Embryos - Absence of Foetal Rejection

Question 1

how are foreign tissues rejected normally

Answer 1

Through activation of cytotoxic lymphocytes and sometimes also through humoral immune responses

Question 2

foetus and placenta - immunologically the same?

Answer 2

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

Question 3

semiallogenic foetus

Answer 3

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

Question 4

what immune cells have been identified within the maternal foetal interface

Answer 4

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

Question 5

factors involved in the protection of the developing foetus from attack by maternal immune system

Answer 5

1. anatomical barrier between baby and mother, through separate circulatory systems within the placenta
2. the antigenic immaturity of the foetus - major histocompatibility (MHC) antigen expression is reduced on trophoblast cells on the foetal side of the placenta
3. 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

Question 6

what influence do the female sex hormones have on the immune environment

Answer 6

oestrogen and progesterone, among other mechanisms, are involved in the skewing of both the local and systemic immune environment towards a Th2 profile

Question 7

what is expressed on trophoblast cells

how does this affect the maternal immune system

Answer 7

expression of certain molecules (HLA-G, E, C) on trophoblast cells inhibit the activation and proliferation of uNK cells and CD8+ T cells

Question 8

theory that explains why the foetus is not rejected - antigens

Answer 8

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)

Question 9

theory that explains why the foetus is not rejected by the mother

Answer 9

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

Question 10

first 6 days of embryonic development

Answer 10

Question 11

hCG

Answer 11

first message sent to the mother

maintains corpus luteum in the 1st trimester

then it’s passed to progesterone to maintain CL

Question 12

define implantation

Answer 12

co-ordinated sequence of complex interactions between genetically different cell types of embryonic and maternal tissues

Question 13

what does successful implantation require

Answer 13

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)

Question 14

what do the invasive cells attach to

Answer 14

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

Question 15

trophoblast invasion

Answer 15

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)

Question 16

immune system during pregnancy

what must the embryo express to allow for this

Answer 16

a special condition in which the woman’s immune system must activate a tolerance mechanism so as not to reject the baby’s body during the entire gestation period

to do this the embryo expresses the HLA G antigen, whose function is to suppress the cells of the mother’s immune system and that there is no rejection