Immune Receptors And Signal Transduction II Flashcards
What are Ig alpha and Ig beta?
They are signaling molecules for the BCR and are also required for assembly and expression of the Ig receptor.
What co-receptors associate with the BCR complex, especially when both the BCR and one or more of the co-receptors arelinked through an antigen complement or antibody complex?
CD21, CD32 and CD19
What provides signal 1 (ag-receptor)?
Binding of the lymphocyte to an Ag via a receptor.
What are requird for cell-cell interaction and the signal transduction events lading to the generation of signal 2?
Costimulatory molecules
What is B cell signaling initiated through?
The BCR-Ig alpha/Ig beta complex.
It results in phosphorylation of tyrosine motifs (ITAMS)
What is the signaling cascade modulated by?
Signals from co-receptors.
In BRC signaling, second messengers are responsible for what?
The activation of transcription factors, followed by activation of the effector function.
What are the regulatory molecules of a B cell?
CD19, 22, 29, 40, 80, 86
What does the B cell receptor complex consist of?
It consists of the Ag receptor in association with Ig alpha and Ig beta.
True or false: the BCR is a transmembrane form of an Ab molecule
True
What do naive mature B cells express on their surface?
IgM and IgD
What Igs do class-switchd B cells and memory B cells express?
IgG, IgA or IgE classes
What is the BCR associated with?
Invariant signaling Ig alpha and Ig beta molecules
How are Igs linked to one another.
Through disulfide bonds.
They are non-covalently associated with the BCR.
What is found in the cytoplasmic tails of Ig alpha and Ig beta?
ITAMs.
ITAMs mediate signaling functions.
What does Src-Syk activation lead to?
The activation of PLC gamma and Ras and Rac small GTPase, which are followed by the activation of several transcription factors:
NFAT
NF-KB
AP-1
What occurs when PLC gamma and Ras are activated?
They turn on genes involved in cell growth, differentiation and survival.
Signal initiation by Ag occurs how?
By cross linking of the BCR. This is facilitated by the coreceptor for the BCR.
In BCR signaling, what does Ag binding facilitate?
It facilitates a conformational change in BCR-associated ITAMs, making them accessible to Src kinases such as Lyn, Fyn and Blk which are linked by lipid anchors to the inside of the plasma membrane.
What do activated Src kinases phosphorylate?
The ITAMs of Ig alpha and Ig beta.
What occurs at lipid rafts of cross-linked BCRs?
Where many adaptors and signaling molecules are concentrated.
What do phosphoryylated ITAMs of Ig alpha and beta provide a docking site for?
The tandem SH2 domains of Syk tyrosine kinase.
What is Syk kinase activated by?
Lyn, fyn and Blk kinases
What does activated Syk phosphorylate?
Tyrosine residus on BLNK and other adaptor proteins.
Once activated Syk phosphorylates tyrosine residues on BLNK, what do recruited enzymes do?
They activate Ras and Rac, PLC gamma 2, and the Btk.
In the Syk pathay, what does the recruitment of enzymes result in?
The activation of downstream effectors, each generally contributing to the activation of distinct signaling pathways:
Ras-MAP kinase pathway
PLC pathway
PKC-beta pathway
What is the pathway downstream of the BCR identical to?
It is identical to the downstream pathway of T cell activation.
What is the result of the Ras MAP kinase activation?
The phosphorylation of various transcriptional factors and regulators culminating in changes in gene transcription.
What are the steps of the Ras MAP kinase activation?
GTP/GDP is recruited to BLNK
An inactive GDP bound Ras is the convertedby SOS from an active GTP-Ras
Once activated, GTP-Ras activates an enzymatic cascade of MAP kinases.
This results in the phosphorylation of various transcriptional factors.
What does Ag recognition by the BCR activate?
Different protein kinases, such as Lyn, BLNK and Syk, which activate PLC gamma 2
What is the function of PLC gamma 2?
It hydrolyzes membrane bound PIP2 into small amounts of DAG and IP3.
What is the function of IP3?
It binds to its receptor IP3R located in the ER membrane and allows the release of stored calcium.
IP3 allows the release of stored calcium. To facilitate the extension of cellular responses, what other route of entry of calcium?
CRAC
What is the function of DAG?
It activates protein kinase C and the Ras-MAP kinases, which ultimately activate transcription factors AP-1 and NF-KB.
Once the increase in intracytoplasmic Ca levels is achieved, what pathway is activated?
The calmodulin-calcineurin pathway, with the final activation of NFAT
What do B cells express?
CR2, CD19 and CD81
What is the function of microbial Ags opsonized by C3d?
They can simultaneously engage both the CR2 molecule and BCR
What is the result of the signaling cascades from the BCR complex and the CR2 complex?
They greatly enhance B cell activation as compared with the response to Ag alone.
What does CR2/CD21 complement coreceptor enhance the activation of?
B cells
What results from the cleavage of C3?
It results in the production of C3b that binds covalently to the microbe or Ag-Ab complex.
What is the receptor that B cells express for C3d?
CR2 or CD21.
What does the complex of C3d and Ag bind to?
B cells, with the BCR recognizing Ag and CR2 recognizing the micro-bound C3d.
What two membrane proteins is CR2 expressed on mature B cells?
CD19
CD81
What is the CR2-CD19-CD81 complex often called?
The B cell coreceptor complex because CR2 binds to Ags through attached C3d at the same time that BCR binds directly to the Ag.