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  1. Seminar Winter Semester 2002/2003 An introduction to immunology • Aim: A very general introduction to immunology. Explain how molecular interactions are essential for the immune system. • Why: Several articles in this seminar deals with interaction between molecules in the immune system. • Some extra motivation why studies of biomolecular interactions are important. Pierre Dönnes pierre@bioinf.uni-sb.de Andreas Hildebrandt anhi@bioinf.uni-sb.de Annette Höglund annette@bioinf.uni-sb.de

  2. Seminar Winter Semester 2002/2003 Outline of the talk • Definition of Immunology • History of immunology • Innate and adaptive immunity • Humoral and cellular responses – B and T cells (specific interactions) • Cancer • HIV/AIDS Pierre Dönnes pierre@bioinf.uni-sb.de Andreas Hildebrandt anhi@bioinf.uni-sb.de Annette Höglund annette@bioinf.uni-sb.de

  3. Seminar Winter Semester 2002/2003 Immunology • Immunology is the study of our protection from foreign macromolecules or invading organisms and our responses to them. • Host – e.g. me!!!! • Foreign macromolecule, antigen – e.g. virus protein, worm, parasite (Everything that should not be in my body) Pierre Dönnes pierre@bioinf.uni-sb.de Andreas Hildebrandt anhi@bioinf.uni-sb.de Annette Höglund annette@bioinf.uni-sb.de

  4. Seminar Winter Semester 2002/2003 A Short History of Immunology • ~ 430 B.C: Peloponesian War, Thucydides describes plague – the ones who had recovered from the disease could nurse the sick without getting the disease a second time • 15th centurry: Chinese and Turks use dried crusts of smallpox as ”vaccine” • 1798: Edward Jenner – smallpox vaccine Pierre Dönnes pierre@bioinf.uni-sb.de Andreas Hildebrandt anhi@bioinf.uni-sb.de Annette Höglund annette@bioinf.uni-sb.de

  5. Seminar Winter Semester 2002/2003 Jenner - Smallpox vaccine • Noticed that milkmades that had contracted cowpox did NOT get smallpox • Test on an 8 year old boy, injected cowpox into him (NOT very nice……) • Follwed by exposure to smallpox • Vaccine was invented (latin vacca means ”cow”) Pierre Dönnes pierre@bioinf.uni-sb.de Andreas Hildebrandt anhi@bioinf.uni-sb.de Annette Höglund annette@bioinf.uni-sb.de

  6. Seminar Winter Semester 2002/2003 Pierre Dönnes pierre@bioinf.uni-sb.de Andreas Hildebrandt anhi@bioinf.uni-sb.de Annette Höglund annette@bioinf.uni-sb.de

  7. Seminar Winter Semester 2002/2003 Immunology history cont. • Since 1901 there have been 19 Nobel Prizes for immunological research. • Examples: Discovery of human blood groups (1930) and Transplantation immunology(1991) Pierre Dönnes pierre@bioinf.uni-sb.de Andreas Hildebrandt anhi@bioinf.uni-sb.de Annette Höglund annette@bioinf.uni-sb.de

  8. Seminar Winter Semester 2002/2003 Innate (non-specific) immunity Adaptive (specific) immunity The immune system Immune system • Anatomic barriers (Skin,mucous membranes) • Physological barriers (temperature, pH) • Phagocytic Barriers (cells that eat invaders) • Inflammatory barriers (redness, swelling, heat and pain) • Antigen specificity • Diversity • Immunological memory • Self/nonself recognition Pierre Dönnes pierre@bioinf.uni-sb.de Andreas Hildebrandt anhi@bioinf.uni-sb.de Annette Höglund annette@bioinf.uni-sb.de

  9. Seminar Winter Semester 2002/2003 Humoral and cellular immunity(antibody mediated or cellular) Pierre Dönnes pierre@bioinf.uni-sb.de Andreas Hildebrandt anhi@bioinf.uni-sb.de Annette Höglund annette@bioinf.uni-sb.de

