Transcript Seminar Winter Semester 2002/2003

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
[email protected]
Andreas Hildebrandt
[email protected]
Annette Höglund
[email protected]
Seminar
Winter Semester 2002/2003
Outline of the talk
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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
[email protected]
Andreas Hildebrandt
[email protected]
Annette Höglund
[email protected]
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
[email protected]
Andreas Hildebrandt
[email protected]
Annette Höglund
[email protected]
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
[email protected]
Andreas Hildebrandt
[email protected]
Annette Höglund
[email protected]
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
[email protected]
Andreas Hildebrandt
[email protected]
Annette Höglund
[email protected]
Seminar
Winter Semester 2002/2003
Pierre Dönnes
[email protected]
Andreas Hildebrandt
[email protected]
Annette Höglund
[email protected]
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
[email protected]
Andreas Hildebrandt
[email protected]
Annette Höglund
[email protected]
Seminar
Winter Semester 2002/2003
The immune system
Immune system
Innate (non-specific) immunity
Adaptive (specific) immunity
•Anatomic barriers (Skin,mucous
membranes)
•Antigen specificity
•Physological barriers
(temperature, pH)
•Immunological memory
•Phagocytic Barriers (cells that eat
invaders)
•Diversity
•Self/nonself recognition
•Inflammatory barriers (redness,
swelling, heat and pain)
Pierre Dönnes
[email protected]
Andreas Hildebrandt
[email protected]
Annette Höglund
[email protected]
Seminar
Winter Semester 2002/2003
Humoral and cellular immunity
(antibody mediated or cellular)
Pierre Dönnes
[email protected]
Andreas Hildebrandt
[email protected]
Annette Höglund
[email protected]
Seminar
Winter Semester 2002/2003
B cells
Surface bound antibody
Antibody secreting B cell
Antigen
B-cell
Soluble antibodies, circculate in the body
Pierre Dönnes
[email protected]
Andreas Hildebrandt
[email protected]
Annette Höglund
[email protected]
Seminar
Winter Semester 2002/2003
Antibody secreting B cell
B-cell
Virus killed
Pierre Dönnes
[email protected]
Andreas Hildebrandt
[email protected]
Annette Höglund
[email protected]
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
[email protected]
Andreas Hildebrandt
[email protected]
Annette Höglund
[email protected]
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
[email protected]
Andreas Hildebrandt
[email protected]
Annette Höglund
[email protected]
Seminar
Winter Semester 2002/2003
Antigen presentig cell
Th
MHC II + peptide
Virus infected cell, cancer cell
Tc
Pierre Dönnes
[email protected]
MHC I + peptide
Andreas Hildebrandt
[email protected]
Annette Höglund
[email protected]
Seminar
Winter Semester 2002/2003
Pierre Dönnes
[email protected]
Andreas Hildebrandt
[email protected]
Annette Höglund
[email protected]
Seminar
Winter Semester 2002/2003
Pierre Dönnes
[email protected]
Andreas Hildebrandt
[email protected]
Annette Höglund
[email protected]
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
[email protected]
Andreas Hildebrandt
[email protected]
Annette Höglund
[email protected]
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
[email protected]
Andreas Hildebrandt
[email protected]
Annette Höglund
[email protected]
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
[email protected]
Andreas Hildebrandt
[email protected]
Annette Höglund
[email protected]
Seminar
Winter Semester 2002/2003
Pierre Dönnes
[email protected]
Andreas Hildebrandt
[email protected]
Annette Höglund
[email protected]
Seminar
Winter Semester 2002/2003
Pierre Dönnes
[email protected]
Andreas Hildebrandt
[email protected]
Annette Höglund
[email protected]
Seminar
Winter Semester 2002/2003
Pierre Dönnes
[email protected]
Andreas Hildebrandt
[email protected]
Annette Höglund
[email protected]
Seminar
Winter Semester 2002/2003
Pierre Dönnes
[email protected]
Andreas Hildebrandt
[email protected]
Annette Höglund
[email protected]
Seminar
Winter Semester 2002/2003
Treatment strategies
• Inhibit different stages of the lifecycle.
• HIV protease inhibitors.
• Peptide Vaccines
Pierre Dönnes
[email protected]
Andreas Hildebrandt
[email protected]
Annette Höglund
[email protected]
Seminar
Winter Semester 2002/2003
Pierre Dönnes
[email protected]
Andreas Hildebrandt
[email protected]
Annette Höglund
[email protected]
Seminar
Winter Semester 2002/2003
Pierre Dönnes
[email protected]
Andreas Hildebrandt
[email protected]
Annette Höglund
[email protected]
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
[email protected]
Andreas Hildebrandt
[email protected]
Annette Höglund
[email protected]
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
[email protected]
Andreas Hildebrandt
[email protected]
Annette Höglund
[email protected]
Seminar
Winter Semester 2002/2003
Date
Person(s) talking
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
[email protected]
Andreas Hildebrandt
[email protected]
Annette Höglund
[email protected]