Download week six summary - fundamentals of immunology

Microbiology375
FUNDAMENTALSOF
IMMUNOLOGY
(ASINFORMEDBYMICROBIALPATHOGENS)
CELLSOFTHEIMMUNESYSTEM
ADAPTIVE
INNATE
MICROBIALPATHOGENSACTIVATE
PROTECTIVEBANDTCELLRESPONSES
CANCER: WHENNORMALCELLS
BECOMEFOREIGN INVADERS
CANCERBASICS
• Normallythereisacomplexbalancebetweencell
renewalandcelldeathinthebody.Withcancer,this
balanceisdisruptedandcancercellsproliferateinan
uncontrolledmanner
• Cancer-associatedgenesareinvolvedinthisbalance
Oncogenes:Promotecellularproliferation
Tumor-suppressorgenes:Normallyinhibit
uncontrolledcellularproliferation
• Mutationsinthesegenesleadtodis-regulation
RESOURCESFORINFORMATIONONCAUSESOFCANCER
BREASTCANCERASSOCIATEDGENES
OVERVIEWOFPOTENTIALCANCERCAUSES
GENETIC (HEREDITARYMUTATIONS;BRCA GENEINBREASTCANCERS)
ENVIRONMENTALFACTORS (MUTATIONSDUETORADIATION—XRAY,
UV—TOBACCO,OTHERCARCINOGENS)
DNAANDRNAVIRUSES (EBV,HUMANPAPILLOMAVIRUS,HEPATITISB,
HEPATITISC,HUMANHERPESVIRUS-8)
BACTERIA (HELIOBACTORPYLORI,CHLAMYDIATRACHOMATIS)
IMMUNOSUPPRESSION (HIV,CANCERCHEMOTHERAPY)
WHATTYPEOFCELLSCANBECOMECANCERCELLS?
VIRTUALLYANY TISSUE OFTHEBODYHASCELLSTHATCAN
BECOMEMALIGNANT(EXHIBITUNREGULATEDCELLULAR
PROLIFERATION)ANDMETASTATIC(CANSPREADTO
UNRELATEDTISSUES)UNDERTHERIGHTCIRCUMSTANCES
THEREAREEVENCANCERSOFTHEIMMUNESYSTEM:
LYMPHOMAS(SOLIDTUMORSINLYMPHOIDTISSUE)AND
LEUKEMIAS(INCREASEDNUMBERSOFMALIGNANT
LYMPHOCYTESINBLOODANDLYMPH)
INADDITIONTOUNREGULATEDGROWTH,
CANCERCELLSOFTENDISPLAYUNIQUE
TUMOR-SPECIFICANTIGENS
TUMOR-SPECIFICANTIGENSCANBERECOGNIZEDBYTHE
ADAPTIVEIMMUNESYSTEM
TYPESOFIMMUNERESPONSESTO
TUMOR-SPECIFICANTIGENS
• MayinvolveBcellandCD4Tcell responses
• Antibodiesandcomplement bindtoantigens
onthesurfaceofcancercellsandkillthem
• CD8Tcellsmayrecognizetumorantigen
peptidesonMHCImoleculesandkilltargets
• MacrophagesandNaturalKiller(NK)cells have
receptorsforantibodythatcanrecognizeand
lysetumorcells;NKcellsalsokilldirectly
MORE CELLSOFTHEIMMUNESYSTEM
ADAPTIVE
NKCELLSPLAYANIMPORTANTROLEINIMMUNE
SURVEILLANCEAGAINSTABNORMAL* CELLS
*VIRUSORBACTERIAINFECTEDCELLS,TUMORCELLS
MISSING,ALTEREDORLOWLEVELSOFMHCIRESULTIN
TRIGGERINGOFNKCELLSTOKILL
NKCELLSMEDIATEANTIBODY-DEPENDENT
CELL-MEDIATEDCYTOTOXICITY(ADCC)
Image from http://upload.wikimedia.org/wikipedia/commons/thumb/0/05/Antibody-dependent_Cellular_Cytotoxicity.svg/744px-Antibody-dependent_Cellular_Cytotoxicity.svg.png
TUMORCELLSEVADEADAPTIVEHOSTIMMUNERESPONSES
BYMANYDIFFERENTMECHANISMS
Treg CELLSAREALSOCO-OPTED
AHEALTHYIMMUNESYSTEMPLAYSAN
IMPORTANTROLEINIMMUNE“SURVEILLANCE”
TUMORGROWTH
ANDMETASTISIS
NEWHOPE: IMMUNOTHERAPY
TOHELPTHEIMMUNESYSTEMDESTROY
CANCERCELLS!
ANTIBODY THERAPY
TCELL THERAPY
GENE THERAPY
NKCELL THERAPY
WEAREINAN
ERAOFHIGHLY
PERSONALIZED
MEDICINE TO
TREATCANCER
TRANSPLANTATIONIMMUNOLOGY
THEFLIPSIDEOFTHECANCERIMMUNITYCOIN:
AVOIDING REJECTIONOFDONORTISSUES
THEFATHEROFTRANSPLANTATIONIMMUNOLOGY
TOLERANCETOSELFANTIGENSISTHERULE
UNIQUEMOSAICOFDIFFERENTINHERITEDMHC
MOLECULES(MAJORTRANSPLANTATIONANTIGENS)
DONORCELLSEXPRESSMANYDIFFERENT TRANSPLANTATION
ANTIGENS TOARECIPIENT’SIMMUNESYSTEM
MANYMORE“MINOR”TRANSPLANTATIONANTIGENS
TRANSPLANTATIONANTIGENSARERECOGNIZEDASFOREIGN
POTENTIALOUTCOMES
AFTERTISSUE
TRANSPLANATION
POTENTIALOUTCOMES
AFTERTISSUE
TRANSPLANATION
POTENTIALOUTCOMES
AFTERTISSUE
TRANSPLANATION
BLOODGROUPANTIGEN
MIS-MATCHESCANLEAD
TOACUTEGRAFTFAILURE
TRANSPLANTATIONIMMUNOTHERAPY
PREVENTINGORREDUCINGRECIPIENTT,BANDNKCELL
RESPONSESTODONORTISSUES
MONOCLONAL
ANTIBODIESARE
USEFULFOR
TRANSPLANTATION
IMMUNOTHERAPY
“KEY”TOTHETVCOMMERCIALSTOUTING
IMMUNOTHERAPEUTICMONOCLONALANTIBODIES
THEREARE
INTERESTING
THINGSTOBE
LEARNEDFROM
THEULTIMATE
“TRANSPLANT”!
THURSDAY:REVIEWSESSION
FOLLOWEDBYFINALEXAM