Immunology of Pregnaancy Flashcards
Case study 1: A young woman had her 9th consecutive miscarriage. Her
marriage broke down shortly afterwards.
But within months of finding a new partner, she conceived again
and the pregnancy went without a hitch. - why? (2)
Woman’s immune system took offence to the 1st choice of partner
- over-reacting to the tissue carrying his genes and expelling the fetus.
Infertility, recurrent miscarriage, premature delivery and a dangerous complication of pregnancy, pre-eclampsia, may be strongly linked to immunological abnormalities.
Immunological problems to solve during pregnancy (4)
Half of the fetal genome derives from the father but, unlike a mismatched organ transplant, it isn’t normally rejected!!!!
- Fetal tissue is half foreign – has to be protected from rejection
- Mother’s immune defence must be sufficient during pregnancy to ensure survival
- Fetus often immunologically immature at birth – must have maternal antibodies to ensure survival
How does the baby manage to avoid the mothers immune system?
The maternal/fetal interface is central to overcoming these problems. This interface occurs at the placenta
Dev. of placenta - Where are the mother and babies cells in direct contact? (4)
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The maternal-fetal interface:
1.Syncytiotrophoblast layer covering the placenta is bathed in maternal blood
2.Invading trophoblast come into contact with decidual immune cells
3.Invading trophoblast come into contact with decidual blood vessels
Why is it diff. to study immunology of human pregnancy? (2)
most immune cells in peripheral blood- easy accessible by taking a blood sample
but blood situated in pregnancy = diff. to get access to
- Syncytiotrophoblast layer covering the placenta is bathed in maternal
blood (2)
The syncytiotrophoblast is a multi-nucleated layer which arises from fused cytotrophoblasts.
It forms a barrier and performs endocrine functions as well as gas and nutrient exchange from maternal blood - in direct contact w/ immune cells in maternal blood.
- Invasive extravillous trophoblast are in contact with decidual immune
cells (2)
The extravillous trophoblast are differentiated fetal cells which invade into the maternal decidua to transform maternal spiral arteries.
Here they encounter a large infiltration of maternal immune cells in the decidua before they head to arteries
- Invasive extravillous trophoblast are in contact with decidual vascular
cells (3)
The extravillous trophoblast are differentiated fetal cells which invade
into the maternal decidua to transform maternal spiral arteries
here they are at the spiral arteries: the trophoblast dependent model takes place ( immune cells needed for remodelling = temp. loss of endothelial layer + big lumen): trophoblasts express endothelial markers = direct contact of fetal and maternal immune cells
How does the mother could mount an immune response? - immune cells are present at the maternal-fetal interface? (5)
Decidua:
> 40% decidua = leukocytes in early pregn.
- of these approx. 70% are NK cells (killing or cytokine prod.)
-approx 20% = macrophages
- t+b cells make up remaining 10%
Intervillous space + sprial arteries:
same immune cells as maternal blood immune cells
Decidual natural killer cells diff to peripheral NK’s -70% (4)
- dNK cells are different to peripheral blood (pb)NK cells
- Their pattern of receptor expression is unique and they are
identified by CD56hiCD16lo (low in PNK) - They have been identified as being essential to pregnancy in the
mouse and they may play a role in human decidual remodelling
through the cytokines which they secrete
= don;t kill but encourage to sec. cytokines = trophoblast invasion
Macrophages in pregnancy - diff to peripheral monocytes 20% (4)
*dMac have a different phenotype to peripheral blood monocytes
*Broadly, macrophages may be:
– M1: pro-inflammatory, secrete (cytokines + GF’s) TNF-α, IL-6
– M2: anti-inflammatory, secrete (reg. factors) IL-10, VEGF
- Decidual macrophages are more M2-like than M1-like (anti-inflammatory)
How do trophoblast evade the immune response? - Medawar’s theories (3)
*Physical separation of maternal and fetal tissues
*Antigenic immaturity of fetal tissues
*Mother is immunologically inert
- Is there a physical separation of maternal and fetal tissues? (6)
- Fetus separated from the mother by the fetal trophoblast cells
- Fetal and maternal circulation is separated
- Maternal cells cannot reach the fetus
But:
- In humans, IgG can cross into the fetal blood via a placental transport mechanism.
- Therefore IgG directed against fetal antigens could also be transferred
fetus is separated but the fetal trophoblast cells are not!
Why doesn’t fetal antigens harm the baby? (2)
Most fetal blood group and histocompatibility antigens are widely distributed on the fetal cells and tissues - IgG would be diluted out.
Many fetal antigens are also present as soluble forms in the fetal blood and amniotic fluid - IgG would be mopped up by free soluble antigen.
- Is there antigenic immaturity of fetal tissues? (4)
- Histocompatibility antigens are targets for rejection
- MHC haplotypes inherited from both parents and are co-dominantly expressed
MHC1a (classical): (HLA-A, HLA-B, HLA) -presenting antigens to CD8+ T cells
interacting with NK cells highly polymorphic
MHC1b (non-classical): (HLA-E, HLA-F, HLA-G) - minimally polymorphic
MHCII: (HLA-DP, HLA-DQ, HLA-DR) - presenting antigen to CD4+ T cells