Lecture 10

Question 1

What is signal transduction?

Answer 1

the process of converting a signal from one form to another

Question 2

What are the components of the Immunological Synapse? (4)

Answer 2

1. TCR MHC : peptide complex
2. co-stimulatory molecules
3. co-receptor MHC peptide complex
4. cell-adhesion molecules

Question 3

what constitutes the costimulatory signal?

Answer 3

• B7 (present only when infection is present)
• CD28 (B7 receptor molecule)

Question 4

what is the role of CD3?

Answer 4

relays the signal that a synapse has formed

Question 5

what does ITAM do?

Answer 5

• target of phosphorylation and protein docking/binding
• allows signal transduction

Question 6

where does T-cell activation occur?

Answer 6

immunological synapse

Question 7

what are the initial steps of t-cell signal transduction?

Answer 7

1. Lck phosphrylates ITAM
2. ZAP-70 binds/docks to ITAM
3. ZAP-70 phosphorylates and activates PLC-γ
4. PLC-γ cleaves PIP2 into DAG and IP3

(from there, three different pathways are initiated)

Question 8

what are the protein-tyrosine kinases in t-cell signal transduction? (2)

Answer 8

Lck and Zap-70

Question 9

what is the most important kinase in t-cell signal transduction?

(i.e. initiates the three pathways)

Answer 9

Zap-70

Question 10

What are the steps of the IP3 signal transduction pathway?

Answer 10

1. IP3 stimulates opening of Ca2+ channels
2. Ca2+ activates Calcineurin
3. Calcineurin phosphorylates NFAT
4. NFAT induces gene transcription (of IL-2, etc.)

Question 11

What are the steps of the DAG signal transduction pathway?

Answer 11

Part 1:
1. DAG activates PKC-θ
2. PKC-θ phosphorylates IκB, which is bound to NFκB, and degrades it.
3. NFκB translocates to the nucleus and induces gene transcription

Part 2:
1. DAG activates RAS
2. RAS activates the MAP kinase cascade
3. MAP kinase cascade activates Fos
4. Fos combines with Jun (a proetin activated by transmembrane protein CD28) to from AP-1
5. AP-1 translocates to the nucleus to induce transcription

Question 12

what are the three transcription factors obtained from t-cell and b-cell signal transduction?

Answer 12

1. NFκB
2. AP-1
3. NFAT

Question 13

What are the initial steps of B-cell signal transduction?

Answer 13

1. Lyn, Fyn, and Blk phosphorylates Igα and Igβ
2. Syk binds/docks to Igα/Igβ ITAM
3. Syk phosphorylates and activates PLC-γ
4. PLC-γ cleaves PIP2 into DAG and IP3
5. Syk also phosphorylates GEFs for no reason.

(from there, three different pathways are initiated)

Question 14

what are the kinases in b-cell signal transduction?

Answer 14

Lyn, Fyn, Blk, Syk

Question 15

what is the most important kinase in b-cell signal transduction

(i.e. induces the three pathways)

Answer 15

Syk

Question 16

what is the role of the B Cell Coreceptor (CR2)?

Answer 16

facilitates binding with costimulatory signal (binds to iC3b and C3d on the pathogen surface)

Question 17

what is the role of CD19?

Answer 17

cytoplasmic domain for b cell signal transduction

Question 18

what is an immunological synapse between?

Answer 18

a dentritic cell and a t cell

Question 19

what are the main comonents of the synapse in c bell activation? what is the synapse between?

Answer 19

• b cell receptor
• Igα
• Igβ
• its between a pathogen and a b cell

Question 20

what is the component that down-regulates immune responses by interfering with signalling pathways?

Answer 20

CTLA4