Ch 7 Book Questions Flashcards
Which of the following is an example of G protein-coupled receptor (GPCR)?
a. T cell antigen receptor (TCR)
b. The B cell antigen receptor (BCR)
c. CD4
d. Interlukin-2 (IL-2)receptor
e. Chemokine receptor CCR7
e. Chemokine receptor CCR7
All chemokine receptors, including CCR7, are GPCRs. The lymphocyte antigen receptors (TCR, BCR), CD4, and IL-2 receptor signal via associated proteins or non-receptor tyrosine kinases.
The cytoplasmic tails of the signaling polypeptides found in lymphocyte antigen receptor complexes (BCR and TCR) contain regions that become phosphorylated upon antigen recognition and then bind ZAP family kinases. These regions are called:
a. Immunoreceptor tyrosine-based activating motifs (ITAMs)
b. Fc regions
c. Toll-like IL-1R (TIR) domains
d. Complementarity determining regions
e. Nod like receptor ( NLR) domains
a. Immunoreceptor tyrosine-based activating motifs (ITAMs)
ITAMs are found in the cytoplasmic tails of CD3 and ζ proteins of the TCR complex and Igα and Igβ proteins of the BCR complex. ITAMs contain pairs of tyrosine residues that become phosphorylated by Src family kinases after antigen recognition, and then serve as docking sites for ZAP70 in T cells or Syk in B cells. ZAP70 and Syk are tyrosine kinases that become active after binding to ITAMs and then phosphorylate adaptor proteins and other kinases.
What role does CD4 and CD8 on T cells play in the early signaling events during T cell activation?
a. Like CD3 and ζ proteins, CD4 and CD8 contain ITAMs in their cytoplasmic tails that serve as docking sites for protein tyrosine kinases (PTKs)
b. CD4 and CD8 have intrinsic phosphatase activity in their cytoplasmic tails that remove phosphates from ITAMs on CD3 and ζ proteins
c. When CD4 and CD8 bind to MHC molecules on antigen presenting cells, the MHC molecules become active kinases that activate the APCs
d. CD4 and CD8 have Src family PTKs associated with their cytoplasm tails, which are brought into proximity of and phosphorylate the CD3 and ζ ITAMs upon antigen recognition.
e. Upon antigen recognition, the cytoplasmic tails of CD4 and CD8 became phosphorylated and bind JAK family kinases, which then phosphorylate STAT family proteins.
d. CD4 and CD8 have Src family PTKs associated with their cytoplasm tails, which are brought into proximity of and phosphorylate the CD3 and ζ ITAMs upon antigen recognition.
Lck, a Src family PTK, is noncovalently associated with the cytoplasmic tails of both CD4 and CD8, and Lck phosphorylates CD3 and ζ chain ITAMs when CD4 and CD8 bind to MHC molecules during antigen recognition. CD4 and CD8 do not have ITAMs, intrinsic kinases, phosphatases or JAK kinase binding sites in their cytoplasmic tails. MHC molecules also do not have intrinsic kinase activities.
In the T cell calcium signaling pathway induced by antigen recognition, which enzyme and transcription factor are activated?
a. IκB kinase, NFκB
b. Jun kinase (JNK), AP-1
c. Erk kinase, Fos
d. JAK3, STAT4
e. Calcineurin, NFAT
e. Calcineurin, NFAT
In the calcium pathway, TCR signaling leads to an increase in cytosolic calcium ion (Ca++) concentration, which activates the phosphatase calcineurin, leading to dephosphorylation of the transcription factor NFAT. Dephosphorylated NFAT enters the nucleus and stimulates transcription of various genes that promote T cell proliferation and differentiation. Calcineurin inhibitors, such as cyclosporin and tacrolimus, are widely used as immunosuppressant drugs for transplant recipients
How does the complement system enhance B lymphocyte activation?
a. Generation of the membrane attack complex on B cell membrane allows calcium ions (Ca++) to enter the B cell and stimulate calcium-dependent enzymes
b. Opsonization of protein antigens with C3b promotes B cell phagocytosis of protein antigens, enhancing B cell-T cell collaboration
c. C1q binding to membrane IgM will activate BCR signaling
d. C3d bound to a microbial surface will bind to complement receptor 2 (CR2) on B cells, generating kinase activity by the CR2-CD19-CD81 complex
e. C5a binding to its receptor on B cells stimulates Ig heavy chain gene expression
d. C3d bound to a microbial surface will bind to complement receptor 2 (CR2) on B cells, generating kinase activity by the CR2-CD19-CD81 complex
CR2 is expressed on B cell membranes in a complex with CD19 and CD81. CR2 binds to C3d, a proteolytic product of C3b that remains covalently bound to microbial surfaces after complement activation. If CR2 binds C3d on a microbe at the same time that microbial surface antigens bind to membrane Ig, signaling through the CR2-CD19-CD81 complex enhances BCR signaling resulting in enhanced B cell activation.
Which of the following proteins involved in attenuation of immune signaling become associated with immunoreceptor tyrosine inhibitory motifs (ITIMs)?
a. E3 ubiquitin ligases
b. SH2 domain-containing tyrosine phosphatases (SHP-1, SHP-2)
c. Suppressors of cytokine signaling (SOCS)
d. CTLA-4
e. PD-1
b. SH2 domain-containing tyrosine phosphatases (SHP-1, SHP-2)
ITIMs are found in the cytoplasmic tails of inhibitory receptors on NK cells, T cells, and B cells. ITIMs bind SHP-1, SHP-2, and SH2 domain-containing inositol phosphatase (SHIP). These phosphatases remove phosphates from tyrosines in signaling intermediates downstream of activating receptors. The other choices are not associated with ITIMs. E3 ubiquitin ligases are intracellular enzymes that tag proteins for lysosomal and proteosomal degradation, and some E3 ubiquitin ligases, such as Cbl-b, are involved in endocytosis and degradation of the TCR. Suppressors of cytokine signaling (SOCS) inhibit JAK-STAT and TLR signaling. CTLA-4 and PD-1 are membrane proteins that inhibit T cell activation when they bind ligands on other cells.
In the cannonical NF-κB signaling pathway downstream of the TNF receptor, TLRs, and antigen receptors, what role does IκB kinase (IKK) complex play?
a. IKK enters the nucleus and phosphorylates NF-κB that has bound to the promoters of proinflammatory genes
b. IKK binds to NF-κB, preventing it from entering the nucleus
c. Activated IKK phosphorylates IκBα, which leads to IκBα degradation, allowing NF-κB to enter the nucleus
d. IKK enters the nucleus and binds to the promoters of pro inflammatory genes
e. IKK phosphorylates NFκB, allowing NF-κB to enter the nucleus
c. Activated IKK phosphorylates IκBα, which leads to IκBα degradation, allowing NF-κB to enter the nucleus
NF-κB is kept in the cytoplasm by bound IκBα. The function of the IKK complex is to remove IκBα, allowing NF-κB to enter the nucleus and promote the transcription of proinflammatory genes. IKK must be activated by TRAF signals generated originating from cell surface receptors. This leads to activation of the IKKβ subunit of IKK which phosphoryaltes IκBα. Phosphorylated IκBα is then ubiquitinated and degraded by the proteasome.
