L5: T Cell Development and Diversity

Question 1

What is a T cell?

Answer 1

cell derived from the common lymphoid progenitor that has a TCR (T cell receptor). They kill cells infected with viruses and other intracellular pathogens. They supply helper signals which activate B cells and macrophages.

Question 2

Where are T cells generated? Where do they mature and develop?

Answer 2

Bone marrow. Then move to thymus to develop. Then secondary lymph tissue

Question 3

What type of Ig molecules do T cells secrete?

Answer 3

T cells do not secrete Immunoglobulin molecules.

Question 4

What links the alpha and beta chains of the TCR on T cells?

Answer 4

disulfide bonds

Question 5

What are the alpha and beta chains of the TCR composed of?

Answer 5

a constant and variable region

Question 6

What are the two lineages of TCR on T cells? Which is more common?

Answer 6

alpha-beta and gamma-delta.

Most cells are alpha-beta

Question 7

What are the differences between alpha-beta T cells and gamma-delta T cells?

Answer 7

gamma-delta T cells do not recognize peptide/MHC complexes (not MHC-restricted), found primarily in mucosal epithelium, they mature outside the thymus, and are thought to have a significant role in recognition of lipid antigens

Question 8

What type of antigens do gamma-delta T cells recognize?

Answer 8

lipids and carbohydrates

Question 9

What is the CD3 complex?

Answer 9

signal transduction unit for the TCR. It is found on all T cells.

Question 10

What are ITAMS?

Answer 10

immunoreceptor tyrosine-based activation motifs. They reside on the intracellular part of the CD3 complex. They initiate signaling cascade upon antigen-recognition through the TCR.

Question 11

What happens in T cells with defective CD3 complexes?

Answer 11

They are unable to become activated after recognizing an antigen

Question 12

Describe the structure differences between CD4 and CD8.

Answer 12

CD4 is a single chain, set of 4 Ig-like domains.

CD8 is a heterodimer composed of an alpha and beta set of chains with Ig domains.

Question 13

What is the CD28 protein?

Answer 13

It s a T cel surface marker that binds B7 molecules on antigen presenting cells (co-stimulation). It is found on all T cells.

Question 14

What type of cells have B7 molecules?

Answer 14

only professional antigen presenting cells.

Question 15

What is the Fas ligand molecule?

Answer 15

T cell surface marker that binds to Fas expressed on the surface of target cells, initiating apoptosis.

Question 16

What are adhesion molecules?

Answer 16

Surface proteins on T cells that initiate interactions between T cells and APC or target cells as well as vascular epithelium

Question 17

How is the thymus organized?

Answer 17

It is divided into two primary regions: the cortex and the medullary region.
Cortex has many T cells and network of epithelial cells. Has some macrophages also.
Medullary region is highly populated with dendritic cells and has Hassall’s corpuscles. Negative selection (removal of self T cells) occurs in medullary region.
There is a corticomedullary junction between the two areas.

Question 18

What is Hassall’s corpuscle?

Answer 18

a site of cell destruction of dying thymocytes.

Question 19

Where does positive selection of thymocytes occur in the thymus?

Answer 19

In the cortex.

Question 20

What happens to T cells when they enter thymus?

Answer 20

They move into cortex and they begin to proliferate rapidly. The cortical epithelial cells in the thymus express both MHC class I and II molecules. T cell begins to rearrange TCR genes. Beta first, then alpha, then cell expresses complete T cell receptor on surface, expressing CD3 and alpha and beta as well as both CD4 and CD8. 
At this point T cell type is not determined. Positive selection occurs. If T cell can react enough with cortical epithelial cells, they will receive survival signals and change their surface phenotype and start moving to the medullary region. By the time it reaches the corticomedullary junction, it is either a CD4 or CD8 cell type. 
In the medullary region they undergo negative selection for self-derived peptides. If it has high affinity for any antigen-presenting cells in medullary region, it will be terminated by apoptosis. If not, it will leave the thymus and enter circulation for travel to secondary lymphoid tissue

Question 21

What is a tingible body macrophage?

Answer 21

a macrophage in cortical region of thymus that takes up dying lymphocytes. They stain very darkly (tingible)

Question 22

What type of CD+ are T cells in the cortex of the thymus?

Answer 22

They are double positive, meaning they express both CD4 and CD8 at the same time until they are positively selected for one or apoptosis.

Question 23

What are the first TCR variable region genes to rearrange?

Answer 23

beta, gamma, and delta chain genes.

Question 24

What would happen if gama and delta chain rearrangement were to occur first?

Answer 24

T cell will be a gamma-delta T cell

Question 25

What would happen if beta chain rearragnement is the first to happen?

Answer 25

It will associate with an invariant chain (pT-alpha; a surrogate alpha chain) and the CD3 complex to form the pre-T cell receptor complex. Once the pre-TCR is epxressed, beta, gamma, and delta gene rearrangement cease.
pre-T cell begins to proliferate and alpha chain gene rearrangement begins and associates with beta chain.

Question 26

Is alpha chain rearrangement analogous to heavy or light chain rearrangement in B cells?

Answer 26

Light chain - single constant domain, a V region joined to a J region segment.

Question 27

Is beta chain rearrangement analogous to heavy or light chain recombination?

Answer 27

Heavy chain - single V, single D, single J region gene segment

Question 28

What do RAG enzymes do?

Answer 28

catalyze recombination of single V region with a single J region or with a J and a D region segments.

Question 29

What is first step in B rearangment?

Answer 29

Single D segment joins to single J segment to form a DJ junction. This then joins a single V region gene segment.

Question 30

How can you determine the stage at which neoplastic events take place in T cells?

Answer 30

look at the surface phenotypes. If it has CD34 it is in the bone marrow, still in development. Etc.

Question 31

If a T cell tumor has CD3 and CD8 on its surface, what stage did the neoplasty occur?

Answer 31

occurred in adult T-cell. Can be anywhere in the periphery.

Question 32

If a neoplastic event takes place in a stem cell, what surface markers would you expect on the surface? where did this occur?

Answer 32

CD34, bone marrow

Question 33

If a T cell tumor has CD10, CD19, and CD20 on its surface, what stage did the neoplasty occur?

Answer 33

in the lymphoid progenitor, in the thymus.

Question 34

What cell surface markers are present in the thymocyte stage of T cell development? where are thymocytes found?

Answer 34

CD1, thymus

Question 35

If cytokeratins are found on the surface of a T cell tumor, what developmental stage did this occur in and in what location?

Answer 35

occured in a thymic stromal cell or epithelial cell. Happened in the thymus.