Autoimmunity

Question 1

What are some examples of autoimmune disease?

Answer 1

Question 2

What is autoimmunity?

Answer 2

= failure of immune system

• presence of antibodies and T-lymphocytes directed against normal components of the human body = autoantigens

presence of self-reactive B cells (autoantibodies) and/or T cells

Lead to autoimmune diseases

Question 3

What is central tolerance?

Answer 3

= destroy self-reactive T or B cells before they enter the circulation

• If immature B cells in bone marrow encounter antigen in a form which can crosslink their IgM apoptosis is triggered

T cell selection happens in the thymus:

• If the T cell doesn’t bind to any self-MHC at all –> death by neglect (apoptosis)
• If the T cell binds self MHC too strongly - apoptosis triggered –> negative selection)
• But…
  
  • If the T cell binds self MHC weakly, this is the signal to survive –> positive selection

Question 4

How can a T cell developing in the thymus encounter MHC bearing peptides expressed in other parts of the body?

Answer 4

A specialised transcription factor allows thymic expression of genes that are expressed in peripheral tissues = AIRE - autoimmune regulator

• = promotes self tolerance by allowing the thymic expression of genes from other tissues
• “allows a T cell to recognise any proteins expressed in the body, to bind strongly to then be killed”
• Mutations in AIRE result in multi-organ autoimmunity

Question 5

What is peripheral tolerance?

Answer 5

Question 6

What might trigger a breakdown of self tolerance?

Answer 6

• Loss of/problem with regulatory cells
• Release of sequestered antigen
• Modification of self
  
  • For example citrullination
  • Conversion of arginine into citrulline (changing charge and shape - turning self peptide into non-self peptide) –> this can be increased by inflammation
  • Autoantibodies to citrullinated proteins seen in arthritis - which is now used for clinical diagnosis
• Molecular mimicry
  
  • For example rheumatic fever
  • Disease is triggered by infection with streptococcus pyogenes
  • Antibodies produced for the infection may cross-react with cardiac muscle
  • Fools the immune system into recognising its peptide by making a response against a foreign peptide

Question 7

What are autoimmune diseases that are mediated by IgG which can be transferred across the placenta?

Answer 7

Question 8

What are Th17 cells?

Answer 8

= are helper T cells that produce the cytokine IL-17

• Highly inflammatory and produce cytokines which are involved in the recruitment, migration and activation of immune cells