Download Title goes here - Center for Biological Sequence Analysis

CENTER FOR BIOLOGICAL SEQUENCE ANALYSIS
Immunological Bioinformatics
Biopeople
Tutorial 2011
Technical University of Denmark - DTU
Department of systems biology
CENTER FOR BIOLOGICAL SEQUENCE ANALYSIS
the immune system
A brief summary
Technical University of Denmark - DTU
Department of systems biology
•
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
mmunological Bioinformatics Tutorial
Technical University of Denmark - DTU
Department of systems biology
C EN TER F OR BIOLOGIC A L SEQU EN C E A N A LY SIS
Vaccination
C EN TER F OR BIOLOGIC A L SEQU EN C E A N A LY SIS
mmunological Bioinformatics Tutorial
Technical University of Denmark - DTU
Department of systems biology
Effectiveness of vaccines
C EN TER F OR BIOLOGIC A L SEQU EN C E A N A LY SIS
mmunological Bioinformatics Tutorial
1958 start of small pox
eradication program
Technical University of Denmark - DTU
Department of systems biology
Skin
Toll like
receptors
Scavenging Cells
Epithelia
Shizuo Akira & Kiyoshi TakedaNature Reviews
Immunology 4, 499-511 (July 2004)
©
The innate immune system
Barriers, cells, and receptors
mmunological Bioinformatics Tutorial
Technical University of Denmark - DTU
Department of systems biology
C EN TER F OR BIOLOGIC A L SEQU EN C E A N A LY SIS
Tears
•
Unspecific
•
Antigen independent
•
Immediate response
•
No training/selection hence no memory
•
Pathogen independent (but response might be
pathogen type dependent)
mmunological Bioinformatics Tutorial
Technical University of Denmark - DTU
Department of systems biology
C EN TER F OR BIOLOGIC A L SEQU EN C E A N A LY SIS
The innate immune system
http://tpeeaupotable.ifrance.com/ma%20photo/bilharzoze.jpg
Parasite
Virus
The adaptive immune system
mmunological Bioinformatics Tutorial
Pathogen specific
Technical University of Denmark - DTU
Department of systems biology
C EN TER F OR BIOLOGIC A L SEQU EN C E A N A LY SIS
Bacteria
•
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
mmunological Bioinformatics Tutorial
Technical University of Denmark - DTU
Department of systems biology
C EN TER F OR BIOLOGIC A L SEQU EN C E A N A LY SIS
Diversity is a hallmark of the
(adaptive) immune system
C EN TER F OR BIOLOGIC A L SEQU EN C E A N A LY SIS
Diversity is a
hallmark of
the (adaptive)
immune
system
mmunological Bioinformatics Tutorial
Technical University of Denmark - DTU
Department of systems biology
Cartoon by Eric Reits
mmunological Bioinformatics Tutorial
Technical University of Denmark - DTU
Department of systems biology
C EN TER F OR BIOLOGIC A L SEQU EN C E A N A LY SIS
Humoral immunity
Antibodies
C EN TER F OR BIOLOGIC A L SEQU EN C E A N A LY SIS
mmunological Bioinformatics Tutorial
Technical University of Denmark - DTU
Department of systems biology
C EN TER F OR BIOLOGIC A L SEQU EN C E A N A LY SIS
Antibody - Antigen
interaction
Fab
Antigen
Epitope
mmunological Bioinformatics Tutorial
Paratope
Antibody
Technical University of Denmark - DTU
Department of systems biology
Antibodies
Virus or Toxin
mmunological Bioinformatics Tutorial
Technical University of Denmark - DTU
Department of systems biology
C EN TER F OR BIOLOGIC A L SEQU EN C E A N A LY SIS
Antibody Effect
The trinity of immunity
