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Immunology (Fach) / Immunity to cancers (Lektion)
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- Immune surveillance (3Es) Elimination Equilibrium Escape
- Tumor antigens tumor-specific: rare (expressed only on tumors) tumor associated: (normal antigen but overexpressed on tumors)
- MHC I presentation 1) virus protein degraded by proteasome 2) Transport into ER by TAP 3) binding of peptide to MHC I 4) Transport via Golgi to surface
- MHC II presentation 1) uptake of extracellular antigen 2) synthesize MHC II with CLIP 3) fusion with endolysosome 4) remove CLIP load Ag on MHC II 5) Transport to surface
- Cross-presentation only dendritic cells 1) extracellular on MHC I (leaky endosomes) 2) intracellular on MHC II (auto-phagosomes)
- examples Tumor antigens 1) cancer/testes antigens (MAGE) 2) viral antigens (E6+E7 of HPV) 3) Differentiation antigens (melan-A) 4) heat shock protein-peptide complexes 5) unique tumor specific antigens
- Mutated tumor antigens 1) point mutation causes new peptide to be presented 2) point mutation creates new epitope for recognition by T-cells
- unmutated tumor antigens 1) normally not expressed protein bound to MHC I 2) overexpressed normal protein recognized by T-cells
- Treg the brakes of the immune system Foxp3 + CD4 + CD25 +++ CTLA-4 +
- Immune escape of tumor 1) Antigen processing and presentation (no TAP/no proteasome/no MHC) 2) Immunosuppression (TGF-β + IL-10) 3) makes Treg
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- Fighting tumors 1) antibodies vs Her2/neu 2) adoptive T-cell therapy (prime cells vs tumor) 3) Dendritic cells (primed, with memory) 4) Killed tumor vaccine 5) Block Tregs 6)Nanoparticles (prime Treg in vivo)