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
How do th1 kill ill macrophages
Fas ligand
Which cytokine induces th2 and is released by th2
Il4
What does th2 do
Eosinophil and mast cell stimulation (both have granules)
Also Ige switching
What T cells are induced by tgf b
T reg and th17
What T cells are induced by il 6
Tfh and th17
What are th17 for
Attract cells like neutrophils to kill fungi mainly
How is effector type determined by pathogen
Pathogen determines pamps
Pamps determine signals down prr
Apc will produce diff cytokines eg il 6 if it’s a fungi to stimulate th17
How does th1 and th2 work antagonistically
Production of Gata 3 tf for th2 production blocks tf T bet which induces th1
Vice versa
Gata 3 Vs T bet
What cells are also inhibited by th1 and th2 responses
Th 17
Which cells do t reg inhibit
Th1,2,17
What would happen if polarisation didn’t occur for th2
Th2 would cause excessive allergy responses if not blocked by T bet
Why is t reg important in pregnancy
Baby have foreign ag which would be attacked by mother’s CD4 and 8 if t regs didn’t suppress apc via il 10 and tgf b
