Immunology and Pregnancy Flashcards
Why is the immune system relevant?
The fetus is an allograft - is not 100% made of mums DNA and should be rejected like a foreign graft
What are the arms of the immune system?
Innate (recognise danger) and adaptive (recognised non-self)
3 sections - what do they recognise, negative selection, antibody?
What do B cells do?
They recognise soluble antigen and produce antibodies that have antigen specific receptors (BcR).
During development antigen specific receptors that bind to self antigens are killed in negative selection
The antibody is a soluble version of the BCR and bind to pathogens and targets them for killing
What is a T cell receptor and what does it bind?
This is analogous to antigen binding region of an antibody/BcR but can’t bind to soluble antigen directly. Antigen peptides must be presented on MHC.
What is negative selection and positive selection in T cells development?|
Negative selection - any that bind to self antigens are killed (some become Tregs to give autoimmunity)
Positive selection - T cells that won’t bind to self MHC are killed
What do class 1MHC present and to what cell?
intracellular antigens to cytotoxic T lymphocytes (CTL)
What do class 2 MHC present and to what cell?
extracellular antigens to helper T cells
What is MHC class 1 found on?
All nucleated cells
How does class 2 MHC show antigen to T cells?
The alpha and beta chains of the MHC form a tetramer with invariant chain and then they go into the endosome where they are cut by proteases before being shown to CD4 helper T cells
What are the T helper cells?
Th1 TH2 Th17 and Tregs and what they differentiate into depends on singals from the innate immune system
What do TH1 cells do?
These recruit macrophages, are inflammatory but can cause tissue damage/autoimmunity
What can Th2 cells do?
Kill parasites and cause allergies
What do tregs do?
Supress other immune responses and supresses autoimmunity
What are CTL’s?
Induces apoptosis through perforin/granzymes
How do T cells respond to allografts?
They kill them
Why do NK cells kill and not kill cells?
Primed to kill any cell unless told not to by KIR binding on MHC on surface of the cell and preventing killing
what is the placental membrane and what does this mean?
This is the name of the type of placental membrane not like describing
A syncytium which means no cell junctions for maternal immune cells to migrate between and no lymphactics
Does fetal tissue express any MHC 2 or MHC1 and why?
express no MHC2 and some MHC1 (mainly HLA-C) which causes them to escape the CTL response
What happens to the NK cells as these should attack the lack of MHC?
Fetal tissue expresses HLA-E and HLA-G which bind to the NK cell inhibitory receptors and they have a specialised phenotype
What is the decidua dendritic cell and what do they produce?
APC’s that are very rare in the decidua which might not be able to exit into the lymph node. They produce IDO and a tolerised phenotype induing a TH2 response.
What are decidua macrophages?
Type of phagocyte which can be inflammatory, kill invaders etc (M2) or anti-inflammatory (M1)
what type of macrophages are peri implantation macrophages?
M1
Later in development they become M2 macrophages - what do these express?
IDO and IL-10 (both immunosuppressive)
Have roles in reorganisation of vasculature in early pregnancy
How is the fetus protected by apoptosing fetal specific T cells?
The pathways of 2 ligands
FasL binds to Fas on activated T cells killing them.
OR
Gal-1 is expressed by decidua NKs, macrophages and endometrium which induces apoptosis of T helper cells and supresses DC.
What does IDO expressed by decidua and trophoblasts do?
Catabolise tryptophan to metabolites such as kynurenine and picolinic acid (these inhibit T cell and NK cell activation).
What can Kyrunine also do (made by IDO)?
Apoptosis of Th1 not Th2 cells
What does chemically inhibiting IDO lead to?
Rejection of allogeneic but not syngeneic fetuses
What does a reduction in Tregs do in pregnancy?
They cause spontaneous abortion if joined with increased inflammatory T helper cells
Pre-eclampsia with increased blood inflammatory: regulatory T cell ratio
What happens if you deplete the Tregs in early pregnancy?
No effect of depletion in syngeneic pregnancy
Reduced viable offspring in a allogeneic mice
CNS1-KO mice can’t make what?
New Tregs
What are Tregs induced by?
TGF-beta, Gal-1 and IDO
What does phosphocholine do in pregnancy?
supresses T and B cell proliferation and inflammatory responses in RA
What is the complement system?
activation results in cascade of cleavage, activation and inflammation which results in the formation of the membrane attack complex to put lysis pores in cells
What does Crry the complement protein do?
Prevents deposition of C3 and C4 and knocking this out leads to unsuccessful births
What are bystander immune supression things?
Reduced allergy, RA, MS but increased susceptability to infection e.g. malaria, HIV and listeria
Can the inflammatory immune response to bacterial infectons lead to preterm labour?
Yes
What causes HDN?
Maternal antibody responds to paternal antibody on the fetal red blood cells causing anaemia, jaundice, brain damage and even death
How do the HDN symptoms arise?
Lysed red blood cells release haemoglobin which is broken down into bilirubin turning skin yellow and entering brain to have toxic results
What is passive immunity and how does this work?
Maternal antibodies can pass through the placenta using the neonatal antibody FcRn and maternal IgA is given to babies through breast milk. Allows baby to have a bit of an immune system
What are the blood group antigens?
A,B and O and Rh
What happens in Rhesus disease during the first pregnancy?
Mother Rh- and father Rh+ the first pregnancy is fine as the mother immune system has never seen this before and during delivary the fetal blood is given to the mother causing an anti-Rh antibody to be raised.
Rhesus disease during the second pregnancy?
The anti-Rh antibodies can enter the fetus causing haemolysis of red blood cells. This gets worse with subsequent pregnancies.
How is HDN treated - preventative?
Parents screened and if father Rh- and mother Rh+ the baby can be screened as can the mother again for antibodies.
Treatment for HDN - if fetus is Rh+?
If fetus Rh+ then rhogam shot is given during pregnancy and after birth which binds the Rh antigen and prevents mother immune system from being sensitised
Mild, Moderate, Severe
What happens if baby is affected by HDN?
Treatment
Mildly Affected - UV treatment (breaks down bilirubin)
Moderately Affected - blood transfusion to stop anaemia
Severely affected - Rh negative blood transfusion given every 10 - 21 days of gestation and treatment after birth
