T Cell Receptor and T lymphocyte development Flashcards
what is matruation of early thymocyte
CD 4- 8-; Tcell receptor (TCR) gene rearrangements
what is maturation of common thymocyte
CD 4+ 8+ ; T cell receptor gene rearrangements; low TCR and CD3 surface expression
what is maturation of mature thymocyte
has a CD 4+ or CD 8+ subset; high TCR and CD3 surface expression; there is somatic recombination of TCR genes
what does positive and negative selection do
most self- reactive T cells are eliminated
All T cells are positive for
TCR ,CD2, CD3, CD28
What are the two antigen-specific TCR dimers
alpha-beta (this is 90-95% of them)
gamma-delta ( this is the rest of them)
what chains are from the V, D, J, and C genes
beta and gamma chains
what chains are made from the V, J, and C genes
alpha and delta chains
what is the whole point of the TCR? what does it complex with
receptors to activate the T cell;
CD3 association initiates signal transduction
if we compare the two classes of the T cell receptors: both have
variable region
constant region
heterodimer binding site of two different chains
T cells move from where to where to where (organs)
from bone marrow ==>thymus
thymus ==> lymph node, spleen, gut associated lymph
T cell progenitor cells differetiate into __ (3)? where?
CD4, CD8, and NKT cells
in thymus
mature T cells circulate where? until?
circulate between blood and lymph tissue until they recognize antigens presented on dendritic cells in lymph tissue
When T cells hit the dendritic cells, what happens
they further mature to become either functional memory T cell or effector T cell
what are some bone marrow derived cells in thymus
macrophage,
dendritic cell,
thymocyte
what are some thymic derived cells in the thymus? where are they?
cortical epithelial cell, ( in the cortex of thymus )
medullary epithelial cell ( in the medulla of thymus )
what thymocytes are in the cortex of thymus
[CD4- CD8-], [CD4+ CD8+]
aka immature thymocytes
what thymocytes are in the medulla of the thymus
[CD4+ CD8-], [CD8+, CD4-]
whats a histo thing that you shouldn’t forget in the thymus
hassal’s corpuscle ( the onion looking thing )
what is CD34 for?
stem-cell surface marker;
what is CD2 for?
adhesion and signaling
what is CD5 for
adhesion and signaling
what is IL-7 ( CD127 for)
a cytokine recedptor
what is CD44 for?
adhesion;
what is CD1A for
MHC class 1 - like molecule
what two marker and/or adhesion components are on uncommitted progenitor cells
CD 34 and CD 44
why do t cells only mature in the thymus
the thymic epithelium have a notch ligand which binds to the notch 1 marker on a thymocyte. the binding cleaves the notch 1 intracellular domain and starts a downstream signal to start transcription in the nucleus
when the TCR rearranges DNA in the thymus, what does it do first and then (beta gene rearrangement)
in the beta, it combines the D and J then it does the VDJ rearrangement.
what enzyme is NECCESSARY for gene rearrangement
RAG - it cleaves the gene and adds some nucleotides to make a sticky end where it just cut
how do you get junctional diversity
the RAG cleaves and makes a sticky end; when the gwo genes are hybridized, the sticky ends don’t always COMPLETELY overlap; you get some extra spots that look like okasaki fragments and those are filled in
this creates diversity.
Ok so the beta chain has gene rearrangement first. what does the beta chain signal after it is created
it is expressed on the surface along with a surrogate alpha chain; the beta gene rearrangement stops and the cell proliferates
successful rearrangement of one beta copy ____
blocks the beta copy on the other chromosome
successful rearragement of one alpha copy ____
does NOT block the alpha copy on the other chromosome; THEREFORE, it can express two different alpha chains
if there is successful gene rearrangement in gamma and delta before beta, what happens
you get a gamma delta t cell
if you have successful gene rearrangment in beta before gamma or delta, what happens
you get a pre-alpha beta t cell. its not committed yet. it will enter a phase of proliferation
where is the delta chain locus
inside the alpha chain locus
what do gamma delta t cells do?
they are always on and have anti-bacterial/viral/tumor functions
CD8 binds
MHC class 1
CD4 binds
MHC class 2
gamma delta t cells recognize
small microbial compounds,
most MHC class 1(ish) when the host is changed or stressed
non protein alkylamines
heat shock proteins
gamma delta t cells don’t have to
… they recognize antigens even if they aren’t presented on MHC molecules
CD8 t cells kill
cells infected with intracellular pathogens or tumor cells
CD4 T cells regulate
(activate OR suppres) other immune cells like B cells, macrophages and tissue cells
how many pieces are in a CD 4
there are 4 subunits that make
antigen specificity determines its fate. what does that mean?
if the T cell receptor interacts with an Ag:MHCI, then it is defined as a CD8+ cell.
what is the first stage of T cell hazing
positive selection
what happens during the first stage of T cell hazing
this positive selection makes sure that the Tcell recognizes the self MHC complex; this makes ensures that the T cell will be loyal, and won’t start hitting for the other team
what is the second stage of Tcell hazing
this is negative selection
what happens during the second stage of T cell hazing
this eleiminates auto-reactive T cells; aka Tcells that strongly bind to self antigen/MHC complex
Igs act as?
receptors and effector molecules
what can cause ineffective negative selection?
if the thymus self antigens are not expressined in the thymus, then the T cells can’t be negatively selected and you get T cells in circulation that will improperly attack self cells
what is the relationship between number of MHC molecules, positive T cell selection, and negative T cell selection
as the number of MHC INCREASES, the # of positively selected cells that survive INCREASES by N times, while the number of negatively selected (killed cells) DECREASES by N times.
what is the best number of MHC isotypes to express
- this way you get the most number of well selected T cells
Di George’s syndrome - 2 things
no or few T cells because of a lacking or small thymus;
symptoms are similar to SCID patients
