Tolerance & Autoimmunity Flashcards Preview

Jason's Neuro Block > Tolerance & Autoimmunity > Flashcards

Flashcards in Tolerance & Autoimmunity Deck (34):
1

Tolerance does what?

protect us from self-reactive lymphocytes

2

Central tolerance happens where for Ts and Bs?

T-Cells: Thymus
B-Cells: Bone Marrow

3

Peripheral tolerance happens where?

Via Tregs

4

4 ways to induce tolerance:

1. delete
2. anergize
3. ignore
4. regulate

5

Compare B-cell vs. T-cell tolerance very generally

B-cell tolerance is less efficient than T-cell tolerance

6

What happens to B-cells that:
1. multivalent self reactive
2. soluble self
3. low affinity non-cross linking?

1. apoptosis
2. anergic
3. ignorance

7

peripheral B-cell tolerance happens how? when?

-don't get CD4 co-stim and they die off
-occurs also via post-somatic hypermutation

8

T-cell in thymus: what are DN? DP?

1. DN = double negative: not CD4 or CD8
2. DP = double positive: both CD4 & 8 then differentiate and commit

9

what is positive selection?

T-cells kept for recognizing self MHC but not too strongly

10

what is negative selection?

T-cells that react too strongly to self are removed

11

what happens to T-cells that don't recognize MHC at all?

death by neglect

12

What is autoimmune regulator of expression (AIRE) transcription factor?

It turns on certain genes in thymic epithelial cells that looks like organ tissues to make the T-cells tolerant to all body structures

13

what happens if you have defects in AIRE?

get autoimmunity because AIRE not there to negative select reactive T-cells that react to organ tissues

14

T-cells in central tolerance happens how?

deletion
selection of T-regs

15

T-cells in peripheral tolerance happens how?

deletion
anergy
ignorance
regulation

16

How do T-cells become anergic?

They don't get the costim (signal 2), and inactivate

17

Tregs suppress ? via which cytokines? 3

all types of T-cells
TGFB
CD25, IL-10

18

nTregs from where?

thymus during T-cell development

19

iTregs from where?

from naive CD4 in presence of TGF-B

20

3 components of autoimmunity:

1. genetic
2. environmental
3. loss of self-tolerance

21

what is it called when antigen is not availble to T-cell?

ignorance

22

How do you control an autoreactive B-cell?

let it die out, no CD4 T-cell co-stim = no maturation = short lived.

23

autoimmune response always with autoimmune disease?

Yes

24

autoimmune disease automatically if you have autoimmune response?

Nope. Response does not equal disease

25

autoimmunity is defined as?

chronic ongoing autoimmune response with ongoing tissue damage

26

B-cells in autoimmunity do what?

make autoantibodies: TypeII Grave's, Type III immune complexes (lupus)

27

T-cells in autoimmunity do what? 3 things, which diseases

1. help b-cells
2. release cytokines
3. CTL killing of stromal cells (DM1, MS)

28

2 classifications of autoimmune disease

1. Organ specific: eg. DM1, MS, myasthenia gravis
2. systemic: Lupus, RA

29

What does Foxp3 gene do?

makes naive CD4s into T-regs to allow for peripheral tolerance

30

central loss of tolerance happens how?

defect in AIRE gene

31

Multiple sclerosis happens how immunologically?

polygenic
CD4 Tcells degrade myelin via Th1-Th17
dysregulation of Tregs

32

what is associated with MS remission?

Th2 responses

33

How do autoimmune diseases bystander effect begin?

1. recognition of self-antigen in presence of inflammation
2. activate DCs/co-stim with self antigens

34

How do autoimmune diseases molecular mimicry effect begin?

pathogen antigens similar to tissues, cross react with autoreactive T/B cells. eg. rheumatic fever