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Immunology > The Life of a T Cell- Mobilizing the Troops > Flashcards

The Life of a T Cell- Mobilizing the Troops Flashcards

1
Q

What cell is the most populous in the spleen?
What other cells are present?

What cell is the minority in the spleen?

A

Mostly B cells

Other cells:

  • macrophages
  • dendritic cells
  • NK cells
  • NK T cells

T cells are in the minority in the spleen

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2
Q

How many different peptides can an HLA molecule bind?

How many can T cells recognize?

A

HLA can present 1000s of different peptides as long as they are similar structurally
T cells can recognize a subset of these peptides

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3
Q

What are the 3 secondary lymphoid organs T cells will go to after they mature in the thymus?

A
  1. Spleen
  2. Lymph node
  3. Peyer’s patch
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4
Q

Deviations from lymphocute levels are a red flag for:

A
  1. infections
  2. malignancies
  3. autoimmune disorders
  4. immunodeficiencies
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5
Q

A CD4 count of less than __________ is a diagnostic indicator of ________________ and the person is of immediate concern for __________________ infections.

A

400
HIV
opportunistic

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6
Q

What virus targets CD4 T cells specifically?

A

HIV

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7
Q

What percent of T cells are DP in the peripheral lymphoid organs?

A

0%

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8
Q

What is the normal ratio of CD4 Tcells to CD8 T cells?

A

1.5/1 or 2/1

there are usually the least NK cells

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9
Q

When a T cell leaves the thymus as a positively-selected CD4 SP or CD8 SP T cell, what is it called? Why?

A

It is a naive T cell still because it won’t be considered mature until it encounters an antigen in the secondary lymphoid organ

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10
Q

Naive T cells can only be activated once they receive three signals. What are they?

A
  1. TCR interacting with APC/Macrophage/DC
  2. CD28 costimulatory molecule (ICOS)
  3. Cytokine receptor
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11
Q

When a naive T cell is activated with the 3 signals, what does it become?

A

an “effector” T cell

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12
Q

Are the three activation signals (TCR/APC, CD28, cytokine receptors) required to activate a memory T cell?

A

nope

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13
Q

Where do the three signals to activate a T cell occur?

A

secondary lymphoid organs following T cell interactions with professional APCs

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14
Q

How does a naive T cell enter the secondary lymphoid organ? What signals are involved?

A

L-selectin on the T cell binds to GlyCAM or CD34 on the HEV of the lymph node (or MadCAM on mucosa to enter Peyer’s patches)

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15
Q

Once in the lymph node or spleen, how is the T cell directed into PALS or perifollicular areas that are rich in T cells?

A

chemokine/cytokine receptor interactions

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16
Q

What is the best APC to present to T cells in lymph nodes and the spleen? How does this cell arrive in LN or spleen?

A

dendritic cells which arrive via lymphatic drainage

(T-cells get into the LN or spleen via blood)

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17
Q

What are the four adhesion molecules on the T cell that allow it to attach to the APC?

A

LFA-1, VLA-4, ICAM-1, CD2

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18
Q

What does LFA1 on the Tcell bind to on the APC?

A

ICAM on the APC

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19
Q

What does ICAM on the T cell bind to on the APC?

A

LFA1 on the APC

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20
Q

What does VLA-4 on the T cell bind to on the APC?

A

VCAM

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21
Q

What does CD2 on the T cell bind to on the APC?

A

LFA3

22
Q

What do the interactions driven by the adhesion molecules between T cells and APCs allow to happen?

A

The T-cell can sample the peptide/HLA molecules on the APC

23
Q

What is the addressin, cytokine receptor and chemotactic factor on the T cell that bring it into the lymph node?

A

L-selectin
CCR7
CXCR4

24
Q

How many foreign agonist peptide/HLA complexes must be on an APC for a TCR to detect it and be activated?

A

3-5

25
Q

What is the “immunological synapse”?

A

The clustering of TCR on the T cell and foreign peptide/HLA on the APC to allow 3-5 HLA complex to be together to activate the T-cell?

26
Q

What are TCR in immunological synapses able to do?

A

Signal and internalize what the HLA/foreignpeptide is presenting and engage more TCRs with the same 3-5 agonist peptide/MHC complexes.

27
Q

What occurs at the interface of TCR and HLA molecules on the APC?

