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Basic Immunology- Module 1 > cytotoxic T cells > Flashcards

cytotoxic T cells Flashcards

1
Q

How is endogenous antigen broken up beofre entry to the ER?

A

proteasome

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2
Q

Describe the peptide binding groove on MHC?

A

slightly curved beta sheets as a base with two alpha helices on top

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3
Q

How many amino acids can the MHC I bind?

A

8-10

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4
Q

How many amino acids can the MHC-II bind?

A

13-25

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5
Q

How are TCRs formed?

A

by rearranging non-continous gene segments

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6
Q

What is the most important costimulation give to naive T cells?

A

CD28- CD80/86

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7
Q

What happens to a naive T cell if there is peptide recognition in the absence of costimulation?

A

activation induced cell death or anergy

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8
Q

What is the function of CTLA4?

A

binds CD80/86 but is inhibitory

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9
Q

What is the difference between the antigens picked up in the spleen and lymph nodes?

A

spleen will pick up bloodstream antigens whereas lymph nodes will pick up antigen in tissues

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10
Q

How can dendritic cells be activated?

A

TLRs and other PRRs; tissues damage or cytokines produced during the inflammatory response

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11
Q

Where are dendritic cells foudn in the lymph nodes?

A

cortex of the lymph node in the T cell areas

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12
Q

Where are macrophages foudn in the lymph ndoes?

A

throught the lymph node but concentrated mainly in the marginal sinus and medullary cords

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13
Q

What happens in the marginal sinus of hte lymph node?

A

afferent lymph collects before percolating through the lymphoid tissue

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14
Q

What happens in the medullary cords of the lymph nodes?

A

effect lymph collects before passing via the effect lymphatics into the blood

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15
Q

What is the function of plasmacytoid DCs?

A

sentinels for viral infections and produce large amoutns of type I IFNS

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16
Q

What receptors do dendritic cells have for phagocytosing antigen?

A

complement; Fc; C-type lectins

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17
Q

What is the nonsepcific method that dendritic cells have for the uptake of antigen?

A

macropinocytosis

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18
Q

What is the benefit of dendritic cells using macropinocytosis in addition to phagocytic receptors to ingest antigen?

A

microbes that have evolved strategies to escape recognition by phagocytic receptors e.g bacteria with thick capsules are ingested

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19
Q

What is cross presentation?

A

when viral antigens which enter dendritic cells via endocytic or phagocytic vesicles may be diverted to the cytosol for proteasomal degrataion and loaded onto MHC I molecules

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20
Q

what is hte purpose of cross presentation?

A

viruses that do not directly infect DCs can stimulate the activation of CD8 cells

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21
Q

In what infections are dendritic cells from the site of infection able to transfer antigen to resident dendiritc cells in the lymph nodes ?

A

herpes simplex or influenza

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22
Q

What chemokine receptor is upregulated in licensed dendritic cells?

A

CCR7

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23
Q

What is the function of CCR7 being upregulated by activated DCs?

A

responds to CCL21 which is produced by lymphoid tissue and facilitiates their migration into local lymphoid tissue; also contributes to their enhanced APC function

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24
Q

As well as MHC and costimualtory molecules CD80 and CD86, what else do activated DCs express?

A

adhesion molecules e.g DC-SIGN; secrete CCL19

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25
Q

What is the function of CCL19 secreted by DCs?

A

specifically attracts naive T cells

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26
Q

What cytokine do activated T cells secrete?

A

IL2

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27
Q

What are the functions of IL-2 produced by activated T cells?

A

maintenance of Tregs; augment T cell proliferation and survival; affects the balance of effector and memory T cells that develop in a primary response to antigen

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28
Q

Which cells produce IFNy?

A

Th1; NK cells; CD8

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29
Q

By what process do cytotoxic T cells kill tagret cells?

A

extrinsic or intrisinc apoptotic pathways

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30
Q

How is transciption of IL-2 in activated T cells caused?

A

antigen recognition by the T cell receptors induces the activation of NFAT; AP-1 and NfkB which bind to the promotor region of IL2 gene

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31
Q

How does the receptor for IL-2 change in resting vs activated T cells?

A

in resting- low affinity (only b and y chains) whereas in activated cells the IL-2 receptor becomes higher affinity due to a chain being added

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32
Q

What si the effect of CD28 on IL-2 production?

A

CD28 activates PI 3-kinase signalling which increases production of AP-1 and NFkB; increases the stability of IL-2

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33
Q

How is IL-2 production restricted in activated T cells?

A

CTLA-4 which competes with CD28 for binding to B7, reduces IL-2 production

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34
Q

How are additional signals (in addition to costimulation from dendritic cells) required for CD8 activation given?

A

CD4 cells which recognise the same antigen as the APC are induced to express IL-2 and CD40 by B7 on dendritic cells

35
Q

what is the effect of CD40 expression on CD4 cells in CD8 activation?

A

CD40L binds CD40 on the dendritic cell which increases expression of B7 and 4-IBBL which gives additional stimulation to the naive T cell

36
Q

What is the effect of IL-2 production by activated CD4 T cells?

A

promotes effector CD8 T cell differentiation

37
Q

What is the effect of IFNy secretion by CD8 T cells?

A

increases Th1 cell differentiation; increases expression of class II MHC molecules and microbiicidal acitivty of macrophages; increases cytotoxic activity of NK cells nad increases differentation of B cells and production of IgG2a

38
Q

What pathway does IFNy signal via?

A

JAK/STAT pathway

39
Q

How does IGNy have a direct antiviral effect?

