Block 3 - I&i: T Cell Development

Front 1

Lymphocytes (progenitor T-cells) destined to become T-cells migrate from the bone marrow to what primary lymphoid organ?

Back 1

Thymus

Front 2

Thymocytes originate from what type of cells?

Back 2

Bone marrow stem cells

Front 3

What are the two lineages of T-cells?

Back 3

alpha:beta and gamma:kappa

Front 4

Thymocytes develop cell-surface proteins related to _________ function.

Back 4

Effector

Front 5

What do thymic epithelial cells secrete that assists with progenitor T-cells migration to the thymus?

Back 5

A chemotactic factor which attracts the progenitor T-cells

Front 6

T/F

T-cell precursors have antigen receptors, CD3, CD4, and CD8 molecules on their cell surface.

Back 6

False!

They lack these.

Front 7

T/F

The developmental process of T-cells is similar to B-cell maturation

Back 7

True!

Front 8

T/F

Assembly of a functional gene is required for each T-cell receptor chain.

Back 8

True!

Front 9

Each productive T-cell receptor gene is expressed as soon as it is made, and it it assembled into one of which 2 receptor complexes?

Back 9

Either a pre T-cell receptor (TCR) or a final TCR

Front 10

T/F

TCR is a membrane-bound glycoprotein that resembles a single, antigen-binding arm of an immunoglobulin (antibody) molecule.

Back 10

True!

Front 11

TCR is composed of what 2 different polypeptide chains?

Back 11

Variable region and constant region

Front 12

How many antigen binding sites are there on the TCR?

Back 12

One

Front 13

What produces the differences in the variable regions of TCR?

Back 13

Gene rearrangements

Front 14

T/F

Once T-cell is stimulated with antigen, no further changes occur in the antigen binding site and/or class switching of constant regions (as in immunoglobulins [B-cells])

Back 14

True!

Front 15

When progenitor cells enter the thymus and interact with thymic stromal cells, this signals what?

Back 15

Signals progenitor cells to proliferate

Front 16

The double negative phase of T cell development is characterized by the absence of what?

Back 16

T-cell coreceptors CD4 and CD8

also no expression of TCR complex

Front 17

Double negative thymocytes first express what?

Then what?

Back 17

CD44

then CD25

Front 18

After progenitor cells enter thymus and proliferate, they express what T-cell specific adhesion molecule?

Back 18

CD2

Front 19

During T-cell development, expression of CD44 (decreases/increases) when TCR genes begin rearrangement.

Back 19

Decreases

Front 20

Which T-cell lineage is more common?

Back 20

alpha:beta

Front 21

There is a race between the different loci of of the TCR gene rearrangements.
a) If the gamma or delta chain rearrangements are completed before a productive beta chain rearrangement, what cell lineage do you get?
b) What about if beta occurs before gamma and delta?

Back 21

a) gamma:delta TCR

b) alpha:beta TCR

Front 22

If a productive beta chain is rearranged first, the beta chain is assembled with a surrogate alpha chain (pTalpha), forming what?

Back 22

Pre TCR

Front 23

a) Which loci, if formed, halt gene rearrangements and cause cells to start proliferating?

b) Once gene recombination is reactivated, which gene loci can form?

Back 23

a) beta, gamma, and delta

b) alpha, delta, or gamma

Front 24

In most cases, a chain receives productive rearrangement first. For example: alpha:beta TCR -> alpha:beta T-cell lineage.

How can the T-cell become committed to the gamma:delta lineage after already having started out with a beta chain?

Back 24

If gamma or delta gene loci achieve rearrangement before the alpha chain does

Front 25

T/F

There is only one chance during T-cell development for a T-cell to become a gamma:delta cell.

Back 25

False!

It can occur during either of the gene loci rearrangement times

Front 26

What happens to thymocytes that fail to achieve productive rearrangements?

Back 26

They die by apoptosis and are phagocytosed by thymic macrophages

Front 27

a) What receptor is expressed on "double negatives?"

b) What receptor is this similar to?

Back 27

a) Pre-T cell receptor

b) Pre-BCR expressed by developing precursor B-cells

Front 28

What do the pre-T cell receptors do?

Back 28

Induce development of the precursor T-cells to the "double positive" phase

Front 29

The "double positive" phase is characterized by what?

Back 29

The T-cells express both CD4 and CD8

Front 30

What are the 2 possible paths for double-negative thymocytes?

Back 30

1. Become large, active "double positive" thymocytes, with CD3, CD4, CD8 and pTalpha:beta

2. Become gamma:delta with CD3, but without CD4 and CD8

Front 31

What are the 2 reasons for "double positive" cells to be destroyed?

Back 31

1. Those bearing antigen receptors for "self" antigens are destroyed by programmed cell death (apoptosis). This prevents an autoimmune reaction.

2. Those that do not react well with MHC antigens are also destroyed

Front 32

What 2 features are required for an effective immune response by T cells?

Back 32

T-cells must not react with "self" antigens and must react well to "self" MHC proteins

Front 33

What are "single-positive" thymocytes characterized by? Where do they go?

Back 33

They have EITHER CD4 or CD8, not both. They are exported to the periphery

Front 34

The survival of thymocytes whose TCRs recognize antigens bound to "self" MHC molecules is called what?

Back 34

Positive selection

Front 35

The deletion of thymocytes whose TCRs recognize "self" antigens is called what?

Back 35

Negative selection

Front 36

T/F

Negative selection is critical in determining whether a double-positive T-cell will become a CD4 or CD8 cell.

Back 36

False!

POSITIVE selection is critical in determining this.

Front 37

Double-positive thymocytes interact through the alpha:beta receptor with a peptied:MHC complex.
a) With MHC-I, which T-cell co-receptor is recruited and which is excluded?
b) With MHC-II, which T-cell co-receptor is recruited and which is excluded?

Back 37

a) MHC-I -> CD8 recruited, CD4 excluded
b) MHC-II -> CD4 recruited, CD8 excluded