Final: Immunological Tolerance and Autoimmunity

Question 1

What is central tolerance?

Answer 1

Induced in immature self-reactive lymphocytes in primary lymphoid organs

Question 2

What is peripheral tolerance?

Answer 2

Induced in mature self-reactive lymphocytes in lymph nodes or peripheral sites

Question 3

What happens to immature lymphocytes that are specific for self-antigens?

Answer 3

1. Deletion by apoptosis
2. Chance in BCR editing
3. Treg development

Question 4

What happens to mature lymphocytes that are specific for self-antigens?

Answer 4

1. Inactivated (anergy)
2. Deleted (apoptosis)
3. Suppressed by Treg

Question 5

Which T cells are positively selected?

Answer 5

T cells that bind to self antigens below a certain threshold

Question 6

How are Treg cells selected?

Answer 6

1. T cells that have strong TCR interactions with self-antigens
2. Can produce anti-apoptotic molecules to protect from negative selection
3. Express FoxP3 and CTLA4
4. Need Cytokine IL 2 for survival

Question 7

How are Treg cells selected in the periphery?

Answer 7

Called induced Treg cells

-FoxP3 expression induced in naive CD4 cells upon Ag recognition in presence of TGF-B and IL-2

Question 8

How are Th17 cells developed?

Answer 8

Needs TGF-B, IL-6, and retinoic acid

Question 9

How do T cells work?

Answer 9

Secrete IL-4, IL-10, TGF-B to promote anti-inflammatory response

Question 10

What are the different mechanisms of tolerance?

Answer 10

1. Functional Unresponsiveness (Anergy)
2. Block in activation (Suppression)
3. Deletion (Apoptosis)

Question 11

How does T cell anergy work?

Answer 11

Treg binds to B7/CD80 with CTLA-4 and PD-1

Question 12

What happens to B cells that have high avidity?

Answer 12

1. Apoptosis

2. Receptor editing

Question 13

What happens to B cells that low avidity?

Answer 13

Anergy

Question 14

What is BCR editing?

Answer 14

1. Pre-B cells recombine locus that encodes K light chain to yield an auto-reactive BCR.
2. B cell is in developmental arrest and continued recombination.
3. Receptor editing of IgL chain

Question 15

How do you attenuate BCR signaling?

Answer 15

Lyn phosphorylates CD22 on B Cell (inhibitor receptor) and recruits SHP-1 tyrosine phosphatase

Question 16

What can lead to B-cell related autoimmunity?

Answer 16

Defects in Lyn, SHP-1 tyrosine phosphatase, CD22 inhibitory receptor

Question 17

How does commensal microbes help the immune system?

Answer 17

Symbiotic bacteria: Inhibit pathogen colonization

• have anti-inflammatory responses
• development of GALT

Question 18

What is AIRE?

Answer 18

AIRE is used in the thymus for negative selection of T cells
-express large number of peripheral self-antigens

If there is a mutation in AIRE, self-reactive T cells are not eliminated

Question 19

How does CTLA-4 inhibit immune cell actions?

Answer 19

Intrinsic: Delivery inhibitory signals
Extrinsic: Makes CD28 unavailable

Question 20

What are immune privileged sites?

Answer 20

Eyes: cornea, anterior chamber, vitreous chamber, sub-retinal space
Brain
Pregnant Uterus
Ovary and Testis
Adrenal Cortex
Hair Follicles

Question 21

How does genetics play a role in autoimmunity?

Answer 21

Problems with MHC genes
Polymorphisms in Non-HLA genes (e.g. CTLA-4)
Environmental factors

Question 22

Autoimmune diseases are associated with class __ HLA alleles

Answer 22

Class II (HLA-DR and HLA-DQ)

Question 23

What is molecular mimicry?

Answer 23

Rheumatic fever triggered by strep infections can cause cross reactivity between strep Ags and cardiac myosin

Question 24

What is polyclonal activation?

Answer 24

Robust inflammatory response

-polyclonal activation of auto-reactive lymphocytes in cytokine field

Question 25

What type of sensitivity is Inflammatory Bowel Disease?

Answer 25

Type IV

Question 26

What type of sensitivity is SLE?

Answer 26

Type III

• auto antibodies
• glomerulonephritis, arthritis, and vasculitis

Question 27

What is rheumatoid arthritis?

Answer 27

Type IV

-Th 17 plays a role