Transcript MATRNAL FETAL RELATIONSHIP AND THE Rh BLOODGROUP

Victoire N. Ndong
Biology 327: Immunology
THE PLACENTA
HOW DOES THE FETUS STAY IMPLANTED
IN THE UTERUS WITHOUT BEING
REJECTED?
MEDAWAR’S THEORIES
The uterus is an “immunologically privileged site”
The fetus is antigenically immature and the
placenta is a neutral barrier.
There is immunosuppression during pregnancy
There will be a transfer of paternal antigen
tolerance.
ANTIGENICITY OF THE PLACENTA
The outer layer of the placenta in contact with
maternal blood never expresses MHC class II
The cytotrophoblast and the syncytiotrophoblast are
MHC class I negative
NK cells could attack
The extravillous trophoblast expresses HLA-C which is
a classical polymorphic MHC class I gene product
HLA-C is less polymorphic than HLA-A and B
HLA-G is monomorphic and it’s expressed on the
syncytiotrophoblast, causes apoptosis of Tcells.
IMMUNOSUPPRESSION
 Indoleamine 2,3-deoxygenase (IDO) prevents tryptophan
catabolism by T cell in placenta hence causing their
inactivation and death.
 Injection of IL-2 causes activation of CD8, CD4 and NK
cells so to prevent this, the placenta secretes
immunosuppressors like Th2 cytokines and the placenta
recruits cells that secrete β2 transforming growth factor
(TGF).
 Increase in the number of rPg on T cells and NK cells after
recognition of paternal antigens, and high progesterone
level cause the secretion TJ6-RTF and PIBF which are
potent immunosuppressors.
 Fas interaction with Fas ligand on Tcell causes apoptosis
IMMUNOTROPHISM
 The size of the placenta increases with the number of
pregnancies .
 The placenta promote more implantation sites
 Colony stimulating factors like IL-3 and GM-CSF produced
by the mother are growth factors for the placenta so the
placenta pushes for allorecognition by T cells to use their
growth factors for it self.
 Allorecognition causes IgG2 cytotoxic antibodies
production and complement activation.
 Placenta sends complement regulatory proteins like DAF
(decay accelarating factor )and MCF (membrane cofactor
protein)
PREGNANCY A Th2 PHENOMENON
During pregnancy there is a suppression of Th1 responses by an increase of Th2
cytokines like anti inflammatory IL-10
IRENE ATHANASSAKIS et al.
Recent research
Recent research have shown that MIC (MHC class I
chain) played a role in immune escape of tumors
MIC is a ligand for the activating site of the NK cell
activating receptor NKG2D
So MIC-NKG2D is good for immune surveillance
However, soluble forms of MIC are produced by
tumors maybe to act as a competitive inhibitors that
block the recognition of the membrane bound MIC
causing a downregulation of NKG2D
High levels of soluble MIC have been found in
pregnancy serum
THE RHESUS BLOOD GROUP MODEL
 Discovered by Landsteiner
 More complex than the ABO blood group model
 It has 54 antigens but the most important is the D
antigen
 Either the person expresses it or he doesn’t
 Inheritance happens in a dominant way DD and Dd
individuals are Rh+ and dd individuals are Rh Rh incompatibility can cause serious problems like
Hemolytic disease of the newborn (HDN)
Hemolytic disease of the newborn
 HDN happens when an Rh- mother is pregnant with
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an Rh positive baby
Fetal red blood cells enter maternal circulation
causing immunization of the mother and production
of IgG antibodies
The IgGs will cross the placenta and attack the fetal
red blood cells
Antibody titers increase with time and for that reason
the first pregnancy is the least at risk
There are many ways of preventing HDN
HDN
PREVENTION OF HDN
•
Intrauterine transfusion of compatible blood
•
Induction of labor right after pulmonary maturation
•
Injection of Rh immune globulin (RhIg) at 28 weeks
of pregnancy and 72 hours after delivery.
SOURCES
 Mincheva-Nilsson L, Nagaeva O, Chen T, Stendahl U, Antsiferoval, Mogren I,
Hernestal J, Baranov V. Placenta-derived soluble MHC class I chain-related
molecules down-regulate NKG2D receptor on peripheral blood mononuclear
cells during human pregnancy: a possible novel immune escape mechanism for
fetal survival.
 Irene Athanassakis, Vagia Farmakiotis, and Lina Papadimitriou, “Uterine
Cytokine Production During the Menstrual Cycle and Preimplantation Stages
in Mice,” Developmental Immunology, vol. 7, no. 1, pp. 33-42, 1999.
doi:10.1155/1999/67137
 Gérard Chaouat, INSERM, Clamart, France. Reproductive Immunology
Standard Article
 Gérard Chaouat, Hôpital A. Béclère, Clamart. Fetal–Maternal Immunological
Relationships Standard Article