Epigenetics from HIV to Immunizationchristl-meyer-science.net/images/PDFs/challenging... · Barbara Mc. Clintock ( Nobelprice for Physiology and Medicine 1983) Transposons „jumping

EpigeneticsfromHIVtoImmunization:NewProspectsonHealthandDisease

1ChristlMeyer,AIDSResearch,Vienna/Austria,2018

„NothinginBiologymakessense,exceptinthelightofevolution“Thisisfroma1973essaybytheevolutionarybiologistandRussianOrthodoxChristianTheodosiusDobzhansky,CriticisingYoungEarthcreationismandespousingEvolutionaryCreationism.(AmericanBiologyTeacher,volume35,125–129)


Overview1. Genetics,HIVandtheImmuneSystem2. Epigenetics3. MicrobesinEvolution4. Immunization5. WhatdoesitmeantobeHuman?


1. Genetics,HIVandtheImmuneSystem2. Epigenetics3. MicrobesinEvolution4. Immunization5. WhatdoesitmeantobeHuman?


ChristlMeyer,AIDSResearch,Vienna/Austria,2018 5

GenesforproteinsRNAmolecules???

6

Genomes:Coding,noncoding,repetitiveelements

PLANTandHUMAN:Bothharbourabout25.000genes

ChristlMeyer,AIDSResearch,Vienna/Austria,2018

Effect of the „kit“-gene


Example:Trisomie21(DownSynrom)


Genduplication as the driving force behind Evolution



OverhalfofourDNAcomesfromretro-transposons,geneticelementsthatindependentlymultiplyandspreadthroughthegenome(deKoningetal.,2011).

OnthemoveThemechanismsbywhicharetrotransposoncalledLINE-1duplicatesitselfandspreadsthroughthehumangenomearebecomingclearer.Martin.eLife2018;7:e34901.DOI:https://doi.org/10.7554/eLife.34901

Inmammals,aretrotransposoncalledLINE-1isresponsibleformostofthesemultiplicationevents,eitherduplicatingitselforlendingits’photocopying’machinerytoothergeneticelements. 11ChristlMeyer,AIDSResearch,Vienna/

Austria,2018

12

Barbara Mc. Clintock ( Nobelprice for Physiology and Medicine 1983) Transposons „jumping genes“



Humansandchimpanzees,whichdivergedfromacommonancestorsome5millionyearsago,differintheirgenomesequencesonlyinabout1–2%.Provirusesfixedinthegermlinecanprovideuswithafossilrecordofviruseslongextinctinthepopulation.InhumanDNAonly2-3%ofthegenomearecoding.97%arenoncoding(formerlycalled„junkDNA“).ThisDNAmightbeinvolvedingeneregulationprocesses.Inhumans,thereareabout80.000provirusesortheirremnants,comprisingabout6-8%ofthegenome,orabouttwiceasmanyasgenes.JohnM.Coffin,ProfofMolecularBiologyandMicrobiology,TuftsUniversity:

„Thereismoreprovirusinusthanthereisusinus“.


15

TheHumanGenomeProjectdiscoveredourgeneticbackgroundbyreducingtheamountofproteincodinggenestoapproximately20.000andaugmentedtheRNAtranscriptions.


1. Alvarez-DominguezJR,HuW,YuanB,etal.GlobaldiscoveryoferythroidlongnoncodingRNAsrevealsnovelregulatorsofredcellmaturation.

Blood.2014;123(4):570-581.2.SabinLR,DelásMJ,HannonGJ.Dogmaderailed:themanyinfluencesofRNAonthegenome.MolCell.2013;49(5):783-794.

3.UlitskyI,BartelDP.lincRNAs:genomics,evolution,andmechanisms.Cell.2013;154(1):26-46.

4.BatistaPJ,ChangHY.LongnoncodingRNAs:cellularaddresscodesindevelopmentanddisease.Cell.2013;152(6):1298-1307.

5.BergmannJH,SpectorDL.Longnon-codingRNAs…..16ChristlMeyer,AIDSResearch,Vienna/

Austria,2018

AleksandraE.Kornienko,ChristophP.Dotter,PhilippM.Guenzl,HeinzGisslinger,BettinaGisslinger,CiaraCleary,RobertKralovics,FlorianM.PaulerandDeniseP.Barlow

“Longnon-codingRNAsdisplayhighernaturalexpressionvariationthanprotein-codinggenesinhealthyhumans“GenomeBiology2016,17:14,DOI:10.1186/s13059-016-0873-8.


