Lecture 11: Cellular basis for immunological tolerance Flashcards Preview

Host Defense > Lecture 11: Cellular basis for immunological tolerance > Flashcards

Flashcards in Lecture 11: Cellular basis for immunological tolerance Deck (31)
1

Define immunological tolerance:

non-responsiveness to specific antigens

2

What are some examples of tolerance?

antigens from self-tissues, foods, commensal bacterium, pregnancy

3

What is the relationship between tumors and immunological tolerance?

tumors impair anti-tumor immunity

4

What is the relationship between tumors and immunological tolerance?

tumors impair anti-tumor immunity

5

Tolerance is induced by what two mechanisms?

1) Central
2) Peripheral

6

What is central tolerance?

elimination of T cells that are reactive to antigens present in the thymus (self antigens)

7

What is peripheral tolerance?

- Tregs (impose suppression to other T cells and accessory cells)
- MDSCs (myeloid derived suppressor cells) myeloid cells that become potent immunoregulatory cells when exposed to inflammatory cytokines like IFNy and kill activated T cells to prevent further stimulation
- Anergy (when T cells are stimulated in a manner that are not "complete" cells become non-responsive to further stimulation

8

What gene allows for thymic negative selection?

AIRE

enables stromal cells to express non-thymic genes and present self-antigens to developing thymocytes

9

What is Hassall's corpuscles important for?

site for generation of regulatory T cells

(cells that have intermediate affinity to self-antigens and are not eliminated by negative selection mature into Foxp3 Tregs)

10

What happens in patients without AIRE?

severe auto-recessive genetic autoimmune disorder

11

What are nTregs?

professional T regulatory cells that impose suppression of other immune cells (T cells)

12

nTregs antigen diversity is limited to _______

self antigens (generated in the thymus due to high affinity against antigens present in the thymus)

13

What are iTregs?

Tregs that can be manipulated by environment (food), commensals, pathogens, tumor

14

iTregs are induced by APCs that are present where?

mucosal environment (intestine)

15

What are cofactors to induce iTregs?

Vitamin A and/or D

16

What inflammatory cytokine is INHIBITORY for induction of iTregs?

IL-6

17

Which 2 cytokines play a major role in iTreg development?

IL-2
TGFb

18

What are Tr1 cells?

produce immunosuppressive IL-10
(and are produced by high amounts of IL-10)

19

Which two cytokines induce development of Tr1 cells?

TGFb
IL-27

20

Are Tr1 cells Foxp3+?

NO

21

What disease results from failure of peripheral tolerance?

IPEX (immune dysregulation, polyendocirnopathy, enteropathy, X-linked)

22

What is IPEX?

systemic autoimmunity (in the 1st year of life)
characterized by LOSS of Foxp3

23

What are MDSCs?

Myeloid Derived Suppressor Cells (heterogeneous population of cells that are defined by myeloid origin and ability to potently suppress T cell responses)

24

What cytokine can activate MDSCs?

IFNy (usually around from pre-existing inflammation)

25

MDSCs are promising therapeutically for what?

anti-tumor responses or to inhibit immune responses for treatment of autoimmune disease or transplant rejection

26

When might a cell be "partially stimulated" and undergo anergy?

When naive T cells are presented antigens in the absence of the CD28 second signal

27

Why do cells that get antigen but not via CD28 signaling die?

because the ligand for CD28 (CD80, 86) is only on a few APCs so when T cells get antigen from other cells, it isn't right.

28

What is CTLA-4?

something expressed by T cells after activation and competes with CD28 for B7 binding

29

What has a higher affinity for B7, CD28 or CTLA-4?

CTLA-4 (wins the competition) and recruits signaling molecules that suppress TCR signaling/blocking antigen activation

30

How are CTLA-4s used to prevent runaway T cell proliferation?

CTLA-4 production increases during antigen-activation of T cells (so it will bind to B7 and outcompete T cell)

31

How are CTLA-4s used in graft vs host disease?

used to block T cell activation from the outside
(accomplished via CTLA-4 IG)