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Immunology > part 8 > Flashcards

part 8 Flashcards

1
Q

what is traf6

A

an adapter protein that involved in cytoplasmic RNA and DNA signaling, especially for cytokine or interferon production.

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2
Q

in TLRs, what ubiquination of traf6 entail

A

a scaffold protein is produced

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3
Q

what do the receptors of the cell determine

A

physiology of the cell

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4
Q

what are the two main target of cell signaling

A

Go straight to the nucleus; gene expression and cell division
Cytoskeleton

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5
Q

properties of the nucleus target

A

For gene expression: cell differentiation.
Gene expression allows for new protein productions

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6
Q

properties of targeting the cytoskeleton

A

Motility, phagocytosis, vesicle production.
Change shape, cell size, motility.

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7
Q

what is the function of kinases

A

they phosphorylate substrates
In other words, it adds phosphate groups and causes a conformational change of enzyme (activation)

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8
Q

what kind of receptor domains are present in kinase receptor classes

A

a kinase domain

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9
Q

what does a kinase domain do

A

Ligand binding dimerizes the receptor, activating the kinases, which phosphorylate each other.

The activated kinases phosphorylate downstream substrates.

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10
Q

what is another way kinases are associated with receptors

A

through noncovalent kinase association

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11
Q

what happens when kinases are covalently associated with each other

A

Ligand binding dimerizes receptors, activating associated kinases, which phosphorylates each other.
Activated kinases phosphorylate downstream substrates.

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12
Q

what is signaling strength dependent on

A

the interaction between the receptors and the ligand.

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13
Q

receptor factors in regards to signal strength

A

Threshold (how many receptors are needed)
Amplitude (strength)
Duration
Regulation (on and off switches)

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14
Q

ligand factors in regards to signal strength

A

Affinity (how well is the ligand binding)
Spatial abundance (how many ligands and where is it located)
Temporal abundance

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15
Q

what type of kinase is found in cytokine signaling

A

Ser/Thr kinases, which phosphorylate only at the serine or threonine amino acids.

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16
Q

what kinase is found in T and B cell signaling

A

Tyrosine kinase (rare), which phosphorylates at the tyrosine amino acid.

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17
Q

what is a protein domain

A

the phosphorylation recognition site of the recognizing protein for a ligand class.

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18
Q

what is an adapter protein

A

The protein that brings different proteins together (multiple bound protein receptors)

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19
Q

what other properties of ligands must be accounted for binding

A

Spacing between ligand and proteins must be correct

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20
Q

how is the signaling pathway started

A

Scaffold protein is phosphorylated by a kinase, and recruits signaling proteins that bind.
All proteins bound have the same domain type of binding (SH2, 3, etc.)
The adapter Grb2 binds to the signaling protein Sos via its SH3 domains.
Activated receptor becomes tyrosine phosphorylated.
Grb2 binds to phosphotyrosine via SH2, bringing Sos to the receptor.

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21
Q

what is the Ras protein

A

has the ability to induce cell proliferation.
When mutated, it is known to cause cancer (doesn’t know how to turn itself off).
It is an oncogene.

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22
Q

when is Ras activated/inactivated

A

Active when bound to GTP
Inactive when bound to GDP

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23
Q

what happens when Ras is activated by GTP

A

signals for cell proliferation

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24
Q

what is a GEF

A

guanine-nucleotide exchange factors
swaps GDP with GTP

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25
Q

what is the relationship between GEF and Ras

A

GEFs swaps GDP with GTP, which activates Ras.

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26
Q

what is an example of a GEF

A

Sos

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27
Q

what turns off the Ras/switches GTP for GDP

A

GAPs

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28
Q

what is a permanent way to turn of cell signaling

A

degradation of proteins

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29
Q

how is the degredation of proteins started

A

Phosphorylated substrates are dephosphorylated.

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30
Q

how are proteins tagged for degradation

A

ubiquitin
K48 is an area where long chains of ubiquitin are attached to the targeted
protein

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31
Q

where are ubiquinated proteins sent to be degraded

A

degradation in proteasome
Can also be degraded in the lysosome

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32
Q

how is ubiquination related to both activation and deactivation

A

Ubiquitination can activate by creating scaffold or deactivate by tagging proteins for degradation by proteasome.

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33
Q

what is the proteins present in the amplification of kinases

A

Raf > Mek > Erk
MAPK > MAPKK > MAPKKK

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34
Q

what does signaling’s second messenger

A

calcium

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35
Q

how does calcium relate to cell signaling/as a second messenger

A

Calcium rapidly diffuses throughout the cell and induces conformational changes in calmodulin.
When calmodulin is bound to calcium, it changes shape, which allows for effector proteins to bind to it.
Calcium is also found in the synaptic cleft when neurotransmitters are released (changes charge) and acts as the second messenger for skeletal/muscle movement.

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36
Q

what are the CD3 prrotein

A

located adjacent to the TCR on both sides, recognition of antigens and subsequent signal transduction and activation of immunocompetent T lymphocytes.

