Flashcards Chapter 5 Lecture

A small organ above the heart; site of T-Cell maturation.

Thymus

Where are T-Cell precursors made?

Bone marrow

Where do T-Cell precursors travel to?

Thymus

T-Cells utalize what kind of signalling?

Notch Signalling

Notch

A receptor on thymocytes.

What does the notch on the thymocyte interact with?

Notch ligand on TEC

What is the end goal of Notch1 signalling?

Commits a thymocyte to becoming a T-cell

When a thymocyte first arrives at the thymus from the bone marrow, it is considered to be:

Double Negative (DN)

What does double negative (DN) mean?

Does not express a coreceptor (CD4 or CD8)

In what part of the thymus does T-cell development take place?

Cortex

What event leads to the development of a double positive (DP) thymocyte?

somatic recombination

What does double positive (DP) mean?

Both subunits (CD4 and CD8) are expressed.

A thymocyte can become:

Regulatory T cell or NK T cell

What process(es) must a thymocyte go through in order to become single-positive?

Positive and negative selection.

Naieve T cell

A T-Cell that has not yet met its antigen.

Three subunits of TCR:

Alpha, Beta, GammaDelta

What TCR is associated with protecting a fetus during development, and mucosal immunity?

Gamma-Delta

How many TCR can a person make?

10^15 to 10^18

What are the three reasons for TCR diversity?

VDJ joining, Junctional diversity (adding nucleotides), Association of Alpha and Beta Chains.

Genes for TCR are broken into different:

Gene segments

What can be said about the process of somatic recombination in T-Cells?

It is random and occurs only in T cells.

Alpha chain combinations:

random J joins random V, many VJ combinations.

Beta chain combinations:

J to D first, then a V joins. many VDJ combinations.

What does a TCR need to "pull" from Alpha and Beta chains?

V, D, J. (one of each).

VDJ recombinase

Complex consisting of RAG1 and RAG2 proteins that bind to/recognize recombination signal sequences (RSS)

Junctional Diversity

Hairpin DNA strands randomly open up, and P Nucleotides are added to the strand. TdT then adds random N nucleotides. The strands come together, and errors are fixed through DNA synthhesis.

Allelic expression refers to:

One beta chain gets expressed.

How many beta chains do T cells express?

One

What chain do most T cells express?

Beta

What do RAG1 and RAG2 do?

Initiate recombination.

Before a thymocyte has a functioning TCR, this must be formed in order to pass the Beta Chain checkpoint:

Pre T Cell Receptor

The Pre-T Cell receptor contains:

Pre-T alpha (PTa) chain, beta chain, CD3 complex.

What is the role of the Pre-T cell receptor?

Ensures T-cell signaling can occur.

After successfully passing through the Beta Chain checkpoint, what happens next?

The alpha chain rearranges.

What does it mean to proliferate?

Grow/divide

What is the end result of most thymocytes that make it to the thymus?

Most do not fully mature into T-Cells; apoptosis.

If at first the newly rearranged alpha chain does not function, what happens?

The chain rearranges again.

When the alpha chain is functional, what does the thymocyte develop into?

A naieve T cell

If the alpha chain is still not functional after another rearrangement, what happens?

Apoptosis.

What is the last step in achieving a functional TCR?

Alpha chain

Positive selection in T cells asks the question:

Can TCR bind to self-MHC molecules? (MHC restriction)

Negative selection in T cells asks the question:

Will TCR recognize MHC-self peptide complexes wit high affinity? (self tolerance)

Why are AIREs important?

Not all proteins are expressed in the thymus. AIRE presents body proteins to T-Cells so they do not self-attack.

What does do AIREs do?

Present the transcription of 100s of proteins to T cells.

What happens to a self-reactive protein that leaves the thymus?

It becomes anergic; not responsive.

What is APECED?

An autoimmune disease characterized by the lack of AIRE.

What body system does APECED affect the most?

The endocrine system.