Tolerance Flashcards

1
Q

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

A

They fail to proliferate > inactivate > anergy

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1
Q

What is the difference between nTregs and iTregs?

A

nTregs develop in the thymus

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

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2
Q

What is the transcription factor for Tregs?

A

FoxP3

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2
Q

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

A

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

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3
Q

What anti-inflammatory mediators do Tregs produce?

A

IL-10

TGFbeta

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4
Q

What are the 3 key factors that lead to autoimmunity?

A

Genetic susceptibility (mainly via HLA)

Environment

Loss of self-tolerance

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5
Q

Where does central tolerance occur for B cells?

A

Bone marrow

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6
Q

What signal causes differentiation of naive T cells into Tregs?

A

TGFbeta

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7
Q

What is an important cause of loss of central tolerance?

A

Loss of AIRE

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8
Q

What is the function of AIRE?

A

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.

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9
Q

Do autoimmune response always lead to autoimmune disease?

A

No, sometimes they are self-limiting

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11
Q

What is positive selection?

A

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

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11
Q

What is the bystander effect?

A

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

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13
Q

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

A

They are killed

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14
Q

What is molecular mimicry?

A

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

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15
Q

Why don’t all autoreactive lymphocytes get activated?

A

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
Q

What are some important causes of loss of peripheral tolerance?

A

Defect in FoxP3

Loss of Tregs and peripheral tolerance mechanisms

17
Q

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

A

Double positive T cells

18
Q

When can B cell peripheral tolerance break down?

A

When T cells are also self reactive

20
Q

Which cells express AIRE?

A

Thymic epithelial cells

21
Q

What is negative selection of T cells?

A

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

22
Q

How does peripheral B cell tolerance work?

A

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
Q

What is the goldilocks theory?

A

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

24
Q

Where does T cell development occur?

A

Thymus