EXAM 2 T Cells: Development Flashcards
T cell progenitors develop in the ___ and migrate to the ___
bone marrow, thymus
positive and negative selection occurs in the ___
thymus
mature T cells migrate to the ___
peripheral lymphoid organs
activated T cells migrate to ___
sites of infection
T-cell precursors rearrange their T cell receptor genes in the ___
thymus
immature T cells that recognize ___ receive signals for survival. those that interact ___ with self antigen are removed from the repertoir.
self MHC, strongly
mature T cells encounter ___ in the peripheral lymphoid organs and are ___
foreign antigens, activated
___ are developing T cells within the thymus
thymocytes
describe gamma delta T cells
- maintain tissue integrity
- do not express CD4 or CD8 co-receptors
- interact with non classical receptors
describe CD4 T cells
- helper T cells
- several subtypes: Th1, Th2, Th17, Tfh, and Treg
- regulate adaptive and innate immune function
- interact with MHC class II
describe CD8 T cells
- cytotoxic T cells
- direct effector function
- interact with MHC class I
the ___ is the site of all T cell development
thymus
TCR development occurs within the ___ of the thymus
cortex
positive and negative selection occurs as thymocytes move from ___ to ___
cortex to medulla
what happens to the thymus as you age?
it involutes
what are the half lives of CD4 and CD8 T cells?
- CD4 T cells - 4.2 years
- CD8 T cells - 6.5 years
the thymus involutes with age, resulting in reduced T cell production, but T cell-mediate immunity is not grossly affected. why?
the long life span of individual T cells and diversity of TCRs is sufficient to provide immunity even after the loss of T cell production as the thymus involutes with age
T cell progenitors don’t commit until they reach the ___
thymus
give an overview of T cell development, including check points
thymic location influences ___
T cell development
describe how thymic location influences T cell development
describe how gene rearrangement dictates T cell lineage
- beta, gamma, and delta genes rearrange first
- gamma or delta rearrangement suppresses beta and alpha
- gamma:delta T cells leave the thymus with little selection
- beta chain production drives CD4 and CD8 expression
- double positive
___ formation initiates the ___ lineage
- beta chain
- alpha:beta
describe how beta chain formation initiates the alpha:beta lineage
beta chain rearrangement forms the ___
pre-TCR
describe beta chain rearrangement
- occurs first
- four attempts
- two attempts per locus
- two genes
- the beta chain locus is organized differently than immunoglobulin chains
- Vbeta - Dbeta - Jbeta → Vbeta - DJbeta
- Vbeta - DJbeta → VDJbeta
describe how beta chain rearrangement forms pre-T cells receptors
- first checkpoint
- beta chain binds a surrogate alpha chain analogue (pTalpha)
- assembles CD3 complex
- signaling drives further development
- RAG function halts
- proliferation
alpha chain rearrangement occurs in ___
pre-T cells
the alpha chain locus can sustain many attempts at a ___
functional rearrangement
describe alpha chain rearrangement
- occurs in pre-T cells
- follows proliferation and CD4/8 expression
- may still develop into gamma:delta T cells
- alpha chain rearrangement excludes gamma:delta T cells
- rearrangement of an alpha chain gene always eliminates the linked delta chain locus
which thymocyte has no CD4 or CD8?
double negative thymocytes
which thymocytes have both CD4 and CD8?
double positive thymocyte
___ and ___ matures thymocytes
positive and negative selection
what do positive selection and negative selection do?
- positive selection - functional TCR
- negative selection - no self-antigen binding
describe positive and negative selection that matures thymocytes
___ selection ensures MHC is bound
positive
during positive selection, ___ cells present MHC I/II: self-peptide complexes. ___ must bind MHC within 3-4 days (alpha chain rearrangement can occur, and binding turns off RAG1/2 complex). weak or no binding of TCR to MHC results in ___, whereas moderate or strong binding results in ___. this is the ___ checkpoint.
- epithelial
- TCR
- apoptosis
- survival
- second
___ selection determines CD4 or CD8 expression
positive
___ selection prevents self-antigen binding
negative
during negative selection, ___ and ___ present self peptides. moderate binding allows the T cell to ___. excessive binding induces ___.
- dendritic cells and macrophages
- live
- apoptosis
following selection, T cells are considered ___. at this point, they can still undergo ___
- naive and mature
- differentiation
mature, naive T cells enter the ___
blood stream
they enter a draining lympho node by two routes: in the blood or in the afferent lymph coming from an upstream lymph node
___ is the signaling component of the TCR
CD3
cortical epithelial cells in the thymus release ___, which is a signaling molecule that tells T cells that they are in the right spot and induces responsivity to ___. these signals allow a ___ to become a ___.
- notch1 - T cell transcription factor complex
- IL-7
- these signals allow an uncommitted T cell progenitor to become a double negative thymocyte committed to the T-cell lineage
during beta rearrangement, what happens if delta:gamma rearrangement happens before beta rearrangement?
the T cell will become a delta:gamma T cell
the same is true for alpha rearrangement - if delta:gamma rearrangement occurs before alpha rearrangement, it will be come a delta:gamma T cell
delta:gamma T cells are not as common as alpha:beta
during beta chain rearrangement, which protein is turned off to allow for proliferation?
RAG
it is then turned back on after proliferation
