lecture 16 - T cell development

Question 1

when does the thymus start to atrophage

Answer 1

high school age

Question 2

where is the site of VDJ recombination in the thymus

Answer 2

Cortex

Question 3

where is the site of negative selection in the thymus

Answer 3

medulla

Question 4

main sit of positive selection In the thymus

Answer 4

cortex

Question 5

high cell density is where in the thymus

Answer 5

cortex

Question 6

ETP stand for

Answer 6

early thymic progenitor

Question 7

what cells have receptors and migrate to the lymph nodes and spleen to see pathogen associated antigens

Answer 7

single positive CD4 or CD8 cells

Question 8

ETPs exit the bone marrow via the

Answer 8

bloodstream and then into the thymus where they become thymic ETPs

Question 9

are early thymic progenitors multipotent

Answer 9

yes when they arrive at the thymus

Question 10

what signals drive T cell commitment

Answer 10

Notch signals

Question 11

What provides the notch signal that directs ETPs to T cell lineage

Answer 11

cTECs (cortical thymic epithelial cells)

Question 12

What cleaves the extracellular notch domain

Answer 12

ADAM10

Question 13

How do cTECs drive notch signalling

Answer 13

They are ligand presenter cells that present ligands to notch receptors which triggers the cleavage events

Question 14

What are the 3 steps of notch receptor signalling?

Answer 14

1. ADAM10 cleaves the extracellular notch domain
2. Y-secretase cleared transmembrane domain
3. Notch intracellular domain activates gene expression in the nucleus

Question 15

What are the ligands that cTECs present? (2)

Answer 15

DLL1 / DLL4

Question 16

E2A is a what and what is it required for

Answer 16

Transcription factor required for early T cell and B cell development

Question 17

Can over expression of the notch intracellular domain enhance T cell development

Answer 17

Yes

Question 18

IL-7 signalling promotes (2)

Answer 18

Survival and proliferation of ETPs

Question 19

TCR rearrangement steps

Answer 19

1. TCRb chain - D-J then V-DJ
2. B-selection - pair rearranged TCRb with pre-Ta to form a pre TCR
3. TCRa chain - V-J rearrange to form functional TCR with B

Question 20

What’s the point of b-selection in TCR rearrangement

Answer 20

Test for stability and function of the b chain to pair with a pre-Ta

Question 21

when does TCRa rearrangement happen

Answer 21

during the double positive phase

Question 22

4 purposes of pre-TCR signalling

Answer 22

survival
proliferation
differentiation
allelic exclusion

Question 23

when does the TCRb rearrangement happen

Answer 23

double negative phase

Question 24

whats the point of a pre-TCR for TCRa

Answer 24

the signalling of the pre-TCR “tells” the TCRa to begin rearranging to produce a full functioning TCR

Question 25

what is allelic exclusion for in pre-TCR signalling

Answer 25

it ensures that you're only getting 1 b chain expressed in your TCR

Question 26

do gamma-delta TCRs use pre-TCRs

Answer 26

no

Question 27

what do most T cells die from

Answer 27

neglect of signalling (lack of survival signal)

Question 28

what do cTECs present in the cortex

Answer 28

antigens via MHC class 1 and MHC class 2

Question 29

what interacts with CD4+ and CD8+ double positive thymocytes

Answer 29

cTECs

Question 30

what kind of selection do cTECs promote

Answer 30

both positive and negative selection

Question 31

what happens in the medulla regarding T cells

Answer 31

single positive T cells interact with medullary thymic epithelial cells (mTECs) and others

Question 32

what do mTECs express and what does it do

Answer 32

expresses Aire which drives expression of tissue restricted antigens

Question 33

what does Aire do

Answer 33

drives expression of tissue restricted antigens (TRAs)

Question 34

negative selection

Answer 34

eliminate T cells that bind self antigens too strongly to prevent autoimmunity

Question 35

Tregs are almost exclusively what cell

Answer 35

CD4

Question 36

loss of AIRE can lead to _____? why?

Answer 36

multi organ autoimmunity because it creates antigens of almost all tissue restricted antigens - so without knowing how a T cell would react to it, auto reactive T cells could get let loose.

Question 37

what kind of antigen do B cell receptors capture

Answer 37

extracellular antigens

Question 38

how can B cells help T cell section

Answer 38

they can present immune related antigens (self antigens) to T cells to prevent autoimmune reaction to a normal immune response (build tolerance)

Question 39

thymoproteosome is essential for what

Answer 39

MHC 1 so CD8

Question 40

what does a thymoproteosome contain

Answer 40

b5t

Question 41

macroautophagosome is essential for what

Answer 41

MHC II

Question 42

what cell can take on identity of another tissue (mimetic cells)

Answer 42

mTECs

Question 43

TRAs

Answer 43

tissue restricted antigens