Lecture 9: Immune Receptors and Signal Transduction II Flashcards
CD81 is necessary for
Normal CD19 expression
Ubiquitin is added to which residues by what
Lysine residues by E3 ubiquitin ligase
PLC function chemokine signaling
PLC hydrolyzes IP2 into IP3 which mobilizes calcium
PLC activates DAG which activates protein kinase C
Type I&2 cytokine receptors engage in what type of signaling pathway
JAK-STAT pathway
Type II also use Tyk-STAT pathway
ITIMs of inhibitory receptors such as CD22/CD32 are phosphorylated by
Src kinase family, which are activated by B lymphocyte activation
p-ITIMs (phosphorylated-ITIMs) recruit
SH2 domain containing tyrosine phosphatases such as SHP and SHIP
Engagement of CD40:CD40L provides and results in
Provides co-stimulation to B cell and results in expression of IL-4R by B cells
CD21
Known as complement receptor 2 CR2
G protein alpha subunit function in chemokine receptor signaling
Inhibits some adenylyl cyclase leading to decreased intracellular cAMP levels
Sykkinases phosphorylate what after activation by what
After activation by Src kinases, Syk kinases phosphorylate critical tyrosine residues on BLNK
CD32 (FcyRIIB) co receptor
Contains an ITIM and negatively regulates BCR signaling
Phosphorylated ITAMs on BCRs provide
Docking site for the tandem SH2 domains of Syk tyrosine kinase
Type II cytokine receptors include receptors for
Also called interferon receptor family
IFN-a/b
IFN-y
IL-10
SHP and SHIP function
Remove phosphates from PIP3 and thus inhibit PI# kinase activity
Type I cytokine receptors
IL-2, 4, 7, 9, 15, 21
There are 5 classes of cytokine receptors, what makes chemokine receptors different from the rest
Chemokine receptors are not single-pass transmembrane proteins
Ag binding to BCR facilitates
Conformation change in BCR-associated ITAMs, making them accessible to Src kinases such as lyn, fyn and blk
-These Src kinases then phosphorylate the ITAMs of Iga and Igb
Invariant signaling Iga and Igb molecules
They are disulfide linked to one another
Non covalently associated with the BCR
Contain ITAMs in their cytoplasmic domains
-ITAMs mediate signaling function
CD19
Functions as the dominant signaling component of B cells
Engagement of TLR results in
Dimerization and recruitment of MyD88 adaptor containing TIR domain, which link TLR/IL-1R to members of IRAK family
IRAK links adaptors to TRAF6, an E3 ubiquitin ligase required for NF-kB activation
CD81 is important for
Linking the membrane CD21-CD19-CD81 complex to the cytoskeleton
Response from BCR/CR2 complex compared with B cell response with just Ag
BCR/CR2 combined cascade greatly enhances the B cell activation compared to response with Ag alone
TCR activation and CD28:CD80/86 costimulation results in
Secretion of IL-4 by activated T cells
G protein b/y subunit function in chemokine signaling
Activates Ras that induces the activation of PI3 kinase gamma
Also activates PLC
IL-1R signaling also induces
MAP kinase activation and phosphorylation of IRF3 and IRF7, inducers of type I interferon transcription
What happens if Lysine 48 is ubiquinated vs lysine 63
Lysine 48 ubiquination targets for destruction
Lysine 63 ubiquination does not target for destruction
CD22 is a
B cell specific inhibitor
TNF activation can result in
NK-kB and MAP kinase activation or the induction of apoptosis
Members of IL-1 or TLR receptor family share
Conserved cytosolic sequence called TIR domain
TNF receptor structure
Preformed trimers
Conserved cysteine rich extracellular domains
First signal to CD4+ T cell in B cell recognition
MHC II complex engagement with TCR:CD3:CD4 complex is first signal
CD21/CD19 co-receptors
Positively regulate B cell activation and serve to lower the Ag threshold for B cell activation
JAK-STAT signaling pathway
Ligand binds which activates cytoplasmic receptor associated JAKs
JAKs phosphorylate tyrosine residues along their receptor chains
SH2 domain containing STATs bind to these residues
STATs are phosphorylated by JAK proteins
STAT proteins dimerize and translocate to nucleus
Which interaction provides costimulation to the CD4 T cell
CD28:CD86/80 interaction
FcyRIIB (CD32) is an important
Attenuator of signaling in activated B cells, DCs and macrophages
Most important TNF receptors
TNFRI, TNFRII, CD40, Fas (First apoptosis signal)
Phosphorylated CD19 activates
PI3 kinase, which in turn activates Btk and PLCy2
Net result of coreceptor activation is that the response of Ag stimulated B cell is greatly enhanced
Role of complements in B cell activation
C3b is degraded into C3d
B cells have C3d receptor called CR2( CD21)
Complex of C3d and Ag binds B cells, with BCR recognizing Ag and CR2 recognize C3d
Lyn kinase involvement in BCR signaling
Lyn kinase is bound to CD19
C3d-CR2 binding brings CD19 in proximity to BCR associated kinases
Lyn kinase amplifies BCR signaling by greatly enhancing phosphorylation of ITAMs in Iga and Igb