Maternal Immune System in Pregnancy Success and Placental Development Flashcards
what is the immune paradox of pregnancy
- 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
what does immune system use to recognise self from non-self
major histocompatibility complex (MHC)
what is MHC
a set of cell surface proteins that help to recognise foreign molecules
in pregnancy, what from the father is recognised by maternal immune system as foreign
MHC from father
is the uterus an immune privileged site
no
is the conceptus immunologically invisible
no
what molecules can mothers immune system recognise as being foreign
MHC molecules
are MHC molecules expressed by conceptus
yes but attenuated
is maternal immune response compromised
no
maternal immunity recognises (?) but does not (?)
- recognises foetus is there
- does not reject
what does the maternal immune system recognise
- recognises paternal and foetal antigens
what does maternal immune system respond with
tolerogenic immune response
what is immune systems job other than discriminating self from non self
discriminating dangerous from benign
which immune responses (out of 2) are important for responding well in terms of pregnancy success
adaptive and innate immune response
name a subtype of cells in adaptive immune system
T lymphocytes
what can T lymphocytes do depending on how they’re programmed
elicit either tolerance or rejection
what do T helper 1 (Th1) elicit
rejection
what do Th17 illicit
rejection
what do Th2 elicit
either rejection or tolerance
what do regulatory T cells (Treg) elicit
tolerance
which T lymphocyte plays a crucial role in immune system function in pregnancy
Treg
how do Treg cells work
- regulate the immune system (including other than T lymphocytes)
- aka police officers of immune system
what do Treg cells act to promote
anti-inflammatory and tolerogenic phenotype
which T lymphocytes can Treg cells regulate
Th1, Th17
if we can get an appropriate response with these tolerogenic Th2 and Treg cells, they are able to do what
constrain / block pro-rejection response from Th1 and Th17 cells
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
capacity to control the immune response
if the capacity to control the immune response is impacted, not having an appropriate response can mean the difference between
- tolerance and therefore birth of a healthy baby
- or infertility or pregnancy complications (eg/ preterm birth, preeclampsia)
what does tolerance lead to in pregnancy regarding the foetus
birth of a healthy foetus
there is an expansion of Treg cells when?
early pregnancy in 1st and 2nd trimester
in cases of recurrent miscarriage, Treg cells are…
reduced
are Treg cells disrupted in pregnancy complications in women
yes
in preeclampsia, Treg cells are….
decreased
in pre-eclampsia what cells in immune system are increased
Th1 and Th17
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
- number of Treg cells
- function of Treg cells
when is maternal immune system first exposed to foreign paternal antigen (& responds)
ejaculation - seminal fluid at coitus
what is the maternal immune response to first exposure of foreign paternal antigen
- exposure to seminal fluid at coitus
- activates an inflammatory cascade that results in education and expansion of Treg cells
education and expansion of Treg cells is important for pregnancy why (2)
- Treg cells important in tolerance to pregnancy
- they have a role in placenta development and maternal vascular adaptations
limited duration of cohabitation (lack of prior partner semen exposure - usually thru natural coitus) is linked with increased risk of (2)?
- preeclampsia
- low birth weight
exposure to a conceiving partner’s semen is linked with healthy pregnancy in women because?
it helps to expand that population of Treg cells in a partner (woman’s Treg cells immunologically responding to foreign antigens in semen)
coitus prior to IVF embryo transfer improves what (2) and why
- improves implantation
- improves live birth rates
- since exposure to conceiving partner’s semen is linked with healthy pregnancy
based on exposure to conceiving partner’s semen, what would cause risk of pregnancy complications
- limited duration of cohabitation (implies through natural coitus)
- IVF embryo transfer
- use of donor sperm or oocytes
remodeling of _____ arteries are an important facet of placental development
spinal
how do spinal arteries change in pregnant vs non-pregnant women
non-pregnant: tightly coiled vessels
pregnant: spinal arteries converted to wide bore conduits
how does conversion of spinal arteries to wide bore conduits in pregnant women occur (2steps)
- 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
endothelial cells and smooth muscle cells get replaced by trophoblast cells so that the vessel is no longer what
under maternal vascular control
regarding local vascular adaptations, preeclampsia is characterised by what (2)
- incomplete transformation of spinal arteries
- shallower invasion of extra villus trophoblast
in preeclampsia, what does shallower invasion of extra villus trophoblast lead to
- leads to high resistance, high velocity, turbulent flow that can damage delicate villus structures of placenta
does deficit in Treg cells affect maternal vascular adaptations to pregnancy and placental development
yes
what are some exposures to our environment that impact the immune response and can impact receptivity for pregnancy
nutrition, obesity, stress, infection, alcohol, environmental toxins
why are exposures in the environment also important in men
- health of male affects quality of his semen and seminal fluid
how does the health of male contributing to quality of his semen and seminal fluid affect pregnancy likelihood
affects semen and seminal fluid ability to prime an appropriate immune response by the maternal immune system
pregnancy tolerance requires balance in T cell response, with enough _____ cells w/ the right ____ to block type __ cells
Treg
functional capacity
type 1
when does immune response to conceptus (embryo) antigens begin
conception
insufficient Treg cells are associated with which 2 pregnancy complications
- miscarriage
- preeclampsia
immune system promotes ____________ required for _____ development to support optimal ________
- vascular adaptations
- placental
- foetal growth
