Tolerance Flashcards
Antibody Feedback
B Cells have low-affinity FcgammaR on surface, so increased antibodies and increased ICs can bind B cells and inactivate/block activation of them to control the response
Stimulation of CD4 Th1 Differentiation
Viruses/some bacteria stimulate DCs to produce IL-12, stimulating NK cells to produce IFNgamma which causes differnetiation to Th1
3 Factors (& actions) Released by CD4 Th1s
IFNgamma induces mac killing of intracellulars
IL-2 is Tc GF
TNF-Beta is proinflammatory
Stimulation of CD4 Th2 Differentiation
Worms and other paths cause NK1.1 cells to secrete IL-4, which promotes Th2 differentiation
2 Factors (& actions) Released by CD4 Th2s
IL-4: Bc GF and IgG/E CS
IL-5: IgA CS
Other Parameter that Determines Th1/Th2
Strength of TCR-MHC II binding b/w Tc and APC:
Strong = Th1
Weak = Th2
Th1/2 Negative Regulation (3 molecules)
Th2 releases TNF-Beta which binds Th1 and inhibits, as well as IL-10 which binds macs and reduces costim signal
Th1 releases IFNgamma which inhibits Th2 prolif
4 Tolerance Mechanisms (& when and result)
Clonal Deletion (maturation) -> death Clonal Anergy (mature Bs/Ts) -> LoF Receptor Editing (Bs change specificity) Active Suppression (Tregs on adult Ts) -> LoF
3 Kinds of Signaling to Result in Tolerance
B - Soluble prot - Anergy
Membrane prot - receptor editing or deletion
T - signal 1 without 2 - anergy
IPEX
FoxP3 deficiency, so no functional Treg and get fatal autoimmunity
APECED
Defective Aire gene so you get AI
Sequestration Example
Ts have never seen intraocular prots, but trauma can expose them and cause immune response
Molecular Mimicry Example
Cross reactive antibodies to strep can break tolerance and also attack cardiac tissue, causing rheumatic fever
