Immunology of Pregnancy II Flashcards
During pregnancy, the endometrium becomes the __. What is its role in pregnancy ?
During pregnancy, the endometrium becomes the DECIDUA; placenta anchors onto it
During pregnancy, which cells predominate in the decidua ?
During pregnancy, Th2 cells predominate over Th1 in the decidua
NOTE: Th2 favours humoral immunity
Reduced Th1 Immunity during Pregnancy
- in the second infection event, non-pregnant mice are able to clear infections better (normal Th1 levels)
- pregnant mice are unable to effectively clear second infection due to reduced Th1 immunity
NOTE: pregnant women have reduced Th1 response to intracellular pathogen = worse outcomes vs non-pregnant
Is there a harmful adaptive immune response against paternal MHC antigens in mice vs humans ?
NO!
Mice = Inbred (mother and father have the same MHC) and wild type (differing MHC) mouse pregnancies will have the ~same litter size
Humans = mismatched MHC have higher reproductive success
If a mother is pregnant with an H-2b fetus and develops an H-2b tumor, can a). She produce H-2b-reactive T cells and b). Reject the H2-b tumor ?
A). Can produce REDUCED % of H-2b T reactive cells
B). Cannot reject H-2b tumor due to tolerance of H-2b fetus
T regs
- CD4+ CD25+ CTLA-4+ Foxp3+
- increase with pregnancy
- maintain tolerance to fetus
How are T regs in pregnancy activated ?
- fetal antigens exit from placenta
- T killer and T helper cells present pregnancy antigens = activate immune response
- TGF-B1 induces T reg cells to suppress immune system activation
NOTE: pregnancy antigens include sperm, seminal plasma and conceptus
Women with __ and __ exposure to seminal plasma from the same partner are at reduced risk for preeclampsia
Women with GREATER and LONGER exposure to seminal plasma from the same partner are at reduced risk for preeclampsia
Can T reg protection of fetus be overcome ?
Yes; adaptive response to protect the mother
- infection can cause fetal loss
T regs are reduced in the following pregnancy complications (3):
- Spontaneous abortions
- Infertility
- Pre-eclampsia
Differentiate peripheral vs decidual/ uterine NK cells
Peripheral NK:
- normally kill cells that do not express self MHC
Decidual/ uterine NK:
- cannot kill since fetal placental cells express different MHC (HLA-G)
- pro-angiogenic factors promote vascular growth of decidua (VEGF, TGF-β1, IL-6 and IL-8)
- produce chemoattractants that encourage placental cell invasion to remodel maternal arteries
- have less CD16 and more CD56 than peripheral NK cells
Function
HLA-G
- the inhibitory ligand
for the the receptor found on all NK cells
= Shuts off cytotoxic effects while
producing proangiogenic factors important for uterine
remodelling
Pregnancy disorders are associated with ___ HLA-G
expression
Pregnancy disorders are associated with reduced HLA-G expression
WIP Spiral artery in non-pregnant, pre-eclampsia vs normal pregnancy
Non-pregnant:
- extends through endometrium
Can decidual NK cells regain cytotoxicity ?
YES:
- Freshly isolated decidual NK cells have reduced cytotoxic activity compared to peripheral NK cells
- However, continued in vitro culture of decidual NK cells regain their cytotoxic activity
