医学遗传学英文版教学课件：10 Genetics of immune system

Chapter10GeneticsofImmuneSystemqiming_14618@MingQi祁鸣,PhD,Dip.ABMG,FACMGHUGOLecturerCAPInspectorCenterforGenetic&GenomicMedicineJamesWatsonInstituteofGenomicSciences&MedicalSchoolofZhejiangUniversityDepartmentofPathologyandLab.Med.UniversityofRochesterMedicalCenterqiming_14618@8820-8274ZJUMSResearchBuildingA713LearningObjectives1.Immune

genestructures2.Geneticcontrolofimmunefunction3.Majordiseasesresultedfromimmunegenedefects

1930NobelPrizeWinner:LandsteinerForhisdiscoveryofABObloodgroups

Thebloodgroups

1.TheABOBloodGroups

A/B/O:9q34

H/h:19q13.3

Se/se:19q13.3(AD)TheHantigenisanintermediatestageinaseriesofsynthesesending,inthepresenceoftheAorBgenes,intheproductionofthecorrespondingAandBantigens.TheSegeneisaregulatorygenecontrollingexpressionofthestructuralgeneHinexternalsecretions.ABOAntigenPathwayTheABOofParentsChildrenImpossibleA×A（IAIA/IAi×IAIA/IAi）A、OB、ABA×O（IAIA/IAi×ii）A、OB、ABA×B（IAIA/IAi×IBIB/IBi）A、B、AB、O-A×AB（IAIA/IAi×IAIB）A、B、ABOB×B（IBIB/IBi×IBIB/IBi）B、OA、ABB×O（IBIB/IBi×ii）B、OA、ABB×AB（IBIB/IBi×IAIB）A、B、ABOAB×O（IAIB×ii）A、BAB、OAB×AB（IAIB×IAIB）A、B、ABOO×O（ii×ii）OA、B、ABParentalandtheirchildren’sABOBloodtypeBombayPhenotypeBombayPhenotype(Bi,hh)TheRhSystemRhantigensarealsoexpressedonthesurfaceofredbloodcells.TheyarefirstdiscoveredintherhesusmonkeyHemolyticDiseaseoftheNewborn:

NaturalImmunity

Thehumoralimmunity:

Bcell,antibodies

AcquiredImmunity

Thecellularimmunity:

CytotoxicTcells

HelperTcells

Generalandanticipatoryimmunesystems

ThehumoralimmunesystemTheCellularImmuneSystemTlymphocytesbecomeCD4+orhelperTcells,ortheycanbecomeCD8+cells,whichinturncanbecomekillerTcells,alsocalledcytotoxicTcells.TheVariabilityoftheMHCComplexThe

"MajorHistocompatibilityComplex”(MHC)

areimportantinacceptanceorrejectionofcellsingraftsorbloodtransfusions.InmicetheMHCcalledH-2InhumansitiscalledHLAfor"HumanLeukocyteAntigen"HLAgenecomplex:6p21.3Nature,1999,401:921~923.

SerologicallydefinedantigensMHCClassI

ClassicalclassIgene:HLA-A(207alleles)

(Agpresentatallcellsurface)

HLA-B(412alleles)

HLA-C(100alleles)Non-ClassicalclassIgene:HLA-E(Agpresentatlimitedtissues)

HLA-F

HLA-GTheMHCclassImoleculeshaveapreferenceforwhatformofantigentheyarebestabletopresentTcytotoxiccells

MHCClassIIClassicalClassIIgene:HLA-DR,HLA-DQ,HLA-DPNon-ClassicalClassIIgene:HLA-DMMHCClassIImoleculesonantigenpresentingcellspresentantigenstoThelpercells.

MHCClassIIIHLAandDisease

Itiswellestablishedthatsusceptibilityand/orresistancetocertaindiseasesisprimarilyassociatedwithgenesencodingpeptide-presentingHLAmolecules.SeeTable10-2,《医学遗传学》金帆等编著AnkylosingSpondylitis(AS)

HLA-B27ACasefromTaiwan一個門診病患罹患龜頭炎已10多年了，且龜頭與包皮處常在最近四年反覆發生潰瘍，時好時壞，其表面有一層白色物質成糊狀，非常癢。兩年前口腔也發生反覆性潰瘍，除了眼睛開始感到視力模糊外，皮膚也長出結節性紅斑或小丘疹。病人自訴從未有不當的性行為，夫妻之間的感情也受到影響。還好終於有醫生診斷出此病人的疾病－貝西氏病（Behcet’sDisease），而挽救了他的婚姻。(文／廖俊正．廖妙淯．陳順天．魏正宗,

MedicineToday

Vol.34,No.5)1980NobelPrizeWinnersBenacerrafSnellDaussetForgenerallydeterminedstructuresonthecellsurfacethatregulateimmunologicalreactionsImmunoglobulins(Ig)=AntibodiesIg:Hchain—γ,μ,α,δ,ε

Lchain—κ,λIgIgH-chaingenerearrangement1987NobelPrizeWinner:TonegawaFor"hisdiscoveryofthegeneticprincipleforgenerationofantibodydiversity."SpecificGeneticImmunodeficienciesMorethan70primaryimmunedeficiencies(PIDs)areknown.Antibodydeficiencydisordersaredefectsinimmunoglobulin-producingBcells.2)Tcelldeficienciesaffectthefunctioninkillinginfectedcellsorhelpingotherimmune