18

Human Genome Nature 409, 860-921 (15 February 2001) / doi: 10.1038/35057062; Received 7 December 2000; Accepted 9 January 2001

Initial sequencing and analysis of the human genome Internationbal Human Genome Sequencing Consortium Eric S. Lander... ...Here we report the results of a collaboration involving 20 groups from the United States, the United Kingdom, Japan, France, Germany and China to produce a draft sequence of the human genome. ...Hundreds of human genes appear likely to have resulted from horizontal transfer from bacteria at some point in the vertebrate lineage. ...Dozens of genes appear to have been derived from transposable elements. ...large recent segmental duplications...much more frequent in humans...


19

Amajorpartoftheimmunesystem:MHC-MajorHistocompatibility–ComplexandHLA-HumanLeucocyteAntigen–Systemgivenewinsightsontheco-evolutionofthespecies,particularlyofmammals(andprimates)withmicrobes.


20

HLAisthemostgenedenseandvariableregionandisrelatedtohealthanddisease!


HLA-sequencesonChromosome6


HLAclasses


6p21.31



HLA 6p21.3

„Virus“bindingsite 25ChristlMeyer,AIDSResearch,Vienna/Austria,2018

http://www.geocities.ws/chiakwongmin/HIV/HIV_photo-picture/

HIVModel



Brummeetal


29JOURNAL OF VIROLOGY, Sept. 2008, p. 9216–9227 Vol. 82, No. 18 0022-538X/08/$08.000 doi:10.1128/JVI.01041-08

Marked Epitope- and Allele-Specific Differences in Rates of Mutation in Human Immunodeficiency Type 1 (HIV-1) Gag, Pol, and Nef Cytotoxic T-Lymphocyte Epitopes in Acute/Early HIV-1 Infection

Zabrina L. Brumme et al. Partners AIDS Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts

The so called mutation of the „HI-Virus“


„Life has a tendency to plurality, being colourfully, to independence, simply to freedom. The totaliarian system demands monolithical unity, uniqueness and discipline.“ (Vaclav Havel, dissident and president – Charta 77 /Chech Republik) 30ChristlMeyer,AIDSResearch,Vienna/

Austria,2018


Whatwerealize

...andwhatishidden.


HIVcannotbethecauseofAIDS–itisageneticfactorinevolution


TheGAG„viralprotease“isunderpositiveselectivepressure


35

„Darkmatter“ofthegenomemayplayamajorbiologicalroleincelldevelopmentandmetabolismincludingdiseaseslikecancer.

InvolvedaremanydifferentNoncodingRNAgenesthathaverecentlybeendetected.


Questions(concerningtests):

1. Isthetestsaveandvalid?2.Doesearlydetectionprolongelife-span?

3.Doesearlydetectionimprovelife-quality?



HIV-Test Insert:


Western Blot Test


40

What does this mean? If you are tested HIV-positive in Germany or Africa, you can fly to Australia or France with your Western-blot test result and be claimed HIV-negative only because of the different standards that are applied.


Sayre,K.R.,Dodd,R.Y.,Tegtmeier,G.,Layug,L.,Alexander,S.S.andBusch,M.P.(1996),

False-positivehumanimmunodeficiencyvirustype1westernblottestsinnoninfectedblooddonors.Transfusion,36:45–52.doi:10.1046/j.1537-2995.1996.36196190514.xLow-riskblooddonors(PCRnegative)canhavefalse-positiveresultsonWBtests.Increaseddetectionofenv-onlyandp24/env-onlyWBsappearsrelatedtothe

enhancedsensitivityofnewerenzymeimmunoassaystogp41andp24antibodies.

KeithR.Sayre,MBA,ProductManager,AIDS/HepatitisBusinessUnit,OrthoDiagnosticSystems,Inc.,Raritan,NJ.RogerY.Dodd,PhD,Head,TransmissibleDiseasesLaboratory,AmericanRedCross,Rockville,MD.GaryTegtmeier,PhD,DirectorofResearch,CommunityBloodCenterofGreaterKansasCity,KansasCity,MO.

