Block D - Pregnancy Flashcards
What is the importance of dendritic cells in the female reproductive tract? (3 marks)
-seminal fluid contains immunomodulatory molecules that interact with DCs, promoting Treg induction to suppress immune activation
-this helps prevent an inflammatory immune repsonse against foreign sperm antigens, allowing successful fertilization
-DC’s are also strategically positioned to detect STIs and pathogens, they act as APCs capturing and processing them, migrating to the lymph nodes and activate naïve T cells, leading to a pathogen-specific immune response
Whats the purpose of Inflammatory Cell Influx at the Site of Semen Deposition? (5 marks)
-pathogen defence: the semen microbiome may carry potential pathogens which need to be neutralized. Inflammatory cells such as neutrophils and macrophages help clear microbes, reducing the risk of STIs
-clearance of dead or damaged sperm: Not all sperm cells reach the oocyte; so macrophages and neutrophils help remove defective or dead sperm, preventing excessive immune activation.
-seminal fluid-induced immune modulation: Seminal plasma contains immunomodulatory factors (e.g., TGF-β, prostaglandins) that recruit immune cells. This controlled inflammation primes the immune system for a shift toward tolerance, essential for: Sperm survival (preventing rejection as foreign cells). Successful implantation and pregnancy (by promoting maternal immune adaptation).
-establishment of maternal tolerance for pregnancy: immune influx helps induce Treg cells, which promote tolerance to paternal antigens in the embryo. This prevents maternal immune rejection of the fetus, which shares paternal-derived proteins.
-tissue remodeling for implantation: Inflammatory mediators contribute to uterine remodeling, making the endometrium more receptive for embryo implantation.
This prepares the uterine environment for successful pregnancy establishment.
define tissue remodeling of the uterus (1 mark)
its a dynamic and tightly regulated process that ensures proper function for implantation, pregnancy and recovery.
Once fertilization occurs, what modifications do the uterus go through? (4 marks)
-decidualization: Stromal cells transform into decidual cells, secreting cytokines and growth factors to support the embryo.
-vascular remodeling: Spiral arteries dilate and lose smooth muscle, improving blood flow to support the growing placenta.
-immune adaptations: Increased regulatory T cells (Tregs) and uterine natural killer (uNK) cells promote tolerance to the fetus.
-extracellular matrix (ECM) changes: Matrix metalloproteinases (MMPs) degrade ECM to allow trophoblast invasion
Briefly describe a trophoblast invasion.
its a fetal-derived trophoblast cells integrate into the maternal endometrium, modifying maternal arteries for placental support.
explain trophoblast mediated antigen presentation. (3 marks)
-Fetal-derived trophoblast cells express paternal antigens and can interact directly with maternal T cells.
-However, trophoblasts at the maternal-fetal interface (e.g., syncytiotrophoblasts) lack classical MHC class I and II molecules, reducing the likelihood of direct maternal T cell activation.
-Instead, trophoblasts express non-classical MHC molecules (e.g., HLA-G, HLA-E, and HLA-F), which interact with maternal regulatory immune cells (Tregs, NK cells) to promote tolerance.
explain dendritic cell mediated/ indirect antigen presentation. (5 marks)
-Syncytiotrophoblasts and fetal cells release exosomes, apoptotic bodies, and microparticles containing paternal antigens.
-These are taken up by maternal dendritic cells (DCs) at the decidua (maternal endometrium during pregnancy).
-Maternal DCs process paternal antigens and present them via MHC class I (for CD8+ T cells) or MHC class II (for CD4+ T cells).
-Tolerance Induction: DCs in the tolerogenic microenvironment of the decidua promote regulatory T cell (Treg) differentiation, which suppresses maternal immune responses against fetal cells.
-Effector Response (Pathological Pregnancy): In cases of immune dysregulation (e.g., pre-eclampsia, recurrent miscarriage), DCs can activate effector CD8+ T cells, leading to fetal rejection.
Name the purpose of dendritic cells in indirect presentation? (1 mark)
to capture fetal antigens and present them to maternal T cells.
Name the purpose of Maternal CD4+ T cells in indirect presentation? (1 mark)
Induce regulatory responses or, in some cases, inflammation.
Name the purpose of Maternal CD8+ T cells in indirect presentation? (1 mark)
Can mediate fetal rejection if improperly regulated.
Fill in the missing word: Tregs suppress maternal CD_+ T cell responses, preventing fetal rejection
CD8+
Name 3 cytokines which promotes Treg differentiation in the uterus
TGF-β, IL-10, and HLA-G
How does DCs inhibit effector T cell proliferation (2 marks)
-Decidual DCs express IDO (indoleamine 2,3-dioxygenase), which depletes tryptophan, inhibiting effector T cell proliferation
-Progesterone and other pregnancy-related hormones favor a Th2-biased immune response, reducing inflammatory Th1 and cytotoxic responses.