  10. Seminar Winter Semester 2002/2003 Antibody secreting B cell Antigen Soluble antibodies, circculate in the body B cells Surface bound antibody B-cell Pierre Dönnes pierre@bioinf.uni-sb.de Andreas Hildebrandt anhi@bioinf.uni-sb.de Annette Höglund annette@bioinf.uni-sb.de

  11. Seminar Winter Semester 2002/2003 B-cell Antibody secreting B cell Virus killed Pierre Dönnes pierre@bioinf.uni-sb.de Andreas Hildebrandt anhi@bioinf.uni-sb.de Annette Höglund annette@bioinf.uni-sb.de

  12. Seminar Winter Semester 2002/2003 T cells • Two types: • Helper T cells (Th): activates other cells • Cytotoxic T cells (Tc): can kill other cells • T cells can only recognize antigens associated with certain molecules (MHC) Pierre Dönnes pierre@bioinf.uni-sb.de Andreas Hildebrandt anhi@bioinf.uni-sb.de Annette Höglund annette@bioinf.uni-sb.de

  13. Seminar Winter Semester 2002/2003 Presentation of antigens to T cells • Proteins (peptides) from inside the cell are presented by MHC I molecules to Tc cells. • Proteins (peptides) from the outside of cells are presented by MHC II molecules to Th cells. • MHC I on almost all cells • MHC II on specialized antigen-presenting cells Pierre Dönnes pierre@bioinf.uni-sb.de Andreas Hildebrandt anhi@bioinf.uni-sb.de Annette Höglund annette@bioinf.uni-sb.de

  14. Seminar Winter Semester 2002/2003 Antigen presentig cell MHC II + peptide Th Virus infected cell, cancer cell Tc MHC I + peptide Pierre Dönnes pierre@bioinf.uni-sb.de Andreas Hildebrandt anhi@bioinf.uni-sb.de Annette Höglund annette@bioinf.uni-sb.de

  15. Seminar Winter Semester 2002/2003 Pierre Dönnes pierre@bioinf.uni-sb.de Andreas Hildebrandt anhi@bioinf.uni-sb.de Annette Höglund annette@bioinf.uni-sb.de

  16. Seminar Winter Semester 2002/2003 Pierre Dönnes pierre@bioinf.uni-sb.de Andreas Hildebrandt anhi@bioinf.uni-sb.de Annette Höglund annette@bioinf.uni-sb.de

  17. Seminar Winter Semester 2002/2003 MHC molecules • Important to study what parts of a protein that binds to MHC molecules. • MHC I binds peptides with 8-10 aa • MHC II bind peptides with 12-25 aa • Potentials of peptide vaccines • Prediction of peptides is important!!!! Pierre Dönnes pierre@bioinf.uni-sb.de Andreas Hildebrandt anhi@bioinf.uni-sb.de Annette Höglund annette@bioinf.uni-sb.de

  18. Seminar Winter Semester 2002/2003 Cancer • The second ranking cause of death after heart disease in the Western world. • most organs and tissues in an organism are in balance (death and renewal) • cancer cells have no control in growth mechanisms, can expand to a large size producing a tumor Pierre Dönnes pierre@bioinf.uni-sb.de Andreas Hildebrandt anhi@bioinf.uni-sb.de Annette Höglund annette@bioinf.uni-sb.de

  19. Seminar Winter Semester 2002/2003 HIV and AIDS • HIV – Human Immunodeficiency Virus • AIDS - Acquired immunodeficiency syndrome • HIV virus binds to Th cells and causes the number of Th cells to decrease. • When the number of Th cells is too low, you have AIDS. Pierre Dönnes pierre@bioinf.uni-sb.de Andreas Hildebrandt anhi@bioinf.uni-sb.de Annette Höglund annette@bioinf.uni-sb.de

  20. Seminar Winter Semester 2002/2003 Pierre Dönnes pierre@bioinf.uni-sb.de Andreas Hildebrandt anhi@bioinf.uni-sb.de Annette Höglund annette@bioinf.uni-sb.de

