Tolerance & Autoimmunity

Question 1

Tolerance does what?

Answer 1

protect us from self-reactive lymphocytes

Question 2

Central tolerance happens where for Ts and Bs?

Answer 2

T-Cells: Thymus

B-Cells: Bone Marrow

Question 3

Peripheral tolerance happens where?

Answer 3

Via Tregs

Question 4

4 ways to induce tolerance:

Answer 4

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

Question 5

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

Answer 5

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

Question 6

What happens to B-cells that:

1. multivalent self reactive
2. soluble self
3. low affinity non-cross linking?

Answer 6

1. apoptosis
2. anergic
3. ignorance

Question 7

peripheral B-cell tolerance happens how? when?

Answer 7

• don’t get CD4 co-stim and they die off

- occurs also via post-somatic hypermutation

Question 8

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

Answer 8

1. DN = double negative: not CD4 or CD8

2. DP = double positive: both CD4 & 8 then differentiate and commit

Question 9

what is positive selection?

Answer 9

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

Question 10

what is negative selection?

Answer 10

T-cells that react too strongly to self are removed

Question 11

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

Answer 11

death by neglect

Question 12

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

Answer 12

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

Question 13

what happens if you have defects in AIRE?

Answer 13

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

Question 14

T-cells in central tolerance happens how?

Answer 14

deletion

selection of T-regs

Question 15

T-cells in peripheral tolerance happens how?

Answer 15

deletion
anergy
ignorance
regulation

Question 16

How do T-cells become anergic?

Answer 16

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

Question 17

Tregs suppress ? via which cytokines? 3

Answer 17

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

Question 18

nTregs from where?

Answer 18

thymus during T-cell development

Question 19

iTregs from where?

Answer 19

from naive CD4 in presence of TGF-B

Question 20

3 components of autoimmunity:

Answer 20

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

Question 21

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

Answer 21

ignorance

Question 22

How do you control an autoreactive B-cell?

Answer 22

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

Question 23

autoimmune response always with autoimmune disease?

Answer 23

Yes

Question 24

autoimmune disease automatically if you have autoimmune response?

Answer 24

Nope. Response does not equal disease

Question 25

autoimmunity is defined as?

Answer 25

chronic ongoing autoimmune response with ongoing tissue damage

Question 26

B-cells in autoimmunity do what?

Answer 26

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

Question 27

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

Answer 27

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

Question 28

2 classifications of autoimmune disease

Answer 28

1. Organ specific: eg. DM1, MS, myasthenia gravis

2. systemic: Lupus, RA

Question 29

What does Foxp3 gene do?

Answer 29

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

Question 30

central loss of tolerance happens how?

Answer 30

defect in AIRE gene

Question 31

Multiple sclerosis happens how immunologically?

Answer 31

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

Question 32

what is associated with MS remission?

Answer 32

Th2 responses

Question 33

How do autoimmune diseases bystander effect begin?

Answer 33

1. recognition of self-antigen in presence of inflammation

2. activate DCs/co-stim with self antigens

Question 34

How do autoimmune diseases molecular mimicry effect begin?

Answer 34

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