Immunology of pregnancy Flashcards
What is pregnancy in terms of immunology?
‘Resetting’ of normal physiological state
What is the immunological paradox?
Fetus is 50% foreign material therefore there is a maternal investment to ensure that the genetic material is passed on
What happens at implantation?
Differential gene expression;
- Increase in g.f. proteolytic enzymes and inflam mediators - FACILITATE IMPLANT
- Change in exp of pt to prevent blasto rejection and inapp blasto invasion
What is the window of implantation?
Period where endometrium develops transient receptivity for embryo
What permits invasion of blasto?
Decidua
What is the primary decidual reaction
?
Uterine stromal cell enlargemnt
uNK prominent
How is intersitial invasion regulated?
- Cytotb diff is faciliated
- maternal decidua has permissive function
- haemochorial placentation in humans
What can a cytoTB progenitor cell diff into?
- CTB
- EVT (invasive)
- ScTB (fusion)
Why is the blasto not rejected>
It has modified self;non-self markers that do not trigger the immune system but instead tell the mother that it is safe and self
What are uNK cells?
NK cells that make up 70% of decidual immune cells
Exp Killer cell Ig-like R (KIR) which bind MHC-1 complex
Less cytotoxic that NK
Synth chemo/cyto that interact with EVT to facilitate invasion
What molecules are expressed on uNK cells?
CD56+ and CD16- (found on all other NK cells)
What HLAs do EVT express?
HLA-G, HLA-C and HLA-E
What is the role of HLA-G?
Only exp on TB - tells mother that it is self
Immunomodulation and preg-ass inflam
What is the role of HLA-C?
comb of HLA-C and KIR determines pregnancy outcome
What is the role of HLA-E?
Presents HLA-G leader peptide
inhib NK cell cytotox
Prevents EVT death
What signal does EVT present?
Says that TB cell is self and not dangerous - needed to stop TB degradation
What combination of HLA and KIR promotes uNK cell activation and EVT invastion?
HLA-C1 and KIR2DS
What happens if HLA-C2 and KIR2DL are present?
Poor EVT invasions
uNK cells are inhibited
Pre-eclampsia?
What happens during interstitial invasion?
EVT migrate from cell columns
Invade decidual glands
Plug spiral artery - remodelling
What drives endovascular invasion?
EVT and uNK
When does endovasc invasion occur?
10-12 weeks
What happens during normal endometrial invasion?
EVT invade artery to inner 1/3 of myometrium
What happens if endo inv fails?
Inv localised to decidua and there is a decrease in maternal blood supply
- preeclampsia
- premature birth
- FGR
- RM
- Placental abruption
placenta creta
No decidua - invasion into myometrium and deeper
Poor placental separation
PP bleeding
What happens to Th1:Th2 balance during pregnancy?
Th2 bias - prog inhib Th1 cell differentiation
Immune response is modified - more ab than cell-mediated
Fetus is protected
What happens in abnormal pregnancy (Th1:Th2)
Th2 bias is not seen
Increased INFy and exagg inflam response
Which ab crosses placenta?
IgG - enters fetal circulation and provides fetus with some immunity
What happens to Ig that cross react with paternal HLA?
They are removed by macrophages
Where are pat HLA foudn?
Placental macrophages and chorionic villus
What is rhesus disease?
Where mother raises ab to fathers rhesus antigens. During first preg the mother creates the ab but they do not cross placenta
During second pregnancy there is rapid prod of IgG against R and they cross ScTb and lyse RBC - fetal anaemia
How is rhesus treated?
With Anti-D which destroys Anti-R+ve IgG
