Lecture 24: Naive, Effector, & Memory T Cells: Activation & Function Flashcards

1
Q

what are the main functions of CD4+ T helper cells?

A

cytokine production, immune polarization

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2
Q

are naive T cells antigen experienced?

A

no

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3
Q

what is the lifespan of CD4+ naive helper T cells?

A

5-7 weeks

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4
Q

what is the lifespan of effector T cells (CD4 and CD8)?

A

3-4 days

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5
Q

what is the lifespan of CD8+ memory cells?

A

years

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6
Q

what is the ratio of CD4 to CD8 T cells in humans?

A

2 CD4 for every 1 CD8

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7
Q

90-95% of CD4 and CD8 T cells use ____ type TCRs

A

alpha beta

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8
Q

if activated, naive T cells undergo ____ to make many copies of themselves that act as effector cells

A

clonal expansion

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9
Q

what happens to effector T cells once an infection has died off?

A

the effector T cells also die off, but some of them can remain as memory cells

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10
Q

naive T cells have already commited to _____, but have not yet committed to _____

A

a CD4+ or CD8+ lineage; T helper subsets (CD4+)

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11
Q

naive T cells require 3 signals for activation, what are they?

A
  1. TCR/MHC peptide presentation
  2. co-stimulation between CD28 and CD80/86
  3. cytokines like IL-2
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12
Q

IL-2 has 3 different potency levels depending on ____

A

which receptor it binds to

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13
Q

what cytokine is critical to T cell proliferation?

A

IL-2

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14
Q

what level affinity IL-2 receptor is expressed by naive T cells?

A

intermediate affinity IL-2RyB

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15
Q

what is the structure of the high affinity IL-2 receptor?

A

IL-2RyBa

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16
Q

after activation, T cells upregulate their ____ chain to have a high affinity IL-2 receptor

A

alpha (CD25)

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17
Q

t/f T cells with the IL-2RyBa have a competitive advantage over naive T cells

A

t

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18
Q

what stage of T cells work to remove pathogen?

A

effector T cells

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19
Q

what T cells make up the effector T cells?

A

CD4+ T helper subsets (Th1, Th2, Th17, Tfh, peripheral T reg cells) and CD8+ cytotoxic T lymphocytes

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20
Q

effector T cells do not require ____ co-stimulation, although ____ binding to target cell ICAMs may provide co-stimulation

A

CD28; LFA-1

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21
Q

what branch of T cells is important for the protection from re-infection?

A

memory T cells

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22
Q

are memory T cells metabolically active?

A

no

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23
Q

the activation requirements of memory T cells are ____(more/less) stringent than those of naive T cells

A

less

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24
Q

memory T cells can be activated by ___ , ____ and ___ cells

A

macrophages, dendritic cells, B cells

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25
Q

naive T cells can only be activated by ____ cells

A

dendritic

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26
Q

memory T cells can be subdivided based on ____ and ___

A

differentiation potential and locations

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27
Q

what are 4 memory T cells subsets?

A
  1. T(scm): memory stem cells
  2. T(cm): central memory cells
  3. T(rm): resident memory cells
  4. T(em): effector memory
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28
Q

where are T(scm) memory T cells found?

A

lymphoid tissues

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29
Q

where are T(cm) memory T cells found?

A

circulation/lymphoid tissues

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30
Q

where are T9rm) memory T cells found?

A

tissues

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31
Q

where are T(em) memory T cells found?

A

circulation / tissues

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32
Q

naive, effector, and memory T cells express different ____ that affect their trafficking and function

A

surface markers

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33
Q

what is CCR7 and its function on T cells?

A

chemokine receptor that receives signal (CCL21. CCL19) to traffic to secondary lymphoid organs

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34
Q

CCR7 is found in high amounts on cells found in what organs?

A

lymphoid tissues (Tscm & Tcm)

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35
Q

what is the function of CD62L (L-selectin) on T cells?

A

lymphocytes extravasation through high endothelial venules

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36
Q

on what cells is CD62L (L-selectin) found?

