Lecture 17 - Linking Innate & Adaptive Immunity (Signaling and Signal 1)

Question 1

What are the two types of receptors?

Answer 1

The two types of receptors are those with intrinsic kinase activity and those with no intrinsic kinase activity.

Question 2

How does initation of signaling differ in the two types of receptors?

Answer 2

In receptors with intrinsic kinase activity, signaling is initiated by dimerization and transphosphorylation while in receptors with no intrinsic kinase activity, signaling is initiated by recruitment of kinase followed by dimerization and transphosphorylation.

Question 3

In which type of receptor is the kinase noncovalently associated with the receptor?

Answer 3

They are noncovalently bonded in receptors with no intrinsic kinase activity.

Question 4

What happens when a protein kinase is activated?

Answer 4

Activation of a protein kinase results in phosphorylation of an adaptor/scaffold. The phosphoprylated scaffold recruits signaling proteins that bind to it.

Question 5

True or False?:

Molecular interactions are determined by domains in their structure that have selective binding properties (ex. SH2 domain).

Answer 5

True

Question 6

Where are signaling proteins recruited to?

Answer 6

Membrane

Question 7

What are the two key modifications involved in signaling?

Answer 7

Phosphorylation and Ubiquitination

Question 8

What are kinases?

Answer 8

Kinases are proteins that phosphorylate other proteins.

Question 9

What are phosphatases?

Answer 9

Phosphatases are proteins that dephosphorylate other proteins.

Question 10

What happens to ubiquitinated proteins?

Answer 10

Ubiquitinated proteins are targeted for degradation by proteasomes or in lysosomes.

Question 11

True or False?:

Only APC:T-cell signal 1 causes intracellular signaling that leads to a change.

Answer 11

False

All three signals result in intracellular signaling.

Question 12

Which APC:T-cell signal is mediated by pMHC:TCR engagement with coreceptor binding?

Answer 12

Signal 1

Question 13

Which APC:T-cell signal is mediated by contact with costimulatory ligands?

Answer 13

Signal 2

Question 14

Which APC:T-cell signal is mediated by cytokines?

Answer 14

Signal 3

Question 15

How does TCR binding initiate signaling?

Answer 15

TCR binding recruits Lck (A coreceptor-associated kinase) that phosphorylates the ITAM domains in the signaling chains.

Question 16

What happens when the ITAM domains are phosphorylated?

Answer 16

The ZAP-70 kinase is activated.

Question 17

What does ZAP-70 do once activated?

Answer 17

It activates four different signaling pathways that lead to the transcription of many genes.

Question 18

Two strains of mice (strain A and strain B) were infected with Influenza virus and the survival data show in the figure below were obtained. Next, both strains were infected again with influenze, and levels of type I interferons (IFN-α and IFN-β) were measured and found to be similar between the two strains. Likewise, cells from both strains expressed similar levels of the IFN-α/β receptor (IFNAR). Which of the following proteins might be more highly expressed in strain B than in strain A following Influenza infection?

• Toll-like receptor 3
• Mx-1 (a gene induced by IFN)
• RIG-I
• MyD88 (an adaptor in PRR signaling)
• NF-κB (a transcription factor in PRR signaling)

Answer 18

Mx-1