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CENTER FOR BIOLOGICAL SEQUENCE ANALYSIS
Technical University of Denmark - DTUTechnical University of Denmark - DTUDepartment of systems biologyDepartment of systems biology
BiopeopleTutorial 2011
Immunological Bioinformatics
CENTER FOR BIOLOGICAL SEQUENCE ANALYSIS
Technical University of Denmark - DTUTechnical University of Denmark - DTUDepartment of systems biologyDepartment of systems biology
the immune systemA brief summary
Technical University of Denmark - DTUTechnical University of Denmark - DTUDepartment of systems biologyDepartment of systems biology
Immunological Bioinformatics Tutorial
Vaccination
• Administration of a substance to a person with the purpose of preventing a disease
• Traditionally composed of a killed or weakened micro organism
• Vaccination works by creating a type of immune response that enables the memory cells to later respond to a similar organism before it can cause disease
Technical University of Denmark - DTUTechnical University of Denmark - DTUDepartment of systems biologyDepartment of systems biology
Immunological Bioinformatics Tutorial
Technical University of Denmark - DTUTechnical University of Denmark - DTUDepartment of systems biologyDepartment of systems biology
Immunological Bioinformatics Tutorial
1958 start of small pox eradication program
Effectiveness of vaccines
Technical University of Denmark - DTUTechnical University of Denmark - DTUDepartment of systems biologyDepartment of systems biology
Immunological Bioinformatics Tutorial
The innate immune system
Barriers, cells, and receptors
SkinTears
Epithelia
Scavenging Cells
Toll like receptors
Shizuo Akira & Kiyoshi TakedaNature Reviews Immunology 4, 499-511 (July
2004)©
Technical University of Denmark - DTUTechnical University of Denmark - DTUDepartment of systems biologyDepartment of systems biology
Immunological Bioinformatics Tutorial
The innate immune system
• Unspecific
• Antigen independent
• Immediate response
• No training/selection hence no memory
• Pathogen independent (but response might be pathogen type dependent)
Technical University of Denmark - DTUTechnical University of Denmark - DTUDepartment of systems biologyDepartment of systems biology
Immunological Bioinformatics Tutorial
The adaptive immune system
Pathogen specific
Bacteria
Virus
Parasite
http://tpeeaupotable.ifrance.com/ma%20photo/bilharzoze.jpg
Technical University of Denmark - DTUTechnical University of Denmark - DTUDepartment of systems biologyDepartment of systems biology
Immunological Bioinformatics Tutorial
• Diversity of lymphocytes
- Huge diversity within a host
- At least 108 different T & B cell clones
• Receptors made by recombination & N-additions
• Somatic mutation during immune response
• Repertoires are (partly) random
- Randomness requires self tolerance
Diversity is a hallmark of the (adaptive) immune
system
Technical University of Denmark - DTUTechnical University of Denmark - DTUDepartment of systems biologyDepartment of systems biology
Immunological Bioinformatics Tutorial
Diversity is a hallmark
of the (adaptive) immune system
Technical University of Denmark - DTUTechnical University of Denmark - DTUDepartment of systems biologyDepartment of systems biology
Immunological Bioinformatics TutorialCartoon by Eric Reits
Humoral immunity
Technical University of Denmark - DTUTechnical University of Denmark - DTUDepartment of systems biologyDepartment of systems biology
Immunological Bioinformatics Tutorial
Antibodies
Technical University of Denmark - DTUTechnical University of Denmark - DTUDepartment of systems biologyDepartment of systems biology
Immunological Bioinformatics Tutorial
Antibody - Antigen interaction
FabAntigen
Epitope
Paratope
Antibody
Technical University of Denmark - DTUTechnical University of Denmark - DTUDepartment of systems biologyDepartment of systems biology
Immunological Bioinformatics Tutorial
Antibody Effect
Virus or Toxin
Antibodies
Technical University of Denmark - DTUTechnical University of Denmark - DTUDepartment of systems biologyDepartment of systems biology
Immunological Bioinformatics Tutorial
The trinity of immunity
Cartoon by Eric Reits
Technical University of Denmark - DTUTechnical University of Denmark - DTUDepartment of systems biologyDepartment of systems biology
Immunological Bioinformatics Tutorial Cartoon by Eric Reits
Technical University of Denmark - DTUTechnical University of Denmark - DTUDepartment of systems biologyDepartment of systems biology
Immunological Bioinformatics Tutorial
Cartoon by Eric Reits
The Cellular immune response
Technical University of Denmark - DTUTechnical University of Denmark - DTUDepartment of systems biologyDepartment of systems biology
Immunological Bioinformatics Tutorial
MHC-I molecules present peptides on the surface of most cells
Technical University of Denmark - DTUTechnical University of Denmark - DTUDepartment of systems biologyDepartment of systems biology
Immunological Bioinformatics Tutorial
CTL response
Healthy cell
Virus-infected
cellMHC-I
Technical University of Denmark - DTUTechnical University of Denmark - DTUDepartment of systems biologyDepartment of systems biology
Immunological Bioinformatics Tutorial
CTL response
Virus-infected
cell
MHC-I
Technical University of Denmark - DTUTechnical University of Denmark - DTUDepartment of systems biologyDepartment of systems biology
Immunological Bioinformatics Tutorial
QuickTime™ and aSorenson Video decompressorare needed to see this picture.
The death of an infected cell
Technical University of Denmark - DTUTechnical University of Denmark - DTUDepartment of systems biologyDepartment of systems biology
Immunological Bioinformatics Tutorial
• The adaptive immune system is extremely diverse
- A immune responds can by raise against any thing foreign!
• Antibodies defines the humoral response
- Antibodies recognize structural properties on the surface of extra cellular antigens
• T cells regulates the cellular response
- CTL’s kill cell that present MHC molecules bound with intra cellular derived foreign peptides
Summary
Technical University of Denmark - DTUTechnical University of Denmark - DTUDepartment of systems biologyDepartment of systems biology
Immunological Bioinformatics Tutorial
Vaccine Challenges
TB
FLU
HCV
HIV
Technical University of Denmark - DTUTechnical University of Denmark - DTUDepartment of systems biologyDepartment of systems biology
Immunological Bioinformatics TutorialImmunological Bioinformatics, The MIT press. +HPV & Rotavirus
Vaccines have been made for 36 of >400
human pathogens
Technical University of Denmark - DTUTechnical University of Denmark - DTUDepartment of systems biologyDepartment of systems biology
Immunological Bioinformatics Tutorial
Deaths from infectious
diseases in the world in
2008
Infectious and parasitic diseases Thousands %
Total8721 15.3
Tuberculosis1342 2.4
STDs excluding HIV120 0.2
Syphilis100 0.2
Chlamydia4 0.0
Gonorrhoea0 0.0
HIV/AIDS1776 3.1
Diarrhoeal diseases2464 4.3
Childhood diseases448 0.8
Pertussis195 0.3
Poliomyelitis (c)1 0.0
Diphtheria8 0.0
Measles155 0.3
Tetanus88 0.2
Meningitis340 0.6
Hepatitis B (d)128 0.2
Hepatitis C (d)69 0.1
Malaria827 1.5
Tropical diseases 133 0.2
Trypanosomiasis54 0.1
Chagas disease10 0.0
Schistosomiasis44 0.1
Leishmaniasis26 0.0
Lymphatic filariasis0 0.0
Onchocerciasis0 0.0
Leprosy12 0.0
Dengue16 0.0
Japanese encephalitis15 0.0
Trachoma0 0.0
Intestinal nematode infections4 0.0
Ascariasis2 0.0
Trichuriasis1 0.0
Hookworm disease0 0.0