LynneLayug,MPH,MT(ASCP),TechnicalOfficer,NationalReferenceLaboratoryforInfectiousDisease,AmericanRedCross,Rockville,MD.SteveS.Alexander,PhD,PrincipalScientist,AIDS/HepatitisResearchandDevelopment,OrthoDiagnosticSystems.

*6MichaelP.Busch,AssociateProfessorinResidence,DepartmentofLaboratoryMedicine,UniversityofCalifornia,SanFrancisco;andVicePresident,ResearchandScientificServices,IrwinMemorialBloodCenters,270MasonicAvenue,SanFrancisco,CA94118-4496.

Articlefirstpublishedonline:28FEB2003


The diagnosis (prognosis) of a serious disease can lead to disease and death – even if the person was not sick before.

This is called the NOCEBO-effect!

The contrary – the PLACEBO-effect is scientifically better examined and proven.


“RPD[rapiddiseaseprogression]wasthreetimesmorelikelytooccurininfantsbornto[AZT]treatedmothers-comparedwith

findingsinuntreatedmothers.”deSouzaRSetal.EffectofprenatalzidovudineondiseaseprogressioninperinatallyHIV-1-

infectedinfants.JAcquirImmuneDeficSyndr.2000Jun1;24(2):154-161

"CombivirisclassifiedbytheFDAasapregnancycategoryCdrug.PregnancycategoryCmeansthatanimalstudieshaveshownanadverseeffectonthefetusandtherearenoadequateandwell-controlledstudiesinhumans"http://www.aidsmeds.com/archive/Combivir_1083.shtml


ComparisonsofCausesofDeathandMortalityRatesAmongHIV-InfectedPersons:AnalysisofthePre-,Early,andLateHAART(HighlyActiveAntiretroviralTherapy)ErasCrum,NancyFMD,MPH*†;Riffenburgh,RobertHPhD‡;Wegner,ScottMD†§;Agan,BrianKMD†∥;Tasker,SybilAMD†¶;Spooner,KatherineMMD†#;Armstrong,AdamWDO†**;Fraser,SusanMD††;Wallace,MarkRMD*†onBehalfoftheTriserviceAIDSClinicalConsortiumJAIDSJournalofAcquiredImmuneDeficiencySyndromes:February1st,2006-Volume41-Issue2-p194-200doi:10.1097/01.qai.0000179459.31562.16EpidemiologyandSocialScienceMethods:Comparisonsofdeath-relatedvariablesduringthe3eraswereperformed.Results:Thenumberofdeathsdeclinedoverthestudyperiod,with987deathsinthepre-HAARTera,159deathsintheearlyHAARTera(1997-1999),and78deathsinthelateHAARTera(2000-2003)(P<0.01).Theannualdeathratepeakedin1995(10.3per100patients)andthendeclinedto<2deathsper100personsinthelateHAARTera(P<0.01).Theproportionofdeathsattributabletoinfectiondecreased,butinfectionremainedtheleadingcauseofdeathinourcohort,followedbycancer.Ofthosewhodied,therewasanincreasingproportionofnon-HIV-relateddeaths(32%vs.9%;P<0.01),includingcardiacdisease(22%vs.8%;P<0.01)andtrauma(8%vs.2%;P=0.01)inthepost-HAARTversuspre-HAARTera.DespitetheabsenceofintravenousdruguseandthelowprevalenceofhepatitisCcoinfectioninourcohort,anincreasingproportionofdeathsintheHAARTerawereattributabletoliverdisease,althoughthenumbersaresmall.

„Medicalerror—thethirdleadingcauseofdeathintheUS“,BritishMedicalJournal(3.5.2016).MartinMakaryfromJohnsHopkinsUniversitySchoolofMedicineinBaltimore.


PERSPECTIVE


Inmedicalhistorydecisionmakingwaspaternalistic.Replacedbypatientautonomy.Thisshiftisexemplifiedinthelegalrequirementofinformedconsenttotreatment.Shareddecisionmakingisnowtheideal.But:Thepatientistheultimativeandauthoritativedecisionmaker,becauseheorshealonedetermineswhatwillbedonetohisorherbodyandhowthisactionwillaffecthisorherlife.


48

Chemical Substances (Medications) can lead to Mutations !


HAARTdrivesEvolutionofHLA/HIV=Humangenes!



