Regulating Acquired Immunity Flashcards
What is tolerance
Removing/stopping responses which are auto immune responses. Eg tcr binding self ag
Are all self ag like insulin present in the thymus?
No they are tissue specific
How do you negatively select for self ag which aren’t present in thymus
Tf AIRE
overrides tissue specific ag and allows expression of eg insulin in the thymus for T cell negative selection
What would aire deficiency cause
Possible Autoimmune responses when T cells leave thymus and not negatively selected for a self ag
B cells undergo receptor editing instead of apoptosis sometimes after negative selection. Do T cells?
Yes T cells can also rearrange their tcr a chain to make them non self reactive = built tolerance
When do B cells become anergic (a type of tolerance mechanism)
If they don’t respond to MULTIVALENT self antigens in bone marrow but recognise self ag
Downregulate their bcr
How do T cells become anergic
If receive no signal 2 in periphery via co stimulators like B7
Some apc don’t have this
Why do some apc not present co stimulators like B7 causing T cell anergy
For them to produce B7 etc they need pamps detection on prr
If the cell is not infected it won’t receive pamps and therefore no costimulator for signal 2
(Reminder MHC always presenting a peptide but not necessarily ag)
What is immunological ignorance
Ag not presented at a sufficient level for b/t cell stimulation = tolerance
What are immunological privilege sites
Areas where immune cells can’t respond to ag bc of barriers and suppressive cytokines eg bbb and the eye / cns
Why is T cell tolerance eg via anergy or receptor editing more important than B cell
Auto reactive B cells need T cell help via t/b conjugates for stimulation which they won’t receive if no T cells available
What are natural t regs made from
T cells which escaped death after negative selection in the medulla
They got converted into t regs which block action of other self reactive T cells = tolerance
Which tf kept T cells negatively selected alive to become natural t regs instead
Fox p3
What induces fox p3 and therefore production of t regs
Tgf b
And
Retinoic acid
What is the different between induced IT reg cells and natural reg cells
It reg cells are from cells escaping negative selection in the periphery via fox p3
They also block action of self reactive T cells
What happens if you have no t reg cells
Autoimmune diseases eg ipex mutation to fox p3
What do t regs release which is suppressing ie stops apc
Il 10 and tgf b
B regs also exist, how do they work
Also release il 10 which is a suppressive cytokine suppressing apc
What is it called when polarisation of T cells is correct for the correct type of pathogen
Quantitatively appropriate
Can CD8 also be t regs
Yes
What is not needed anymore after T cell polarity
Co stimulators
How do th1 promote their own proliferation
Releasing ifn y which induces them in signal 3 (and il 2 release)
How to th1 activate macrophage killing ‘foamy cells’
They have cd40L which binds to cd40 xo stimulator on macrophages and signals
Other than macrophages what other cells do th1 activate
NK and cd8
