CENTER FOR BIOLOGICAL SEQUENCE ANALYSIS Technical University of Denmark - DTU Department of systems...

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


the immune systemA brief summary


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



1958 start of small pox eradication program

Effectiveness of vaccines



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)©



The innate immune system

• Unspecific

• Antigen independent

• Immediate response

• No training/selection hence no memory

• Pathogen independent (but response might be pathogen type dependent)



The adaptive immune system

Pathogen specific

Bacteria

Virus

Parasite

http://tpeeaupotable.ifrance.com/ma%20photo/bilharzoze.jpg



• 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



Diversity is a hallmark

of the (adaptive) immune system


Immunological Bioinformatics TutorialCartoon by Eric Reits

Humoral immunity



Antibodies



Antibody - Antigen interaction

FabAntigen

Epitope

Paratope

Antibody



Antibody Effect

Virus or Toxin

Antibodies



The trinity of immunity

Cartoon by Eric Reits


Immunological Bioinformatics Tutorial Cartoon by Eric Reits



Cartoon by Eric Reits

The Cellular immune response



MHC-I molecules present peptides on the surface of most cells



CTL response

Healthy cell

Virus-infected

cellMHC-I



CTL response

Virus-infected

cell

MHC-I



QuickTime™ and aSorenson Video decompressorare needed to see this picture.

The death of an infected cell



• 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



Vaccine Challenges

TB

FLU

HCV

HIV


Immunological Bioinformatics TutorialImmunological Bioinformatics, The MIT press. +HPV & Rotavirus

Vaccines have been made for 36 of >400

human pathogens



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

CENTER FOR BIOLOGICAL SEQUENCE ANALYSIS Technical University of Denmark - DTU Department of systems...

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