AIDS.2012Jul17;26(11):F21-9.doi:10.1097/QAD.0b013e328355fe8f.Abacavirinducesloadingofnovelself-peptidesintoHLA-B*57:01:an

autoimmunemodelforHLA-associateddrughypersensitivity.NorcrossMA,LuoS,LuL,BoyneMT,GomarteliM,RennelsAD,WoodcockJ,

MarguliesDH,McMurtreyC,VernonS,HildebrandWH,BuchliR.

SourceLaboratoryofImmunology,DivisionofTherapeuticProteins,Officeof

BiotechnologyProducts,CenterforDrugEvaluationandResearch,FoodandDrugAdministration,Bethesda,MD20892,[email protected]

CONCLUSION:Ourresultssupportamodelofdrug-inducedautoimmunityinwhichabacaviraltersthequantityandqualityofself-peptideloadingintoHLA-B57:01.Drug-inducedloadingofnovelself-peptidesintoHLA,

possiblybyabacavireitheralteringthebindingcleftormodifyingthepeptide-loadingcomplex,generatesanarrayofneo-antigenpeptidesthatdrivepolyclonalT-cellautoimmuneresponsesandmultiorgan

systemictoxicity.

50


ChemImmunolAllergy.2012;97:18-31.doi:10.1159/000335613.Epub2012May3.Geneticsandthepotentialforpredictivetestsinadversedrugreactions.

PirmohamedM.TheWolfsonCentreforPersonalisedMedicine,DepartmentofMolecularandClinicalPharmacology,UniversityofLiverpool,Liverpool,[email protected]

Drughypersensitivityreactionsareanimmune-mediatedreactiontootherwiseinnocuousantigensderivedfromdrugs.Thesereactionscanaffectmanydifferentorgans,withtheskinbeingthecommonest.Skininvolvementcanrangeinseveritywithhypersensitivitysyndrome(orDRESS)andtheblisteringreactions(Stevens-Johnsonsyndrome,toxicepidermalnecrolysis),alsotermedseriouscutaneousadversedrug

reactions,beingthemostsevereandmostfeared.Thereisincreasingevidencefortheroleoftheimmunesysteminthepathogenesisofthesereactions,withdrug-specificTcellshavingbeenidentifiedinmany

patients.......HLAgenesasgenomicbiomarkersofpredisposition.The'revolution'startedwithabacavirwherethepredispositionto

hypersensitivitywaslinkedtoHLA-B*57:01,whichwasconfirmedinaclinicaltrial,andwhereitsimplementationhasshowntoreducetheincidenceofhypersensitivityinacost-effectivemanner.Sincethen,associationshavealsobeenshownforallopurinol(HLA-B*58:01)-andcarbamazepine(HLA-B*1502andHLA-A*3101)-inducedseriouscutaneousadversedrugreactions.ThelatterisinterestingsincetheassociationwithHLA-B*1502ispresentin

certainSouth-EasternAsianpopulations,andthepredispositionisphenotypespecific(onlyforSJS/TEN).TheutilityofthisbiomarkerhasbeenshowninaprospectivecohortstudyperformedinTaiwan.Bycontrast,theassociationwithHLA-A*3101isseeninmorediverseethnicgroups,andpredisposestomildaswellmoresevere

cutaneousreactionsassociatedwithcarbamazepine.ItisimportanttonotethatstrongHLAassociationshavealsobeenshownwithanumberofdrugsthatcauseliverinjuryincludingflucloxacillin,lumiracoxib,lapatinibandximelagatran,indicatingthattheimmunesystemisalsoimportantinthepathogenesisof

otherformsofdrug-inducedorgantoxicity.Copyright©2012S.KargerAG,Basel.

Paracelsus:Everythingisdependentontheconcentration


T1 T2

cellproliferation,antibodyproduction,lackofapoptosisT-celldecline

Immunebalance

Stress

?cancer „AIDS“


Soul

Mind Body

54

Asymbioticinteractionthatoriginatesfromthegenesoftheimmunesystemleadstocommunicationparticles(exo-andendosomes)thatactdifferentlywithintheimmunesystem.


