Immunology 1: Tolerance and Autoimmunity

Question 1

Define immune tolerance

Answer 1

Lack of reactiveness of the immune system to things we don’t want to attack:
- Self
- Microbiome
- Fetus
- Drugs/food

Question 2

Explain how central tolerance occurs, and what it achieves

Answer 2

• During lymphocyte development, autoreactive B cells (in bone marrow) and T cells (in the thymus) are killed
• This prevents them from escaping into the environment, where they will be killed

Question 3

How are immune cells periperhally regulated?

Answer 3

Regulatory cells, anergy, and aopotosis

Question 4

What are some useful applications of autoimmunity?

Answer 4

• Clearing debris in a non-inflammatory manner
• Tumour suppression

Question 5

Explain how anergy can be used to neutralise autoreactive t cells peripherally

Answer 5

• If an antigen is presented without costimulation, this means the innate immune system is not activated, and so it is a self antigen
• As such, the T cell is rendered functionally unresponsive

Question 6

How can infection drive autoimmunity?

Answer 6

• Molecular mimicry
• Bystander activation
• Tissue damage from inflammation can release self-antigens into extracellular matrix, providing more opportunity for autoimmunity

Question 7

How can genetic variants alter an individuals chance of autoimmunity? Link this back to mating dynamics

Answer 7

• Different people have different MHC genes; some are better than others at presenting self-antigen
• This is why women can smell MHC molecules; more variation, the better.

Question 8

Which type of autoimmune disease is more likely to be self-limiting vs chronic? Why?

Answer 8

• Organ specific (e.g. DMT1) more likely to be self-limiting
• Systemic (e.g. SLE) more likely to be chronic

Because once you get rid of all the cells you’re attacking, there’s nothing left for organ-specific autoimmunity

Question 9

List 3 reasons why women might have a higher chance of autoimmunity

Answer 9

1. X chromosome is larger; more mutation
2. Reaction against inactive X chromosome
3. Reproductive advantage (pregnancy compensation)

Question 10

What are the three types of hypersensitivity involved in autoimmunity? Summarise them

Answer 10

Type II: autoantibody rxn
Type III: Immune complex deposition (antigen must be soluble)
Type IV: T Cell hypersensitivity

Question 11

Describe anti-glomerular basement membrane disease. What type of hypersensitivity is this?

Answer 11

• Type II (autoantibody) rxn
• Autoreactive t and b cells interact, creating autoreactive plasma cells that produce antibodies that damage the basement membrane of the glomerulus, resulting in vasculitis

Question 12

Using 3 types of autoimmune rxns, explain the pathogenesis of SLE

Answer 12

Step 1: cells undergo apoptosis, triggering autoantibodies (type II rxn) against these contents

Step 2: In the context of poor clearance, resulting immune complexes deposit in tissue, causing inflammation (type III)

Step 3: This triggers activation of autoreactive T cells (Type IV)