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