Flashcards in Lecture 20: Perturbations in the Super System Deck (40)
What is a superantigen?
a bacteria or virus that has developed ways to circumvent our immune system
What 3 major ways do superantigens differ from conventional peptide antigens?
1) React with MHC class II in UNPROCESSED form (is not taken up, digested, and presented)
2) the binding portion of the TCR that reacts with them is NOT within the classic peptide binding groove or antigen specific antibody receptor on B cells but on the SIDE of mononuclear MHC Class II TCR complex
3) elicit massive, immediate primary polyclonal response in T cells
Go over the 3 differences present in a superantigen again?
1) binds to MHC sideways
2) binds to MHC unprocessed
3) elicits massive polyclonal T cell response
What is the effect of superantigens?
cause MASSIVE outpouring of pro-inflammatory cytokines (can lead to severe cytokine storms)
essentially starts a huge TMMI which leads to huge macrophage activation
What is toxic shock syndrome?
massive release of TNFa in response to a superantigen (releases IFNy which activates macs which release TNFa)
TNFa leads to loss of endothelial integrity, decreased vascular resistance, and ultimately shock
What are 3 ways viruses can mediate their effects to evade immune response?
1) increase/decrease production of cytokines
2) upregulate or suppress cytokine receptor display
3) make soluble decoys
shock sydromes are usually caused by _____________
What causes cytokine storm?
rapid activation of T cells
The intensity of the superantigen response is dependent on what?
host's MHC Class II polymorphism
Why are superantigens an ineloquent way to get around the immune response?
because the host doesnt last long (dies soon)
problematic for viruses which require living host
Successful viruses are those that evolved ways to do what?
1) sneak past innate alarm systems like TLRs
2) hijack host genes that are used to modify for suppress immune responses
What is the third highest cause of morbidity and mortality?
True or False: autoimmune disease is caused by self reactive T and B cells
Do genetics play any role in autoimmune disease?
yes! (why monozygotic twins are at greater risk)
Does environment play a role in autoimmune disease?
yes! gluten/celiacs, MS/higher latitudes, etc
What are the 2 major types of tolerance?
Central and peripheral
Describe central tolerance for T cells in the thymus
- negative and positive selection. Positive selects for T cells that recognize host MHC while negative selection selects against those that recognize host (self-reactive T cells)
AIRE driven development of Tregs
How stringent is central tolerance for T cells in the thymus?
VERY 98% of T cells die
What is a main way the thymus prevents autoimmunity?
AIRE (gene expressed and shows maturing T cells host antigens to make sure they won't react)
What happens if a self-epitope is missing from the AIRE presentation?
an auto-reactive cell slips through the thymus and goes out into the periphery
What is the MAIN effector of peripheral tolerance for T cells?
What are the CD markers of Tregs?
4 and 25
What two cytokines can produce Tregs in the periphery during immune reactions?
IL-10 and TGFb
When you see TGFb out in the periphery, what should you think?
it is trying to turn the immune response down
What controls/mediates Treg function?
CTLA4 (controlled by FoxP3) acts as a break
Tregs are influenced by the ratio of _____ to _____
IL-6 to TGFb
Tregs are dependent on which cytokine for growth?
What is HUGE site of peripheral tolerance (relatively new)?
How is tolerance established in the gut?
symbiont PAMPs drive TLRs to induce tolerance