Chapter 16- Tolerance and autoimmunity

1. Chapter 16- Tolerance and autoimmunity • Where we’re going- • Brief look at just a few diseases- • A longer look at theoretical causes

4. Experimental models • Mice that get diseases like diabetes and lupus • Experimental systems

6. Complete Freund’s adjuvant- big stimulator of the immune system!

7. So what causes autoimmunity? • We know about clonal deletion of B cells, and negative selection of T cells- BUT we still have self-reactive T & B cells out there, but they’re anergic- peripheral tolerance-so there’s something about the way a self-reactive T cell normally sees its antigen that suppresses it- and that isn’t working in autoimmunity. • Study the next slide!

8. Multiple events could be involved! EAE, heart attack Ab’s, anti-sperm Ab’s post-vasectomy IDDM Pancreatic cells- hi levels of MHC I &II! 20-9 A viral peptide is presented by MHCII- it looks like self- stimulates self-rxtive Th cell- Self-peptides are not normally on MCHII! LPS, EBV in mono- AIDS patients have viruses & non-specific Ab’s.

11. So- what do we do about these • Steroids- useful, blunt instrument- cyclosporin is slightly less blunt- used in transplantation. • We can NAIL these diseases in mice! Human trials-????

12. Activated T cells have IL2R Vaccinate with dead specific Tcells Competitively inhibit binding of bad peptides with similar peptides.

13. Mice with Lupus- many helped by anti-CD4 Ab’s.

14. Antibodies agains a particular Vb region stopped EAE

15. Things to know • A few diseases and their autoimmune cause- MS, Graves, IDDM, rheumatic fever- mainly cell-mediated or Ab-mediated, or both. • Experimental systems- EAE in particular. • Ways we become autoimmune- Fig. 16-12 • Potential treatments.