A

cells found in lymphoid tissues (Tscm and Tcm)

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37
Q

CD44 is increased after ___

A

T cells activation

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38
Q

CD44 is found in low amounts on ___ T cells and high amounts on ___ T cells

A

naive; effector and memory

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39
Q

CD45RA is found in high amounts on ___ T cells and low in ___ T cells

A

naive, effector and Tscm; low on: Tcm, Tem, and Trm

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40
Q

Cd45RO is found in high amounts on ___ T cells and low amounts on ___ T cells

A

high: Tcm, Tem, Trm; low: naive, effector, and Tscm cells

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41
Q

what are CD45RA and CD45RO?

A

different isoforms of the same protein

42
Q

what is the difference between CD45RA and CD45RO?

A

CD45RO is a more potent signalling molecule, so its upregulation permits faster, stronger signalling

43
Q

which is used on cells that you want to make quickly (like Tcm, Tem, and Trm), CD45RA or CD45RO?

A

CD45RO

44
Q

Fas is high on T cells that have been ____

A

activated

45
Q

what is the function of Fas on T cells?

A

enable fratricide: induction of apoptosis in lymphocytes when they are no longer needed

46
Q

do Tscm recirculate?

A

no

47
Q

do Tscm produce cytokines?

A

no

48
Q

what is the role of Tscm?

A

create other (more differential) memory T cells

49
Q

what is the location of Tcm cells?

A

secondary lymphoid tissue and circulation

50
Q

what cytokines are secreted by Tcm?

A

high IL-2 and not much else

51
Q

what is the role of Tcm cells?

A

can differentiate into different effector subsets based on cytokine signals

52
Q

what is the location of Tem cells?

A

circulation and peripheral tissues

53
Q

what cytokines are released by Tem cells?

A

little IL-2 and many other cytokines

54
Q

what is the location of Trm cells?

A

resident in tissues or original infection

55
Q

MHC 1-restricted CD8+ T cells recognize and eliminate ___ cells

A

altered cells like cancer and virus-infected cells

56
Q

t/f all nucleated cells express MHC 1, so T cells can inspect any MHC 1+ cell

A

t

57
Q

what are the effector molecules of CD8+ T cells?

A
  1. membrane-bound Fas ligand
  2. secreted IFN and TNF (enhance immunity)
  3. secreted perforin and granzymes
58
Q

what are the 3 stages of the CD8+ cell lifecycle?

A
  1. activation phase
  2. effector phase (killing pathogens)
  3. memory phase
59
Q

dendritic cells must be ____ to be allowed to co-stimulate CD8+ T cells (this regulates the activation of cytotoxic T cells)

A

licensed

60
Q

DCs present antigen to helper T cells on class __ MHC

A

2

61
Q

helper T cells signal dendritic cells to upregulate ___ and ___ expression

A

cytokine and co-stimulatory

62
Q

t/f DC licensing and CD8+ cell activation can be sequential or simultaneous

A

t

63
Q

in what organs/locations does DC licensing and CD8+ activation occur?

A

in the lymph nodes or spleen

64
Q

effector T cells upregulate high-affinity IL-2Ra (CD25) and produce IL-2, but not enough to support ____

A

autocrine growth and differentiation

65
Q

what cytokine is needed for the expression of cytotoxic effector molecules (granzyme and perforin)?

A

IL-2

66
Q

once antigen is eliminated, what happens to the IL-2 and CD8 cells?

A

IL-2 levels drop and CD8 cells begin apoptosis by fratricide and the left over memory CD8 cells

67
Q

activated CD8+ T cells may develop into ____ cells or ___ cells

A

Tc1; Tc2

68
Q

once CD8+ T cells differentiate into Tc1 cells, what is their function?

A

secrete IFN-y but not IL-4 and kill by perforin/granzymes and Fas

69
Q

once CD8+ T cells differentiate into Tc2 cells, what is their function?

A

secrete IL-4 and IL-5, but only small amounts of IFN-y and kill primarily by perforin/granzymes

70
Q

what are the primary cytokines secreted by Tc1 cells?

A

IFN-y

71
Q

what is the preferred killing method of Tc1 cells?