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37
Q

what is the structure of CD3s

A

ITAMs are connected to CD3
made of epsilon:delta and gamma:epsilon proteins

38
Q

what do ITAMs phosphorylate

A

tyrosine

39
Q

what other cells have ITAMs

A

APCs that have an Fc receptors (monocytes, macrophages, neutrophils, and Mast cells)

40
Q

what do B cells have to help with signaling

A

Igbeta and Igalpha next to the membrane-bound antibody.
Igb and Iga have ITAMs, too

41
Q

what is the ratio of tyrosine to ITAM

A

2 tyrosines for every ITAM

42
Q

how many TCRs need to be bound for CD4s to activate

A

about 50

43
Q

how many TCRs do T cells have

A

about 10,000 that bind with APCs

44
Q

how many TCRs bound for CD8s to activate

A

a little under 50

45
Q

what is clustering

A

in T cells, you can bind antibodies to CD3 in order to activate the T cell falsely (lab experiment)

46
Q

what is the function of CD28

A

costimulatory receptor
brings in a survival signal

47
Q

what binds to CD28

A

APCs with B7

48
Q

what abilities do BCR and TCRs not have

A

cell signaling capabilities

49
Q

what do T cells depend on for cell signaling

A

CD3 complex (epsilon, delta, zeta, and gamma chains); dimers.

50
Q

what is the structure of the CD3 complex; what binds to what

A

TCR alpha chain binds to epsilon:delta and zeta dimers.
TCR beta chain binds to gamma:epsilon and zeta dimers.

51
Q

what do B cells rely on for signaling

A

Ig alpha and beta

52
Q

what are the interactions of the B and T cell accessories

A

Interactions of accessories are through transmembrane region

53
Q

what interactions do TCRs have

A

charges

54
Q

what interactions do BCRs have

A

hydrophobic interactions/regions

55
Q

what is needed for T cell binding

A

MHC II:Ag
TCR
CD45 receptor (Lck)
ITAMs
CD3 complex dimers

56
Q

what is the first step of T cell signaling

A

TCR:MHCII binding brings in CD28 and 45

57
Q

what does CD45 bring in

A

Lck by dephosphorylation

58
Q

what is Lck

A

a tyrosine kinase

59
Q

what are the different versions of CD45

A

RO and RA

60
Q

what is the second step of T cell signaling

A

Lck phosphorylates ITAMs, which brings in Zap70

61
Q

what does zap70 phosphorylate

A

LAT/SLP76, which brings in scaffolding proteins

62
Q

what are the zap70 scaffolding proteins

A

LAT, SLP76, GADs
These proteins are a complex.
LAT is a protein that is attached to the membrane intracellularly.

63
Q

what does the assembled scaffolding proteins bring in

A

PLC-gamma

64
Q

what is the third step of T cell signaling

A

Lck also phosphorylates CD28, bringing in PI3K

65
Q

what is the fourth step of T cell signaling

A

PI3K phosphorylates PIP2 to 3

66
Q

what does PIP3 attract

A

3 kinases:
Itk
PDK
Atk

67
Q

what happens to PIP2

A

it is cleaved by PLC-gamma into IP3 and DAG

68
Q

what does IP3 do

A

raises Ca from ER, which binds to calmodulin. calmodulin is P into calcineuron phosphatase enzyme

69
Q

what does the calcineuron phosphatase activate

A

the NFAT tx factor (IL2 and cell differentiation)

70
Q

what does DAG do

A

DAG activates GAD (Ras activator) and TRAF6.
TRAF6 is recruited by CARMA1, and activation leads to NF-kappabeta transcription factor
GAD will also activate transcription factors later.

71
Q

what is the most important gene that is activated during T cell activation

A

IL2

72
Q

what is the first signal of TCA

A

TCR

73
Q

second signal of TCA

A

CD28

74
Q

signal 3 of TCA

A

cytokines; chemokines from APC being bound to T cell receptors

75
Q

what do all signals come from in TCA

A

the APC

76
Q

when is IFN secreted

A

by virus-infected cells to neighboring cells
Modulates activation and specific infection through IFN
What the cell should do in order to fight the infection.

77
Q

what is IL2

A

a survival and growth ligand that binds to the IL-2 receptor.

78
Q

what needs to happen in order for T cells to activate

A

there must be a threshold of MHC:Ag:TCR that is met
There is many different peptides/MHCs on the APC

79
Q

what is NF kappa beta

A

a transcription factor protein complexes induces the expression of various pro-inflammatory genes, including those encoding cytokines and chemokines, and also participates in inflammasome regulation

80
Q

how is Lck regulated

A

Lck is regulated CD45, which is a phosphatase (removes phosphates on Lck)

81
Q

what kinse deactivates Lck

A

Csk is a kinase that phosphorylates Lck, which deactivates Lck

82
Q

what are the three transcription factors that result from IP3 and DAG

A

NFAT (IL-2)
AP-1 (proliferation, differentiation and cell death)
TRAF-6 (E3 ligase) to NF-KB (inflammatory responses)

83
Q

what needs to happen simultaneously for IL2 to be produced

A

All three transcription factors need to be made and activated at the same time in order to get IL-2 production.

84
Q

in B cell activation, what is similar to Lck

A

Fyn
Blk
Lyn

85
Q

what is like the CD3;zeta chains in BCA

A

Ig alpha and beta

86
Q

what is Zap70 in BCA

A

Syk

87
Q

what is the B cells CD4 and 8

A

CD19, 21, and 81

88
Q

what is the PLC-gamma in BCA

A

Btk

89
Q

how is cell signaling stopped

A

To turn off, a signal will be sent to express CTLA-4 on the surface.
CTLA-4 outcompetes CD28 for B7, and clusters together.

90
Q

what is an alternative off switch to CTLA4

A

PD1

91
Q

what do naive cells require that memory cells don’t

A

Memory cells do not require CD28 activation, while naive cells absolutely do.

92
Q

what does B7 costimulate with

A

CD28

Immunology (11 decks)

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