Lecture 10 Flashcards
BCR complex
aIg alpha and beta CD79a and cd79b… disulfied linked to each other, non covalently linked to BCR
Co receptors of B cells
CD21, 32 19
Signalling is either…… depending on iif….. is bound
enhanced or inhibinited… ig beta/alpha
Binding of Ag via receptor caues?
signal 1… not sufficient and may lead to anergy
Accessory and costimulatory molecules are bound
signal 2
April and Baff bind to?
BCMA and TACI
BCR can be what two IG?
IgM or IgD
When the Ig are class switched they become?
IgG, IgA, IgE
Srk Syk activation leads to?
PLC gamma and RAS and RAC small GTPase
What transcription factors does PLCgamma effect?
NFAT, NKkB, AP1
These transcrtiption factors regulate?
cell growth, differentiation, and survival
Srcs become active and ? can attach
Lyn, Fyn, Blk lipid anchors PH
phophorlated ITAMs on alpha beta creat dock for?
Sh2, Syk
Lyn, Fyn, and Blk activate?
Syk
Syk phosphorlates?
BLNK
THings that can be activated by BLNK?
RAS and Rac, PLC gamma 2, BTk
Three pathways that can be activated?
RAS-MAP
PLC
PKC- beta
BLNK recruits?
SOS which is the GTP/GDP exchange factor
RAS is converted by SOS to
RAC that activates MAP
Map does?
alteration of key proteins, changes in gene transcription
What activates PLC gamma 2?
Lyn, BLNK, Syk
PLCgamma2 hydrolyzes?
PIP2—> DAG and IP3
IP3 binds to?
IP3R in ER and allows release of stored Ca
What is another activated Ca channel?
CRAC
What does DAG that was activated by PIP2 do?
activates PKC and the RAS-MAP… which ultimate turns on NFkB and Ap1
Once Ca activation is achieved, what is the final thing activated?
NFAT
BRC complex
CR2, CD19, CD81
what can engage both CR2 and BCR?
C3d that has opsonized a microbial Ag
CR2 and CD 21 does what
enhances activation of B cells
Cleavage of 3 does what?
production of C3b and binds covalently to microbe or Ag Ab complex
C3b is further degraded into ?
C3d which remains bound to Ag-Ab complex
What binds the BCR of the the C3d fragment?
CR2
CR2 is expressed on?
mature Bcells with two ore more membrane proteins
What are the membrane boudn proteins expressed when CR2 is present?
CD19 and CD81 also called TAPA1
What makes up the BCR co receptor complex?
CR2-CD19-CD81
CR2 binding C3d brings?
CD19 proxiimity to BCR associated kinases and the CD19 tail becomes phosphorlated
CD19 recruits?
Lyn that applifies signal by phosphorlating ITAMs
CD19 also activates?
PI3
PI3 activates
Btk and PLC gamma 2, bc enzymes must bind to PIP3 on the inner leaflet to be fully activated… this greatly enhances teh signal
T and B and NK are heavily regulated btw stimulatory and inhibitory signals to controll?
collateral damage to host tissue
what collateral damage could occur?
uncontrolled inflammation and lymphoproliferation.. and to prevent actiavtion against self
Inhibitory signals are mediated by?
E3 ubiquitin ligases
What do inhibitroy signals recruit?
phosphatases
ITIMs are phosphorlated by?
Src
key inhibitors of B cells?
FCgammaRIIB and CD22