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Immune system overview in 10 minutes The non-immunologist guide to the immune system
Vaccine development! The arm of Sarah Nelmes, a dairy maid, who had contracted cowpox. Jenner used material from her arm to vaccinate an eight year old boy, James Phipps. (1798).
Vaccines can eradicate pathogens and save lives
Vaccines have been made for 36 of >400 human pathogens Immunological Bioinformatics, The MIT press. +HPV & Rotavirus
MHC Class I pathway Figure by Eric A.J. Reits
MHC-I molecules present peptides on the surface of most cells Figure courtesy Mette Voldby Larsen
CTL response Figure courtesy Mette Voldby Larsen
Encounter with death
Figure by Anne Mølgaard
HLA binding motif SLLPAIVEL YLLPAIVHI TLWVDPYEV GLVPFLVSV KLLEPVLLL LLDVPTAAV LLDVPTAAV LLDVPTAAV LLDVPTAAV VLFRGGPRG MVDGTLLLL YMNGTMSQV MLLSVPLLL SLLGLLVEV ALLPPINIL TLIKIQHTL HLIDYLVTS ILAPPVVKL ALFPQLVIL GILGFVFTL STNRQSGRQ GLDVLTAKV RILGAVAKV QVCERIPTI ILFGHENRV ILMEHIHKL ILDQKINEV SLAGGIIGV LLIENVASL FLLWATAEA SLPDFGISY KKREEAPSL LERPGGNEI ALSNLEVKL ALNELLQHV DLERKVESL FLGENISNF ALSDHHIYL GLSEFTEYL STAPPAHGV PLDGEYFTL GVLVGVALI RTLDKVLEV HLSTAFARV RLDSYVRSL YMNGTMSQV GILGFVFTL ILKEPVHGV ILGFVFTLT LLFGYPVYV GLSPTVWLS WLSLLVPFV FLPSDFFPS CLGGLLTMV FIAGNSAYE KLGEFYNQM KLVALGINA DLMGYIPLV RLVTLKDIV MLLAVLYCL AAGIGILTV YLEPGPVTA LLDGTATLR ITDQVPFSV KTWGQYWQV TITDQVPFS AFHHVAREL YLNKIQNSL MMRKLAILS AIMDKNIIL IMDKNIILK SMVGNWAKV SLLAPGAKQ KIFGSLAFL ELVSEFSRM KLTPLCVTL VLYRYGSFS YIGEVLVSV CINGVCWTV VMNILLQYV ILTVILGVL KVLEYVIKV FLWGPRALV GLSRYVARL FLLTRILTI HLGNVKYLV GIAGGLALL GLQDCTMLV TGAPVTYST VIYQYMDDL VLPDVFIRC VLPDVFIRC AVGIGIAVV LVVLGLLAV ALGLGLLPV GIGIGVLAA GAGIGVAVL IAGIGILAI LIVIGILIL LAGIGLIAA VDGIGILTI GAGIGVLTA AAGIGIIQI QAGIGILLA KARDPHSGH KACDPHSGH ACDPHSGHF SLYNTVATL RGPGRAFVT NLVPMVATV GLHCYEQLV PLKQHFQIV AVFDRKSDA LLDFVRFMG VLVKSPNHV GLAPPQHLI LLGRNSFEV PLTFGWCYK VLEWRFDSR TLNAWVKVV GLCTLVAML FIDSYICQV IISAVVGIL VMAGVGSPY LLWTLVVLL SVRDRLARL LLMDCSGSI CLTSTVQLV VLHDDLLEA LMWITQCFL SLLMWITQC QLSLLMWIT LLGATCMFV RLTRFLSRV YMDGTMSQV FLTPKKLQC ISNDVCAQV VKTDGNPPE SVYDFFVWL FLYGALLLA VLFSSDFRI LMWAKIGPV SLLLELEEV SLSRFSWGA YTAFTIPSI RLMKQDFSV RLPRIFCSC FLWGPRAYA RLLQETELV SLFEGIDFY SLDQSVVEL RLNMFTPYI NMFTPYIGV LMIIPLINV TLFIGSHVV SLVIVTTFV VLQWASLAV ILAKFLHWL STAPPHVNV LLLLTVLTV VVLGVVFGI ILHNGAYSL MIMVKCWMI MLGTHTMEV MLGTHTMEV SLADTNSLA LLWAARPRL GVALQTMKQ GLYDGMEHL KMVELVHFL YLQLVFGIE MLMAQEALA LMAQEALAF VYDGREHTV YLSGANLNL RMFPNAPYL EAAGIGILT TLDSQVMSL STPPPGTRV KVAELVHFL IMIGVLVGV ALCRWGLLL LLFAGVQCQ VLLCESTAV YLSTAFARV YLLEMLWRL SLDDYNHLV RTLDKVLEV GLPVEYLQV KLIANNTRV FIYAGSLSA KLVANNTRL FLDEFMEGV ALQPGTALL VLDGLDVLL SLYSFPEPE ALYVDSLFF SLLQHLIGL ELTLGEFLK MINAYLDKL AAGIGILTV FLPSDFFPS SVRDRLARL SLREWLLRI LLSAWILTA AAGIGILTV AVPDEIPPL FAYDGKDYI AAGIGILTV FLPSDFFPS AAGIGILTV FLPSDFFPS AAGIGILTV FLWGPRALV ETVSEQSNV ITLWQRPLV
HLA binding specificity High information positions If we have binding data, can we accurate describe the binding specificity!
