Lecture 9

Question 1

Where is thymus located?

Answer 1

On top of heart

Question 2

What can HSCs become in thymus?

Answer 2

CD4
CD8
NKT
Tregs

Question 3

When is thymus colonized by HSCs?

Answer 3

7th week of gestation

Question 4

When does thymus begin to produce T cells?

Answer 4

12-13th week of gestation

Question 5

What is DiGeorge syndrome?

Answer 5

• Deletion of chromosome 22
• Present at birth: congenital
• Recurrent infection due to absence of thymus and T cells
• Thymus transplant fixes T cell deficiency

Question 6

Where is FoxN1 located?

Answer 6

Chromosome 17

Question 7

What does FoxN1 code for?

Answer 7

TF essential for maturation of thymic epithelial cell progenitors

Question 8

What does FoxN1 mucation cause?

Answer 8

• Failure of thymus to develop

- Showed thymic epithelial cells were required for normal thymus which was required forT cell development

Question 9

How can FoxN1 be treated?

Answer 9

Thymic implant

Question 10

What is found in thymic cortex?

Answer 10

Developing T cells

Question 11

What is found in thymic medulla?

Answer 11

Mature T cells

Question 12

What is found in thymic septa?

Answer 12

Firbroblasts

Question 13

What are TECs?

Answer 13

Thymic epithelial cells

Question 14

Function of TECs??

Answer 14

1. Cytokines required for growth/differentiatoin of T cells
2. Notch cells required for T cell commitmen
3. Expression of MHC for selecting T celsl

Question 15

3 types of TECS

Answer 15

Cortical
Medullary
Hassals

Question 16

What do TECs derive from?

Answer 16

Endoderm

Question 17

Where do APCs cluster in thymus?

Answer 17

Cortical medullary junction

Question 18

Functions of APC in thymus?

Answer 18

Present antigen for Differentation

Destruction of self reactive T cells

Question 19

What are thymocytes derived from?

Answer 19

Bone marrow HSCs

Question 20

Tool for distinguishing T cell types?

Answer 20

Flow cytometry

Question 21

Good source of HSC CD34 blood cells for transplant ?

Answer 21

Umbilical cord blood

Question 22

What happens to HSC when it enters thymus?

Answer 22

Lineage potential restricted to T cells

Question 23

Why does immune system decline in elderly?

Answer 23

T cell production slows

Question 24

4 developmental steps in T cells?

Answer 24

1. T lineage commitment
2. Proliferentiation and differentiation
3. Pos/neg selection
4. Maturation

Question 25

What does notch signalling do?

Answer 25

- Causes CD34 cell to move away from myeloid lineage (B, moncyte, DC) where then can now only become T/NK - Further notch signaling terminates potential of NK develoment

Question 26

Where does notch signal come from?

Answer 26

Notch ligand DL4 & 1

Question 27

What is the Pre T cell?

Answer 27

- Commited to T lineage - Expresses CD1A - Rearranging Gamma, delta, and beta gens

Question 28

What can pre T cells become?

Answer 28

Alpha Beta T cell | Gamma Delta T cell

Question 29

What is necessary for recomination of pre T?

Answer 29

RAG1/2 | IL7

Question 30

What is IL7 required for?

Answer 30

T cell rearrangment

Question 31

Stage after pret T?

Answer 31

- CD4ISP - CD4 immature single positive - Exress CD3/4 - Can become alpha beta or gamma delta

Question 32

What ends rearrangement?

Answer 32

ERK

Question 33

What expresses CD3

Answer 33

ISP

Question 34

What is beta selection?

Answer 34

- Selects only ISP cells with functional TCR beta genes | - Rest will be signalled to die

Question 35

What cells undergo beta selection?

Answer 35

ISP

Question 36

What happens to ISP cells selected for survival in beta selection?

Answer 36

- Become double positive cells | - Express both CD3 and CD4

Question 37

T cell selction generate allelic exclusion?

Answer 37

- No | - Positive seletion will ensure that each cell has only one specificity however

Question 38

What do DP cells rearrange?

Answer 38

Alpha chain

Question 39

What does alpha chain rearrangment cause?

Answer 39

Delta deletion

Question 40

Can DP cell have two different alpha chains?

Answer 40

Yes but positive selction will fix this

Question 41

What can DP cell become?

Answer 41

CD4 or CD8

Question 42

What happens in positive selection?

Answer 42

- DP cells presented with self antigen in MHCI/II and if they have low affinity they surive - Surviving cells shut down RAG and replicate

Question 43

What happens to DP cells that do not recognize self peptide?

Answer 43

Undergo apaptosis

Question 44

What does positive selection skew towards

Answer 44

Reaction to self peptide and autoreactive T cells

Question 45

What is negative selection?

Answer 45

Deletion of T cell with strong affinity to MHC and antigen

Question 46

What does negative selection establish?

Answer 46

Central tollerance

Question 47

Where does negative selection occur?

Answer 47

Cortical medullary region where [DC] is high to eat self reactive cell

Question 48

What is AIRE?

Answer 48

Gene that allows for expression of peripheral tissue antigen in thymic cells to test for self reactivity

Question 49

Diseases with AIRE deficiency?

Answer 49

APECED / APS1

Question 50

What are APECED / APS1?

Answer 50

Auto immune deficiency resulting from AIRE deficiency

Question 51

What to TCR gamma delta cells develop from?

Answer 51

ISP

Question 52

Gamma delta T cell CD4 or 8 positive?

Answer 52

Negative for both

Question 53

Gamma delta T cell CD4 use MHCI or MHCII?

Answer 53

Neither - bind antigen directly

Question 54

What do NKT cells develop from ?

Answer 54

DP T cell

Question 55

Function of NKT?

Answer 55

Rapidly produce cytokines necessary for TH1 & TH2 when triggered

Question 56

What do Tregs develop form?

Answer 56

CD3/4 positive T cells

Question 57

What is required for Treg development?

Answer 57

FOXP3

Question 58

T reg disease?

Answer 58

IPEX