BIOLOGY PRESENTATION
The placenta
The placenta is a temporary organ that connects the mother and the fetus, it transfers nutrients
and oxygen from the mother to the fetus and it also transports the fetus waste like carbon dioxide
from the fetus.
Show the picture of the placenta and show the different parts of the placenta
Placental antigenecity
Because it’s a foreign tissue the placenta has much specificity that permits it to stay in the uterus
and not be rejected. For example It has been shown that the outer layer of the placenta that is
close to maternal blood never expresses MHC class II it’s only normal because we know that
MHC II causes causes the activations of CD8 cytotoxic T cells and that would be bad for the
embryo. Induced expression of MHC class II in mice caused a 100% abortion.
It was also shown that the trophoblast and the syncythiotrophoblast are MHC class I negative in
order to evade some immune response. However we learned in class that NK cells not only kill
the The MHC containing the wrong peptides, but they also kill cells that don’t express MHC.
The reason the cell are still alive is because they express a type of polymorphic MHC I that
found in human it’s called HLA-C (human leukocyte antigen) it’s the human MHC and HLA C
is the less polymorphic of all the HLA just to keep the barrier as neutral as possible.
Immunosuppresion is a way of suppressing the immune response to protect the fetus against
rejection. Two scientists called Munn and Mellor have shown that trophoblast IDO (indoleamine
2-3 dioxygenase) prevents tryptophan catabolism of T cells and causes their inactivation and
their death in the placenta. Neutralization of IDO in the placenta causes abortion. Injection of IL2 also can cause abortion because it activates CD8 cells and Nk cells.
Good effect of father’s antigen
After seeing the paternal antigen, NK cells and CD8 T cells express more rPG which is the
receptor for progesterone and the high doses of progesterone present induce the secretion of
regenrationa dn tolerance factors (RTF) and progesterone induced blocking factors (PIBF).
Maternal recognition of paternal antigens is beneficial, because it introduces immune
suppression.
Immunotrophism
Multiparous placentas are bigger and they have more implantation sites. It’s because colony
stimulating factors (CSF) like Il-3 and granulocyte macrophages CSF (GM-CSF) produced by
the maternal T cells are growth factors for trophoblasts. So the placenta forces the
allorecognition (recognition of paternal antigens) by T cells to receive growth factors. The
placenta also produces decay accelerating factors to prevent IgG2 from recognizing paternal
alloantigens.
When it comes to fetal maternal relationships the first question that comes in people’s mind is
how does the fetus do to nestle in the uterus and not to be rejected? Because it’s semi allogeneic
meaning it has not only antigens from the mother but also antigens from the father which are
foreign. It’s even more important for ART (assisted reproduction techniques) where the fetus is
totally allogeneic.
To answer that question a scientist by the name of Medawar came up with four theories:
First he says the uterus is an immunologically privileged site meaning any tissue can be grafted
there without rejection. Some scientis have done experiment in which they implanted paternal
skin graft in the uterus and it was rejected meaning not any tissue can be implanted on the uterus
without rejection only the trophoblast can.
Second he said that the fetus is antigenically immature meaning it doesn’t express
histocompatibility antigens and the placenta is a neutral barrier between the mother and the fetus.
Once again it was shown that indeed the fetus produces
Third that there systemic immunosuppression
The last theory is that after successive pregnancies, there will be a transferable tolerance to
paternal grafts.
NK cells and HLA G
We talked earlier about HLA C and how it helped prevent killing by the NK cells. It has been
found however that the syncytiotrophoblast expresses sHLA-G which is a quasi monomorphic
MHC class I antigen and it causes activated T cells to undergo cell death and apoptosis and they
can’t induce allorecognition because they are monomorphic. Because in some primates they
found that HLA-G was not found in primates and they were still having normal pregnancies, it
has been hypothesized that HLA-G is not an absolute requirement for successful pregnancies
except for ART. It also has an important role in anti viral defenses because it presents viral
peptides.
Knocking out Nk cells causes impaired growth of the placenta so it produces growth factors
necessary for functional and successful pregnancies.
Th1 versus Th2 response
During pregnancy, Th1 type cytokines produce proinflammatory responses and excessive
proinflammatory responses can cause tissue damage. IFN γ is the main Th1 cytokine. In order to
avoid that response there are more Th2 cytokines like IL-10 (anti inflammatory) that are
produced during pregnancy that’s why they call it a Th2 phenomenon. In a paper they were
trying to show the amount of Th2 cytokines produces show paper explain and they showed that
the level of Il-10, Il-3 and GM-CMS increased. GM-CSF and Il-3 fortify placental barriers and
help implantation.
The Rhesus model
The rhesus blood group is more complex than the ABO blood group, it comprises 54 different
antigens but the most common is antigen D. We can use a simple model to predict the
inheritance with two alleles one D and one small d which doesn’t have the D antigen. So
individuals that are DD and Dd are Rh + and individuals that are dd are Rh negative. Rh group
incompatibilies can cause serious problems during transfusion but the model that relates to my
subject is the mother-fetus imncompatibility. It happens when an Rh negative mother carries and
Rh positive baby. At some point during the pregnancy, the fetal red blood cells will enter the
maternal circulation and that causes maternal immunization meaning the mother will produce
antibodies against the Rh antigen and those IgG will cross the placental barrier and attack the
fetal cell. During the first pregnancy, the consequences are pretty low because the mother wasn’t
given enough time to produce enough antibodies but in subsequent pregnancies, the antibody
titers will increases causing more risk of haemolytic diseases (destruction of the fetus blood cells
by the mother’s antibodies).
To prevent HDN there can be intrauterine transfusion of compatible blood or inducement of
labor after the lungs have matured enough and the mother can also be given Rh immune globulin
at 28 weeks of pregnancy and 72 hours after delivery so that the it binds any fetal red cells in the
maternal circulation with the Rh antigen before the mother is able to produce an immune
response.
Anestrus in rodent is a period a sexual inactivity
Eostrus: Right before ovulation
Proestrus: period of ovarian maturation
Irene athanassaki