  21. Seminar Winter Semester 2002/2003 Pierre Dönnes pierre@bioinf.uni-sb.de Andreas Hildebrandt anhi@bioinf.uni-sb.de Annette Höglund annette@bioinf.uni-sb.de

  22. Seminar Winter Semester 2002/2003 Pierre Dönnes pierre@bioinf.uni-sb.de Andreas Hildebrandt anhi@bioinf.uni-sb.de Annette Höglund annette@bioinf.uni-sb.de

  23. Seminar Winter Semester 2002/2003 Pierre Dönnes pierre@bioinf.uni-sb.de Andreas Hildebrandt anhi@bioinf.uni-sb.de Annette Höglund annette@bioinf.uni-sb.de

  24. Seminar Winter Semester 2002/2003 Treatment strategies • Inhibit different stages of the lifecycle. • HIV protease inhibitors. • Peptide Vaccines Pierre Dönnes pierre@bioinf.uni-sb.de Andreas Hildebrandt anhi@bioinf.uni-sb.de Annette Höglund annette@bioinf.uni-sb.de

  25. Seminar Winter Semester 2002/2003 Pierre Dönnes pierre@bioinf.uni-sb.de Andreas Hildebrandt anhi@bioinf.uni-sb.de Annette Höglund annette@bioinf.uni-sb.de

  26. Seminar Winter Semester 2002/2003 Pierre Dönnes pierre@bioinf.uni-sb.de Andreas Hildebrandt anhi@bioinf.uni-sb.de Annette Höglund annette@bioinf.uni-sb.de

  27. Seminar Winter Semester 2002/2003 Problems with HIV/AIDS • - No major resistant population • - Disease progresses even with ‘protective IR’ • - No knowledge of what IR is protective • - How to elicit a protective IR? • - Provirus prevents total eradication • - Resistance depends on HIV exposure • - No suitable animal model • - Legal impediments to prophylactic approach • Clinical trial ethical problems • - HIV clades – can’t have a worldwide approach Pierre Dönnes pierre@bioinf.uni-sb.de Andreas Hildebrandt anhi@bioinf.uni-sb.de Annette Höglund annette@bioinf.uni-sb.de

  28. Seminar Winter Semester 2002/2003 Papers in the seminar!!!! • Detailed ab initio prediction of lysozyme-antibody complex with 1.6 Å accuracy (Thomas) • A Structure-Based Algorithm to Predict Potential Binding Peptides to MHC I Molecules with Hydrophobic Binding Pockets (Edilson) • Prediction of MHC II-binding peptides using an evolutionary algorithm and artificial neural networks (Esteban) Pierre Dönnes pierre@bioinf.uni-sb.de Andreas Hildebrandt anhi@bioinf.uni-sb.de Annette Höglund annette@bioinf.uni-sb.de

  29. Date Person(s) talking Seminar Winter Semester 2002/2003 30/10/02 Pierre, Andreas, Annette 06/11/02 Shah, Jamaialam; Andreas 13/11/02 No seminar 20/11/02 Josiane, Xavia Pareira; Pierre 27/11/02 Zhu, Hongbo; Raneru, Srinivas 04/12/02 De Aguiar, Edilson; Binsl, Thomas 11/12/02 No seminar 18/12/02 No seminar Christmas Holiday 08/01/03 Hofmann, Andreas; Graf, Cosima ;Annette 15/01/03 Kaspar, Melanie; Walter, Peter 22/01/03 Kunz, Kerstin; Andres, Daniel 29/01/03 Hussong, René; Yasir, Iqbal 05/02/03 Madrigal-Mova, Cristian; Leon-Soto, Esteban 12/02/03 Abdelhak, Bellamou; Safdar, Ali 19/02/03 Hutter, Barbara; Bingding, Huang Pierre Dönnes pierre@bioinf.uni-sb.de Andreas Hildebrandt anhi@bioinf.uni-sb.de Annette Höglund annette@bioinf.uni-sb.de