An introduction to immunology

1
An introduction to immunology
Seminar Winter Semester 2002/2003

• 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_at_bioinf.uni-sb.de
Annette Höglund annette_at_bioinf.uni-sb.de
Andreas Hildebrandt anhi_at_bioinf.uni-sb.de
2
Outline of the talk
Seminar Winter Semester 2002/2003

• 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_at_bioinf.uni-sb.de
Annette Höglund annette_at_bioinf.uni-sb.de
Andreas Hildebrandt anhi_at_bioinf.uni-sb.de
3
Immunology
Seminar Winter Semester 2002/2003

• 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_at_bioinf.uni-sb.de
Annette Höglund annette_at_bioinf.uni-sb.de
Andreas Hildebrandt anhi_at_bioinf.uni-sb.de
4
A Short History of Immunology
Seminar Winter Semester 2002/2003

• 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_at_bioinf.uni-sb.de
Annette Höglund annette_at_bioinf.uni-sb.de
Andreas Hildebrandt anhi_at_bioinf.uni-sb.de
5
Jenner - Smallpox vaccine
Seminar Winter Semester 2002/2003

• 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_at_bioinf.uni-sb.de
Annette Höglund annette_at_bioinf.uni-sb.de
Andreas Hildebrandt anhi_at_bioinf.uni-sb.de
6
Seminar Winter Semester 2002/2003
Pierre Dönnes pierre_at_bioinf.uni-sb.de
Annette Höglund annette_at_bioinf.uni-sb.de
Andreas Hildebrandt anhi_at_bioinf.uni-sb.de
7
Immunology history cont.
Seminar Winter Semester 2002/2003

• 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_at_bioinf.uni-sb.de
Annette Höglund annette_at_bioinf.uni-sb.de
Andreas Hildebrandt anhi_at_bioinf.uni-sb.de
8
The immune system
Seminar Winter Semester 2002/2003
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_at_bioinf.uni-sb.de
Annette Höglund annette_at_bioinf.uni-sb.de
Andreas Hildebrandt anhi_at_bioinf.uni-sb.de
9
Humoral and cellular immunity (antibody mediated
or cellular)
Seminar Winter Semester 2002/2003
Pierre Dönnes pierre_at_bioinf.uni-sb.de
Annette Höglund annette_at_bioinf.uni-sb.de
Andreas Hildebrandt anhi_at_bioinf.uni-sb.de
10
B cells
Seminar Winter Semester 2002/2003
Surface bound antibody
B-cell
Pierre Dönnes pierre_at_bioinf.uni-sb.de
Annette Höglund annette_at_bioinf.uni-sb.de
Andreas Hildebrandt anhi_at_bioinf.uni-sb.de
11
Seminar Winter Semester 2002/2003
Antibody secreting B cell
Virus killed
Pierre Dönnes pierre_at_bioinf.uni-sb.de
Annette Höglund annette_at_bioinf.uni-sb.de
Andreas Hildebrandt anhi_at_bioinf.uni-sb.de
12
T cells
Seminar Winter Semester 2002/2003

• 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_at_bioinf.uni-sb.de
Annette Höglund annette_at_bioinf.uni-sb.de
Andreas Hildebrandt anhi_at_bioinf.uni-sb.de
13
Presentation of antigens to T cells
Seminar Winter Semester 2002/2003

• 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_at_bioinf.uni-sb.de
Annette Höglund annette_at_bioinf.uni-sb.de
Andreas Hildebrandt anhi_at_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_at_bioinf.uni-sb.de
Annette Höglund annette_at_bioinf.uni-sb.de
Andreas Hildebrandt anhi_at_bioinf.uni-sb.de
15
Seminar Winter Semester 2002/2003
Pierre Dönnes pierre_at_bioinf.uni-sb.de
Annette Höglund annette_at_bioinf.uni-sb.de
Andreas Hildebrandt anhi_at_bioinf.uni-sb.de
16
Seminar Winter Semester 2002/2003
Pierre Dönnes pierre_at_bioinf.uni-sb.de
Annette Höglund annette_at_bioinf.uni-sb.de
Andreas Hildebrandt anhi_at_bioinf.uni-sb.de
17
MHC molecules
Seminar Winter Semester 2002/2003

• 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_at_bioinf.uni-sb.de
Annette Höglund annette_at_bioinf.uni-sb.de
Andreas Hildebrandt anhi_at_bioinf.uni-sb.de
18
Cancer
Seminar Winter Semester 2002/2003

• 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_at_bioinf.uni-sb.de
Annette Höglund annette_at_bioinf.uni-sb.de
Andreas Hildebrandt anhi_at_bioinf.uni-sb.de
19
HIV and AIDS
Seminar Winter Semester 2002/2003

• 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_at_bioinf.uni-sb.de
Annette Höglund annette_at_bioinf.uni-sb.de
Andreas Hildebrandt anhi_at_bioinf.uni-sb.de
20
Seminar Winter Semester 2002/2003
Pierre Dönnes pierre_at_bioinf.uni-sb.de
Annette Höglund annette_at_bioinf.uni-sb.de
Andreas Hildebrandt anhi_at_bioinf.uni-sb.de
21
Seminar Winter Semester 2002/2003
Pierre Dönnes pierre_at_bioinf.uni-sb.de
Annette Höglund annette_at_bioinf.uni-sb.de
Andreas Hildebrandt anhi_at_bioinf.uni-sb.de
22
Seminar Winter Semester 2002/2003
Pierre Dönnes pierre_at_bioinf.uni-sb.de
Annette Höglund annette_at_bioinf.uni-sb.de
Andreas Hildebrandt anhi_at_bioinf.uni-sb.de
23
Seminar Winter Semester 2002/2003
Pierre Dönnes pierre_at_bioinf.uni-sb.de
Annette Höglund annette_at_bioinf.uni-sb.de
Andreas Hildebrandt anhi_at_bioinf.uni-sb.de
24
Treatment strategies
Seminar Winter Semester 2002/2003

• Inhibit different stages of the lifecycle.
• HIV protease inhibitors.
• Peptide Vaccines

Pierre Dönnes pierre_at_bioinf.uni-sb.de
Annette Höglund annette_at_bioinf.uni-sb.de
Andreas Hildebrandt anhi_at_bioinf.uni-sb.de
25
Seminar Winter Semester 2002/2003
Pierre Dönnes pierre_at_bioinf.uni-sb.de
Annette Höglund annette_at_bioinf.uni-sb.de
Andreas Hildebrandt anhi_at_bioinf.uni-sb.de
26
Seminar Winter Semester 2002/2003
Pierre Dönnes pierre_at_bioinf.uni-sb.de
Annette Höglund annette_at_bioinf.uni-sb.de
Andreas Hildebrandt anhi_at_bioinf.uni-sb.de
27
Problems with HIV/AIDS
Seminar Winter Semester 2002/2003

• - 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 cant have a worldwide approach

Pierre Dönnes pierre_at_bioinf.uni-sb.de
Annette Höglund annette_at_bioinf.uni-sb.de
Andreas Hildebrandt anhi_at_bioinf.uni-sb.de
28
Papers in the seminar!!!!
Seminar Winter Semester 2002/2003

• 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_at_bioinf.uni-sb.de
Annette Höglund annette_at_bioinf.uni-sb.de
Andreas Hildebrandt anhi_at_bioinf.uni-sb.de
29
Seminar Winter Semester 2002/2003
Pierre Dönnes pierre_at_bioinf.uni-sb.de
Annette Höglund annette_at_bioinf.uni-sb.de
Andreas Hildebrandt anhi_at_bioinf.uni-sb.de