55-T Cell Development Flashcards Preview

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Flashcards in 55-T Cell Development Deck (38)
1

differentiation of t cells

occurs in thymus

2

production of common lymphoid progenitor cell

bone marrow
migrate to thymus

3

thymus

found above heart
increase in size until puberty and then replaced by fat tissue

4

Di George's syndrome

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

5

CATCH-22

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

6

thymocytes

immature t cell present in thymujs

7

checkpoints for maturation of t cells

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

8

expression of surface proteins can differentiate individual stages

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

9

Notch1

first checkpoint
critical in determining T cell lineage

10

Notch1 ligands

on thymus

11

loss of Notch

B cells developed in thymus

12

gain of notch function

t cells in bone marrow

13

TCR structure

alpha and beta chains
transmembrane domain and constant and variable extracellular region

14

CD3 d, e, y, TCR z

drive intracellular signaling

15

antigen bound MHC

activated TCR

16

variable regions of TCR formed by what

somatic recombination

17

TCR alpha chain recombination

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

18

TCR beta chain recombination

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

19

12/23 rules

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

20

RAG 1 and 2

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

21

coding joint

region of DNA that will encode functional gene

22

signal joint

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

23

coding joint recombination

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

24

combinatorial diversity

random recombination of VDJ

25

junctional diversity

random addition of nucleotides during VJD recombination

26

rearrangement of TCR B chain

occurs first, can only occur once on one allele

27

rearrangement of TCR A chain

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

28

pre TCR A chain

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

29

2 T cell subtypes

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

30

what is TCR tested for after production

functionality and self reactivity

31

non functional TCR

die by death by neglect
Don't react with MHC

32

self reactive TCR

die by negative selection, react with self antigens

33

positive selection

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

34

fate of double positive T cells- lineage choice

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

35

Defects in TCR a and b

lack of mature T cells

36

mutation in intracellular signaling molecules

lack of mature T cells
immunosuppressed
die within 1 year

37

T cell acute lymphoblastic leukemia

cancer cells from thymocytes
common childhood leukemia

38

T cell lymphomas

from mature peripheral T cells
found in older patients