Lecture 10 - Lymphocyte receptor Signaling

What is proliferation coupled to?

Signal transduction

Label this diagram (CD4, MHC2, TCR, CD3, ITAMs, CD28, B7)

What is B7? When is it expressed?

Expressed by dendritic cells when there is an infection

What does immunological synapse mean?

T-cells requiring T-cell receptor binding to an MHC and Cd28 binding to B7 for signal

Where is CD28 found? What does it bind?

On T-cells and binds B7 on dendritic cells that are infected

What relays the signal?

CD3 complex

What is the CD28 and B7 signal considered?

A co-stimulatory signal

What molecules has a signalling domain for what other molecules that stabilizes the co receptor complex? Where are they in relation to CR2? (Exam)

CD19 stabilizes CD81 and they are next too CR2

There are three signal transduction pathways, how are they activated?

Co-receptor binds and sends costimulatory signal, Lck is bound to CD4/CD8, and it then phosphorylates ITAMs of CD3 complex, this makes ITAMs docking sites for most important kinase ZAP-70, ZAP70 phosphorylates PLCy and it cleaves PIP2 into IP3 and DAG

What is Lck?

A tyrosine kinase

What is involved with the first pathway of signal transduction?

Ip3 signals Ca2+ store opening, Ca2+ activates Calcineurin that dephosphorylates NFAT that activates gene transcription of IL2

What is involved with the second pathway of signal transduction?

DAG activates protein kinase C (PKC), PKC activates NF-kB to activate transcription

What is involved with the third pathway of signal transduction?

DAG associates with RAS, RAS activates Fos, Fos forms AP-1 that activates gene transcription

IL-2 is important for B-cell activation, but it is also the most important cytokine for?

T-cell activation

What do these three signaling pathways lead to

Differentiation and proliferation

How are B-cells activated?

B cell receptor complex involving antigen bound to BCR as well as IgB and IgA (similar function as CD3)

What leads to the recruitment of kinases in B-Cell activation?

multiple antigens on pathogen will bind to BCRs causing them to cluster that then causes Kinase recruitment

What are these kinases? (First kinases that lead to activation of a major kinases)

Blk, Fyn, Lyn

What do these kinases do?

Phosphorylate ITAMs on IgB and IgA

What is responsible for the costimulatory signal for B-Cells?

C2 binding to C3d

How is C3d made?

When C3b binds to pathogen surface it will bind to CR1 and factor I, Factor I cleaves it to iC3b and then C3d on the pathogen surface

What is the major kinase of B-Cells that activates the same three pathways as T-Cells?

SyK

What is CTLA4?

Expressed by active T-cells instead of CD28 by inactive T-cells

What is the inhibitory signal for T-Cells?

PD-1

What is the inhibitory signal for B-cells?

BTLA