Answers possible in English, German and Swiss German (mix is also okey)

Halin: T cell mediated Autoimmunity
1) Give a definition of “Autoimmunity”
2) What are immune mechanisms to prevent autoimmunity?
- Central Tolerance: Which organs are involved? (thymus and bone marrow) Which proteins are expressed? (tissue-specific proteins) Who is responsible for expression of tissue-specific proteins in thymus? (transcription factor AIRE)
- Antigen segregation: Name some immunoprivileged sites. How do they achieve to be so isolated? (Surrounded by barriers like BBB, high expression of Fas ligand, generate immunosuppressive environment)
- Peripheral anergy
- Regulatory T cells: Do you know an example where regulatory T cells are associated with autoimmunity? (I didn’t know. Just mentioned that autoimmune and also atopic people have less Tregs. She probably meant the FOXP3 gene whose knockout leads to decreased function of Tregs and therefore autoimmunity)
3) Name genes that lead to T-cell mediated autoimmunity when defect.
-AIRE and MHC genes
MHC genes: Which disease is caused? (Certain MHC II versions favour T cell activation regardless which peptide is presented --> favour AI. Disease: Diabetes Type I.
4) Which T cells are involved in T1D? Which MHC molecule do they bind? What is the mechanism?
Cytotoxic CD8+ T cells recognize insulin peptide on MHC I of pancreatic beta-cells and kill them.
5) How do you explain that a certain MHC II variant leads to T1D regarding that T1D mechanism depends on CD8+ T cells recognizing MHC I?
CD4 cells recognize antigen on MHC II --> CD4 T cells provide help to CD8 T cells to get activated

Neri: Generation of Therapeutic Antibodies
1) Tell me the whole story of AB production - from murine Abs to fully human Abs.
2) Production of mouse antibody: What is the crucial step in hybridoma technology?
Fusion of B cells with cancer cells (myeloma cells) to generate long lived AB producing B cells.
3) Which part in humanized Abs is human and which is from murine origin?
4) Name 2 methods to generate fully human Abs
Phage display and transgenic mice.
5) Which challenges do you face with transgenic mice? Can you express every protein with them?
Works well in general but may have problems with conserved proteins. Conserved proteins would cause problems with self-tolerance.