Immunology of the pregnancy Flashcards
Why does developing foetus need to be ignored by maternal immune system?
- Antigens from both the male and female DNA. > The MHC I and II proteins will differ between the two as well as a multitude of antigens which differ between individuals of the same species – alloantigens.
What leukocytes are found in the decidua?
> How does maternal immune system interact with foetus?
- On the maternal side there are several different leukocytes which direct the response against the developing embryo
> Placenta is the point at which the maternal immune system can interact with the foetus
Describe the 3 ways trophoblast cells regulate immune system?
1- Lack MHCII + have non classical MHC I
> Lack of MHC usually results in NK Cell killing > Cells express HLA-G which inhibits NK killing ligands.
> NK Cells are a modified phenotype which are less cytotoxic
2- Regulatory Cytokines
> Secrete chemokines and cytokines to promote M2 macrophages and Tregs.
> IL-15 & TGFβ promotes a modified NK phenotype and promote vascular remodelling.
> Monocytes become M2 macrophages and remodel the tissue to allow implantation and growth.
3- Nutrient Depletion
> Express high levels of the enzyme indoleamine 2,3-dioxygenase (IDO) which depletes the tryptophan. > This is essential for T cells which when starved show reduced responsiveness.
Predominant immune cells + responses change throughout pregnancy through 3 distinctive phases.
- Name the phases
1- Initial Inflammation – Implantation
2- Strong Th2 – foetal development
3- Th1 and inflammation – preparing for labour and delivery
What happens during the first trimester - Inflammation (4)
- Initiate embryo implantation into the uterine wall a strong inflammatory response is initiated similar to a wound response
1- Active breakdown and restructuring of the decidua.
2- IL-6, CXCL8, IL-5 ,GM-CSF, CXCL1, CCL4 & TNFα are released from endometrial stromal cells and infiltrating cells
3- Adhesion molecules are upregulated on epithelial cells of the uterus lumen and mucins are removed
4- Uterine Macrophages and DCs upregulate tissue remodelling and angiogenesis. They stay in the tissue and don’t travel to the lymph nodes
What happens during the second trimester - Th2 type response
- Explain why we have an abundance of Tregs in decide of subsequent pregnancies?
- What is associated with spontaneous abortion?
- Promoting foetal growth and tolerance is needed as the pregnancy continues, foetal hCG can signal to leukocytes to inhibit inflammation
1- Ongoing pro-inflammatory signals can lead to miscarriage and strongly inflammatory infections can lead to preterm birth
2- Macrophages, NK cells and Tregs need to establish an anti inflammatory environment. Decidual macrophages have an M2 like phenotype. They remove dying trophoblast cells preventing release of paternal antigens.
- Tregs specific for paternal antigens can be found in abundance in the decidua in subsequent pregnancies suggesting that antigens are presented under tolerant conditions to prevent possible immune responses
- Spontaneous abortion can be associated with low levels of Tregs and elevated TH17 cells. TH17 are important in protection from microbes but numbers are kept in check by Tregs
What happens during the third trimester - Inflammation and Th1 type response
- To prepare for labour and delivery inflammatory signals are induced in response to the foetus maturing
1- Inflammation and the influx of immune cells into the myometrium for contraction of the uterus to initiate labour
2- Amniotic fluid levels of IL-1β, IL-6 & TNFα are elevated during labour.
3- Surfactant protein A from foetal lungs can act as a ligand for TLR4
Damage molecules are also present at high levels at the end of pregnancy and stimulate inflammation through damage receptor recognition.
4- Activated macrophages migrate to the uterus and induce uterine contractions
1- What part of foetal immune system is formed by the end of the 1st trimester?
2- Foetal dendritic cells present maternal antigens what happens then…
3- What part of the immune system forms from 13.5 weeks?
4- Foetal blood contains high numbers of what immune cells but what is the issue with it?
5- What is transferred across the placenta at approx 14 weeks?
1- All components of complement system.
2- Activate regulatory T cells teaching the foetus what is self and non self and ensuring the foetus doesn’t attack the mother
3- Payers patches
4- High numbers of lymphocytes ~79% and mononuclear cells but is poor at forming memory.
5- Maternal IgG
Why does IgG transfer have the potential to be detrimental?
- Rhesus + father … Rhesus - mother could be carrying Rhesus + foetus
- Transfer of blood from the foetus to maternal circulation can induce IgG antibody response
- Mother develops antibodies to the Rhesus + RBC…. these can cross the placental barrier and alligunate the foetal blood of the next foetus blood ( Haemolytic disease of the newborn)
After birth is baby is RHD+ and mother is RHD- what is offered?
- Anti-immunoglobulin D will be offered within 72hrs.
> Anti-D immunoglobulin neutralises rhesus antigens.
> Would be offered if there’s a risk that RhD antigens have passed from baby to maternal circulation e.g. bleeding, invasive procedure, abdominal injury
> Also administered in third trimester if maternal blood is Rhd negative
What is a contributor to miscarriage?
- Preterm labour = mild infection inducing exaggerated inflammatory response (viral infections)
> Infection > pro inflammatory cytokines > activates immune system > leads to placental damage
TLRs 3,7,8 & 9 secrete IFNβ
A viral infection in the placenta could trigger a mild inflammatory response resulting in: (2)
- Sensitising the mother to infection from other microorganisms
- Promoting an inflammatory response in the foetus
