Perturbations Super System

Question 1

What is a superantigen response?

Answer 1

certain bacteria and viruses secrete toxins that bridge CD4 to MHC class 2 and fool CD4 into thinking a specific antigen has been seen and a costimulatory signal has been given

• can activate up to 20% of available CD4 cells
• elicits a POLYCLONAL T cell response

Question 2

How efficient is the superantigen response? Does it affect everyone the same?

Answer 2

• least efficient way bacteria use to circumvent immune responses
• degree of activation varies with MHC2 locus polymorphism

Question 3

What does the activation of so many CD4s in the superantigen response lead to?

Answer 3

Huge TMMI response
macrophage activation
proinflammatory cytokines
**Systemic Toxicity

• can lead to cytokine storm
• inefficient cause host will die pretty fast

Question 4

What type of hypersensitivity would a superantigen induce?

Answer 4

Delayed hypersensitivity–uncontrolled TMMI

Question 5

What are the steps of a super antigen?

Answer 5

1. bridge CD4 and Mac
2. Th1 makes huge amount of INF gamma
3. Macrophages release huge amount of TNF alpha
4. loss of endothelial integrity, decreased vascular resistance
5. shock
6. death

Question 6

What are strategies that pathogens evade the immune response through MHC and cytokines?

Answer 6

1. take over ways the apcs alert the immune response that they are infected (MHC)
2. increase or decrease cytokine production
3. upregulate or suppress cytokine receptor display
4. make soluble decoys

Question 7

What are other ways pathogens can evade the immune system?

Answer 7

1. downregulate TLRs
2. steal immune genes to their advantage
3. inhibit apoptosis by increasing BcL display or blocking caspase system
4. induce Cd4,25 t cell production that specifically blocks responses against them
5. suppress DC function
6. worms can prevent IgE
7. Bacteria can hide until favorable
8. express suppressive microRNAs -prevent cell from making viral response

Question 8

What do viruses infected cells secrete?

Answer 8

1. cytokine inhibitors
2. cytokine mimics
3. complement inhibitors
4. protease inhibitors

Question 9

What are some examples of common autoimmune diseases?

Answer 9

1. lupus
2. rheumatoid arthritis
3. diabetes
4. MS
5. celiac disease

Question 10

Just because someone has autoantibodies does it mean they have autoimmune disease?

Answer 10

no

Question 11

What plays a role in autoimmune?

Answer 11

genes, sex, environment(gluten)

Question 12

Is there a change in distribution from normal in autoimmune disease (such as for diabetes)?

Answer 12

yes

tremendous skewing of certain inherited MHC that put children at higher risk for diabetes

Question 13

What is central tolerance?

Answer 13

T cell related
-maintenance of central tolerance that develops by thymic deletion of self-reactive thymocytes
AIRE driven development of Tregs

Question 14

What does AIRE do with some cells that are mildly autoreactive?

Answer 14

converts them to tregs

Question 15

What happens if AIRE is missing a self epitope?

Answer 15

now you have an anti-something coming through and aire wont recognize it so it lets it though, now you have an auto- cell out there

Question 16

What is peripheral tolerance?

Answer 16

Fox P3, CD4, 25 cells that have emigrated from the thymus

or developed in periphery as a regulatory step during an immune reaction by induction with TGF-B or IL 10

-increasing evidence that AIRE is also expressed in peripheral lymphoid tissue and mandates regional tolerance

Question 17

What is Treg function controlled by?

Answer 17

CTLA which is controlled by FOxP3

CTLA 4 on T-cells act as brake

Tregs are influenced by ratio of TGF b to IL 6

Need IL2 but can’t make it

Polymorphisms of IL2 sources can determine T reg function

Question 18

What is the newest thing in peripheral tolerance?

Answer 18

gut
-bacteria are symbionts that exploit our TLR system with their PAMPs–>drive TLRs to induce tolerance, not activation of the innate immune system

-bacteria can hydrolyze fiber to short chain fatty acids that promote T reg homeostasis (too much or too little bad)

Question 19

When does autoimmunity occur?

Answer 19

When central tolerance or peripheral tolerance fails

Question 20

What are 4 defects in Tcell tolerance lead that can lead to autoimmunity?

Answer 20

1. inadequate display of AIRE in thymus/complete loss of AIRE(multiple auto-immune endocrine diseases)
2. Complete loss of FoxP3 function mutation (widespread T and B autoimmune reaction)
3. Partial loss of CTLA 4 gene (complete loss is fatal)
4. MUST FIND FROM SMALL GROUP!!

Question 21

Tolerance can also depend on?

Answer 21

TLR function

DC function

Question 22

How is it possible Diabetes type 1 works?

Answer 22

1. viruses directly infect pancreatic beta cells and initiate CD8 attack against them
2. Exhibit antigens that mimic beta cell antigens and CD8 mistakenly attack beta cells
3. infect non beta cell sites in the pancreas and incite collateral damage to beta cells (such as in TMMI response)

Question 23

Where do you find Th17 cells?

Answer 23

autoinflammatory sites
-chronic inflammation- neutrophils

-same as normal Th17 but now the antigen is “self”

(acute neutrophil is 8)

Question 24

What are some ideas of why DC signaling favors IL 23?

Answer 24

1. viral or hormonal induced loss of T reg enforcement
2. genetic differences in TLR, DC
3. aire defects

Question 25

Are there autoreactive B cell antibodies?

Answer 25

yes but usually not destructive, because matching autoreactive t-cell won’t be there