immunology of pregnancy · immune system to the fetus 2. immunology of pregnancy the studies in the...
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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
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Immunology of Pregnancy
Medawar recognized the paradox that the fetus is (in genetic terms) a semi-allograft which escapes rejection. The presence of immune cells at the implantation site has been considered as a proof of a response by the maternal immune system to the fetus
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Immunology of Pregnancy
The studies in the area of Immunology of Pregnancy have focused on Graft-Host response
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Immunology of Pregnancy: Old Paradigms
Mechanical Barrier Suppression of the Maternal Immune System Th-2 type Immune Response
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Mechanical Barrier: Old
The placenta prevents the movement of cells and antigens from the fetus to the mother and from the mother to the fetus
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Mechanical Barrier: New
Evidence for traffic in both directions across the maternal-fetal interface includes studies reporting migration of maternal cells into the fetus and the presence of fetal cells in the maternal circulation.
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Suppression of the maternal Immune System: Old
Pregnancy is characterized by a state of immune suppression
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Suppression of the Maternal Immune System: New
Maternal antiviral immunity is not affected by pregnancy
HIV+ pregnant women do not suffer from AIDS-like disease
✦Systemic Immune Suppression represents a danger to the species
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Pregnancy is a TH2 Inflammatory condition: Old
Pregnancy is a TH2 condition and inflammation is detrimental for pregnancy
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Inflammation and Pregnancy: New
Inflammation is necessary for Implantation and parturition
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Inflammation and Wound Repair: The implantation wound
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New Aspects for Placenta-Maternal Immune Interactions
Role of the maternal immune system during pregnancy
Role of the placenta as an immune regulator Role of the placenta during infection
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The Role of Maternal Immune
Cells During Pregnancy:
Effect of Depletion of Maternal
Immune cells
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Maternal Immune System: Necessary for the Success of
Pregnancy
Natural Killer Cells- transformation of the blood vessels by the trophoblast Macrophages- Migration and survival of the trophoblast T Regs- Maintenance of tolerance Dendritic Cells-Implantation
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Redefining the Immunology of Pregnancy
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The Placenta is an Immune Regulatory Organ
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Inner Cell Mass
Trophoblast
Blastocyst
Cavity
Dendritic Cells
Natural Killer Cells
Neutrophils
Blood Vessels
T reg
Bacteria
Macrophage
TLR
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Trophoblast Maternal Immune
Interactions
Graft/Host response vs Tumor/immune interactions
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The Placenta as a Natural
Tumor
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Immune cells Promote Cancer cells
migration, invasion and vascularization
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Immune cells Promote Trophoblast cells migration, invasion and vascularization
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Infection and Pregnancy: Old Paradigms
Response to infection during pregnancy has focused on the maternal immune system as the main and only player. Maternal immune system is suppressed to prevent responses to paternal antigens. Increased mortality during pregnancy due to infection has been attributed to maternal immune suppression.
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Mother
Placenta Fetus
Response
Virus
Bacteria
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Infection and Pregnancy:
New Paradigms.
The maternal immune system is not suppressed during pregnancy. The placenta plays a critical role in the response to infections, affecting not only the fetus but the maternal systemic immune response.
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Infection and Pregnancy
Therefore: – There are major limitations to our
understanding of the role of infection during pregnancy.
– These limitations have a severe impact on how we:
• Identify women at risk for preterm birth • Treat pregnancy complications due to infections • Prevent maternal mortality during pandemics
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Virus
Mother
Placenta Fetus
Bacteria Bacteria
Response
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The inflammatory status of the placenta will influence the development of the fetal immune system as well as the
maternal immune responses.