Immune Receptors and Signal Transduction Part II (Lec 9)

Question 1

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

Answer 1

CD19 and CD81

Question 2

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

Answer 2

BCR

Question 3

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

Answer 3

tyrosine phosphorylated

Question 4

Phosphorylated CD19 activates what?

Answer 4

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

Question 5

PI3 kinase is required for the activation of what?

Answer 5

Btk and PLCy2

Question 6

The BCR complex consists of what?

Answer 6

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

Question 7

What are the three B cell co-receptors?

Answer 7

CD21, CD32, CD19

Question 8

In regards to BCR signaling, what is signal 1?

Answer 8

binding of lymphocyte to an Ag via receptor

Question 9

In regards to BCR signaling, what is signal 2?

Answer 9

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

Question 10

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

Answer 10

invariant Ig alpha and Ig beta molecules

Question 11

Ig alpha and Ig beta contain ITAMs where?

Answer 11

in their cytoplasmic tails

note: ITAMs mediate signaling function

Question 12

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

Answer 12

NFAT, NF-kB, and AP-1

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

Question 13

Signal initiation by Ag occurs by what?

Answer 13

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

Question 14

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

Answer 14

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

Question 15

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

Answer 15

Src

Question 16

True or false?

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

Answer 16

true

Question 17

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

Answer 17

ITAM phosphorylation and recruitment of Syk to the ITAM

Question 18

Activated Syk phoshporylates critical tyrosine residues on ___

Answer 18

BLNK (B cell linker protein)

Question 19

CR2/CD21 complement coreceptor complex does what?

Answer 19

enhances activation of B cells

Question 20

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

Answer 20

binds covalently to the microbe or Ag-Ab complex

Question 21

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

Answer 21

C3d

Question 22

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

Answer 22

CR2 or CD21

Question 23

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

Answer 23

bound C3d

Question 24

Inhibitory signalin gis lymphocytes is mediated by what?

Answer 24

inhibitory receptors and enzymes known as E3 ubiquitin ligases

Question 25

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

Answer 25

phosphotases

Question 26

What are the two key inhibitory receptors in B cells?

Answer 26

FcyRIIB: B cells, DCs and macrophages CD22: only B cells

Question 27

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

Answer 27

ITIMs

Question 28

P-ITMs recruit SH2 domain which contains what?

Answer 28

tyrosine phosphotases such as SHP and SHIP

Question 29

What do SHP and SHIP remove phosphates from?

Answer 29

PIP3 note: this inhibits PI3 kinase activity

Question 30

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

Answer 30

lysine

Question 31

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

Answer 31

lysine-48 type - protein targeted for degradation lysine-63 type -generates structure for latching the marked proteins onto other specific proteins

Question 32

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

Answer 32

canonical pathway uses BCRs and TCRs

Question 33

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

Answer 33

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

Question 34

True or false? | Canonical NF-kB signaling results in rapid and transient nuclear translocation NF-kB

Answer 34

true

Question 35

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

Answer 35

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

Question 36

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

Answer 36

p105 and p100, which function as NF-kB inhibitors

Question 37

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

Answer 37

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

Question 38

``` 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 ```

Answer 38

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

Question 39

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)

Answer 39

type I

Question 40

True or False? | All of the type I and type II cytokine receptors engage JAK-STAT signaling pathway

Answer 40

true

Question 41

True or false? | In regards to the JAK-STAT pathway, STATs phosphorylate JAKs

Answer 41

false, JAKs phosphoylate tyrosine on STATs

Question 42

Another name for the Type II cytokine receptor is what?

Answer 42

interferon receptor family

Question 43

Do type II cytokine receptors contain the WSXWS motif?

Answer 43

no

Question 44

The interferon receptor family includes receptors for what?

Answer 44

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

Question 45

A characteristic of this receptor family is preformed trimers

Answer 45

TNF receptor family

Question 46

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

Answer 46

gene expression

Question 47

True or False? | signaling of some TNF receptors may lead to apoptosis

Answer 47

true

Question 48

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

Answer 48

IL-1 receptor family (TLRs)

Question 49

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?

Answer 49

TIR domain-containing adaptors

Question 50

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

Answer 50

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

Question 51

True or false? | IL-1 receptor signaling also includes MAP kinase activation

Answer 51

true

Question 52

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

Answer 52

activation of the associated G protein

Question 53

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

Answer 53

GTP bound G alpha subunit and G beta/gama complex

Question 54

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

Answer 54

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

Question 55

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

Answer 55

Ras which induces the activation of PI3Ky and PLC

Question 56

In regards to chemokine receptor signaling, PLC generates what?

Answer 56

IP3

Question 57

In regards to chemokine receptor signaling, IP3 does what?

Answer 57

mobilizes calcium from non-mitochondrial stores

Question 58

In regards to chemokine receptor signaling, DAG activates what?

Answer 58

calcium independent and calcium dependent protein kinase C