Chapter 9: Immunologic tolerance & autoimmunity

Question 1

A healthy immune system is able to discriminate between

Answer 1

self and nonself antigens

and

commensal from non-commensal microbes

Question 2

failure to prevent a response to self antigens results in…

Answer 2

autoimmunity

Question 3

failure to prevent a response to commensal microbes results in

Answer 3

chronic inflammation

Question 4

What are the principle mechanisms of central T cell tolerance?

Answer 4

• negative selection = deletion (CD4+ and CD8+)
• development of regulatory T cells (CD4+)

Question 5

What are the principle mechanisms of peripheral T cell tolerance?

Answer 5

• anergy
• suppression
• deletion

Question 6

What does deletion do in peripheral T cell tolerance?

Answer 6

apoptosis
- no activation of anti-apoptotic mechanisms (costimulators and cytokines)

Question 7

What does suppresion do in peripheral T cell tolerance?

Answer 7

block in activation using regulatory T cells

Question 8

What does anergy do in peripheral T cell tolerance?

Answer 8

functional unresponsiveness
- TCR does not send activating signal
- T cell engages in inhibitory receptors (CTLA-4 and PD-1)

Question 9

What are the two ways of T cell anergy?

Answer 9

1. TCR does not send activating signal bc of no costimulator
2. T cell engages an inhibitory receptor (CTLA-4 or PD-1)

Question 10

What does inhibitory receptor CTLA-4 do?

Answer 10

blocks and removes B7 costimualtor from antigen presenting cells

Question 11

What does inhibitory receptor PD-1 do?

Answer 11

inhibits signaling within cell

Question 12

What does T cell anergy do?

Answer 12

leads to unresponsive (anergic) T cells

Question 13

Regulatory T cells develop in the…

Answer 13

thymus (mostly) or peripheral tissue

Question 14

How do regulatory T cells supress immune responses?

Answer 14

1. cytokine signaling
2. CTLA-4 expression (removes B7 from APC)
3. high amounts of IL-2 receptor (depletes IL-2 locally)

Question 15

How do peripheral T lymphocytes that do not have self-antigens not go through apoptosis?

Answer 15

anti-apoptotic mechanisms activated by costimulators (B7) and cytokines from APC during a response to a foreign antigen

Question 16

What are the prinicple mechansims of central B cell tolerance?

Answer 16

• apoptosis (deletion)
• reduced receptor expression, signaling (anergic B cell)
• receptor editing: expression of new Ig regions (non-self reactive B cell)

Question 17

What are the prinicple mechansims of peripheral B cell tolerance?

Answer 17

anergy
deletion
regulation by inhibitory receptors

Question 18

What happens when there is a failure of self-tolerance?

Answer 18

• activation of self-reactive lymphocytes
• self-reactive effector lymphocytes
• tissue injury: autoimmune disease

Question 19

What happens when there is an induction of costimulators on APCs to self antigen T cells?

Answer 19

autoimmunity

Question 20

What are ways that self-reactive T cells can result in autoimmunity?

Answer 20

• induction of costimulators of APC
• molecular mimicry