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Immunology > Immune Receptors and Signal Transduction Part II (Lec 9) > Flashcards

Immune Receptors and Signal Transduction Part II (Lec 9) Flashcards

1
Q

CR2 is expressed on mature B cells as a complex with what two other membrane proteins?

A

CD19 and CD81

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2
Q

CR2 binds to Ags through attached C3d at the same time that ___ binds directly to the Ag

A

BCR

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3
Q

C3d binding to CR2 brings CD19 in proximity to BCR-associatated kinases, and the cytoplasmic tail of CD19 rapidly becomes ___ ___

A

tyrosine phosphorylated

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4
Q

Phosphorylated CD19 activates what?

A

PI3 kinase which in turn, further augment signaling initiated by Ag binding to BCR

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5
Q

PI3 kinase is required for the activation of what?

A

Btk and PLCy2

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6
Q

The BCR complex consists of what?

A

Ag receptor in association with Ig alpha and Ig Beta (CD79a and CD79b)

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7
Q

What are the three B cell co-receptors?

A

CD21, CD32, CD19

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8
Q

In regards to BCR signaling, what is signal 1?

A

binding of lymphocyte to an Ag via receptor

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9
Q

In regards to BCR signaling, what is signal 2?

A

accessory and costimulatory molecules on the surface of B cells are required for cell-cell interaction and the signal transduction events leading to activation

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10
Q

Membrane IgM on the surface of mature B cells is associated with what?

A

invariant Ig alpha and Ig beta molecules

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11
Q

Ig alpha and Ig beta contain ITAMs where?

A

in their cytoplasmic tails

note: ITAMs mediate signaling function

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12
Q

Activation of PLCy and Ras lead to the activation of what transcription factors?

A

NFAT, NF-kB, and AP-1

note: when PLCy and Ras are activated, they turn on genes involved in cell growth, differentiation, and survival

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13
Q

Signal initiation by Ag occurs by what?

A

cross-linking of the BCR and is facilitated by the coreceptor for the BCR

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14
Q

Ag binding facilitates a conformational change in BCR-associated ITAMs, making them accessible to Src Kinases such as?

A

Lyn, Fyn, and Blk which are lined by lipid anchors to the inside of the plasma membrane

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15
Q

Cross-linking by multivalent Ags brings together and activates ___ kinases which phosphorylate the ITAMs of Ig alpha and Ig beta

A

Src

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16
Q

True or false?

Cross-linked BCRs enter lipid rafts where many adaptors and signaling molecules are concentrated

A

true

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17
Q

Ag-dependent cross-linking of the BCR or the activation of the BCR coreceptor-dependent mechanism results in what?

A

ITAM phosphorylation and recruitment of Syk to the ITAM

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18
Q

Activated Syk phoshporylates critical tyrosine residues on ___

A

BLNK (B cell linker protein)

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19
Q

CR2/CD21 complement coreceptor complex does what?

A

enhances activation of B cells

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20
Q

Cleavage of C3 results in the production of C3b which does what?

A

binds covalently to the microbe or Ag-Ab complex

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21
Q

C3b is further degraded into a fragment called ___ which remains bound to the microbial surface or on Ag-Ab complex

A

C3d

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22
Q

B cells express a receptor for C3d. What is it?

A

CR2 or CD21

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23
Q

The complex of C3d and Ag binds to B cells, with the BCR recognizing Ag and CR2 recognizing what?

A

bound C3d

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24
Q

Inhibitory signalin gis lymphocytes is mediated by what?

A

inhibitory receptors and enzymes known as E3 ubiquitin ligases

25
Q

Inhibitory receptors usually recruit and activate ___ that counter signaling events induced by Ag receptors

A

phosphotases

26
Q

What are the two key inhibitory receptors in B cells?

A

FcyRIIB: B cells, DCs and macrophages

CD22: only B cells

27
Q

The ___ of inhibitory receptors can be phosphorylated by Src family kinases linked to lymphocyte activation

A

ITIMs

28
Q

P-ITMs recruit SH2 domain which contains what?

A

tyrosine phosphotases such as SHP and SHIP

29
Q

What do SHP and SHIP remove phosphates from?

A

PIP3

note: this inhibits PI3 kinase activity

30
Q

Ubiquitin is a 76-amino acid protein that is transferred to ___ residues on specific substrates that are recognized by specific E3 ubiquitin ligases

A

lysine

31
Q

What are the two lysine types of ubiquitin and what do they do?

