chapter 8 Flashcards
VERY early thymocyte development occurs in the _____________________
bone marrow
Describe T cell development starting from the bone marrow:
-T-cell precursors begin their travel through the thymus at the cortex
-T-cells that survive selection migrate into the medulla
What happens during the positive/negative selection stages?
the cell becomes a single positive CD4+ or CD8+
Recombination of TCR gene segments also occurs in the DN stages, yielding either _______________T cell
an αβ or a γδ
What is the name of the receptor that commits cells to the T cell lineage?
notch
During which stage does TCR rearrangement begin in?
DN2
Which receptor rearrangements are one of the first to take place?
TCRβ
What is the process of Beta selection that double negative thymocytes undergo?
-A successfully produced β chain is paired with the pre-Tα chain
-After β-selection has occurred, thymocytes are at the DP stage of development
-Pos./neg. selection occurs, yielding mature SP T cell
Double positive thymocytes make up what percentage of thymic cells?
80%
What does positive selection select for?
selects thymocytes bearing receptors capable of binding self-MHC molecules, resulting MHC restriction
What does negative selection select for?
selects against thymocytes bearing high-affinity receptors for self-MHC/self-peptide complexes, resulting in self-tolerance
Most cells (95%) fail positive selection and fail to receive what?
needed survival signals
How does positive selection ensure MHC restriction?
-most cells die by neglect before they could reach a negative selection stage
-those that can bind MHCs shift from DP to SP
Where do thymocytes learn MHC restriction
the thymus
How does negative selection ensure self-tolerance?
-clonal deletion
-clonal arrest
-clonal anergy
-clonal editing
definition of clonal deletion
induction of apoptosis in cells with too strong anti-self signaling/binding
definition of clonal arrest
autoreactive T cells are prevented from maturing further
definition of clonal anergy
autoreactive T cells are inactivated
definition of clonal editing
second or third chances at rearranging a non-self reactive TCRa gene
What is the instructive model of lineage commitment?
-TCR/CD4 and TCR/CD8 co-engagement generate unique signals
-the signals generated instruct the T cells which lineage to fully commit to
what is the stochastic model of lineage commitment?
-positively selected thymocytes randomly downregulate either CD4 or CD8
-only those cells with the correct coreceptor receive signals to continue development
What is the kinetic signaling model of lineage commitment?
-cells commit to the CD4 lineage of they receive a continuous signal
-cells commit to CD8 lineage if the stimulation signal is interrupted
What are the other types of lymphocytes that DP thymocytes may commit to?
-NKT cells
-Intraepithelial lymphocytes
-regulatory T cells
describe NKT cells
-express a TCR with an invariant TCRa chain
-interact with CD2 molecules presenting lipid antigens
describe intraepithelial lymphocytes
usually CD8 but also have features of innate immune cells
describe regulatory T cells
CD4 subset that helps to quench adaptive immunity
what is apoptosis
-programmed cell death without triggering inflammation
-controlled process of dismantling cells
what is necrosis
-results from injury
-release of cell contents=inflammation
