Embryos - Absence of Foetal Rejection Flashcards
how are foreign tissues rejected normally
Through activation of cytotoxic lymphocytes and sometimes also through humoral immune responses
foetus and placenta - immunologically the same?
immunologically different
but not recognised as foreign tissue and rejected by mother’s immune system
part of placenta is made up of contribution from trophoblast
semiallogenic foetus
sharing only 50% genetic relatedness with the mother, the remainder being with the father
therefore cells and molecules of the immune system interact in such a way as to prevent rejection of the semiallogenic foetus and support its growth and development
what immune cells have been identified within the maternal foetal interface
uterine natural killer cells - 70%
macrophages - 20%
T cells (CD4+, CD8+, gamma delta (gd) T cells, regulatory T cells) - 10%
dendritic cells - few
B cells - few
factors involved in the protection of the developing foetus from attack by maternal immune system
- anatomical barrier between baby and mother, through separate circulatory systems within the placenta
- the antigenic immaturity of the foetus - major histocompatibility (MHC) antigen expression is reduced on trophoblast cells on the foetal side of the placenta
- development of an immunosuppressive environment within the uterus - immune cell reactivity within the uterus is substantially reduced during pregnancy, thus preventing adverse immunological responses against the conceptus
what influence do the female sex hormones have on the immune environment
oestrogen and progesterone, among other mechanisms, are involved in the skewing of both the local and systemic immune environment towards a Th2 profile
what is expressed on trophoblast cells
how does this affect the maternal immune system
expression of certain molecules (HLA-G, E, C) on trophoblast cells inhibit the activation and proliferation of uNK cells and CD8+ T cells
theory that explains why the foetus is not rejected - antigens
foetal tissues don’t present foreign antigens
neither of the 2 main classes of MH antigens are expressed on the syncytiotrophoblast and non-villous cytotrophoblast (cytotrophoblastic shell)
but these antigen are present on the cells of the foetus and the stromal tissues of the placenta
the other minor histocompatibility antigens follow a similar pattern
however, other minor antigens are expressed on the trophoblastic tissues
breaks can eventually appear in the placental barrier and foetal red and white blood cells have been found in the maternal blood, as the placenta grows
(not clear why they don’t sensitise the maternal immune system)
theory that explains why the foetus is not rejected by the mother
mother’s immune system is “paralysed” during pregnancy
yet the mother can mount immune responses to infections and tissue grafts
there is the possibility of a selective repression of the immune response to foetal antigens, but the Rh incompatibility response shows that this is not universally the case
first 6 days of embryonic development
hCG
first message sent to the mother
maintains corpus luteum in the 1st trimester
then it’s passed to progesterone to maintain CL
define implantation
co-ordinated sequence of complex interactions between genetically different cell types of embryonic and maternal tissues
what does successful implantation require
trophoblast penetration of several tissue components to reach maternal blood supply
epithelial lining of uterus
basal lamina
underlying stroma
(this sequence of events resembles invasion of malignant tumours)
what do the invasive cells attach to
must attach to ECM proteins - secrete proteases capable of degrading these proteins and migrate through the degraded ECM
during implantation and subsequent placentation in the human, populations of trophoblast cells invade the endometrium and maternal vasculature within the uterus
once reaching spiral arteries within the myometrium, trophoblast invasiveness ceases
trophoblast invasion
unlike tumour cells, which typically exhibit uncontrolled invasion, trophoblast invasion is tightly regulated
sub-optimal trophoblast invasion has been shown to occur in the pregnancy disease states of pre-eclampsia and intrauterine growth retardation (1st pregnancy - some immune component causes a smaller placenta than should be => lower BW baby)