Question 1

The Rac/JNK pathway activates which signaling component?&#10;A) Fos&#10;B) Jun&#10;C) AP-1&#10;D) NF-kB

Accepted Answer

The Rac/JNK pathway activates Jun, while the Ras/ERK pathway activates Fos. The AP-1 transcription factor comprises Fos and Jun components. The NF-kB pathway is a separate signaling pathway from the others. However, all participate in the activation of IL-2 synthesis, along with NFAT signaling.

Question 2

The activation of the TCR through interaction with either MHC class I or class II molecules leads to signaling pathways that activate protein synthesis of:&#10;A) IL-1&#10;B) IL-2&#10;C) TNF&#10;D) ZAP-70

Accepted Answer

When the TCR binds to either MHC class I or class II, depending on the type of T cell, the response is production of IL-2, which leads to growth and proliferation of T cells, as well as a variety of other outcomes. IL-1 and TNF are proinflammatory products produced primarily by macrophages. ZAP-70 is an adaptor protein that is located on T cells and is involved in signaling pathways that lead to IL-2 synthesis.

Question 3

Cyclosporine A binding to cyclophilin blocks T cell activation by:&#10;A) Inhibiting calcineurin and NFAT&#10;B) Inhibiting RAP by binding to FKBP-12&#10;C) Inhibiting IL-2 binding to the IL-2 receptor&#10;D) Inhibiting calcineurin and protein kinase C (PKC)

Accepted Answer

The drug cyclosporine A binds to cyclophilin, which inhibits calcineurin. The result is blockage of T cells activation because NFAT, the downstream target of calcineurin, is not translocated to the nucleus and IL-2 is not synthesized.

Question 4

Which of the following is/are part of the high affinity IL-2 receptor?
I. a-Chains
II. b-Chains
III. g-Chains

A) I only
B) III only
C) I and II
D) II and III
E) I, II, and III

Accepted Answer

The high affinity IL-2 receptor contains all three chains, while the low affinity receptor only contains the a-chain and the intermediate affinity receptor contains the b-chain and g-chains.

Question 5

The major defect in X-linked severe combined immunodeficiency (SCID) is:&#10;A) Inability to produce IL-2&#10;B) Lack of ZAP-70 protein kinase&#10;C) Inability to produce B or T cells&#10;D) Lack of g-chain in interleukin receptors

Accepted Answer

In X-linked SCID, a genetic defect renders the patient unable to produce g-chains, which are key components of a variety of different interleukin receptors, most notably the IL-2 receptor. The absence of these receptors is significant because when exposed to a pathogen, activation of lymphocytes, synthesis of antibodies, and NK cell development are impaired, which is very dangerous for the patient. Most infants with this disorder die from infections within 1 year.

Question 6

The downstream signaling target of CD28/B7 activation is:&#10;A) NF-kB&#10;B) PIP2/IP3&#10;C) Rac/JNK&#10;D) PLCg1/DAG/PKC

Accepted Answer

The immuno-receptor tyrosine-based activation motifs (ITAMs) on the cytoplasmic tails of CD28 are phosphorylated and recruit phosphotidylinositol 3-kinase (PI3-kinase). PI3-kinase phosphorylates and activates multiple downstream targets, including phosphotidylinositol-3,4,5-triphosphate (PIP3), which accelerates the removal of the inhibitor of NF-kB.

Question 7

Which of the following is an example of autocrine signaling?&#10;A) An NK cell responding to IL-12 produced by a macrophage.&#10;B) A macrophage responding to TNF made by the same macrophage.&#10;C) A T helper cell responding to IL-2 produced by a neighboring T cell.&#10;D) A neutrophil responding to IL-1 produced by vascular endothelial cell.

Accepted Answer

Autocrine signaling occurs when a cell responds to a product that same cell made. In this example the macrophage has receptors for TNF, and it produces the TNF that binds to its own TNF receptors. The other options are examples of paracrine signaling, in which a cell responds to a product produced by a nearby cell. The third type of signaling is endocrine signaling, in which a cell responds to a product made by a distant cell.

Question 8

The activation of inositol-1,4,5-triphosphate (IP&#8323;) signaling results in:&#10;A) Activation of NF-kB signaling&#10;B) Release of intracellular calcium&#10;C) Phosphorylation of downstream targets&#10;D) Formation of the immunological synapse

Accepted Answer

IP₃ signaling leads to release of intracellular calcium stores. This signaling process occurs for numerous reasons inside the cell, including muscle contraction and blood clotting. In the immune response, IP₃ signaling and release of intracellular calcium stores result in activation of NFAT. The released calcium binds to calmodulin, which activates calcineurin. Calcineurin activates NFAT, which is one of the transcription factors required for IL-2 synthesis.

Question 9

What is one reason that basiliximab or daclizumab would be a better option for renal transplant patients than cyclosporine A?&#10;A) Cyclosporine causes renal toxicity.&#10;B) Cyclosporine stimulates the immune system.&#10;C) Basiliximab and daclizumab increase renal function.&#10;D) Basiliximab and daclizumab inhibit the whole immune system, not just T cells.

Accepted Answer

Cyclosporine, while it does reduce immune function, causes increased renal toxicity, which is dangerous for renal transplant patients, putting them at risk for damage to their newly-transplanted organ. The monoclonal antibodies work to antagonize the IL-2 receptor so IL-2 cannot bind to the receptor, thus blocking T cell activation. However, the monoclonal antibodies do not work to improve renal function, and do not block all immune responses.

Question 10

What is the purpose of adaptor proteins in signal transduction?&#10;A) Activate transcription&#10;B) Facilitate dimerization of receptors&#10;C) Anchor the receptor to the membrane&#10;D) Carry the signal from the membrane into the cytoplasm

Accepted Answer

Adaptor proteins facilitate interactions between signaling molecules to carry the signal from the membrane to cytoplasmic signaling components deeper inside the cell. They are not involved in anchoring or dimerization of the receptor, nor do they activate transcription.

Deck 7: Intracellular Signaling and T Cell Activation