Immunology of pregnancy Flashcards
(26 cards)
What are the maternal physiological adaptations to pregnancy
Endocrine, respiratory, cardiovascular, gastrointestinal, renal function + fluid homeostasis, reproductive, immune system, metabolic, resetting of normal physiological values
Why is pregnancy an immunological paradox
The fetus is 50% foreign
Maternal investment ensures genetic material is passed on
Maternal tolerance of fetal semi-allograft
Explain the differential gene expression at implantation
Increase in growth factors, proteolytic enzymes + inflammatory mediators to facilitate implantation
Change in expression of proteins involved in immune response to prevent blastocyst rejection and inappropriate blastocyst invasion
Very little of the immune system is fully downregulated as it is still required
Describe human implantation
Intestitial
Regulated invasive process
Hypoxic conditions (2-5% O2 relative to uterus)
Facilitates cytotrophoblast differentiation
Maternal decidua = permissive
Haemochorial placentation
What are 2 features of the primary decidual reaction
Uterine stromal cell enlargement
uNK cells more prominent
What is the function of cytotrophoblast cells
Fuse into multinucleate syncytiotrophoblast
Differentiate into invasive phenotype extravillous trophoblast cells responsible for differentiation
What is the function of uNK cells
Involved in synthesis of cytokines and chemokines
Facilitate EVT invasion
What are the steps of implantation
- Loose adherence/apposition
- Interstitial invasion
- Spiral artery remodelling and endovascular invasion
Describe interstitial invasion
EVTs migrate from cell columns
Invade decidual glands
Limited by decidua basalis
uNK cells may be required for or limit invasion
Describe spiral artery remodelling
Before- small bore, high resistance, facilitates hypoxia
EVTs plug spiral artery
Remodelled- wide bore, low resistance
Describe the immunological markers on maternal immune cells, EVTs, syncytiotrophoblast and uNK cells
Maternal immune cells- Normal self: non-self markers, normal immune response
EVTs- Modified self: non-self markers, modified maternal immune response
Syncytiotrophoblast- No self: non-self markers, MHC negative, no maternal response
uNK cells- CD56 +ve, CD16 -ve, KIR receptors
Describe the different HLAs and their functions
HLA-G: immunomodulation with IL8, IL10, VEGF, PGF. Involved in pregnancy associated inflammation
HLA-C: polymorphic, paternal specificity, combinations of HLA-C:KIR determine implantation outcome
HLA-E: presents HLA-G linear peptide, inhibits uNK cells cytotoxicity, prevents EVT death
What is an advantagous combination of HLA:KIR
Fetal HLA-C1 + maternal KIR-B (KIR2DS)
uNK cells activated, promotes EVT invasion
What is a disadvantagous combination of HLA:KIR
Fetal HLA-C2 + maternal KIR-A (KIR2DL)
uNK cells inhibited, poor EVT invasion
Pre-eclamspia
What are the observations that suggest T-helper cells function in pregnancy
Cell-mediated autoimmune disease (Th1) symptoms improve during pregnancy eg. rheumatoid arthiritis
Antibody-mediated autoimmune disease (Th2) symptoms worsen during pregnancy eg. systemic lupus erythematosus
What signals cause Th0 to differentiate into Th1
IL2, IL3, IL8, GM-CSF, INFy, high TNF
What signals cause Th0 to differentiate into Th2
IL4, IL5, IL6, IL9, IL10, IL13, GM-CSF, low TNF
What is the T-helper cell change during pregnancy
Placental fetal trophoblast cells secrete IL4 and IL10
Push Th0 towards Th2 differentiation
Th1 (cell mediated immunity) is modified/partly suppressed, humoral immunity still active
What is the immunological basis of IUGR
Th2 bias not observed, INFy up, exaggerated inflammatory response, acute allograft rejection
What is the normal maternal immune response to fetus
Maternal immune system removes antibodies that cross-react with fetal antigens- paternal HLAs presented on placental macrophages and chorionic villus.
Immune complexes removed by macrophages
Why do maternal antibodies cross the placenta
Th2 cells promote B cell activation, antibodies made, IgG crosses the placenta and binds fetal Fc receptors on the syncytiotrophoblast, actively transported to chorionic villi, enters fetal circulation providing some immunity for fetus
Describe Rhesus disease
Haemolytic disease of the newborn
Maternal IgG raised against paternal antigens on fetal red blood cells, cross reacting paternal antigens not removed
First pregnancy = sensitisation. Fetal blood mixes at term/postnatally, maternal immune response typically IgM but doesn’t cross placenta. Creates memory B cell.
Second pregnancy = rapid response. IgG due to memory B cells, cross the placenta. Lysis of fetal red blood cells causing fetal anaemia and fetal death
What is Anti-D prophylaxis
In rhesus disease, Anti-D destroys the Rhesus negative IgG. Fetal red blood cells not attacked
Describe normal and failed endovascular invasion
Normal- EVTs invade along artery into third myometrium, acquisition of maternal blood supply
Failes- invasion localised to decidua, reduced acquisition of maternal blood supply. Various pathologies- preeclampsia, prematurity, placental abruption, recurrent miscarriage, FGR
