5. Tolerance Flashcards
t cell central tolerance
positive selection: in cortex of thymus, kept if respond to MHCI, apoptosed if not
negative selection: in medulla of thymus, apoptosed if respond to self-antigens, kept if not
b cell central tolerance
if respond to self-antigens:
- high affinity BCR undergo receptor editing
- unsuccessful receptor editing are apoptosed
- weak recognition undergo anergy stimulation (unresponsive)
disadvantage of tolerance
depletes the repertoire - less diversity for new and unseen pathogens
may be needed for tumours or regulating inflammation
t cell peripheral tolerance (names of processes)
ignorance, anergy, apoptosis and Tregs
t cell ignorance
hidden/sequestered in certain places (eye, BBB), insufficient activation in low doses, only expressed at certain times (eg puberty) so not selected during early development
apoptosis of t cells
activation of fas and fasL, Bax, Bad and Bim (BCL2)
Treg types
natural vs inducible
CD4 vs CD8
FoxP3 expression
cell contact dependent Treg action
perforin and granzymes
CTLA4 expression
cell contact independent Treg action
IL10 and TGFb secretion
IL2 clearance
b cell peripheral tolerance
anergy/exhaustion - chronic, low level
apoptosis - acute, high level
exclusion - partially activated, dont develop into plasma cells, dont enter lymphoid follicles
uncontrollable immune responses arise from…
allergy, autoimmunity, transplants
pathogenesis of most autoimmune disorders
genetic: HLADQ, DR
environmental: food, deficiencies, microbes
immunity: vitD deficiency and disrupted by leaky gut
affect women more
