Lecture 10 Development and Survival of Lymphocytes Flashcards
The precursor for T cells develops in the ______ and migrates to the ______
bone marrow; thymus
T cells that interact with _____ receive signals for survival. If they interact with ______ they are removed from the repertoire
self MHC;
self antigens
Mature T cells migrate to the _______ where they encounter _______ and are activated
peripheral lymphoid organs;
foreign anitgens
What do activated T cells do?
proliferate and eliminate infection
What are the two key parts of the thymus?
cortex and medulla
Which phagocytes are present in the thymus?
macrophages and dendritic cells
scid mice are immunocompromised because they can’t ______
do V(D) J
nu mice are immunocompromised because they ______
don’t have thymus epithelial cells
scid mice that receive ______ from nu mice can make mature T cells
bone marrow stem cells
nu mice that receive ______ from scid mice can make mature T cells
thymus graft in kidney
____ of cells die in the thymus
98%
Double negative (CD3-, 4-, 8-) thymocytes can differentiate into either ____ or _____ thymocytes
CD3+gamma:delta (4-, 8-) OR
CD3+ pT alpha:beta 4+, 8+ (double positive
Double negative thymocytes enter the thymus in ______ near the corticomedullary junction and migrate through _______ to the ______
small venules; cortex; medulla
As double negative cells proliferate they interact with _______ cells
corticoepithelial
the medulla contains only ______ T cells
mature single positive
DN1 cells express
CD44 and Kit
DN2 cells express
CD44, Kit, CD25
Cells are irreversibly committed to becoming Tcells at ___ stage
DN2
___ is alpha chain of IL-2
CD25
As ____ begin to rearrange beta chain, they become low in ____ and ____
DN2; CD44 and Kit
DN3 cells express _____ and _____ and are rearranging ___ chain locus
CD25
low CD44 and Kit
beta
the beta chain can pair with ____ in association with CD3 to stop _____ rearrangement
pTalpha
beta
pTalpha:beta triggers ______ to stop and loss of _____
cell proliferation; CD25
DN4 cells express
negative for CD44 and CD25, they have complete beta chain though
Dbeta to J beta rearrangement occurs in
DN2
Vbeta to J beta rearrangement occurs in
DN3
gamma:delta T cells are found in ____ and ___ sites and lack expression of ____ and ___
epithelial, mucosal;
CD4, CD8
____ locus is found within alpha
delta
rearrangements start ______ and whichever finish first will prevail
independently
complete gamma:delta TCR rearrangement will produce strong ___ signal to block production of alpha:beta
Erk
_____ is favored because a surrogate molecule can mimic ___ chain to block gamma:delta
alpha:beta; alpha (pTalpha)
____ is first to develop day 14-18 and migrates to the skin. It secretes _______
V gamma 5;
KGF, inflammatory cytokines and chemokines
Next to develop day 16-19 is V gamma __ and it goes to ____. They secrete ___
6;
lung, dermis, uterus;
IL-17
After day 17 of development, Vgamma4 goes to ____ and Vgamma 1,2,7 go to ____
spleen; lymph nodes
germline gene process occurs in _______ cell
maturing double negative thymocyte
beta chain rearrangement: D to J occurs in ____ cell
CD25+ Cd44low thymocyte rearranging beta-chain genes
beta chain: V to DJ occurs in ______ cell
Cd25+ CD44low thymocyte cytoplasmic Beta+
surface expression of beta chain with pTalpha results in following processes:
beta rearrangement stops,
cell proliferates,
CD4/CD8 induction,
alpha transcription
surface expression of beta chain with pTalpha occurs in ____ cells
CD4-8- -> CD4+8+
surface pTalpha:beta+
CD3low
alpha rearrangement: V to J results in the following processes:
surface expression of alpha:beta:CD3
selective events begin
pTalpha:beta induce signals that cause phosphorylation and degradation of ____ which halts ______ and induce _____ and ______
Rag2; beta chain rearrangement; cell proliferation and CD4/8 induction
pre-TCR is signaled constitutively by ___
Lck
pre-TCR triggers expression of _______ phase in DN4 and _____ are repressed
proliferative; RAG1:RAG2
a cell with a successfully rearranged _____ chain will give rise to many CD4+8+ progeny that can have unique ____ chains
beta;
alpha
when the proliferative phase ends, ______ are transcribed again
RAG1 and RAG2
When alpha:beta TCR are expressed, _______ can begin
selection by self peptide:self MHC
_____ is required for single negative thymocyte
ZAP70
alpha chains will undergo rearrangements until _______ or ______ occurs
positive selection OR cell death
multiple rearrangements can occur for ____ chains because there are multiple V segments
alpha
alpha rearrangement occurs when the thymocyte is CD4/CD8 _______
positive
MHC molecules in the _____ limit the repertoire of MHC that TCR can respond to
thymus