Autoimmunity

Question 1

Explain self tolerance

1) Central tolerance
2) Peripheral tolerance
3) B cells

Answer 1

Central tolerance (leaky, not 100%) - T cells

• Self reactive T cells deleted in the thymus
• Treg cells are generated - go out and maintain self tolerance

Peripheral tolerance - T cells

• CTLA4 inhibitory molecules
• Anergy: DCs presenting self antigens don’t express costimulation
• Ignorance: DCs with self antigens either don’t go to a certain part of the body (e.g. eye) or are killed if they try to get in there.
• Peripheral Treg cell - TGF-beta, IL10

B cell

• Deletion - as B cells mature, autoreactive B cells get deleted
• Anergy - B cells get desensitised when exposed to low level of self antigen
• Lack of T cell help - if T cell tolerance works, B cells never get that 2nd signal so B cells just die
• Clonal ignorance - self antigen is so low it won’t activate B cells

Question 2

Examples of drug induced lupus

Answer 2

Procainamide
Hydralazine
Minocycline
TNFi

Question 3

Pathogenesis of coeliac disease

Answer 3

Gliadin (high in glutamine and proline) resistant to digestive enzymes –> TTG deamidates certain glutamine residues –> creates deamidated gliadin (DAG) –> DAG has increased affinity for HLA-DQ2.5/DQ8 –> HLA+DAG peptides activate gluten specific CD4 T cells –> inflammatory response + also provide T cell help to B cells –> generate ab (anti-TTG)