55

The whole cell-communication in and between cells of an organism depends on the activity of molecules like RNAs, Proteins, Exo- and Endosomes, Informosomes and Clathrines, to mention just some of them. The Journal of Immunology, 2005, 174: 4779–4788. HIV Type 1 Can Act as an APC upon Acquisition from theHost Cell of Peptide-Loaded HLA-DR and CD86 Molecules1 Jocelyn Roy, Genevie`ve Martin, Jean-François Gigue`re, Dave Be´langer, Myriam Pe´trin,and Michel J. Tremblay2


56

TheHumanMicrobiomeProject(HMiP)triestospecifythegenesofthemicrobeslivingonandinourbodies.Wehave10-foldmoremicrobesthanwehavecellsinahumanbeing.


57

Evolutionisacceleratedby(ancient)lateral(horizontal)genetransferfrommicrobestotheirhosts.


58

Humansunderwentanevolutionaryadaptionprocesswhichwasinfluencedbygeography.Thisresultedindifferencesincludingtheimmunesystem.PeopleofAfricandescentshowreducedneutrophilcountduetoaregulatoryvariant.ThereisalsoanextensivegeneticdiversityintheHLAclassIIregionofAfricansfromGambiaandMalawi.ThisdiversityistwiceasextensiveasfoundinnorthernEuropeans.InconsequencewefinddifferencesinhumoralresponsesbetweenEthiopianandSwedishpersonswhoareclaimedtobe“infected”byHIV.


59

Doxiadisetal.stateaphylogeneticevidencethatsupportsthenotionofthegenerationofnewHLA-DRBgenesasadynamicandsteadilyongoingprocess.Thisisduetothepresenceofindels(insertions/deletions),mainlymappingtointron.


60

THEHIVGENOME„...analysisoftheproteinsofthevirusdemandsmassproductionandpurification...

Irepeat,wedidnotpurify.“LUCMontagnier,PasteurInstitute,July18th1997

From:EleniPapadopulosEleopulosBiophysicist,DepartmentofMedicalPhysics,RoyalPerthHospital,Perth,WesternAustralia


Phylogenetictreeof„HIV“

P.M.SharpandB.H.Hahn/ColdSpringHarbPerspectMed2011;1:a006841www.perspectivesinmedicine.org 61ChristlMeyer,AIDSResearch,Vienna/

Austria,2018

62

Conclusion:HIVmeansevolutionaryadaptedgeneticvariationinsteadofvirusmutation!


63

„OpenReadingFrames“Leadingtovariations

HIV-model


64

HumanGenomeNature409,860-921(15February2001)/doi:10.1038/35057062;Received7December2000;Accepted9January2001

InitialsequencingandanalysisofthehumangenomeInternationbalHumanGenomeSequencingConsortiumEricS.Lander......Herewereporttheresultsofacollaborationinvolving20groupsfromtheUnitedStates,theUnitedKingdom,Japan,France,GermanyandChinatoproduceadraftsequenceofthehumangenome....Hundredsofhumangenesappearlikelytohaveresultedfromhorizontaltransferfrombacteriaatsomepointinthevertebratelineage....Dozensofgenesappeartohavebeenderivedfromtransposableelements....largerecentsegmentalduplications...muchmorefrequentinhumans...


„HIV“isfoundmostneargenesandCGsequences/bacterialorigin;

Zaninietal.eLife2015;4:e11282.DOI:10.7554/eLife.11282https://www.sciencedirect.com/science/article/pii/S0092867402008644

PopulationgenomicsofintrapatientHIV-1

evolution


66

MHCofthevertebrateimmunesystem:• Non-randomdistribution• IncreasedgenedensityintheMHC/HLA

Crisp,Aetal.Expressionofmultiplehorizontallyacquiredgenesisahallmarkofbothvertebrateandinvertebrategenomes.GenomeBiology;12March2015


67

TranscriptionalanalysisforhostfactorsrequiredbyHIV-1wasperformedbyRNAinterference.Morethan250HIV-dependencyfactorswereidentified.Theseproteinsparticipateincellularfunctions.Transcriptionalanalysisrevealedthatthesegeneswereenrichedforhighexpressioninimmunecells.


68

Jeremiasetal.claimthathumansemenisbothaninducerofananti-inflammatoryTH2immuneresponseandaninhibitorofTH1cellmediatedimmunity.Why?Thisprotectsthemalegenesinthefetus.


