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06. HDM Test 2 > 1. T Cell Mediated Immunity > Flashcards

1. T Cell Mediated Immunity Flashcards

1
Q

What chemokine draws naive T Cells to the lymph nodes?

How does it accomplish this?

A

CCR7, L-Selectin, Integrin

Lymph node chemokines bind and increase integrin dependent adhesion as well as migration through the High Endothelial Venules (HEV).

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2
Q

What is the intermediate between DAG and NF-κB in the T Cell receptor pathway?

A

PKC (Protein Kinase C)

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3
Q

What is an ITAM?

A

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

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4
Q

What is the primary factor in T Cell contraction after infection?

What pathway clears T Cells that are no longer useful?

A

IL-2 starvation

Intrinsic apoptotic pathway

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5
Q

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?

A

T-bet

BLIMP-1

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6
Q

What is the most abundant lymphocyte population in the body over a lifetime?

A

Memory T Cells

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7
Q

What interleukin is produced by naive T Cells after contact with an antigen, which stimulates them to proliferate through autocrine signaling?

A

IL-2 (and “other cytokines”)

pg 106

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8
Q

What signals production of the PD1 ligand? (PD1L)

A

IFN-y (gamma)

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9
Q

What are the three steps of differentiation into Treg cells?

A

TGFß

SMAD2-SMAD4

FOXP3

Treg

slide 25

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10
Q

What are the three steps of differentiation into Th2 cells?

A

IL-4

STAT 6

GATA-3

Th2

slide 25

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11
Q

What is the function of CD28 and CTLA-4?

What is their ligand?

A

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

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12
Q

What is the function of CD40?

A

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.

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13
Q

How long does it take a Naive T Cell to respond to an infection?

What about a Memory T Cell?

A

5-7 days

1-3 days

(memory cells respond much faster)

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14
Q

What does IP3 do in the T Cell receptor pathway?

A

Increases intracellular Ca+ and activates NFAT

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15
Q

What transcriptional factor is produced first after CD4+ T Cell activation?

A

c-Fos

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16
Q

What are the three steps of differentiation into Th17 Cells?

A

IL-6

STAT3

RORyt (gamma tau)

Th17

slide 25

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17
Q

What does PLC-1 produce in the T Cell receptor pathway?

A

IP3 and DAG

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18
Q

What keeps T Cells from leaving the lymph nodes before they are activated?

What changes after activation to allow them to leave?

A

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.

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19
Q

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?

A

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.

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20
Q

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?

A

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.

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21
Q

What is the function of T-bet?

A

Regulates transcription of genes encoding perforin, granzymes, and IFN-γ

Vital in differentiation of CD8+ T Cells and Th1 Cells

22
Q

What T Cell antigen does not get processed into a peptide before activating a T Cell?

A

Superantigens

23
Q

What does GRB2 phosphorylate in the T Cell receptor pathway?

A

PLC-1

24
Q

What is the function of Central Memory T Cells (TCM)?

Where are they located?

A

Proliferation of memory T Cells

Mainly in the lymph nodes and spleen, do circulate in the blood though.

25
Q

Where will you find naive T Cells?

A

Circulating from lymph node to lymph node looking for their antigen.

26
Q

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?

A

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.

27
Q

What is recruited by phosphorylated LAT in the T Cell activation pathway?

A

GADS and GRB2

28
Q

What do Resident Tissue Memory Cells do (TRM)?

A

Sit in the epithelial barrier and wait for their pathogen to come by.

Produce IFN-γ and TNF

29
Q

When is CD40L increased in activated T Cells?

A

24-48 hours after antigen exposure

30
Q

What may be responsible for the longevity of memory T Cells over other T Cells?

A

Increased amounts of anti-apoptotic proteins

Slow self renewal of the pool

31
Q

What is the function of LFA - 1?

What is its ligand?

A

Adhesion and signal transduction on CD4+ T Cells

ICAM-1

pg 108

32
Q

What is the primary role of CTLA4 over PD1?

A

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.

33
Q

After phosphorylation of ZAP by LCK, what two things does ZAP turn around and phosphorylate?

What is the function of these two proteins?

A

LAT and SLP-76

They serve as a scaffold to recruit other signaling molecules

34
Q

What two HEV endothelial cell proteins bind to CCR7 on the T Cell to activate chemotaxis?

A

CCL19 and CCL21

35
Q

What is bound by superantigens?

A

MHC Class II and the V region of the Beta subunit of the TCR, locking them together and causing activation.

36
Q

What two cytokines stimulate anti-apoptotic proteins and low-level proliferation in memory T Cells?

A

IL-7

IL-15

37
Q

What are the three steps of differentiation into Th1 cells?

A

IL-12

STAT4

T-bet

Th1

slide 25

38
Q

What is the function of LCK?

A

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.

39
Q

What type of cell can present and activate naive T Cells?

A

Only dendritic cells

40
Q

After it binds to its ITAM, what phosphorylates ZAP-70?

A

LCK

LCK phosphorylates the ITAM, allowing ZAP to bind to it - then it turns around and phosphorylates ZAP itself.

41
Q

What is the function of Effector Memory T Cells (TEM)?

A

Circulate in the blood and produce IFN-γ / TNF or become cytotoxic

42
Q

What are phytohemaglutinin and Staphylococcal enterotoxins?

A

Superantigens that can activate any T Cell regardless of its variable region.

43
Q

Why are adhesion molecules (like integrins and LFA-1) necessary for a T Cell response to an antigen?

A

The TCR must contact the MHC long enough to elicit a response

44
Q

What are the 6 major functions of IL-2

A

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

45
Q

What is different about the LFA-1 in a naive T Cell and an effector T Cell?

A

The LFA-1 of a naive T Cell is in a low affinity state compared to an effector T Cell

pg 110

46
Q

What is the function of PD-1?

What is its ligand?

A

Inhibitory receptor on the surface of CD4+ T Cells

PD-L1 / PD-L2

pg 108

47
Q

Out of all the necessary signals for normal T Cell activation, which one is always first?

A

Response to the antigen.

48
Q

What is the intermediate between DAG and the MAPK pathway?

A

Ras

49
Q

Other than IL-2 starvation, what three regulatory mechanisms are mentioned to contribute to immune response contraction?

A

CTLA4 and PD-1 activity

Apoptosis induced by TNFR1 and Fas

Treg cell product inhibition

50
Q

What 5 things are neccessary for initiation of a T Cell response?

A

TCR contact to MHC

CD8 or CD4 contact to MHC

Adhesion molecules

Costimulators

Cytokines

51
Q

What cells of the peripheral tissue secrete IL-10?

A

Tregs

Alternative Macrophages

06. HDM Test 2 (9 decks)

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