A

lysine-48 type - protein targeted for degradation

lysine-63 type -generates structure for latching the marked proteins onto other specific proteins

32
Q

What is the difference between canonical and non-canonical NF-kB signaling patwhays?

A

canonical pathway uses BCRs and TCRs

33
Q

In regards to canonical NF-kB signaling, what protein normally sequesters NF-kB into the cytoplasm? What triggers it?

A

IkBa; triggered by numerous signals, including those mediated by innate and adaptive immune receptors

34
Q

True or false?

Canonical NF-kB signaling results in rapid and transient nuclear translocation NF-kB

A

true

35
Q

What does non-canonical NF-kB signaling rely on?

A

phosphorylation-induced p100 processing, which is triggered by signaling form a subset of TNFR members

36
Q

In regards to non-canonical NF-kB signaling, NF-kB1 and NF-kB2 are translated as what precursor proteins?

A

p105 and p100, which function as NF-kB inhibitors

37
Q

In regards to non-canonical NF-kB signaling, proteasome-mediated processing of p105 and p100 does what?

A

produces the mature NF-kB1 and NF-kB2 proteins (p50 and p52) and also results in disruption of the IkB-like function of these precursor proteins

38
Q 
Give the effector function for each effector mediator
IL-10
IL-17A/17F/22
IL-4/5/13
IL-4/21
IFN gamma/TNF
Granzyme B/Perforin/FASL
A

IL-10: antiinflammatory

IL-17A/17F/22: inflammation

IL-4/5/13: allergic responses

IL-4/21: germinal center help

IFN gamma/TNF: macrophage activation

Granzyme B/Perforin/FASL: killing of infected cells

39
Q

This type of cytokine receptor typically consists of unique ligand-binding chains one or more signal-transducing chains, which are often shared by receptors for different cytokines (WSXWS motif)

A

type I

40
Q

True or False?

All of the type I and type II cytokine receptors engage JAK-STAT signaling pathway

A

true

41
Q

True or false?

In regards to the JAK-STAT pathway, STATs phosphorylate JAKs

A

false, JAKs phosphoylate tyrosine on STATs

42
Q

Another name for the Type II cytokine receptor is what?

A

interferon receptor family

43
Q

Do type II cytokine receptors contain the WSXWS motif?

A

no

44
Q

The interferon receptor family includes receptors for what?

A

IFN alpha/beta, IFN gamma, IL-10, IL-20, and IL-22

45
Q

A characteristic of this receptor family is preformed trimers

A

TNF receptor family

46
Q

TNF receptor family have conserved cystein-rich extracellular domains and shared intracellular signaling mechanisms that stimulate what?

A

gene expression

47
Q

True or False?

signaling of some TNF receptors may lead to apoptosis

A

true

48
Q

The members of this receptor family share a conserved cytosolyic sequence called the Toll-like/IL-I receptor domain

A

IL-1 receptor family (TLRs)

49
Q

In regards to the IL-1 receptor family, the engagement of the IL-1R or TLRs results in receptor dimerizaiton and the recruitment of one or more of four known what?

A

TIR domain-containing adaptors

50
Q

In regards to the IL-1 receptor family, the adaptors link TLRs/IL-1 receptors to different members of what family?

A

IRAK, which in turn, link adaptors to TRAF6, an E3 ubiquitin ligase required for NF-kB activation

51
Q

True or false?

IL-1 receptor signaling also includes MAP kinase activation

A

true

52
Q

In regards to chemokine receptor signaling, the engagement of a GPCR by a chemoattractant results in what?

A

activation of the associated G protein

53
Q

In regards to chemokine receptor signaling, G proteins dissociates into what?

A

GTP bound G alpha subunit and G beta/gama complex

54
Q

In regards to chemokine receptor signaling, the alpha subunit inhibits what?

A

adenyl cyclase leading to a decrease of intracellular cAMP-levels and cAMP-dependent protein kinase activity

55
Q

In regards to chemokine receptor signaling, the beta/gamma complex activates what?

A

Ras which induces the activation of PI3Ky and PLC

56
Q

In regards to chemokine receptor signaling, PLC generates what?

A

IP3

57
Q

In regards to chemokine receptor signaling, IP3 does what?

A

mobilizes calcium from non-mitochondrial stores

58
Q

In regards to chemokine receptor signaling, DAG activates what?

A

calcium independent and calcium dependent protein kinase C

Immunology (12 decks)

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