Dr. Fernandez Flashcards
which signals from the thymus drive T cell development
NOTCH, IL-7
NOTCH leads to
protease cleavage of intracellular domain–> soluble domain removes repressive transcription factors and turns on expression of genes
IL-7 is secreted by ____
thymic stromal cells
role of IL-7
drives survival, proliferation, differentiation
where does positive selection occur
cortex
where does negative selection occur
medulla
what happens in positive selection
binding of TCR to thymic MHC is tested–> if it binds cell survives and thymocyte maturation continues. If weak or no binding–> apoptosis
what happens in negative selection
removes T cells that strongly bind to self peptides, AIRE expression plays a role in negative selection
what is AIRE
autoimmune regulator
what cell types help mediate negative selection
dendritic cells and macrophages
functional changes with dendritic cells
endocytosis, morphological changes in lymph nodes, maturation
what pathways do dendritic cells use to process and present antigens
micropinocytosis, macropinocytosis
only ____ cells contribute to the activation of naive T cells
dendritic
what are 3 processes that help T cells enter lymph nodes during infection
T cell adhesion molecules interact w/ adhesion molecules on the vascular endothelium in lymph node, chemokines direct T cells to enter lymph node, T cell squeezes thru endothelial cells
___, ____, and ___ are involved of homing T cells into lymph nodes
naive T cell L-selectin, LFA-1, CCR7
T cell ____ and dendritic cell ____ are needed for T cells to assess antigens
T cell LFA-1 and dendritic cell ICAM-1
first signal required for T cell activation
TCR recognition of antigen and MHC, CD4/CD8 co-receptors binding to MHC
second signal required for T cell activation
co-stimulatory: T cell CD28 receptor binding to B7 ligand on dendritic cell
what suppresses T cell activation
CTLA-4
how does CTLA-4 suppress T cell activation
it competes with CD28 for B7 ligand; it has a higher binding affinity for CD28
what does CTLA-4 play a role in
tolerance to self-antigens
TCR/co-receptor/co-stimulatory signals lead to activation of ___
a series of kinases
what are the primary kinases involved in T cell activation
LCK and ZAP70
what does LCK do
phosphorylates the intracellular chains of the CD3 zeta chain (ITAMS) and then ZAP-70 docks on