What is the mechanism of action of Recurrent Pregnancy Loss? (1 mark)
Defective Treg induction leads to excessive maternal CD8+ T cell activation against fetal antigens.
What is the mechanism of action of Pre-eclampsia? (1 mark)
Inadequate trophoblast invasion and immune tolerance result in poor placental perfusion.
What is the mechanism of action of Fetal Rejection (Miscarriage) (1 mark)
Dysregulated antigen presentation activates maternal effector T cells.
Match the following:
1. Direct presentation (by trophoblasts)
2. Indirect presentation (by maternal DCs)
3. Tregs and immune modulation
4. Immune dysregulation
Limited, due to non-classical HLA molecules.
Major pathway for fetal antigen recognition.
Ensure maternal tolerance to paternal antigens.
Can lead to pregnancy complications.
- Direct presentation (by trophoblasts) → Limited, due to non-classical HLA molecules.
- Indirect presentation (by maternal DCs) → Major pathway for fetal antigen recognition.
- Tregs and immune modulation → Ensure maternal tolerance to paternal antigens.
- Immune dysregulation → Can lead to pregnancy complications.
how does progesterone modulate the immune system? (1 mark)
promotes immune tolerance by increasing regulatory T cells (Tregs) and suppressing pro-inflammatory responses.
how does estrogen modulate the immune system? (1 mark)
Enhances Treg function and promotes a Th2-dominant immune response, favoring antibody production over inflammatory reactions.
how does Human Chorionic Gonadotropin (hCG) modulate the immune system? (1 mark)
Inhibits maternal T cell activation and supports trophoblast survival.
Which dominant response does the immune system shift towards, Th1 or Th2? why? (2 marks)
-The maternal immune system shifts away from Th1-mediated inflammation (which promotes cytotoxicity) and toward a Th2-dominated response, which favors antibody production and suppresses cytotoxic responses.
-This protects the fetus from CD8+ T cell attack while still allowing the mother to fight extracellular pathogens.
What is the role of asymmetric antibodies?
-Asymmetric antibodies are antibodies that have unequal heavy chain glycosylation . These antibodies are often less likely to activate the complement system and may reduce immune activation.
-The production of asymmetric antibodies helps to prevent maternal immune rejection of the fetus, which carries paternal antigens.
Which type of NK cell is more abundant in tissues of the uterus? CD56 dim or bright? (5 marks)
-CD56 bright.
-They are less cytotoxic than CD56^dim NK cells and are involved in immune regulation rather than direct cytotoxicity.
-CD56^bright NK cells play a key role in the initial stages of placentation, where they interact with trophoblast cells (the fetal-derived cells that form the placenta).
-These NK cells secrete cytokines such as VEGF (vascular endothelial growth factor) and TGF-β, which promote vascular remodeling, angiogenesis, and trophoblast invasion into the maternal tissue.
-These processes are essential for the formation of a functional placenta and the establishment of adequate blood flow to the fetus.
Which of the following is the main structural component of the placental barrier that prevents direct maternal-fetal immune contact?
a) Decidua basalis
b) Syncytiotrophoblast
c) Cytotrophoblast
d) Amniotic sac
b) Syncytiotrophoblast
What is the primary reason syncytiotrophoblasts are resistant to pathogen invasion?
a) They secrete large amounts of pro-inflammatory cytokines.
b) They lack intercellular junctions, forming a continuous multinucleated layer.
c) They actively engulf maternal immune cells.
d) They produce antibodies against foreign antigens.
b) They lack intercellular junctions, forming a continuous multinucleated layer.
Which of the following is the main mechanism by which the placenta avoids maternal immune rejection?
a) Upregulation of MHC class I molecules
b) Expression of non-classical HLA-G molecules
c) Increased activation of maternal cytotoxic T cells
d) Production of maternal IgM antibodies
b) Expression of non-classical HLA-G molecules
Which type of maternal immune cells play a major role in tolerating fetal antigens?
a) Neutrophils
b) Regulatory T cells (Tregs)
c) B cells
d) Dendritic cells
(b) Regulatory T cells (Tregs)
Which enzyme suppresses maternal T cell activation by depleting tryptophan at the maternal-fetal interface?
a) Indoleamine 2,3-dioxygenase (IDO)
b) Superoxide dismutase (SOD)
c) Lactate dehydrogenase (LDH)
d) Catalase
a) Indoleamine 2,3-dioxygenase (IDO)
What type of maternal antibody is selectively transported across the placenta to the fetus?
a) IgA
b) IgM
c) IgG
d) IgE
c) IgG
How is maternal IgG transferred across the placenta?
a) Passive diffusion
b) Phagocytosis by fetal macrophages
c) FcRn receptor-mediated endocytosis
d) Direct secretion by trophoblast cells
c) FcRn receptor-mediated endocytosis
Why is IgM not transferred across the placenta?
a) It is rapidly degraded in the maternal bloodstream.
b) It is too large to pass through the placental barrier.
c) The fetus does not require IgM for immune protection.
d) It is actively destroyed by syncytiotrophoblasts.
b) It is too large to pass through the placental barrier.
