S2 I&i Exam 4: T Cell Development

Front 1

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

What attract the progenitor T-cells here?

Back 1

Thymus


thymic epithelial cells secrete chemotactic factor which attracts progenitor T-cells

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:delta

Front 4

Thymocytes develop cell-surface proteins related to _________ function.

Back 4

Effector

Front 5

T/F

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

Back 5

False!

They lack these.
(only mature T-cells have these)

Front 6

T/F

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

Back 6

True!

(less complicated)

Front 7

Each productive T-cell receptor gene is expressed as soon as it is made, and is assembled into a receptor complex w/ one of which 2 receptors?

Back 7

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

Front 8

TCR is composed of what 2 different polypeptide chains?

Back 8

Variable region and constant region

Front 9

What produces the differences in the variable regions of TCR?

Back 9

Gene rearrangements

Front 10

How many antigen binding sites are there on the TCR?

Back 10

One

Front 11

T/F

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

Back 11

True!


(same as for B-cell Igs)

Front 12

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

Back 12

Signals progenitor cells to proliferate
&
Expression of CD2

Front 13

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

Back 13

T-cell coreceptors CD4 and CD8

also no expression of TCR complex

Front 14

Double negative thymocytes first express what?

Then what?

Back 14

CD44

then CD25

Front 15

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

Back 15

Decreases

Front 16

Which T-cell lineage is more common?

Back 16

alpha:beta

Front 17

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

b) What about if beta occurs before gamma and delta?

Back 17

a) gamma:delta TCR

b) alpha:beta TCR

Front 18

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

Back 18

Pre TCR

Front 19

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

b) Once gene recombination is reactivated, which gene loci can continue to rearrange?

Back 19

a) beta, gamma, or delta (which ever produced first)


b) alpha, delta, or gamma (if not already produced)

Front 20

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 20

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

Front 21

T/F

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

Back 21

False!

It can occur during either of the gene loci rearrangement times

Front 22

What happens to thymocytes that fail to achieve productive rearrangements?

Back 22

They die by apoptosis and are phagocytosed by thymic macrophages

Front 23

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

b) What receptor is this similar to?

Back 23

a) Pre-T cell receptor

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

Front 24

What do the pre-T cell receptors do?

Back 24

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

Front 25

The "double positive" phase is characterized by what?

Back 25

The T-cells express both CD4 and CD8

Front 26

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

Back 26

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

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

Front 27

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

Back 27

1. Those bearing antigen receptors for "self" antigens, prevents an autoimmune reaction.

2. Those that do not react well with MHC antigens

(T-cells must not react with "self" antigens & must react well to "self" MHC proteins for and effective immune response)

Front 28

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

Back 28

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

Front 29

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

Back 29

Positive selection

Front 30

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

Back 30

Negative selection

Front 31

T/F

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

Back 31

False!

POSITIVE selection is critical in determining this.

Front 32

Double-positive thymocytes interact through the alpha:beta receptor with a peptide: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 32

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