Tolerance Flashcards Preview

Hugh's MD1 Neuro > Tolerance > Flashcards

Flashcards in Tolerance Deck (24):
1

What happens to T cells that are recognise their peptide of MHC but don't get the second signal (CD80/86)

They fail to proliferate > inactivate > anergy

1

What is the difference between nTregs and iTregs?

nTregs develop in the thymus

iTreg differentiate in the periphery from naive T cells in response to TGFbeta

2

What is the transcription factor for Tregs?

FoxP3

2

How does CTLA-4 would to tone down the T cell response?

Activated T cells express CTLA-4, this binds strongly to B7 on APCs. When these two interact, a inhibitory signal is sent to the T cells in order to tone down IL-2 production

3

What anti-inflammatory mediators do Tregs produce?

IL-10

TGFbeta

4

What are the 3 key factors that lead to autoimmunity?

Genetic susceptibility (mainly via HLA)

Environment

Loss of self-tolerance

5

Where does central tolerance occur for B cells?

Bone marrow

6

What signal causes differentiation of naive T cells into Tregs?

TGFbeta

7

What is an important cause of loss of central tolerance?

Loss of AIRE

8

What is the function of AIRE?

Facilitates expression of self-ag's that wouldn't otherwise be found in the thymus so that new TCRs can be tested for self-reactivity.

9

Do autoimmune response always lead to autoimmune disease?

No, sometimes they are self-limiting

11

What is positive selection?

Only TCRs that can recognise self-MHC are selected to survive. If they can't, they die by neglect

11

What is the bystander effect?

Infectious agent causes damage releasing self ag and activating DCs > nearby self reactive T cell can receive both signals from a DC

13

What happens to B cells that exhibit extensive self reactivity in the bone marrow?

They are killed

14

What is molecular mimicry?

A foreign ag has a similar structure to a self ag so that ab's against the foreign ag also targets the self ag.

 

Eg M protein from strep causing rheumatic heart disease

15

Why don't all autoreactive lymphocytes get activated?

They do see their antigen

They don't get the co-stim signal for APCs

They (B cells) don't get the signal from T cells

16

What are some important causes of loss of peripheral tolerance?

Defect in FoxP3

Loss of Tregs and peripheral tolerance mechanisms

17

At what development stage do T cells undergo positive and negative selection?

Double positive T cells

18

When can B cell peripheral tolerance break down?

When T cells are also self reactive

20

Which cells express AIRE?

Thymic epithelial cells

21

What is negative selection of T cells?

TCR that have too strong affinity to self-MHC are selected against. Die by apoptosis

22

How does peripheral B cell tolerance work?

B cells requires CD40L from T cells for full activation otherwise antigen cross-linking causes the development of only short lived plasma cells. So generally, B cells will only be activated fully in the presence of a foreign antigen that is recognised by the BCR and TCR

23

What is the goldilocks theory?

Only TCRs that are moderately reactive with self-MHC are allowed to survive

24

Where does T cell development occur?

Thymus