Maternal Immune System in Pregnancy Success and Placental Development

Question 1

what is the immune paradox of pregnancy

Answer 1

• foetus and placenta contains 50% of father’s genes
• so developing foetus and placenta are foreign to female body
• but maternal immune system does not reject foetus and placenta

Question 2

what does immune system use to recognise self from non-self

Answer 2

major histocompatibility complex (MHC)

Question 3

what is MHC

Answer 3

a set of cell surface proteins that help to recognise foreign molecules

Question 4

in pregnancy, what from the father is recognised by maternal immune system as foreign

Answer 4

MHC from father

Question 5

is the uterus an immune privileged site

Answer 5

no

Question 6

is the conceptus immunologically invisible

Answer 6

no

Question 7

what molecules can mothers immune system recognise as being foreign

Answer 7

MHC molecules

Question 8

are MHC molecules expressed by conceptus

Answer 8

yes but attenuated

Question 9

is maternal immune response compromised

Answer 9

no

Question 10

maternal immunity recognises (?) but does not (?)

Answer 10

• recognises foetus is there
• does not reject

Question 11

what does the maternal immune system recognise

Answer 11

• recognises paternal and foetal antigens

Question 12

what does maternal immune system respond with

Answer 12

tolerogenic immune response

Question 13

what is immune systems job other than discriminating self from non self

Answer 13

discriminating dangerous from benign

Question 14

which immune responses (out of 2) are important for responding well in terms of pregnancy success

Answer 14

adaptive and innate immune response

Question 15

name a subtype of cells in adaptive immune system

Answer 15

T lymphocytes

Question 16

what can T lymphocytes do depending on how they’re programmed

Answer 16

elicit either tolerance or rejection

Question 17

what do T helper 1 (Th1) elicit

Answer 17

rejection

Question 18

what do Th17 illicit

Answer 18

rejection

Question 19

what do Th2 elicit

Answer 19

either rejection or tolerance

Question 20

what do regulatory T cells (Treg) elicit

Answer 20

tolerance

Question 21

which T lymphocyte plays a crucial role in immune system function in pregnancy

Answer 21

Treg

Question 22

how do Treg cells work

Answer 22

• regulate the immune system (including other than T lymphocytes)
• aka police officers of immune system

Question 23

what do Treg cells act to promote

Answer 23

anti-inflammatory and tolerogenic phenotype

Question 24

which T lymphocytes can Treg cells regulate

Answer 24

Th1, Th17

Question 25

if we can get an appropriate response with these tolerogenic Th2 and Treg cells, they are able to do what

Answer 25

constrain / block pro-rejection response from Th1 and Th17 cells

Question 26

if we don't get right response - due to not having right amount of Treg cells OR if their function impaired - it can impact what

Answer 26

capacity to control the immune response

Question 27

if the capacity to control the immune response is impacted, not having an appropriate response can mean the difference between

Answer 27

- tolerance and therefore birth of a healthy baby - or infertility or pregnancy complications (eg/ preterm birth, preeclampsia)

Question 28

what does tolerance lead to in pregnancy regarding the foetus

Answer 28

birth of a healthy foetus

Question 29

there is an expansion of Treg cells when?

Answer 29

early pregnancy in 1st and 2nd trimester

Question 30

in cases of recurrent miscarriage, Treg cells are...

Answer 30

reduced

Question 31

are Treg cells disrupted in pregnancy complications in women

Answer 31

yes

Question 32

in preeclampsia, Treg cells are....

Answer 32

decreased

Question 33

in pre-eclampsia what cells in immune system are increased

Answer 33

Th1 and Th17

Question 34

what 2 factors are critical for Treg cells to determine whether going to have tolerogenic immune response & healthy pregnancy OR pro-rejection response & no pregnancy / pregnancy complications

Answer 34

- number of Treg cells - function of Treg cells

Question 35

when is maternal immune system first exposed to foreign paternal antigen (& responds)

Answer 35

ejaculation - seminal fluid at coitus

Question 36

what is the maternal immune response to first exposure of foreign paternal antigen

Answer 36

- exposure to seminal fluid at coitus - activates an inflammatory cascade that results in education and expansion of Treg cells

Question 37

education and expansion of Treg cells is important for pregnancy why (2)

Answer 37

- Treg cells important in tolerance to pregnancy - they have a role in placenta development and maternal vascular adaptations

Question 38

limited duration of cohabitation (lack of prior partner semen exposure - usually thru natural coitus) is linked with increased risk of (2)?

Answer 38

- preeclampsia - low birth weight

Question 38

exposure to a conceiving partner's semen is linked with healthy pregnancy in women because?

Answer 38

it helps to expand that population of Treg cells in a partner (woman's Treg cells immunologically responding to foreign antigens in semen)

Question 39

coitus prior to IVF embryo transfer improves what (2) and why

Answer 39

- improves implantation - improves live birth rates - since exposure to conceiving partner's semen is linked with healthy pregnancy

Question 40

based on exposure to conceiving partner's semen, what would cause risk of pregnancy complications

Answer 40

- limited duration of cohabitation (implies through natural coitus) - IVF embryo transfer - use of donor sperm or oocytes

Question 41

remodeling of _____ arteries are an important facet of placental development

Answer 41

spinal

Question 42

how do spinal arteries change in pregnant vs non-pregnant women

Answer 42

non-pregnant: tightly coiled vessels pregnant: spinal arteries converted to wide bore conduits

Question 43

how does conversion of spinal arteries to wide bore conduits in pregnant women occur (2steps)

Answer 43

- invasion of extra villous trophoblast from developing placenta - in coordination with maternal immune cells including uterine natural killer cells => help to remodel spinal arteries & displace endothelial cells that would normally line the artery and smooth muscle cells

Question 44

endothelial cells and smooth muscle cells get replaced by trophoblast cells so that the vessel is no longer what

Answer 44

under maternal vascular control

Question 45

regarding local vascular adaptations, preeclampsia is characterised by what (2)

Answer 45

- incomplete transformation of spinal arteries - shallower invasion of extra villus trophoblast

Question 46

in preeclampsia, what does shallower invasion of extra villus trophoblast lead to

Answer 46

- leads to high resistance, high velocity, turbulent flow that can damage delicate villus structures of placenta

Question 47

does deficit in Treg cells affect maternal vascular adaptations to pregnancy and placental development

Answer 47

yes

Question 48

what are some exposures to our environment that impact the immune response and can impact receptivity for pregnancy

Answer 48

nutrition, obesity, stress, infection, alcohol, environmental toxins

Question 49

why are exposures in the environment also important in men

Answer 49

- health of male affects quality of his semen and seminal fluid

Question 50

how does the health of male contributing to quality of his semen and seminal fluid affect pregnancy likelihood

Answer 50

affects semen and seminal fluid ability to prime an appropriate immune response by the maternal immune system

Question 51

pregnancy tolerance requires balance in T cell response, with enough _____ cells w/ the right ____ to block type __ cells

Answer 51

Treg functional capacity type 1

Question 52

when does immune response to conceptus (embryo) antigens begin

Answer 52

conception

Question 53

insufficient Treg cells are associated with which 2 pregnancy complications

Answer 53

- miscarriage - preeclampsia

Question 54

immune system promotes ____________ required for _____ development to support optimal ________

Answer 54

- vascular adaptations - placental - foetal growth