55-T Cell Development

Question 1

differentiation of t cells

Answer 1

occurs in thymus

Question 2

production of common lymphoid progenitor cell

Answer 2

bone marrow

migrate to thymus

Question 3

thymus

Answer 3

found above heart

increase in size until puberty and then replaced by fat tissue

Question 4

Di George’s syndrome

Answer 4

have no thymus
defects in number of mature t cells
chromosome 22
severe immunodeficiencies
CATCH-22

Question 5

CATCH-22

Answer 5

Di George's syndrome
cardiac abnormality
abnormal facial structures
Thymus aplasia
cleft palate
hypocalcemia/hypoparathyroidism
on chromosome 22

Question 6

thymocytes

Answer 6

immature t cell present in thymujs

Question 7

checkpoints for maturation of t cells

Answer 7

notch signalling for lineage fate
rearrangement of TCR chains
positive and negative selection
selection of Cd4 or 8

Question 8

expression of surface proteins can differentiate individual stages

Answer 8

using CD4 and CD8
double negative-most immature, no CD4 or 8
double positive-middle, both CD4 and 8
single positive- most mature, only 1 CD4 or 8

Question 9

Notch1

Answer 9

first checkpoint

critical in determining T cell lineage

Question 10

Notch1 ligands

Answer 10

on thymus

Question 11

loss of Notch

Answer 11

B cells developed in thymus

Question 12

gain of notch function

Answer 12

t cells in bone marrow

Question 13

TCR structure

Answer 13

alpha and beta chains

transmembrane domain and constant and variable extracellular region

Question 14

CD3 d, e, y, TCR z

Answer 14

drive intracellular signaling

Question 15

antigen bound MHC

Answer 15

activated TCR

Question 16

variable regions of TCR formed by what

Answer 16

somatic recombination

Question 17

TCR alpha chain recombination

Answer 17

multiple copies of V and J, 1 copy of constant combined to form 1 V, J, C

Question 18

TCR beta chain recombination

Answer 18

multiple V, D, J, and 2 constant combined to form 1 V, D, J, C

Question 19

12/23 rules

Answer 19

recombination signal sequences spaced by 23 base pairs on 3’ end and 12 base pairs on 5’ end

Question 20

RAG 1 and 2

Answer 20

recognize RSS (recombinational signal sequence) and cleave RSS to form closed hairpin loop

Question 21

coding joint

Answer 21

region of DNA that will encode functional gene

Question 22

signal joint

Answer 22

intervening DNA sequence that is removed by somatic recombination
Ku70/80 recruit DNA ligase to ligate ends

Question 23

coding joint recombination

Answer 23

RSS brought together
RAG1 and 2 generates hairpin loop
Ku70/80 recruits DNA-PK and artemis to open hairpin loop
Ku70/80 releases DNA-PK and artemis and recruits TdT to fill in nucleotides

Question 24

combinatorial diversity

Answer 24

random recombination of VDJ

Question 25

junctional diversity

Answer 25

random addition of nucleotides during VJD recombination

Question 26

rearrangement of TCR B chain

Answer 26

occurs first, can only occur once on one allele

Question 27

rearrangement of TCR A chain

Answer 27

occurs second, can occur multiple times on both alleles, but only one is expressed
continues to rearrange until functional chain is produced or until it runs out of V and J regions-apoptosis

Question 28

pre TCR A chain

Answer 28

associates with rearranged TCR B chain
mediates intracellular signaling pathways, proliferation of immature thymocytes, expression of CD4 and CD8, rearrangement of TCR a locus

Question 29

2 T cell subtypes

Answer 29

alpha/beta
delta/gamma
once one is expressed the other goes away- mutually exclusive

Question 30

what is TCR tested for after production

Answer 30

functionality and self reactivity

Question 31

non functional TCR

Answer 31

die by death by neglect

Don’t react with MHC

Question 32

self reactive TCR

Answer 32

die by negative selection, react with self antigens

Question 33

positive selection

Answer 33

TCRs that are functional and non self reactive, only 2%

Question 34

fate of double positive T cells- lineage choice

Answer 34

down regulate CD8
competent signalling differentiate into CD4
non competent signaling downregulate CD4 and become CD8

Question 35

Defects in TCR a and b

Answer 35

lack of mature T cells

Question 36

mutation in intracellular signaling molecules

Answer 36

lack of mature T cells
immunosuppressed
die within 1 year

Question 37

T cell acute lymphoblastic leukemia

Answer 37

cancer cells from thymocytes

common childhood leukemia

Question 38

T cell lymphomas

Answer 38

from mature peripheral T cells

found in older patients