Which of the following infections can cross the placental barrier and cause fetal harm?
a) Streptococcus pyogenes
b) Zika virus
c) Staphylococcus aureus
d) Candida albicans
b) Zika virus
Which of the following is NOT a factor that contributes to immune tolerance at the maternal-fetal interface?
a) High levels of progesterone and estrogen
b) Upregulation of maternal NK cell activity
c) Secretion of IL-10 and TGF-β
d) Downregulation of MHC class I expression on trophoblast cells
(b) Upregulation of maternal NK cell activity
What is the main barrier between maternal and fetal blood?
Syncytiotrophoblast
Which placental layer prevents direct immune contact?
Syncytiotrophoblast
Why do syncytiotrophoblasts lack intercellular junctions?
To prevent pathogen invasion
Which fetal cells invade the maternal decidua?
Extravillous trophoblasts (EVTs)
Which cells line fetal capillaries in the placenta?
Fetal endothelial cells
Which MHC molecule is expressed by the placenta to evade immune attack?
HLA-G
Which maternal immune cells suppress fetal rejection?
Regulatory T cells (Tregs)
Which enzyme depletes tryptophan to inhibit T cells?
Indoleamine 2,3-dioxygenase (IDO)
Which cytokines create an immunosuppressive environment?
IL-10 and TGF-β
Why don’t maternal NK cells attack the placenta?
HLA-G inhibits NK cell activation
Which maternal antibody crosses the placenta?
IgG
Which receptor allows IgG transfer?
FcRn receptor
Why can’t IgM cross the placenta?
It’s too large
What type of immunity does maternal IgG provide?
Passive immunity
When does fetal IgG reach its peak?
Third trimester
Can most bacteria cross the placenta?
No
Which infections are part of the TORCH complex?
Toxoplasmosis, Other (syphilis, Zika), Rubella, CMV, Herpes
Why can some viruses cross the placental barrier?
They use placental receptors
Which immune cells in the placenta help fight infections?
Hofbauer cells (fetal macrophages)
Discuss the mechanisms by which the placenta protects the fetus from the maternal immune system and infections. (10 marks)
-Syncytiotrophoblast layer forms a continuous, multinucleated barrier that prevents direct contact between maternal immune cells and fetal tissues.
-cytotrophoblast layer provides additional protection by maintaining cellular integrity
-fetal endothelial cells line fetal capillaries, further controlling molecular transport
-low MHC Expression syncytiotrophoblasts lack classical MHC class I and II molecules, preventing recognition by maternal T cells.
-HLA-G Expression inhibits maternal NK cell activation, preventing fetal rejection.
-regulatory T Cells (Tregs) suppress maternal immune responses to fetal antigens.
-indoleamine 2,3-dioxygenase (IDO) depletes tryptophan, inhibiting maternal T cell activation.
-FcRn receptors transport maternal IgG to the fetus, providing passive immunity.
-IgM is too large to cross the placenta, preventing harmful maternal immune responses.
-Limited Pathogen Entry since Most bacteria and large pathogens cannot cross the placental barrier, but some viruses (e.g., Zika, CMV) can. (1 mark)
What is the mechanism of action for recurrent pregnancy loss? (7 marks)
-fetus is semi-allogenic, requiring immune tolerance through Tregs immune supression
-there is shown to be a decreased level of Tregs in patients with RPL, this would lead to a maternal immune attack against fetal antigens
-reduced Tregs would reduce HLA-G expression on trophoblasts, increasing NK cell and cytotoxic T cell attack
-there is also high NK cell activity which exhibits high cytotoxicity compared to uterine NK cell, this damaging trophoblast cells, creating excessive inflammation and preventing placental development
-an increased Th1 favoured response aligns with RPL as a pro-inflammatory response through TNF-α and IFN-γ production, damaging trophoblast
-autoimmune condition where maternal antibodies attack placental phospholipids could be a factor in RPL, as it can lead to clot formation and fetal loss
-unregulated complement activation (especially C3 and C5a) can lead to trophoblast damage and pregnancy loss.
