W21-L6: Self, Non-self discrimination

Question 1

What is B cell Central Tolerance?

Answer 1

• Deletion

* Anergy

Question 2

What is B cell Peripheral Tolerance?

Answer 2

Need 2 signals for the mature B cell to respond and survive

• Ignorance/Anergy/death (Lack of co-stimulation/T cell help)

Question 3

T/F

B cell tolerance is more efficient than T cell tolerance

Answer 3

False

Question 4

Where does T cell development occur?

Answer 4

Thymus

Question 5

Double positive (DP) thymocytes undergo which selection processes following the expression of a TCR?

Answer 5

1. Positive selection-thymocytes that express TCRs capable of recognising self-MHC are selected to survive
2. Negative selection–removal of immature lymphocytes that have strong reactivity to self peptide

Question 6

What controls expression of tissue specific antigens?

Answer 6

AIRE genes

Question 7

What do defects in AIRE lead to?

Answer 7

failure of negative selection for some antigens, and result in autoimmunity

Question 8

What is T cell central tolerance?

Answer 8

Involves immature/developing lymphocytes and occurs in primary lymphoid organs

• Deletion
• Selection of Tregs

Question 9

What is T peripheral central tolerance?

Answer 9

Involves mature lymphocytes and occurs in secondary lymphoid organs, and peripheral tissues

• Deletion
• Anergy
• Ignorance
• Regulation

Question 10

What two signals are required for activating naive T cells?

Answer 10

1. TCR-peptide MHC interactions

2. Co-stimulation

Question 11

Without co-stimulation, T cells become…

Answer 11

anergic

Question 12

What are iTregs?

Answer 12

derived following activation of naïve CD4 T cells in the presence of TGF ß

Question 13

What do iTregs secrete and express?

Answer 13

Secrete immunosuppressive cytokines - IL-10 and TGF ß, Express CTLA4 and inhibit co-stimulation

Question 14

How does CTALA4 work?

Answer 14

Binds B7 on APC more avidly than CD 28 on niave T cells and delivers inhibitory signals to activated T cells

Question 15

What are 3 key components of autoimmunity?

Answer 15

1. Genetic susceptibility
2. Environmental
3. Loss of self-tolerance

Question 16

What are the two types of autoimmune disease?

Answer 16

1. Organ-specific: Confined to particular organs or cell types and the
   antigens recognized are organ specific
2. Systemic: Multiple tissues of the body are targeted and the antigens recognized are more ubiquitous

Question 17

What are some diseases related to B cell autoimmunity?

Answer 17

1. Graves disease (stimulating Ab)
2. Myasthenia Gravis (inhibitory Ab)
3. SLE (immune complex deposition)

Question 18

What are some diseases related to T cell autoimmunity?

Answer 18

1. Insulin dependent diabetes mellitus (IDDM)

2. Multiple sclerosis (MS)

Question 19

Type 1 insulin dependent diabetes mellitus is characterised by?

Answer 19

autoimmune destruction of pancreatic β-cells, characterised by infiltration of lymphocytes, weak autoantibody response, T cell reactivity to islet proteins

Question 20

What genes are more frequently found in Type 1 insulin dependent diabetes mellitus?

Answer 20

HLA DR3-DQ2 and DR4-DQ8

Question 21

Multiple Sclerosis is characterised by?

Answer 21

CD4 T cells specific for myelin antigens promote an inflammatory response and degrade the myelin sheaths covering nerve axons

Question 22

Which genes are associated with multiple sclerosis?

Answer 22

HLA-DR15 and HLA-DQ6

Question 23

What is Molecular mimicry?

Answer 23

• Antigens from pathogen are similar in shape to autoantigens
• Able to cross react with autoreactive T cells/B cells