Immunology Of Pregnancy - NICHD

Immunology-InflammationGil Mor M.D., Ph.D.Professor and DirectorDivision of Reproductive SciencesReproductive Immunology UnitDepartment of Obstetrics, Gynecology& Reproductive SciencesYale University School of MedicineEditor in Chief, American Journal of Reproductive Immunology1

Immunology of PregnancyMedawar recognized the paradox thatthe fetus is (in genetic terms) a semiallograft which escapes rejection.The presence of immune cells at theimplantation site has been consideredas a proof of a response by the maternalimmune system to the fetus2

Immunology of PregnancyThe studies in the area of Immunologyof Pregnancy have focused on GraftHost response3

Immunology of Pregnancy:Old ParadigmsMechanical BarrierSuppression of the Maternal ImmuneSystemTh-2 type Immune Response4

Mechanical Barrier: OldThe placenta prevents the movement ofcells and antigens from the fetus to themother and from the mother to the fetus5

Mechanical Barrier: NewEvidence for traffic in both directionsacross the maternal-fetal interfaceincludes studies reporting migration ofmaternal cells into the fetus and thepresence of fetal cells in the maternalcirculation.6

Suppression of the maternalImmune System: OldPregnancy is characterized by a state ofimmune suppression7

Suppression of the MaternalImmune System: NewMaternal antiviral immunity is notaffected by pregnancyHIV pregnant women do not suffer fromAIDS-like disease Systemic Immune Suppressionrepresents a danger to the species

Pregnancy is a TH2Inflammatory condition: OldPregnancy is a TH2 condition andinflammation is detrimental forpregnancy

Inflammation and Pregnancy:NewInflammation is necessary for Implantationand parturition

Inflammation and WoundRepair: The implantation wound

New Aspects for PlacentaMaternal Immune InteractionsRole of the maternal immune systemduring pregnancyRole of the placenta as an immuneregulatorRole of the placenta during infection

The Role of Maternal ImmuneCells During Pregnancy:Effect of Depletion of MaternalImmune cells

Maternal Immune System:Necessary for the Success ofPregnancyNatural Killer Cells- transformation of theblood vessels by the trophoblastMacrophages- Migration and survival ofthe trophoblastT Regs- Maintenance of toleranceDendritic Cells-Implantation15

Redefining theImmunology of Pregnancy16

The Placenta is an ImmuneRegulatory Organ17

Natural Killer CellsInner Cell MassMacrophageBlastocystCavityBlood VesselsTLRTrophoblastDendritic CellsT-regBacteriaNeutrophils

Trophoblast Maternal ImmuneInteractionsGraft/Host response vs Tumor/immuneinteractions

The Placenta as a NaturalTumor

Immune cells Promote Cancer cellsmigration, invasion and vascularization

Immune cells Promote Trophoblast cellsmigration, invasion and vascularization

Infection and Pregnancy:Old ParadigmsResponse to infection during pregnancyhas focused on the maternal immunesystem as the main and only player.Maternal immune system is suppressedto prevent responses to paternalantigens.Increased mortality during pregnancydue to infection has been attributed tomaternal immune suppression.23

VirusBacteriaMotherPlacentaFetusResponse

Infection and Pregnancy:New Paradigms.The maternal immune system is notsuppressed during pregnancy.The placenta plays a critical role in theresponse to infections, affecting not onlythe fetus but the maternal systemicimmune response.

Infection and PregnancyTherefore:– There are major limitations to ourunderstanding of the role of infection duringpregnancy.– These limitations have a severe impact onhow we: Identify women at risk for preterm birth Treat pregnancy complications due to infections Prevent maternal mortality during pandemics

VirusBacteriaBacteriaMotherPlacentaFetusResponse

The inflammatory status of the placentawill influence the development of thefetal immune system as well as thematernal immune responses.

Immunology-Inflammation Gil Mor M.D., Ph.D. Professor and Director Division of Reproductive Sciences Reproductive Immunology Unit Department of Obstetrics, Gynecology& Reproductive Sciences Yale University School of Medicine Editor in Chief, American Journal of Reproductive Immunology 1