C EN TER F OR BIOLOGIC A L SEQU EN C E A N A LY SIS
Cartoon by Eric Reits
mmunological Bioinformatics Tutorial
Technical University of Denmark - DTU
Department of systems biology
C EN TER F OR BIOLOGIC A L SEQU EN C E A N A LY SIS
mmunological Bioinformatics Tutorial
Cartoon by Eric Reits
Technical University of Denmark - DTU
Department of systems biology
Cartoon by Eric Reits
C EN TER F OR BIOLOGIC A L SEQU EN C E A N A LY SIS
The Cellular
immune response
mmunological Bioinformatics Tutorial
Technical University of Denmark - DTU
Department of systems biology
mmunological Bioinformatics Tutorial
Technical University of Denmark - DTU
Department of systems biology
C EN TER F OR BIOLOGIC A L SEQU EN C E A N A LY SIS
MHC-I molecules present peptides on the
surface of most cells
Healthy
cell
mmunological Bioinformatics Tutorial
MHC-I
Virusinfected
cell
Technical University of Denmark - DTU
Department of systems biology
C EN TER F OR BIOLOGIC A L SEQU EN C E A N A LY SIS
CTL response
mmunological Bioinformatics Tutorial
MHC-I
C EN TER F OR BIOLOGIC A L SEQU EN C E A N A LY SIS
CTL response
Virusinfected
cell
Technical University of Denmark - DTU
Department of systems biology
mmunological Bioinformatics Tutorial
QuickTime™ and a
Sorenson Video decompressor
are needed to see this picture.
Technical University of Denmark - DTU
Department of systems biology
C EN TER F OR BIOLOGIC A L SEQU EN C E A N A LY SIS
The death of an infected cell
Summary
The adaptive immune system is extremely diverse
•
Antibodies defines the humoral response
-
•
A immune responds can by raise against any thing
foreign!
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
mmunological Bioinformatics Tutorial
Technical University of Denmark - DTU
Department of systems biology
C EN TER F OR BIOLOGIC A L SEQU EN C E A N A LY SIS
•
• TB
• FLU
• HCV
• HIV
mmunological Bioinformatics Tutorial
Technical University of Denmark - DTU
Department of systems biology
C EN TER F OR BIOLOGIC A L SEQU EN C E A N A LY SIS
Vaccine Challenges
C EN TER F OR BIOLOGIC A L SEQU EN C E A N A LY SIS
Vaccines have been
made for 36 of >400
human pathogens
mmunological
Bioinformatics
Tutorial
Immunological Bioinformatics,
The MIT press.
Technical University of Denmark - DTU
Department of systems biology
+HPV & Rotavirus
Infectious and parasitic diseases
Thousands
%
Total
8721
15.3
1342
2.4
120
0.2
100
0.2
4
0.0
0
0.0
1776
3.1
2464
4.3
448
0.8
195
0.3
1
0.0
8
0.0
155
0.3
88
0.2
340
0.6
128
0.2
69
0.1
827
1.5
133
0.2
54
0.1
10
0.0
44
0.1
26
0.0
0
0.0
0
0.0
12
0.0
16
0.0
15
0.0
0
0.0
4
0.0
2
0.0
0
0.0
Tuberculosis
STDs excluding HIV
Syphilis
Chlamydia
Gonorrhoea
Diarrhoeal diseases
Childhood diseases
Pertussis
Poliomyelitis (c)
Diphtheria
Measles
Tetanus
Meningitis
Deaths from
infectious
diseases in
the world in
2008
mmunological Bioinformatics Tutorial
Hepatitis B (d)
Hepatitis C (d)
Malaria
Tropical diseases
Trypanosomiasis
Chagas disease
Schistosomiasis
Leishmaniasis
Lymphatic filariasis
Onchocerciasis
Leprosy
Dengue
Japanese encephalitis
Trachoma
Intestinal nematode infections
Ascariasis
Trichuriasis
Technical University of Denmark - DTU
1Department of systems 0.0
biology
Hookworm disease
C EN TER F OR BIOLOGIC A L SEQU EN C E A N A LY SIS
HIV/AIDS