C2 Pregnancy

Question 1

Implantation

Role of blastocyst

Answer 1

Blastocyst degrades the endometrial ECM to invade the uterus.

• Apoptosis of endometrial epithelial cells occurs at embryo implantation site
• Numerous macrophages are present at the implantation site & act to engulf apoptotic cells

Question 2

Gestation
Role of myometrium
What is 1. Basal plate 2. Chorionic plate
- Describe the anatomical barrier

Answer 2

Responsible for contractions
1. The maternal portion of the placenta = basal plate
2. Fetal portion of placenta
- Anatomical separation of mother & baby by placenta for protection of the baby
(not a proper separation as things can cross more a ‘selective filter’)

Question 3

Describe cytokine shift in pregnancy

Answer 3

Shift towards Th2 subtype indicator of successful pregnancy
(IL-4, IL-13)
- Opposite true for Th1: could result in spontaneous abortion (IFNy, IL-12)
- Th1, Th17, detrimental

Question 4

1. In mice what does estrogen drive

2. Describe Treg numbers in mruine estrus cycle

Answer 4

1. Treg expression (Foxp3 mRNA)
2. Treg no. vary in the uterus in murine estrus cycle & are increased during pregnancy
   - high in anticipation of transplantation
   - high during pregnancy
   (cytokines also increase)

Question 5

For successful pregnancy are high or low Treg cells required?

• what does the opposite result in
• what do Treg cells Inhibit/ supress etc.
• what cytokines do Treg cells produce

Answer 5

High no. Tregs (+ strong suppression of Th1)
= tolerance & normal pregnancy
Low Treg vs Th1 = immunity to fetus: infertility, miscarriage, preeclampsia
- Inhibit proliferation & cytokine production of CD4/CD8 Tc, Bc & supress Ig production, cytotoxic function of NK cells, maturation of DC & macrophages
- produce immunosuppressive cytokines: IL-10 & TGFB

Question 6

Describe the effect of progesterone on immune cells

Answer 6

Proinflammatory functions are downmodulated by estrogen & progesterone
Macrophages & DC
- accumulate after implantation around the decidua + in the uterus throughout pregnancy
- Could be detrimental to pregnancy if they were to present fetal Ag to Tc, so believed they are suppressed, or tolerogenic

Question 7

Describe effect of female sex steroids (Progesterone & estrogen) on

1. T
2. B cells

Answer 7

1. Progesterone and estrogen both favour production of Th2 associated cytokines & inhibit the Th1 associated cytokine
2. Estrogen causes a reduction in pre-B cells & IL-7 responsive cells in the BM
   Progesterone via PIBF stimulates production of asymmetric antibodies

Question 8

Uterine NK cells are mostly what type
Describe functions of uNK cells
- What has been found in women with increased activated peripheral blood NK cells

Answer 8

CD56 bright (low lytic)

1. Protect trophoblasts bearing paternal antigens from maternal immune system
2. Protect mother from trophoblast invasion and limit trophoblast expansion
3. Regulate restructuring of maternal spiral arteries
4. Protect the uterus against infection
   - Recurrent pregnancy losses, infertility and assisted reproductive failure

Question 9

Which cells play a role in labor & why was this suggested

Answer 9

(increased no:) Neutrophils, macrophages, chemokines & Tc

- shown in upregulation of chemokines & pathways regulating immune cell trafficking

Question 10

What causes increased CXCL8 expression

When does CCL2 increase

Answer 10

1. Stretch of uterine myometrial cells
2. Expression sig upregulated immediately before &during labour
   Expression stimulated by mechanical stretch
   Increased accumulation of CCL2 in term myometrium is regulated by progesterone
   CCL2 = Monocyte Chemoattractant Protein-1

Question 11

As part of post partum repair, how does the uterine mass decrease

Answer 11

Apoptosis
Neutrophil entry
Enzyme release
Phagocytosis of cellular debris

Question 12

Why is the uterine mucosa unique amongst other mucosal sites

Answer 12

As it undergoes regular changes in structure in response to cyclical changes in sex steroids

Question 13

Progesterone affect on Bc

Answer 13

Stimulates production of asymmetric antibodies (via Progesterone Induced Blocking Factor, PIBF)

• IgG molecules with altered structures
• Ineffective at activating effector functions typically associated with Ab
• (e.g. opsonisation for phagocytosis & complement fixation)
• Protects fetus by acting as blocking Ab
• Higher levels of asymmetric Ab exist in healthy pregnant women than recurrent (spontaneous) aborters.

Question 14

What cant cross placental barrier

Answer 14

IgA 		
Blood cells   
Pulmonary TB
Rhinovirus (common cold) 
IgM   
Maternal hormones

Question 15

What part of the decidua interacts with the trophoblast

Answer 15

decidua basalis