69

HIVisanaturalproductinspermswhichhasitsoriginintheHLAandprotectsthefetusfrommaternalrejectionofpaternalantigensbyshiftingT1toT2.HeterosexualtransmissionofHIVisonlysuggestedwithadditionalpathogensinSTDs.Homosexualtransmissionisduetorejectionofalloantigens.Allogeneicimmunityprotectsfrominfectionbutcanberelatedtoallergiesalsointheoffspring.ThusHIVpositivitymeansanallergicreaction!


70

MultipleinteractionsincellcommunicationareprovedconcerningHIV,specificallyinGALT(gutassociatedlymphoidtissue)whichmakessenseforprotectingthebodyfromstrangeinvadersfromnutrition!



retrotransposon-mediateddiversity. https://openi.nlm.nih.gov/detailedresult.php?img=PMC2913931_1752-0509-4-96-1&req=4

Figure1:HIV-Humanproteininteractionnetwork.19HIVproteinsthatinteractwith1452humanproteinsthrough3959interactions.BluenodesarehumanproteinsandrednodesareHIVproteins.

72

Gp120isactiveasasuperantigenthatincreasesTh2relatedantibodyproductionininfectionsasa“booster”andmightbeduetoallergyandautoimmunity.Stressisinvolvedingeneexpression.„HIV“canbeprotectivetocancer.MedicationsandHAARTmighthavedifferent(negative)impactsonthebalanceoftheTh1/Th2-system.


73

The whole cell-communication in and between cells of an organism depends on the activity of molecules like RNAs, Proteins, Exo- and Endosomes, Informosomes and Clathrines, to mention just some of them. The Journal of Immunology, 2005, 174: 4779–4788. HIV Type 1 Can Act as an APC upon Acquisition from theHost Cell of Peptide-Loaded HLA-DR and CD86 Molecules1 Jocelyn Roy, Genevie`ve Martin, Jean-François Gigue`re, Dave Be´langer, Myriam Pe´trin,and Michel J. Tremblay2



TheRNA-family

Source:CDC.EstimatedHIVincidenceamongadultsandadolescentsintheUnitedStates,2007–2010.HIVSurveillanceSupplementalReport2012;17(4)http://www.cdc.gov/hiv/topics/surveillance/resources/reports/index.htm#supplemental.Subpopulationsrepresenting2%orlessoftheoverallUSepidemicarenotreflectedinthischart.Abbreviations:MSM,menwhohavesexwithmen;IDU,injectiondruguser.

AfricanAmericansaccountedforanestimated44%ofallnewHIVinfectionsamongadultsandadolescents(aged13yearsorolder)in2010,despiterepresentingonly12%to14%oftheUSpopulation.

AfricanAmericansaretheracial/ethnicgroupmostaffectedbyHIV.



“RPD[rapiddiseaseprogression]wasthreetimesmorelikelytooccurininfantsbornto[AZT]treatedmothers-comparedwith

findingsinuntreatedmothers.”deSouzaRSetal.EffectofprenatalzidovudineondiseaseprogressioninperinatallyHIV-1-

infectedinfants.JAcquirImmuneDeficSyndr.2000Jun1;24(2):154-161

"CombivirisclassifiedbytheFDAasapregnancycategoryCdrug.PregnancycategoryCmeansthatanimalstudieshaveshownanadverseeffectonthefetusandtherearenoadequateandwell-controlledstudiesinhumans"http://www.aidsmeds.com/archive/Combivir_1083.shtml


78

The nervous and the immune system share a lot of biochemical molecules, i. e. Hormons (Cortisol) Transmitter (Gamma-Amino-Butyrat) Interleukine Il 2, Il 10...) Both systems are involved in learning processes! The Immune-System comprises high variability and fluctuation through Transposable Elements. It has to distinguish between SELF and NON-SELF! Learning means to add NEW informations to knowledge!


79

Anergy

Anergy is the missing reaction to an antigen by shuting down the immune reaction. Anergy is a mechanism by which the immune system prevents T-cells from attacking the bodies own tissues. Anergy is a permanent characteristic. Under normal conditions it is not reactivated. Some systems are activated despite anergy by Interleukin-2. Problems: puberty and infectious tissues (lung cells with virus-infection).


