T Cell Development In Thymus

Front 1

Identify and characterize the structure of the thymus and its cellular components

Back 1

1) Capsule
2) Subscapular region
3) cortex
4) medulla

Front 2

List the factors that convert stem cells into thymocytes commited to the T cell lineage?

Back 2

1) something with a 7
2) other things
3) thats all

Front 3

Describe the sequence of events that lead to expression of an alpha beta T cell receptor

Back 3

1) gene expression
2) gene rearrangements
3) double selection
4) self and non self

Front 4

Distinguish the process of positive and negative selection of T cells in the thymus?

Back 4

positively select those t cells with the right receptors
negatively select those that respond to self

Front 5

Name the 7 structures of the thymus

Back 5

1) capsule
2) trabeculae
3)subscapular epithelium
4) cortex
5) medulla
6) corticomedullary junction
7) Hassall's corpuscle

Front 6

Name the cells of the thymus?

Back 6

1) cortical epithelial cell - thymus
2) thymocyte (bone marrow
3) medullary epithelial cell from thymus
4) dendritic cell in medulla from bone marrow
4)macrophage in medulla from bone marrow

Front 7

What is the critical signaling molecule for commitment to the T cell lineage?

Back 7

notch 1 (first step, notch 1)

Front 8

What are the phenotypic markers of the uncommited vs commited to T cell lineage?

Back 8

CD 23 = uncommitted and germline TCR Genes
CD2, IL7 = committed and rearranging has begun

Front 9

What are the 4 types of cells that thymocytes can develop into?

Back 9

-gamma delta T cells
-alpha beta T cells (includes CD4/8)
-regulatory T cells
-NK t cells

Front 10

Please describe the 10 steps of T cell development in the thymus?

Back 10

1) progentor cells arrive in thymus via HEV in medulla (from bone marrow)
2) cell proliferation at corticomedullary junction
3) double negative T cells commit to T lineage in cortex
4) rearrange B genes
5) check point for pre TCR
6) proliferating double negative pre-T cells
7) immature double positive T cells away from dendritic cell
8) rearrange alpha genes
9) check point for TCR
10) mature into double positive cells at corticomedullary junction

Front 11

What is the 7 step overview of T cell development in thymus?

Back 11

1) commitment to T cell lineage
2) proliferation and differentiation into double positive CD 3+ thymocytes in subscapular region
3) Generation of TCR
4) Commitment to alphabeta or delta gamma lineage
5) positive selection of alpha beta TCR in cortex
6) Negative selection of alpha beta TCR at corticomedullary junction
7) export to peripheral secondary lymphoid tissues leave thymus via HEV

Front 12

What are the two types of T cell receptor?

Back 12

1) alpha:beta
2) gamma: delta

Front 13

What are the steps and marking of the decision of the T cell to become either gamma delta?

Back 13

1) CD34 uncommitted progenitor
2) CD2 commited double negative T cell progenitor
3) gamma and delta chains rearrange and recieves signal to stop rearrangement
4) make gamma delta TCR

Front 14

What are the steps to become alpha:beta T cell?

Back 14

1) CD 34 uncommited progenitor
2) CD 2 committed double negative progenitor
3) double negative T cells rearrange beta, gamma and delta loci
3) beta chain rearranges
4) pre TCR assembles
5) expression of CD 8 and CD 4
6) uncommitted double positive thymocyte with a b chain on the surfaec

Front 15

What stage does the T cell make the decision to become a gamma delta or alpha beta t cell?

Back 15

DN stage

Front 16

What protein promotes recominbation of TCR genes?

Back 16

RAG

Front 17

How many attempts and chances are there to achieve a productive rearrangement of the loci of the T cell?

Back 17

2 attempts
four chances

Front 18

After gene rearrangement occurs what happens?

Back 18

a productive beta chain pairs with a surrogate alpha chain

Front 19

When do you get the transition of double negative to double positive?

Back 19

when you are rearranging the alpha beta and gamma genes

Front 20

What does recombination of the alpha locus always do to the possibility of becoming a gamma delta T cell?

