breakout 7 Flashcards
central tolerance occurs during
lymphocyte development
in central tolerance, B cells in
bone marrow
in central tolerance, T cells in
thymus
peripheral tolerance
occurs in other part of the body, including lymph nodes
in peripheral tolerance, B cells can become
anergic
in peripheral tolerance, T cells can become
anergic or undergo apoptosis
anergizing BCR signaling
hypophosphorylated ITAM inhibits NF-kB
deleting BCR signaling
hyperphosphorylated ITAM leads to increase ERK1/2
In the absence of T cell help, B cells that recognize self
antigen in periphery become anergic bc they have no survival signals from T cell
Central T lymphocyte tolerance occurs in
thymus
central T lymphocyte tolerance involves
immature “double positive” T cells and strong recognition to antigens results in apoptosis
T cells that recognize self antigen in thymus undergo
apoptosis
antigen presentation, in absence of co-stim by B7-CD28 results in
T cell anergy
why is co-stim needed for T cells?
- B7-CD28 co-stim is necessary to stabilize IL-2 production
- IL-2 necessary for T cell survival
mechanisms of peripheral T cell tolerance:
anergy and costimulation
CD28 : CD80/86 interaction
increases IL-2 transcription
stabilizes IL-2 transcripts
results of CD28:CD80/86 interaction
self reactive cell receives:
no CD28 stimulation
lack of sufficient IL-2
anergized T cell
Mechanisms of Peripheral T cell tolerance:
deletion and overstimulation
excessive signaling of TCR by self antigen leads to induction of apoptosis thorugh Fas/FasL interactions
Peripheral T cell tolerance:
regulatory T cells
subpopulation of T cells that can inhibit activation of T cells that secrete IL-10 and TGF-beta to suppress inflammation
what could tregs be used for
autoimmune diseases and transplant rejection
B cells center tolerance:
anergy -> antigen type, conc, phosphorylation, signaling reponse
soluble, low, hypo, loss of NFkB
B cells central tolerance:
apoptosis -> antigen type, conc, phosphorylation, signaling, response
multi-variant, high, hyper, ERK1/2
B cells peripheral tolerance:
anergy -> survival signal, response
lack of BAFF, Lack of T cell help
T cells central tolerance:
apoptosis -> cell type, antigen binding
CD4+CD8+ T cells and tight binding
T cells peripheral tolerance:
anergy -> survival signal, response
reduced IL-2 and lack of T cell help
