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HDM (Sophia's) > T Cell-Mediated Immunity: Activation of T cells by Cell-Associated Antigens > Flashcards

T Cell-Mediated Immunity: Activation of T cells by Cell-Associated Antigens Flashcards

1
Q

Where do resident tissue memory T cells reside?

What do they do?

A

in epithelial barrier tissue

produce INF gamma and TNF and are specific for pathogens and Ags that have been through barrier before

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2
Q

What is VLA-4 and what does it bind?

What does this cause?

A

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

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3
Q

How do activated CTLs kill infected cells?

A

w/ perforin and granzymes –> apoptosis and eaten by macrophages = CLEAN KILL so viruses don’t escape to infect other cells

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4
Q

What is LFA-1 (beta2 integrin) and what does it bind to?

What does this do?

A

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

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5
Q

What is CCR7 and what does it bind to?

What does this do?

A 
CCR7 = receptor on naive T cell --> binds CCL19 or CCL21 on HEV
effect = activation of integrins and chemotaxis
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6
Q

What are the costimulatory receptors on T cells?

A

CD28

ICOS

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7
Q

What cells are CD80 and CD86 on?

A

DCs, macrophages, B cells

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8
Q

When is PD1 expressed/bound during immune response?

A

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

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9
Q

Where do central memory T cells (Tcm) hang out?

What do they do?

A

in LNs, spleen, and blood

produce IL-2 and proliferate to make a lot of effector cells

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10
Q

What does blimp-1 do?

A

promotes generation of memory T cells (transcription factor)

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11
Q

Where do effector memory T cells reside?

What do they do?

A

circulate in blood

do NOT proliferate; produce IFN gamma and TNF or become cytotoxic

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12
Q

What cells is CD28 on?

A

T lymphocytes

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13
Q

What does TGF beta induce in T cells?

A

SMAD2/SMAD4 –> FOXP3 –> Treg cell –> tissue remodeling/anti-inflammatory

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14
Q

What does IL-12R induce in T cells?

A

STAT4 –> Tbet–> Th1 cell

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15
Q

What are the inhibitory receptors on t cells?

A

PD-1

CTLA-4

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16
Q

What type of T cell is IL-2 super important for, and research has shown it can’t live without it?

A

T regulatory cells

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17
Q

What is the anti-apoptosis signal that IL-2 stimulates in Ag-stimulated T cells?

A

BcI-2

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18
Q

How does IL-2 specifically stimulate cell cycle progression in T cells?

A

degrades the cell-cycle inhibitor p27

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19
Q

What is ICOS and what is its function?

A

receptor on T cells

when it binds ICOS-L from APC –> costimulation of effector and Tregs; generation of follicular helper T cells

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20
Q

Once T cells are activated, where do they go?

A

either in the lymphoid organs to help B cells or migrate to sites of infection to help activate macrophages

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21
Q

What does Tbet induce in a CD4+ T cell?

A

drives differentiation into an effector cell

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22
Q

What is the effect of CD80/86 binding to CD28 on a T cell?

A

positive costimulation –> generation of regulatory T cells

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23
Q

In general, what is IL-2 important for?

A

autocrine growth factor for all T cells
signals NK cells and CTLs to kill
induces death later

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24
Q

Where is ICOS-L (CD275) found?

A

DCs, macrophages, B cells, other cells

25
Q

When does CD40L expression peak in T cells?

A

24-48 hours after activation

26
Q

What does IL-4R induce in T cells?

A

STAT6 –> GATA3 –> Th2 cell

27
Q

Where is CTLA-4 stored in T cells?

When is it activated?

A

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

28
Q

What does IL-6R induce in T cells?

A

STAT3 –> RORgammaT –> Th17 cell

29
Q

What are the 3 T cell homing receptors on naive T cells discussed?

A

L-selectin
LFA-1 (beta 2 integrin)
CCR7

30
Q

What is a superantigen and how does it work?

A 
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
31
Q

Genetically, how do T memory cells relate to effector T cells?

A

memory cells are generated from effector cells through epigenetic modification
(have similar DNA methylation patterns)

32
Q

What is CXCR3 and what does it bind?

What does this cause?

A

CXCR3 = homing receptor on activated T cell –> binds CXCL10 –> activation of integrins and chemotaxis

33
Q

Once an Ag is eliminated from the body, what happens to the number of effector T cells?

A

number declines leaving only memory T cells

34
Q

Where do naive CD8 t cells recognize Ags? from what cells specifically?

A

in lymph nodes

from DCs

35
Q

What are ITIMs?

A

immunoreceptor tyrosine-based inhibitory motifs

sites for tyrosine phosphatases that counteract actions of ITAMs

36
Q

How is IL-2R alpha expression induced and what does it do?

A

IL-2 –> IL-2Ralpha expression –> high affinity IL-2R alpha beta gamma c complex –> t cell proliferation

37
Q

Where are E/P selectin ligands and what do they bind? What does this cause?

A

on activated T cell –> bind E/P selectin on endothelial cells –> initial weak adhesion to endothelium at site of infection

38
Q

How do we think memory cells survive in a quiescent state without an Ag?

A

memory cells express increased levels of anti-apoptotic proteins

39
Q

What is CTLA-4 and what is its function?

A

receptor on T cells

when it binds CD80/86 –> inhibition of immune responses

40
Q

What is the best known inducer of PD1-L expression?

A

interferon gamma from Th-1 cells

41
Q

What cells can activate naive T cells?

A

only dendritic cells

42
Q

What is the CD40L pathway?

A

Ag recognition in T cell –> CD40L expression –> binds CD40 on APCs –> APCs secrete cytokines and make more B7 –> activate T cells

43
Q

How do the number of memory T cells for a specific Ag compare to the number of naive T cells for the same Ag?

A

10 to 100 fold more memory cells

44
Q

Ag recognition by naive T cells induces secretion of what cytokine?
What occurs after that?

A

IL-2 –> clonal expansion

45
Q

How does CD69 signaling affect T cells?

A

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

46
Q

What cytokines do superantigens induce?

A

TNF, IL-1, and IL-2

47
Q

What are the 2 phenotypes of T helper cells?

What determines their function?

A

Th1 and Th2

cytokines they are able to produce

48
Q

What is PD-1 and what is its function?

A

receptor on T cells

when it binds PD-L1 or PD-L2 –> negative regulation of T cells

49
Q

What are the 3 homing receptors on activated T cells discussed?

A

E and P selectin ligand
LFA-1 or VLA-4
CXCR3

50
Q

When is IL-2R alpha at peak expression in T cells?

A

24 hrs after activation

51
Q

What signal do CTLs release to activate macrophages to digest the cells they apoptose?

A

IFN-gamma

52
Q

What cytokines induce the expression of anti-apoptotic proteins and stimulate low-level proliferation in memory T cells?

A

IL-7 and IL-15

53
Q

What cells can effector T cells recognize Ags from?

A

macrophages and B cells

54
Q

What are the 3 signals required for the proliferation and differentiation of T lymphocytes into effector and memory cells?

A
  1. Ag recognition
  2. costimulation
  3. cytokines
55
Q

Where does activation of naive T cells occur?

A

in the central part of lymph nodes

56
Q

What cytokines does IL-2 costimulate T cells to secrete?

A

IL-4
Il-5
IFN-gamma

57
Q

What are adjuvants and how do they work?

A

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

58
Q

What can activated dendritic cells release to help T lymphocytes develop into Th1 effector cells?

A

IL-12

59
Q

What is the maintenance of memory cells dependent on?

A

cytokines

but not Ags!

HDM (Sophia's) (10 decks)

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