A

by inducing PKR which binds to dsRNA and inihibits translation of dsRNA; stimulates NFkB and activates caspase 8-apoptosis

40
Q

What cytokines do CD8 T cells produce?

A

MIP-1b; IL2; TNFa and IFNy

41
Q

What is the function of MIP-1b?

A

chemoattractant for NK cells; monocytes and others

42
Q

What are the 2 main mechanisms for CD8 T cell killing?

A

Fas-FasL apoptosis and perforin

43
Q

What effect does binding of MHC and TCR and B7.1 (CD80) and CD28 have on the APC?

A

induces expression of CD40 and B7.2 (CD86)

44
Q

what effect does binding of MHC and TCR and CD80 on CD4 T cell?

A

induce expression of CD40L and CD28 between CD86 result in full activation of CD4 T cell

45
Q

What does 4-1BBL bind to on hte CD8 cell?

A

4-1BB which is induce by initial activation of CD8

46
Q

What type of receptor is Fas?

A

TNF family

47
Q

What happens when the intrinsic pathway of apoptosis is induced?

A

mitochondria swell and leak releasing cytochrome c into the cytosol

48
Q

What does cytochrome in the cytosol bind to?

A

apaf-1

49
Q

What happens when cytochrome c binds to apaf-1?

A

apaf-1:cytochrome c complex self assembles into an apoptosome

50
Q

What is hte function of the apoptosome?

A

recruits an initiator caspase - procaspase 9 which aggregates

51
Q

What happens when procaspase 9 aggregates with the apoptosome?

A

it is activates and activates procaspase 3

52
Q

What happens when caspase 3 is activated?

A

cleaves enzymes e.g ICAD which released CAD which enters the nucleas to cleave DNA

53
Q

What is the release of cytochrome c from the mitochondria mediated by?

A

Bcl-2 proteins

54
Q

What defines the Bcl-2 family of proteins?

A

presence of BH domains

55
Q

Give examples of pro-apoptotic Bcl-2 proteins called executioners?

A

Bax; Bak and Bok

56
Q

What induces the anti-apoptotic family of Bcl2?

A

stimuli which promote cell survival

57
Q

Give an example of an anti-apoptotic Bcl-2 family protein?

A

Bcl-2; Bcl-W

58
Q

What is the function of sentinels- pro-apoptotic Bcl2 family members?

A

block the activity of anti-apoptotic proteins or stimulate the executioner pro-apoptotic proteins

59
Q

Give examples of sentinel Bcl2 proteins?

A

Bad; Bid and PUMA

60
Q

What is the difference between the extrinsic and intrinsic pathways of apoptosis?

A

extrinsic pathway is stimulated by activation of death receptors by extracellular ligands; intrinsic pathway is stimualted by noxious stimuli; lack of growth factors required for survival

61
Q

What are cytotoxic granules?

A

modified lysosomes that contain 3 cytotoxic effecto proteins: perforin; granzymes and granulysin. and proteoglycan serglycin

62
Q

What is the function of perforin?

A

perforatings target cell membrane which causes direct damage and allows access of other cytotoxic granules

63
Q

What is the function of granzymes?

A

activate apoptosis once delivered into the target cell

64
Q

What si hte function of granulysin?

A

has antimicrobial activity and at high concentrations induces apoptosis

65
Q

What is hte function of proteoglycan serglycin?

A

acts a scaffold forming a complex with perforin and granzymes

66
Q

How do granzymes trigger apoptosis?

A

directly activate caspases and damage mitochondria which activates caspases

67
Q

Aside from Fas, what other ligands can induce apoptosis in cells?

A

TNF-a and LTa which bind to TNFR-1 on target cells

68
Q

What are the 2 forms of granzyme?

A

A- damages mitochondria; B-cleaves caspase3 and cleaves BID which disrupts the mitochondrial membrane

69
Q

How do phagocytic cells recognise cells undergoing apoptosis?

A

phosphatidylserine replaces phosphatidylcholine as the main phospholipid on the cell membraen

70
Q

What stimualtes the production of preformed cytotoxic proteins?

A

any ligation with TCR (starts when meet DC; then also whenenver it meets a TCR and releases them-to replenish)

71
Q

How is DNA cleaved in apoptosis?

A

into regularly sized fragments to form the DNA ladder

72
Q

What is required for release of cytotoxic granules?

A

calcium

73
Q

What happens to stop the cell from undergoing necrosis after cell membrane has pore ?

A

needs to be reparied

74
Q

what is found on the intracellular portion of Fas?

A

fas-associated death domains (FADD) to which caspases bind

75
Q

why do T cell upregulate both Fas and FasL on activation?

A

need to die after doing their job: activation induced cell death

76
Q

What are car T cells?

A

T cells expressing a chimeric antigen receptor (specific for tumour antigen)

77
Q

What are hte methods for studying CD8 T cell responses?

A

staining with tetramers(quanitfies sepcific T cells); target cell killing assays(label target cells with fluorescence); ELISpot assays-cytokine secretion and intracellualr cytokine staining

78
Q

What is Lck attached to CD4 via?

A

zinc ion

79
Q

What proteins bridges LAT and SLP-76?

A

Gads

80
Q

What does the stimulation of CD28 cause?

A

phosphorylation and recruitment of PI3k

81
Q

What type of domains does PIP3 bind in proteins?

A

PH

82
Q

What is cell death characterised by?

A

blebbing of the cell membrane and fragmentation of the nuclei

83
Q

In what form does BID cause release of cytochrome c from the mitochondria?

A

trunkated form

84
Q

When does C1 complex bind to antibody?

A

when it is aggregated to the surface of a bacterium

Basic Immunology- Module 1 (31 decks)

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