BCR and Co-receptors etc Flashcards
B cell signaling is initiated through what molecules?
the Ig(alpha)/Ig(betA) complex
What does +(Igalpha/Igbeta) stimulation do?
the phosphorylation of their ITAMs via tyrosine kinases
CD21
is CR2
it is the complement receptor type 2; BCR coreceptor
“Co receptor complex” is made from what molecules?
CD19, CD21, CD81
what do the co-receptors do?
they modulate signal transduction initiated by the Ig(a)/Ig(B) complex
Src-Syk activation in B cells leads to
PLC –> Rac and Map PWs –> NFkB, AP-1, NFAT –> cell growth, differentiation, survival
Signal ____ by ___ occurs by cross linking of the BCR and is facilitated by the ______ for the BCR
initiation by Ag, and is faciliated by the coreceptors for the BCR
Ad-dependent cross linking of the BCR results in
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
C3d
opsonin product of C3b cleavage
it can bind both BCR and CR2 simultaneously
enhances B cell response more than Ag alone
the role of CR2/CD21
two possible roles
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
“CD19/CD21/CD81 complex” why is it called that?
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
Inhibitory Signaling:
what receptors are involved, what generic enzymes are involved, and what “big” enzyme is involved
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
how does the ITIM work (generally)
ITIM encounters ligan extracellularly
ITIM recruits Src kinase to be phosphorylated
P-ITIM recruits SH2 domain tyrosine phosphatases
What are the key inhibitory receptors on the B cell?
CD22 and Fc(gamma)RIIB
Fc(gamma)RIIB
inhibitory receptor on B cells and MOs too
CD22
inhibitory receptor on B cells only
E3 Ubituitin Ligases : how does it work
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)
canonical NF-kB Signaling Pathway
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)
canonical NF-kB signaling: 4 traits, and 3 outcomes, main kinase
rapid/transient
independent of protein synthesis
responds to numerous stimuli
diverse functions
1) inflammatory response
2) Proliferation
3) survival
TGF-activated kinase-1 (TAK1)
non-canonical NFkB signaling: 4 traits, 3 outcomes, main kinases
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)
what is the role of proteosome process of p105/p100
p105-p100 are the NF-kB precursors, proteosome proecessing creates their active forms p50 and p52
Cytokine Receptor families
Type I cytokine receptor, also called
hematopoietin receptor
uses jak-stat
Type II cytokine receptor
also uses JAK-stat
ligans are IFN-alpha/beta
IFN gamma
IL-10
IL-22
TNF receptor family
uses TRAF kinase
all the weird names
TNFs, CD50, Fasl, BAFF, etc
IL-1 receptor family
uses IRAK kinase
IL-1, 18, 33
G protein coupled receptors
G proteins
chemokines ligands
how are cytokine receptor families classified?
on the basis of their conserved extracellular domain structures
4/5 are single pass beta sheets
conserved cystein and WSXWS
type 1, all use jak stat
uses jak stat but no WSxWS region
type II cytokine receptor
IFNs, IL-10, IL-20, IL-22p
pre-formed trimer, cysteine rich extracellular domains, some lead to apoptosis OR NfkB and MAP kinase activation
TNF receptor family,
TNFs and all weird names
creates AP-1, NF-kB, and IRF-3, and CREB
IL-1 receptor family (TLRs)
shares a TLR receptor domain
IL-1 receptor family
uses IRAK family
uses TRAF6, E3 Ubiq. Ligase –> NFkB
uses MAP kinases, IRF –> IFN
