Lecture 20: Perturbations in the Super System Flashcards Preview

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Flashcards in Lecture 20: Perturbations in the Super System Deck (40)
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1

What is a superantigen?

a bacteria or virus that has developed ways to circumvent our immune system

2

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

3

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

4

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

5

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

6

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

7

shock sydromes are usually caused by _____________

superantigens

8

What causes cytokine storm?

rapid activation of T cells

9

The intensity of the superantigen response is dependent on what?

host's MHC Class II polymorphism

10

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

11

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

12

What is the third highest cause of morbidity and mortality?

autoimmune disease

13

True or False: autoimmune disease is caused by self reactive T and B cells

true

14

Do genetics play any role in autoimmune disease?

yes! (why monozygotic twins are at greater risk)

15

Does environment play a role in autoimmune disease?

yes! gluten/celiacs, MS/higher latitudes, etc

16

What are the 2 major types of tolerance?

Central and peripheral

17

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

18

How stringent is central tolerance for T cells in the thymus?

VERY 98% of T cells die

19

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)

20

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

21

What is the MAIN effector of peripheral tolerance for T cells?

Tregs

22

What are the CD markers of Tregs?

4 and 25

23

What two cytokines can produce Tregs in the periphery during immune reactions?

IL-10 and TGFb

24

When you see TGFb out in the periphery, what should you think?

it is trying to turn the immune response down

25

What controls/mediates Treg function?

CTLA4 (controlled by FoxP3) acts as a break

26

Tregs are influenced by the ratio of _____ to _____

IL-6 to TGFb

27

Tregs are dependent on which cytokine for growth?

IL-2

28

What is HUGE site of peripheral tolerance (relatively new)?

the gut

29

How is tolerance established in the gut?

symbiont PAMPs drive TLRs to induce tolerance

30

What happens if you are missing AIRE gene?

multiple autoimmune diseases