Block C - immunology of pregnancy 1

Question 1

what does the immune system do for mismatched transplants ?

Answer 1

The immune system treats mismatched transplants in the same way as microbes, it mounts an immune response. Problem of organ rejection caused by adaptive immune response against polymorphic gene products for example ABO blood group antigens, MHC molecules.

Question 2

how is the maternal foetal interface unique ?

Answer 2

The maternal-foetal interface is unique as it must promote tolerance to the foetus as well as also maintaining defence against a diverse array of possible pathogens during pregnancy.

Question 3

foetal expressed paternal antigens ?

Answer 3

Foetal-expressed paternal antigens are foreign (non-self) to the maternal immune system. The maternal immune system must tolerate the semi-allogeneic foetus to support pregnancy.

Question 4

stages of pregnancy ?

Answer 4

The stages of pregnancy include

Intercourse

Fertilisation

Implantation

Gestation (1st trimester,2nd trimester,3rd trimester)

Parturition

Post-partum repair

Question 5

hormone changes in pregnancy ?

Answer 5

There are hormonal changes associated with pregnancy as the progesterone and oestrogen levels rise in pregnancy. These hormonal changes interact with the immune system.

Question 6

myometrium ?

Answer 6

muscle layer in uterus

Question 7

immune cells found in the endometrium ?

Answer 7

leukocytes represent 6-20% of the total cells in fallopian tubes, endometrium, cervix & vaginal mucosa. These are highly organised lymphoid tissue which is distributed throughout the female reproductive tract & is influenced by progesterone & oestrogen. Organised lymphoid aggregates are found in the basal layer of the endometrium, consisting of a B cell core, surrounded by T cells (mainly CD8+)

Question 8

function of the endometrium ?

Answer 8

The function of the endometrium is to allow blastocyst implantation and to support pregnancy

Question 9

dynamic tissue undergoes cycles in the endometrium ?

Answer 9

The endometrium in humans is a dynamic tissue that undergoes repeat cycles involving sequential proliferation, differentiation, breakdown and repair. These cycles of tissue remodelling ensure the endometrium is in a receptive state during the implantation window.

Question 10

process of cleavage , blastocyst formation and implantation ?

Answer 10

The process of cleavage, blastocyst formation and implantation begins with ovulation and when fertilisation occurs. Then there is a series of cleavage events , then an early blastocyst forms 5 days later, before the blastocyst implants around day 8/9.

Question 11

decidua ?

Answer 11

Decidua is uterine lining (endometrium) during pregnancy.

Question 12

immediate response to semen and where was this first seen ?

Answer 12

The immediate response to insemination in mammals is a rapid and dramatic influx of inflammatory cells into the site of semen deposition. This inflammatory reaction to semen was first observed in rabbits.

Question 13

what does the inflammatory response to seminal fluids have a central role in ?

Answer 13

The inflammatory response to seminal fluids has a central role in female tract processing of seminal material and recovery of tissue homeostasis after mating. In addition, there is mounting evidence to suggest that exposure to seminal fluids can proactively influence subsequent events in the female tract to promote conception and progression of pregnancy.

Question 14

what does seminal plasma contain ?

Answer 14

Seminal plasma contains a number of immunological molecules including: TGF-B, IL-8 (chemokine to attract immune cells), IFN-y and prostaglandin E, which modulates the uterine immune environment to prevent foetal rejection.

Question 15

seminal plasma contacts the uterine endothelium and mediators such as GM-CSF, IL-6, LIF and cytokines (CCL2, CXCL1, CCl5 are produced why ?

Answer 15

These recruit cells into the site such as dendritic cells, macrophages and neutrophil

Question 16

role of dendritic cells ?

Answer 16

Dendritic cells process and present seminal antigen to activate maternal immune tolerance, macrophages secrete growth factors, MMP’s and enzymes for tissue remodelling.

Question 17

role of neutrophils ?

Answer 17

Furthermore, neutrophils clear debris and pathogens which could have been introduced during mating.

Question 18

what is important after ejaculation to tolerate the conceptus ?

Answer 18

The initial presentation of paternal alloantigen’s to maternal T cells after ejaculation is suggested to be crucial for tolerance of the conceptus, which displays the same paternal antigens during implantation a few days later.

Question 19

what did clinical studies show anout exposure to semem at the same time of embryo transfer for IVF?

Answer 19

Clinical studies in humans have shown that live birth rates in couples undergoing IVF treatment are significantly improved when women are exposed to semen at the time of embryo transfer.

Question 20

treatment of seminal plasma to women experiencing recurrent spontaneous abortion ?

Answer 20

Treatment of women suffering from recurrent spontaneous abortion with seminal plasma pregnancies has been reported to improve pregnancy success

Question 21

what is there needed a fine balance for maternal uterus during implantation ?

Answer 21

There has to be a fine balance between pro and anti-inflammatory mechanisms within the maternal uterus during implantation.

Question 22

what must the blastocyst degrade to invade the uterus ?

Answer 22

Blastocyst must degrade the endometrial extracellular matrix to invade the uterus, apoptosis of endometrial epithelial cells occurs at embryo implantation site and numerous macrophages are present at the implantation site & act to engulf apoptotic cells.

Question 23

gestation ?

Answer 23

Gestation is humans is 9 months, while in mice it is 3 weeks. Irrespective of how long there are 3 trimesters, which are of equal duration, this allows us to draw comparison between species.

Question 24

what is responsible for contraction during labour ?

Answer 24

myometrium , the muscle layer around the uterus is involved during labour

Question 25

maternal portion of the placenta ?

Answer 25

The maternal portion of the placenta = basal plate

Question 26

fetal portion of placenta ?

Answer 26

Fetal portion of placenta = chorionic plate

Question 27

spiral arteries ?

Answer 27

There are a number of veins and arteries emanating from the cord, form the mother’s side there are spiral arteries to allow exchange of substances across the placenta.

Question 28

what cannot cross the placenta ?

Answer 28

IgA

Blood cells

Pulmonary TB

Rhinovirus (common cold)

IgM

Maternal hormones

Question 29

cytokine shift theory ?

Answer 29

This cytokine shift theory was introduced by Wegmann et al (1993), however this does not take Th17 and T regulatory cells into account. In this theory it is a shift towards a Th2 response for successful pregnancy such as IL-4, IL-13 rather than Th1 cytokines. It was also noted that a Th1 response (inflammation) such as IFN-y and IL-12 was associated with a spontaneous abortion.

Question 30

Treg cells ?

Answer 30

Treg cells are important in successful pregnancy, whereas Th1 and Th17 are detrimental to pregnancy.

Treg cells are CD4+ CD25+ Foxp3+, Tregs produce the immunosuppressive cytokines IL-10 and TGF-beta which are anti-inflammatory.

Question 31

what is the part of the decidua that interacts with the trophobloasts ?

Answer 31

That part of the decidua that interacts with the trophoblast is the decidua basalis.

Question 32

Treg number (FOXP3)

Answer 32

Treg numbers (FoxP3) vary in the uterus with the murine oestrus cycle and are increased during pregnancy there are high in anticipation of transplantation and remain high during pregnancy. Chemokines also cycle with the oestrus cycle in animals as well as FoxP3.

Question 33

what does Tregs inhibit ?

Answer 33

Tregs inhibit proliferation & cytokine production of CD4+, CD8+ T cells, B cells, and supress Ig production, cytotoxic function of NK cells, maturation of DCs & macrophages.

Tregs that suppress Th1 are associated with normal pregnancy where a reduction in Treg cells and an increase in Th1 response is associated with infertility, miscarriage and preeclampsia.