Reproductive immunology Flashcards
1
Q
Why doesn’t the mother reject the foetus?
A
- Like cancer cells, the foetal tropjoblast cells invade deep into maternal uterine tisue, which is half-mismatched to the foetus and full of maternal NK cells
2
Q
What is the Innate Immune system?
A
- Resistance not improved by repeated infection
- Soluble factors :
- Lysozyme complement acute phase proteins e.g. CRP, interferons
Cells - Phagocytes (monocytes and neutrophils), natural killer cells
3
Q
What is the adaptive immune system?
A
- Resistance improved by repeated infection
- Antibody
- T lymphocytes, B lymohocytes
4
Q
What are the types of T cells?
A
- CD4
- Helper cells :
- TH1
- TH2
- CD8 (Cytotoxic lymphocytes)
5
Q
How is the immune system activated during the journey of pregnancy?
A
- Success of pregnancy dependent on the ability of the maternal immune system to change and adapt to each specific developmental stage
1.) Before pregnancy (periovulation stage)
2.) After Coitus
3.) During pregnancy : - First trimester
- Second trimester
- Third trimester
6
Q
What is the periovulation stage?
A
- phenotypeas and numbers of immune cells at implantation are determined earlier in the m cycle as the uterus prepares for potential pregnancy
- The endometrial surface layer of the uterus contains the greatest anundance of immune cells
- These progressively increase through the proliferative and periovulatory phases of the mestrual cycle - due to influx of leukocytes from the periphery in response to ovarian hormone-regulated chemokine and cytokine expression and proliferation of existing uterine populations
- ## The ensuing immune cell repetoire plays a major role in deciding in whether the uterine endometrium will be receptive or refractive to embryo implantation in the secretory phase.
7
Q
What is after coitus?
A
- the stage where seminal fluid containing paternal alloantigens and soluble and sperm-associated immune-regulatory factors induces a proinflammatory response in the ectocervix
- Local release of cytokines and chemokines cause recruitment of immune cells into the local environment and primes Treg cells that are actively recruited , along with neutrophils, DCs, macrophages and mast cells, into the uterine endometrium
- Here, the different immune cell populations fulfil a range of anti-inflammatory, immune-suppressive , and tissue remodelling functions to support embryo implantation
8
Q
What is the immunologic process during a successful pregnancy?
A
- 1st trimester : implantation and placentation : a pro-inflammatory stage
- 2nd trimester : amti-inflammatory stage of foetal growth : TH2- type tissue environment
- 3rd trimester : A pro-inflammatory switch necessary for labour
9
Q
Describe the inflammatory process during the first trimester of pregnacy?
A
- Human implantation can be divided into appositition, adhesion/attachment and invasion/penetration
- During appositiion, the blastocyst exoresses L-selectins
- At the beginning of the adhesion phase, the blastocyst promotes the cleavage of MUC-1 at the implantations site to ensure successful attachment
- Cytokines such as Leukemia inhibitory factor (LIF), play an important role during human implantation by supporting the embryo-endometrial interactions
- During the invasion or penetration phase, the trophoblast cells from the blastocyst penetrate the endometrial epithelium into the stroma
- The extra-villous trophoblast cells start proliferating and differentiating into inner cytotrophoblast and outer syncytiotrophoblast
- Once implantation is initiated and the embryo breaches the luminal epithelium, the stromal cells surrounding the embryo transform into decidualised xells
- The normal post-implantation decidua is rich in immune infiltrates comprise both innate and adaptive immune cells. Approc 70% decidual NK cells, 20% are macrophages, 1.7% are dendritic cells (DCs) and approx 3-10% are T cells. B cells are rare
- Immune cells are not recruited to the decidua as a response to a foreign or non self foetus but instead are actively and specifically recruited to facilitate proper implantation and promote a successful pregnancy
10
Q
What is the maternal-foetal interface?
A
- composed of the maternal decidua and placental trophoblasts
- Highly specialised tissue with a unique and time-limited function : to nourish and support development of the semi-allogeneic foetus and protect it from inflammatory or immune-mediated injury
11
Q
What is decidua formation?
A
- foetally and maternally mediated remodelling of the spiral arteries so that the placenta becomes bathed in maternal blood. Facillitates the exchange of nutrients, gases and waste
- After implantation, the endothelial lining of the spinal arteries is eroded, creating a fibrinoid wall embedded with invasive foetal placental trophoblasts
- Maternal leukocytes, such as NK cells and macrophages , have been implicated in this remodelling process.
- The dilation of the spiral arteries, which decreases the force and maximises the volume fo the maternal blood bathing the placenta
12
Q
What are Uterine NK cells?
A
- 70% of the whole decidual cells leucocytes population
- Unique phenotype CD56 and CD16
- Low cytotoxicity
- induce generation of Treg
- uNK = potent source of immunoregulatory cytokines; tissue remodelling matric metalloproteinases (MMPs), and angiogenic factors. These various factors mediate extracellular matric remodelling, trophoblast invasion, and angiogenesis, which are key processes in placentation and establishment of early pregnancy at the maternal-foetal interface
- Why do uNK not threaten foetal survival?
- d NK cell cytolytic action is low at base line
- Non classical MHC I molecule interaction (HLA-E, HLA-G) on trophoblast cell.
13
Q
What are decidual macrophages?
A
- 20% of the whole decidual cells I ucocytes
population in the first trimester and are pr sent
throughout pregnancy. M2 (immunomodulatory)
phenotype.
Play a role in early spiral artery remodeling by
producing factors associated with tissue
remodeling matrix metalloproteinases (MMP-9)
and angiogenesis (vascular endothelial growth
factor [VEGF]).
Decidual macrophages phagocytose apoptotic
cells in remodeled vascular wall and apoptotic
trophoblast cells,
Secretion of transforming growth factor-beta-I
(TGF-ß1), responsible for inhibition of human uNK
cell— mediated lysis of invasive cytotrophoblast.
14
Q
What is the role of dendritic cells in blastocyst implantation?
A
- Factors secreted by DCs remove the mucin layer of the surface epithelium of the uterus, exposing adhesion molecules that will facilitate the attachment of the embruo
- Promoting tolerace to paternal antigens
15
Q
Whar are regulatory T / Treg cells ?
A
- During pregnancy, Treg cells have a central role in maintaining an anti-inflammatory environment by preventing effector-type immune responses
against paternal antigens. - A systemic expansion of Treg cells specific for paternally derived antigens is observed in early pregnancy, indicating that their function is to protect fetal cells that express paternal antigens from rejection by the maternal immune
system. - Treg cells are also present in the decidua of healthy pregnant women, and they persist after delivery and rapidly accumulate during subsequent
pregnancies, which indicates a memory-type regulatory response. - Infertility has been proposed to be associated with reduced expression of
the transcript encoding the Treg cell-associated transcription factor forkhead
box protein P3 (FOXP3) in endometrial tissue.