HLA specificity clustering A0201 A0101 A6802 B0702
More MHC molecules: more diversity in the presented peptides 1% probability that MHC molecule presents a peptide Different hosts sample different peptides from same pathogen.
Pathogen variability –Millions of viral particles within a given host Pathogen diversity –Different viral subtypes circulating in different parts of the world
HIV subtypes (Gag protein) C B AE A D
Epitope identification 56 (1.5%) 9mer are conserved among all 15 Clade A gag sequences
Viral escape Figure courtesy Mette Voldby Larsen ??? ?? ???? The virus of today is different from the virus of tomorrow (Viral escape)
Vaccine design. Polytope construction NH2 COOH Epitope Linker M C-terminal cleavage Cleavage within epitopes New epitopes cleavage
Immune system overview in 10 minutes The non-immunologist guide to the immune system Morten Nielsen Department of Systems Biology DTU.
CENTER FOR BIOLOGICAL SEQUENCE ANALYSISTECHNICAL UNIVERSITY OF DENMARK DTU T cell Epitope predictions using bioinformatics (Hidden Markov models) Morten.
CENTER FOR BIOLOGICAL SEQUENCE ANALYSISTECHNICAL UNIVERSITY OF DENMARK DTU Sequence motifs, information content, logos, and HMM’s Morten Nielsen, CBS,
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Ch. 43 The Immune System Objectives LO 2.28 The student is able to use representations or models to analyze quantitatively and qualitatively the effects.
Sequence motifs, information content, logos, and HMMs Morten Nielsen, CBS, BioCentrum, DTU.
Antigens & HLA Dr.Ghada Boghdadi. Objectives: * Define antigen and hapten. * Define immunogenicity & antigenicity. * Define epitope. * Describe the chemical.
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ImmunoGrid Towards a Clinically Relevant Systems Biology Model for the Human Immune System Dr. Clare Sansom Bedlewo, Poland May 2006.
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Viruses. At the boundary of life, between the macromolecules (which are not alive) and the prokaryotic cells (which are), lie the viruses and bacteriophages.
Applied Immunology Aftab Jasir, European Centre for Disease Prevention and Control (ECDC) European Public Health Microbiology training program (EUPHEM)
Aim: How do vaccinations protect us against disease ? Immunity is the ability of an organism to resist disease by identifying and destroying foreign substances.
1 Viruses. 2 Are Viruses Living or Non-living? Viruses are non living They have some properties of life but not others They cant maintain a constant internal.
Immune System. First line of defense The skin serves as a physical barrier to prevent the passage of many disease-causing microorganisms. The skin is.
Making Peptides for Presentation A Pictorial Introduction SAMSI 3 March 2005.
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Viruses. Viral Disease Please put your name on the index card and the number of your beaker. List # 1-3 on the card. You will meet with 3 different people.
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