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. Seminar Winter Semester 2002/2003 Pierre Dönnes Annette Höglund Andreas Hildebrandt

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 Seminar Winter Semester 2002/2003 Pierre Dönnes Annette Höglund Andreas Hildebrandt

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) Seminar Winter Semester 2002/2003 Pierre Dönnes Annette Höglund Andreas Hildebrandt

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 Seminar Winter Semester 2002/2003 Pierre Dönnes Annette Höglund Andreas Hildebrandt

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”) Seminar Winter Semester 2002/2003 Pierre Dönnes Annette Höglund Andreas Hildebrandt

Seminar Winter Semester 2002/2003 Pierre Dönnes Annette Höglund Andreas Hildebrandt

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) Seminar Winter Semester 2002/2003 Pierre Dönnes Annette Höglund Andreas Hildebrandt

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 Innate (non-specific) immunityAdaptive (specific) immunity Seminar Winter Semester 2002/2003 Pierre Dönnes Annette Höglund Andreas Hildebrandt

Humoral and cellular immunity (antibody mediated or cellular) Seminar Winter Semester 2002/2003 Pierre Dönnes Annette Höglund Andreas Hildebrandt

B cells B-cell Antigen Antibody secreting B cell Soluble antibodies, circculate in the body Surface bound antibody Seminar Winter Semester 2002/2003 Pierre Dönnes Annette Höglund Andreas Hildebrandt

B-cell Antibody secreting B cell Virus killed Seminar Winter Semester 2002/2003 Pierre Dönnes Annette Höglund Andreas Hildebrandt

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) Seminar Winter Semester 2002/2003 Pierre Dönnes Annette Höglund Andreas Hildebrandt

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 Seminar Winter Semester 2002/2003 Pierre Dönnes Annette Höglund Andreas Hildebrandt

Th Tc Virus infected cell, cancer cell Antigen presentig cell MHC II + peptide MHC I + peptide Seminar Winter Semester 2002/2003 Pierre Dönnes Annette Höglund Andreas Hildebrandt

Seminar Winter Semester 2002/2003 Pierre Dönnes Annette Höglund Andreas Hildebrandt

Seminar Winter Semester 2002/2003 Pierre Dönnes Annette Höglund Andreas Hildebrandt

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 aa Potentials of peptide vaccines Prediction of peptides is important!!!! Seminar Winter Semester 2002/2003 Pierre Dönnes Annette Höglund Andreas Hildebrandt

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 Seminar Winter Semester 2002/2003 Pierre Dönnes Annette Höglund Andreas Hildebrandt

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. Seminar Winter Semester 2002/2003 Pierre Dönnes Annette Höglund Andreas Hildebrandt

Seminar Winter Semester 2002/2003 Pierre Dönnes Annette Höglund Andreas Hildebrandt

Seminar Winter Semester 2002/2003 Pierre Dönnes Annette Höglund Andreas Hildebrandt

Seminar Winter Semester 2002/2003 Pierre Dönnes Annette Höglund Andreas Hildebrandt

Seminar Winter Semester 2002/2003 Pierre Dönnes Annette Höglund Andreas Hildebrandt

Treatment strategies Inhibit different stages of the lifecycle. HIV protease inhibitors. Peptide Vaccines Seminar Winter Semester 2002/2003 Pierre Dönnes Annette Höglund Andreas Hildebrandt

Seminar Winter Semester 2002/2003 Pierre Dönnes Annette Höglund Andreas Hildebrandt

Seminar Winter Semester 2002/2003 Pierre Dönnes Annette Höglund Andreas Hildebrandt

- 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 Problems with HIV/AIDS Seminar Winter Semester 2002/2003 Pierre Dönnes Annette Höglund Andreas Hildebrandt

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) Seminar Winter Semester 2002/2003 Pierre Dönnes Annette Höglund Andreas Hildebrandt

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