Back 20

rearrangement of alpha chain gene always eliminates the linked delta chain locus

Front 21

What are the four steps of becoming alpha beta?

Back 21

1) gene rearragenment at beta locus
2) expression of Beta
3) joining with surrogate alpha
4) alpha recombination deletes delta and you are committed to alpha beta

Front 22

What happens during the positive seelction of alpha beta cells in the thymus?

Back 22

1) weak or no binding to MHC - cell dies
2) strong or moderate binding cell lives

Front 23

How dou you get from a double positive T lymphocyte to a single positive T lymphocyte?

Back 23

binding of MHC, the MHC class you bind determines what kind of T lymphocyte you will be

Front 24

What happens when you have a transgenic receptor restricted to MHCa and your stroma expresses MHCa?

Back 24

single positive CD8 T cells

Front 25

Where does negative selection take place?

Back 25

near the corticomedullary junction

Front 26

What happens with negative selection?

Back 26

too tight binding - die
moderate binding - cells live

Front 27

What drives negative selection?

Back 27

antigen

Front 28

What drives positive selection?

Back 28

mhc

Front 29

What is AIRE?

Back 29

causes expression of several hundred tissue specific geens to be transcribed in subpopulation of epithelial cells of thymus. they can be bound during negative selection and thus help with autoimmunity

Front 30

What is FoxP3 T-Reg cells and what do they do?

Back 30

FoxP3 T-Reg cells help body with supressing response of self reactive CD 4 T cells

Front 31

How do FoxP3 T reg cells help with self tolerance?

Back 31

they interact with the same APC as the CD4 self reactive cell and supress it via cytokines

Front 32

What are the characteristics of T cells that leave the thymus?

Back 32

mature
self restricted
self tolerant
single positive CD4 or CD8

Front 33

Where do T cells go after they are done developing in the thymus?

Back 33

secondary lymphoid tissue via HEV

Front 34

What are the disorders of T cell development? (5)

Back 34

1) DiGeorge syndrome
2) IPEX
3) APECED
4) SCID
5) Common gamma chain deficiency

Front 35

What is DiGeorge Syndrome and its cause?

Back 35

thymus fails to develop
T cells are absent but B cells are made

Front 36

What causes IPEX?

Back 36

Immune dysregulation polyendocrinopathy, enteropathy, X linked Syndrome
-Caused by deficiency in FOXP3
-Mostly affects boys
-autoimmunity towards tissue esp gut, skin,, thyroid

Front 37

What is APECED and what are its causes?

Back 37

Autoimmune polyglandular syndrome type I
-AIRE gene deficient
-no autoimmunity

Front 38

What is SCID and what causes it?

Back 38

SCID is caused by problem with RAG and is caused by T cell deficiency

Front 39

What is common gamma chain deficiency and what is its cause?

Back 39

Common gamma chain receptor for cytokines Il2, IL4, IL7, IL9 is mutated
-immunodeficiency

Front 40

How does TCR undergo recombination?

Back 40

using RSS sequence

Front 41

What is an important difference between B cell and T cell diversity?

Back 41

after T cell is stimulated with antigen there is no further rearrangements to it

Front 42

What is the difference between binding sites for antigen between B cell and T cells?

Back 42

1)T cells have single binding site for antigen
2) T cell also binds MHC

Front 43

How many types of constant reginos are there in the T cell?

Back 43

1 C alpha
2 C beta

Front 44

What are the alpha and beta chain variable regions?

Back 44

Beta has D and J and V
Alpha only has V and J

Front 45

Are there more J loci on the alpha or beta locus?

Back 45

alpha locus

Front 46

What does a TCR need to be coexpressed with?

Back 46

CD3

Front 47

Which cells have more junctional diversity B or T?

Back 47

T

Front 48

Which cells have more total diversity B or T?

Back 48

T

Front 49

What are the 2 things a TCR must recognize?

Back 49

peptide
MHC

Front 50

Where does CD8 bind on MHC?

Back 50

alpha 3

Front 51

Where does CD4 bind on MHC?

Back 51

B2