A

Immunological synpase where the TCR can

  1. receive signals
  2. Recycle
  3. Serially engage the APC
28
Q

What is the role of CD28 when a Tcell meets an APC?

A

It is a constimulatory molecule that binds B7-1/B7-2 on the APC to elicit a signal cascade (SIGNAL 2)

29
Q

Due to its short cytosolic tail, abTCR is unable to efficiently signal into the T-cell. What must it associate with?

A

CD3 epsilon/delta and gamma/epsilon and zeta/zeta subunits

30
Q

When the TCR is engaged by an antigen, what is the first step in the signal transduction pathway? (what molecule is activated and what is its function?)

A

LCK tyrosine kinase is activated and phosphorylates the ITAMs on the CD3 subunits

31
Q

When ITAMs begin being phosphorylated by the LCK tyr-kin, what other kinase is recruited and what is its function?

A

ZAP-70 phosphorylates LAT (“linker of activated T cells”)

32
Q

What is LAT?

A

Linker of Activated T-cells. It is stimulated by ZAP70 and serves as a docking site for PLC-gamma (phospholipase C) which increases intracellular calcium.

33
Q

Why is it important for intracellular calcium to go up in T-cell transduction pathway?

A

Ca activates the calcineurin signaling molecule which activates various transcription factors (NFKb, NFAT, MAPK)

34
Q

What structure on the APC binds to the CD28 molecule on the T-cell?

A

B7-1/B7-2 (also called CD80/CD86)

35
Q

What three transcription factors are elicited by T-cell signal transduction?

A

NFAT, NFkB, MAP kinases

36
Q

What drug inhibits calcineurin shutting off T-cell activation? What is this drug used for?>

A

Cyclosporine is used as an immunosuppressant to help with transplant rejection

37
Q

What two drugs are currently FDA approved as immunosuppressants to help with transplant rejection?

A

FK506 and cyclosporine

38
Q

What 5 antigen binding receptors use Src family tyrosine kinases to transmit signal in their cells?

A 
TCR (CD3)
BCR (Iga, Igb)
NK activating receptor (DAP12)
Fc Receptor (FcgammaRIII)
Neuronal receptors (CD3 zeta and epsilon)
39
Q

What costimulatory molecule is responsible for “signal 2” in T-cell activation?

A

CD28 which binds to two surface molecules (b7-1/b7-2 aka CD80/86) on the antigen presenting cell

40
Q

When CD28 on the T-cell binds to CD80/86 on the APC, what happens next?

A

The CD28 cytoplasmic tail gets phosphorylated at its tyrosine residues allowing PI3K to associate with it and initiate the activation of additional proteins

41
Q

What associates with the CD28 molecule when it has been phosphorylated?

A

PI3K

42
Q

When signal 1 and 2 on the T-cell converge on NF-kB, what occurs?

A

NFkB translocates to the nucleus to transcribe and release IL-2.

43
Q

If a naive T cell receives a strong signal1, but no signal two, what happens?

A

It is not activated and becomes functionally impaired (anergy)

44
Q

What 4 changes in cell surface proteins occur upon T-cell activation?

A
  1. increased chemokine receptors
  2. up-regulation of CD40L (used to activate B cells)
  3. Increased SIP1
  4. expression of IL-2 receptor, CD25
45
Q

What is IL-2?

What does it bind to when it is operating in an autocrine fashion?

A

A growth factor that supports T-cell division.

When it is working in an autocrine fashion, it binds to CD25 on the T-cell surface

46
Q

When IL-2 is working in a paracrine fashion, what does it bind to and what is its function?

A

It works to help the CD8 cells expand

47
Q

What is the function of CD40L?

A

It helps T cells interact with B cells and macrophages to help activate them

48
Q

Mutation to CD40L results in what?

A

Failure of T and B cells to interact which means that they cannot class switch or go through somatic mutation and leads to Hyper-IgM

49
Q

Signal 1 and 2 are most important for cell__________.

Signal 3 is required to give the cell __________.

A

growth and expansion

function

50
Q

What provides signal 3 to the T-cell?

A

cytokines and chemokines

51
Q

What is S1P1?

What drug can block its expression?

A

it is a cell surface molecule on the T-cell that allows it to leave LN and thymus to go to the target tissue.

It is blocked by FTY720

Immunology (25 decks)

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