Immunology of Pregnancy I Flashcards
Protection of Immunologically-Foreign Fetus
- Placenta; relatively efficient barrier
— preventing access of activated T cells to the fetus
— preventing fetal cells from entering maternal circulation
Is placenta from the mother or the fetus ?
From the fetus, which attaches to mother’s uterus
Roles of Human Placenta
- oxygen + nutrient exchange
- removal of wastes
- barrier against maternal immune response and infections
Describe ST cells
- multinucleated, single-cell layer
- formed from fusion of cytotrophoblast
- directly in contact with maternal blood
- attach onto uterine wall
NOTE: Syncytiotrophoblast
Is the ST barrier effective against pathogens ?
not for TORCH infections:
- Toxoplasmosis
- Other – syphilis, varicella-zoster, parvovirus B19, Zika
- Rubella
- Cytomegalovirus
- Herpes
Primary CMV transmission rate
40% transmission rate from maternal to fetus
Routes of congenital infections (3)
- Across the membranes
— into amniotic cavity - Villous placenta
— from maternal blood - Extravillous placental
— through uterine wall
Define microchimerism
- Bi-directional trafficking of fetal and maternal cells
- Low levels of fetal cells exit placenta
- Detected decades after delivery and likely persist for a lifetime
NOTE: highly conserved across species
Is the ST barrier effective against maternal cells ?
- Mostly; activated T cells
EXCEPT microchimerism
Positive effects of Microchimerism for Mother
- Existing T regs may enhance fetal protection in the next pregnancy
- Pluripotent fetal microchimeric cells may differentiate into and replace diseased cells in maternal tissues e.g. islet cells
Positive effects of Microchimerism for Fetus
- Protection against abortion in next generation pregnancies under conditions that interrupt fetal tolerance mechanisms
- May contribute to maturity of immune response in fetus
- Increased T regs may dampen inflammation from microbial colonization, training the neonatal immune response
- Reduced rejection of transplants
Negative effects of Microchimerism
- Autoimmunity
How does placenta protect fetus from immune system ?
- **ST doesn’t express typical MHC ** = maternal T cells cannot kill fetus
- ST expresses non-classical MHC (HLA-G, -E, -C) = maternal NK cells cannot kill fetus
- ST has dysfunctional Fas ligand = fetus ST can kill maternal immune cell BUT maternal immune cells cannot kill fetus
How does IDO protect placenta ?
Non-pregnancy:
- Normally expressed in circulating monocytes, macrophages
and dendritic cells
- Increased by infection and inflammatory cytokines
Pregnancy:
- Constantly expressed at maternal-fetal interface; doesn’t require activation
- IDO removes tryptophan (converts to kynerinin) = inhibits T cell proliferation
Possibility of offspring if an IDO Inhibtor is present/ absent in an Syngeneic vs Allogeneic pregnancy
Possible = Syngeneic pregnancy with/ without IDO inhibitor; Allogeneic pregnancy without IDO inhibitor
No offspring = Allogeneic pregnancy with IDO inhibitor
