Lecture 11: Activation of T Lymphocytes Flashcards

1
Q

Ag recognition by T cells induces what

A

Secretion of IL-2 which causes T cell proliferation

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2
Q

Three signals required for proliferation and differentiation of T lymphocytes into memory cells

A

Ag recognition (signal 1)
Costimulation (signal 2)
Cytokines (signal 3)

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3
Q

Activation of naïve T cells requires

A

Presentation of Ag by dendritic cell

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4
Q

CD28:CTLA4 complex on T cells is

A

Inhibitory signal

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5
Q

CD28:CD80/86 complex on T cell is

A

Activating signal

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6
Q

CD2:CD48/59 complex on T cell is

A

Adhesion with APCs

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7
Q

LFA1:ICAM1 complex on T cell is

A

Adhesion with APCs

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8
Q

Ag recognition without costimulation may cause

A

Formation of anergic or unresponsive T cells

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9
Q

Costimulatory molecule expression on unactivated DCs

A

Low levels of costimulatory molecules, not enough to activate naïve T cells

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10
Q

What stimulates the differentiation of naïve T c ells into effector cells, and it is released by what

A

IL-12 released by activated DCs

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11
Q

APCs express ___ while T cells express ____ (in the context of B7/CD28 complexes)

A

APCs express ligands while T cells express receptors

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12
Q

CTLA4 mediated immune checkpoint

A

Induced in Naïve T cells at the time of their initial response to Ag

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13
Q

Naïve and memory T cells express high levels of ____ but do not express ___

A

Naïve/memory T cells express high levels of CD28 but do not express CTLA4 which is stored in intracellular vesicles

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14
Q

When is CTLA4 expressed

A

After the TCR is triggered by Ag encounter- the stronger the stimulation, the greater the amount of CTLA4

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15
Q

CTLA4 functions as a

A

Signal dampener to maintain a consistent level of T cell activation

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16
Q

Major role of PD1

A

Not at the initial T cell activation stage

  • Regulates inflammatory responses in tissues by effector T cells recognizing Ag in peripheral tissues
  • Activated T cells upregulate PD1 and express it in tissues
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17
Q

PD1 ligand expression is induced by

A

Inflammatory signals in the tissues

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18
Q

PD1 Ligand function

A

Downregulate the activity of T cells and thus limit collateral damage in response to infection

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19
Q

What is the best characterized signal for PD1L induction

A

IFN-y released by Th1 cells

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20
Q

Excessive induction of PD1 on T cells (in setting of chronic Ag exposure) can induce

A

An exhausted or anergic state in T cells

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21
Q

Quick steps in generation of Th1 cells

A

IL-12 activates STAT4 which leads to expression of T-bet which facilitates generation of Th1 cells

22
Q

Quick steps in generation of Th2 cells

A

IL-4 activates STAT6 that leads to expression of GATA-3 which facilitates generation of Th2 cells

23
Q

Quick steps in generation of Treg cells

A

TGF-b activates SMAD2-SMAD4 which promotes the expression of FOXP3 and the generation of T regulatory cells

24
Q

SAgs

A

Most powerful T cell mitogens ever discovered
Not processed into peptides
Simultaneously bind MHC II molecules (not in peptide binding groove) and the V region of the B-subunit of the TCR

25
Q

SAgs induce

A

A robust proliferation of SAgs-activated T cells which produce massive amounts of pro-inflammatory cytokines TNF, IL-1 and IL-2 which may lead to shock

26
Q

IL-2 costimulates T cells to produce

A

IL-4, IL-5 and IFN-y

27
Q

How does IL-2 help reduce apoptosis and stimulate the cell cycle

A

Induces anti-apoptotic protein Bcl-2

Stimulates cell cycle progression by degradation of cell cycle inhibitor p27

28
Q

IL-2 is required for the ____ and ____ of ____

A

Survival and function of Treg cells

29
Q

Function of newly expressed CD69 on activated T cell

A

Retention in lymph node

30
Q

Function of newly expressed IL-2R on activated T cell

A

Proliferation

31
Q

Function of newly expressed CD40L on activated T cell

A

Activation of APCs

32
Q

Function of newly expressed CTLA-4 on activated T cell

A

Control of response

33
Q

CD69 function explained

A

CD69 associated and inhibits the function of S1P(1), inhibiting egress from LNs
CD69 binding reduces surface expression of S1PR1

34
Q

Result of CD69 binding to activated T cell

A

T cell is retained in the LN long enough to receive signals that initiate proliferation and differentiation
CD69 expression decreases after cell division

35
Q

Blood and lymph S1P extracellular concentration vs lymphoid organ S1P extracellular concentration

A

Blood/lymph S1P concentration is high, which causes down regulation of S1PR1. When it enters the lymph organ with low [S1P], it begins to re-express higher levels of S1PR1

36
Q

CD40L expression is induced by

A

Ag recognition by T cell. Takes 24-48 hours

37
Q

CD40:CD40L complex between T-cell/APC may stimulate

A

The expression of more B7 (CD28) molecules and the secretion of cytokines that activate T cells

38
Q

As the level of costimulation and IL-2 decrease, what else decreases

A

The levels of anti-apoptotic proteins in the cell

39
Q

What triggers the mitochondrial intrinsic pathway of apoptosis with respect to the decline of T cell responses

A

IL-2 starvation

40
Q

What cells constitute the most abundant lymphocyte population in the body during lifetime

A

Memory T cells

41
Q

Linear model of memory T cell differentiation

A

Most effector cells die, some survivors develop into memory cells

42
Q

Majority of memory T cells reside where

A

In tissue sites- lymphoid tissues, intestines, lungs, skin

43
Q

T-bet function in effector T cells

A

Drives differentiation of effector cells in CD4+ cells

44
Q

Blimp-1 function

A

Promotes the generation of memory cells

45
Q

Resident memory T cells (Trm)

A

Produce IFN-y and TNF and are specific for pathogens/Ags that have been encountered previously

46
Q

Central memory T cells (Tcm)

A

Express chemockine CCR7 and L-selectin and home to LNs, spleen and circulate in blood

47
Q

Effector memory T cells (Tem)

A

Circulate in the blood
Do not proliferate, but produce IFN-y and TNF or become cytotoxic
Upon entering tissue, Tem cells can become Trm cells and reside in epithelial barrier tissues

48
Q

How do memory cells survive in quiescent state without Ag

A

They express increased levels of anti-apoptotic proteins

49
Q

Memory T cell response compared to naïve T cell

A

Larger, faster, enhanced responses
Naïve cells take 5-7 days, memory cells take 1-3 days
There are more memory cells specific for a particular antigen than there are naïve cells

50
Q

Maintenance of memory cells is dependent upon

A

Cytokines, but does not require Ag presence

51
Q

What cytokines induce expression of anti-apoptotic proteins and stimulate low level proliferation

A

IL-7 and IL-15

52
Q

Quick steps in generation of Th17 cells

A

IL-6 activates STAT3 the leads to expression of RORyt which facilitates generation of Th17 cells