80

ALLOANTIGENs An allergic reaction against variants of molecules (glyco-proteins, nucleic acids) of the same species might occur if the variants of contact (blood-components, leucocytes, sperms) activate the immune-system. Those people might also test „HIV-positive“


81

The Nobel Prize in Physiology or Medicine 2011 Bruce A. Beutler and Jules A. Hoffmann: Discoveries concerning the Activation of Innate Immunity Steinman : Discovery of the Dendritic Cell and its Role in Adaptive Immunity: Mediating the Communication between innate and adaptive immunity.

Toll-like receptor ligands will directly alter the functions of regulatory T cells

DendriticCells


82

HIV- antibodies are • Autoantibodies as we all produce them. • Allergy-antibodies, which are induced by molecular similarity. • A hint for an active or • Imbalanced immune-system (stress). • Increased after some vaccinations.

HIV – „Viruses“ are • Particels of cell-communication (Endo- and Exosomes).


83

The Rest belongs to other diseases or wrong diagosis! Like hunger, malaria, tuberculosis, lung- and gut-infections, drugs.


84

AIDS is gene expression and / or self-organized mutation (genome extension) and therefore EVOLUTION under elevated stress.

The aim is the survival under unfavorable environmental conditions. Medications themselves bring on these situations by which the cell responds with mutations.


1. Genetics,HIVandtheImmuneSystem2. Epigenetics3. MicrobesinEvolution4. Immunization5. WhatdoesitmeantobeHuman?


86

Epigenetics Stimuli from the environnement change gene expression. This effect can be transmitted through generations.


Psychoneuroimmunology Psychoneuroimmunology (PNI) is an interdisciplinary field of research, which deals with the interaction of the nerve system, the hormone system and the immune system. The scientific basis is that messenger molecules (like hormones and other substances) of the nervous system influence the immune system and vice verse.


Pregnancy and the future of the next generations:


InstituteofScienceinSocietyReport30/09/15

OrganicFoodduringMother'sPregnancyReducesRiskofMaleBirthDefects

ExpectingmotherseatingmostlyorganicproducereduceriskofurogenitalanomaliesinmaleoffspringDrEvaSirinathsinghji

Pesticidesaretheotherobviouscandidatefortheobserveddisparityindisease

ratesbetweenthoseeatingorganicversusconventionalfoods.Severalclassesofpesticidehavebeenshowntohaveendocrinedisruptingeffectsincludingglyphosate,2,4-D,atrazine,endosulfan,linurin,vinclozolinanddichlorodiphenyldichloroethylene(DDE).


90

Syncytin-mediatedcell–cellfusion

DupressoirAetal.PNAS2005;102:725-730

©2005byNationalAcademyofSciences

Syncytin and placenta development


91

Syncytin, whichisexpressedbyendogenousretrovirusesofthepregnantwomen,leadstocell-fusionbybuildinguptheplacentainnormaldevelopment.

DupressoirAetal.PNAS2005;102:725-730

Humans have 400% more of retroviral genes than of human genes


Why it is so important that mothers breastfeed their babies:

• The antibodies of the mother protect the child from infections. • The emotional relationship and the primal sense of trust are strengthened.


93

EVOLUTION and MUTATION

Extinction of the Population

Extiction of the Individual

„genechaos“Lackofgenetic

diversity


94

Result: The more of Stress The more of Mutations.


Prenatalstressaltersthebraintranscriptomeinmalenewbornoffspring.

ZucchiFCR,YaoY,WardID,IlnytskyyY,etal.(2013)MaternalStressInducesEpigeneticSignaturesofPsychiatricandNeurologicalDiseasesintheOffspring.PLoSONE8(2):e56967.doi:10.1371/journal.pone.0056967http://www.plosone.org/article/info:doi/10.1371/journal.pone.0056967


Normalcellularhomeostasisisadelicatebalancebetweentherateandmagnitudeofoxidantformationandtherateofoxidantelimination.Oxidativestresscan,therefore,bedefinedasthepathogenicoutcomeoftheoverproductionofoxidantsthatoverwhelmsthecellularantioxidantcapacity. 96ChristlMeyer,AIDSResearch,Vienna/

Austria,2018


Documents

Epigenetics from HIV to Immunizationchristl-meyer-science.net/images/PDFs/challenging... · Barbara Mc. Clintock ( Nobelprice for Physiology and Medicine 1983) Transposons „jumping