A

perforin, granzymes, Fas ligand

72
Q

what are the main cytokines secreted by Tc2?

A

IL-4 and IL-5

73
Q

what is the preferred method of killing for Tc2?

A

perforin and granzymes

74
Q

CD8+ cell mediated destrcution of target cells consists of what 4 steps?

A
  1. conjugate formation
  2. cytoplasmic rearrangement & membrane attack / death signal delivered
  3. CTL-target cell dissociation
  4. target cell destruction
75
Q

in CD8+ killing of target cells, how long does it take for conjugate formation?

A

minutes

76
Q

in CD8+ killing, conjugation formation involevs the formation of a ___ complex

A

supramolecular complex (SMAC)

77
Q

in the congugation formation step of CD8+ killing, the CD8 cell bind to the foreign antigen and ____ stabilize the interaction between CTL and target cell

A

LFA-1 and LFA-3

78
Q

in CD8 killig of target cells, during the conjugation formation step, TCR signalling causes a transient increase in avidity of ___ for ICAMS on the target cells that lasts ____ minutes

A

LFA-1; 5-10 min

79
Q

in CD8 killing of a target cell, in the cytoplasmic rearrangement step, the ____ polarizes to the SMAC

A

centrosome/microtubule organizing center (MTOC)

80
Q

in CD8 killing of a target cell, during the cytoplasmic rearrangement, ___ and ___ containing perforin and granzymes reorient in the cytoplasma and concentrate near the CTL and target cell interface

A

golgi stacks and storage granules

81
Q

in CD8+ cell killing, the CD8 cells release granule contents into the space between the 2 cells by the process of ___

A

exocytosis

82
Q

perforin monomers in the presence of Ca++ do what?

A

change in conformation and insert into the target cell membrane, then polymerize into pores that trigger endocyosis in response to membrane damage

83
Q

in CD8 killing mechanism, granzyme binds to ___ on target cells and the resulting complex is ____

A

mannose-6-phosphate receptors; internalized into vesicles

84
Q

____ allows granzyme B to be released from the vesicle into the cytoplasm where it cleaves substrates to initiate ____

A

perforin; apoptosis

85
Q

how long after the CD8 cell dissociates from the target cell does death occur?

A

15 min to 3 hrs after

86
Q

how do CD8 cells protect themselves from their own perforin and granzyme?

A

by expressing serpins (serine protease inhibitors) that inhibit granzyme B

87
Q

t/f apoptosis is a quiet death where the cell components are recycled and intracellular contents are not released

A

t

88
Q

the perforin/granzyme and Fas ligand cytoxic pathways depend on the sequential activation of ____

A

caspases

89
Q

what are caspases?

A

cysteine proteases that cleave proteins after an aspartic acid residue

90
Q

____ can directly cleave pro-caspase-3 and can also celave Bid

A

granzyme B

91
Q

when granzyme B cleaves pro-caspase-3 and Bid, it induces release of ____ from mitochondria

A

cytochrome C

92
Q

active caspase 9 cleaves ____

A

pro-caspase-3

93
Q

caspase-3 activations leads to the activation of endonucleases that _____ and additional proteases that ____

A

frament target cell nuclear DNA; disassemble target cell cytoskeleton

94
Q

what happens to viral DNA when a CD8 cell targets the cell containing viral DNA?

A

viral DNA is fragmented, preventing viral replication during the interval before cell destruction

95
Q

how do CD4+ cells promote the development of CD8 memory cells?

A

release cytokines

96
Q

are CD4+ cells required in the recall process of CD8+ memory cells?

A

no

97
Q

t/f memory T cell responses typically reflect the same diversity as the primary response

A

t

98
Q

activated memory T cells secrete enough ____ for proliferation and differentiation into effector CTL

A

IL-2

99
Q

t/f it would be extremely rare to see a cell with BOTH CD45RA and CD45RO

A

t

100
Q

what is the central SMAC vs peripheral SMAC?

A

where the interaction between target cell and T cell is happening; peripheral is where the interaction is stabilized by adhesion molecules