BCR and Co-receptors etc

Question 1

B cell signaling is initiated through what molecules?

Answer 1

the Ig(alpha)/Ig(betA) complex

Question 2

What does +(Igalpha/Igbeta) stimulation do?

Answer 2

the phosphorylation of their ITAMs via tyrosine kinases

Question 3

CD21

Answer 3

is CR2

it is the complement receptor type 2; BCR coreceptor

Question 4

“Co receptor complex” is made from what molecules?

Answer 4

CD19, CD21, CD81

Question 5

what do the co-receptors do?

Answer 5

they modulate signal transduction initiated by the Ig(a)/Ig(B) complex

Question 6

Src-Syk activation in B cells leads to

Answer 6

PLC –> Rac and Map PWs –> NFkB, AP-1, NFAT –> cell growth, differentiation, survival

Question 7

Signal ____ by ___ occurs by cross linking of the BCR and is facilitated by the ______ for the BCR

Answer 7

initiation by Ag, and is faciliated by the coreceptors for the BCR

Question 8

Ad-dependent cross linking of the BCR results in

Answer 8

ITAM phosphorylation by a Src group, recruitment of Syk to the ITAM, and phosphorylation events leading to activation of these PWs:

PLC
PKC-beta
Ras-MAP

Question 9

C3d

Answer 9

opsonin product of C3b cleavage

it can bind both BCR and CR2 simultaneously

enhances B cell response more than Ag alone

Question 10

the role of CR2/CD21

two possible roles

Answer 10

complement co-receptor complex

C3 –> C3b
C3b binds to microbe OR Ag-Ab complex
C3b –> C3d
C3d receptor is CR2

C3d-microbe OR C3d-Ab-Ag binds to B cell: BCR rec. Ag and CR2 rec. C3d

Question 11

“CD19/CD21/CD81 complex” why is it called that?

Answer 11

is often called the B cell coreceptor complex

It’s called that because CR2 often binds to C3d bound Ag at the same time the BCR binds directly to Ag

CR2 binding to C3d brings CD19 into proximity to BCR-associated kinases, which causes the CD19 tail to be phosphorylated —> lyn recruitment –> Igalpha/Igbeta phosphorylation

CD19 phosporylation –> P13 kinase activation –> PLC(gamma) –> B cell activation enhancement

Question 12

Inhibitory Signaling:

what receptors are involved, what generic enzymes are involved, and what “big” enzyme is involved

Answer 12

1) needed to control inflammation
2) ITIMs are the immunoreceptor tyrosine inhibitory motifs
3) ITIMs recruit phosphatases that counter signaling events
4) E3 ubiquitin ligases are one of the primary mediators of inhibition

Question 13

how does the ITIM work (generally)

Answer 13

ITIM encounters ligan extracellularly
ITIM recruits Src kinase to be phosphorylated
P-ITIM recruits SH2 domain tyrosine phosphatases

Question 14

What are the key inhibitory receptors on the B cell?

Answer 14

CD22 and Fc(gamma)RIIB

Question 15

Fc(gamma)RIIB

Answer 15

inhibitory receptor on B cells and MOs too

Question 16

CD22

Answer 16

inhibitory receptor on B cells only

Question 17

E3 Ubituitin Ligases : how does it work

Answer 17

it transfers a 76 a.a. protein to tyrosine residues on the target molecule. it is SPECIFIC for that molecule.

two methods

lyrsine-48 and lysine-63

lysine-48 attaches and marks a specific protein for destruction

lysine-63 attaches to a molecule which causes it to attach to a third molecule (non-cannoical NF-kB signaling)

Question 18

canonical NF-kB Signaling Pathway

Answer 18

used by both TCR and BCR
adaptive and innate

integral mechanisms

1) IKK-mediated IkBa phosphorylation
i. IkBa is degraded by proteosome
2) results in rapid/transient nuclear translocation of RelA/p50 (NF-kB)

Question 19

canonical NF-kB signaling: 4 traits, and 3 outcomes, main kinase

Answer 19

rapid/transient
independent of protein synthesis
responds to numerous stimuli
diverse functions

1) inflammatory response
2) Proliferation
3) survival

TGF-activated kinase-1 (TAK1)

Question 20

non-canonical NFkB signaling: 4 traits, 3 outcomes, main kinases

Answer 20

slow/persistent
protein-synthesis dependent
responds to a subset of TNFR signals
specific functions

1) chemokine synthesis
3) lymphoid stroma
3) survival

relies on phosphorylation-induced p100 processing
NF-kB inducing kinase (NIK-1)

RelB-P52 (NF-kB)

Question 21

what is the role of proteosome process of p105/p100

Answer 21

p105-p100 are the NF-kB precursors, proteosome proecessing creates their active forms p50 and p52

Question 22

Cytokine Receptor families

Type I cytokine receptor, also called

Answer 22

hematopoietin receptor

uses jak-stat

Question 23

Type II cytokine receptor

Answer 23

also uses JAK-stat

ligans are IFN-alpha/beta
IFN gamma
IL-10
IL-22

Question 24

TNF receptor family

Answer 24

uses TRAF kinase

all the weird names

TNFs, CD50, Fasl, BAFF, etc

Question 25

IL-1 receptor family

Answer 25

uses IRAK kinase

IL-1, 18, 33

Question 26

G protein coupled receptors

Answer 26

G proteins

chemokines ligands

Question 27

how are cytokine receptor families classified?

Answer 27

on the basis of their conserved extracellular domain structures

4/5 are single pass beta sheets

Question 28

conserved cystein and WSXWS

Answer 28

type 1, all use jak stat

Question 29

uses jak stat but no WSxWS region

Answer 29

type II cytokine receptor

IFNs, IL-10, IL-20, IL-22p

Question 30

pre-formed trimer, cysteine rich extracellular domains, some lead to apoptosis OR NfkB and MAP kinase activation

Answer 30

TNF receptor family,

TNFs and all weird names

Question 31

creates AP-1, NF-kB, and IRF-3, and CREB

Answer 31

IL-1 receptor family (TLRs)

Question 32

shares a TLR receptor domain

Answer 32

IL-1 receptor family
uses IRAK family
uses TRAF6, E3 Ubiq. Ligase –> NFkB
uses MAP kinases, IRF –> IFN