Autoimmunity general principles

Question 1

What is autoimmunity?

Answer 1

Genetics + environment + immune system

Damage to specific organ or systemic

Question 2

what is tolerance?

Answer 2

Adaptive immune cells taught not to recognise self during development

Question 3

What are the two types of tolerance

Answer 3

Peripheral and central

Question 4

T cell selection

Answer 4

Pkuripotent stem cell forms lymphoid progenitor
Lymphoid -> lymphocytes
Lymphoid in bone marrow = B cell, some migrate to thymus and form T cell
Entrance to thymus through portico-medullary junction
T cells form CD4 and CD8 (single positive)
Cells move into thymus medulla

Question 5

Central tolerance

Answer 5

Self-MHC I molecules are DP and form SP CD8+
Those with moderate avidity for self MHC are kept, those without are apoptosed
Those with low avidity binding to self-peptides by self-MHC form naive CD8 cell
Self-MHC ii forms SP CD4+
Same process as above but forms naive CD4

Question 6

Peripheral tolerance

Answer 6

• Regulatory T cells to regulate CD4+ and CD8+ cells
• Treg interacts with APC and release anti-inflammatory cytokines which inactivates APC
• T reg cells kill the APCs - granzymes etc
• T cell receptor engagement and CD8 engagement
• Treg cell has CDMA4 antigen
• IL-2 is very important in proliferation
• Treg takes up IL-2 so Teff not activated
• Signal two requires stimulation from APC

Question 7

Autoimmunity checkpoints

Answer 7

Failure of central/peripheral tolerance
Presentation of autoantigen
Co-stimulation

Question 8

Grave’s disease

Answer 8

• Overproduction of thyroid hormones
• Thyroid-pituitary axis
• Autoantibodies behave like TSH (no neg feedback loop)
• Anti-TSH antibodies, T3/4 is high
• Common in young/middle aged women and often runs in families
• Test by blood test - measure t3/4 and tsh
• Treated by medicine, radioiodine therapy and thyroid surgery
• 1 in 200 people