced by TNFR1 and Fas
Treg cell product inhibition
What 5 things are neccessary for initiation of a T Cell response?
TCR contact to MHC
CD8 or CD4 contact to MHC
Adhesion molecules
Costimulators
Cytokines
What cells of the peripheral tissue secrete IL-10?
Tregs
Alternative Macrophages
