Immunological Implications of Pregnancy

Question 1

EVT

Answer 1

Extravillous Trophoblasts

Question 2

ST

Answer 2

Syncytiotrophoblasts

Question 3

EVT and ST both function as ____ immune cells

Answer 3

Innate

Question 4

These cells modulate localized innate immune responses for fetus during implantation and all the way to parturition

Answer 4

EVT and ST

Question 5

3 major functions of STs?

Answer 5

1. Fused cells = no leaks
2. Shed extracellular vesicles for crosstalk between cells in decidua
3. FcRn-IgG transport from maternal circulation

Question 6

STs have a dense actin skeleton and fused cells that physically resist?

Answer 6

Invasion of bacteria

Question 7

What cell is the FcRn-IgG transport seen in?

Answer 7

STs - Syncytiotrophoblasts

Question 8

Describe the FcRn-IgG transport seen in STs

Answer 8

STs have a specialized Fc receptor for protective transport of IgG across their epithelium WITHOUT degradation
- This gets IgG from the maternal circulation into the fetal circulation

Question 9

Why is it important to get IgG into fetal circulation?

Answer 9

So it can provide the same protection to the fetus that it does for the mother

Question 10

STs transport IgG into fetal circulation. Can they do other antibodies and if so which ones?

Answer 10

NO

Question 11

EV

Answer 11

Syncytiotrophoblastic vesicles

Question 12

Syncytiotrophoblasts shed many vesicles into maternal circulation and placenta. What is the main one?

Answer 12

Exosomes

Question 13

What are the 3 functions of the STs shedding vesicles?

Answer 13

1. Downregulate adaptive immune responses
2. Stimulate innate inflammatory responses
3. Regulate metabolism and vascular responses

Question 14

An ____ in the number of ST shed vesicles can be seen with pre-eclampsia, gestational diabetes and pre-term birth

Answer 14

INCREASE

Question 15

What 4 cytokines/ligand do EVTs (extravillous trophoblasts) secrete?

Answer 15

IL-15
IL-10
TGF-beta
PD-1 - inhibitory T cell ligand

Question 16

EVTs secrete IL-15 to?

Answer 16

Reduce cytotoxicity of dNKs

Question 17

EVTs secrete IL-10 to?

Answer 17

Support M2 differentiation

Question 18

EVTs secrete TGF-beta to?

Answer 18

Support Treg differentiation

Question 19

What cell releases HLA-G?

Answer 19

EVTs

Question 20

What is the function of HLA-G?

Answer 20

Influences phenotype of immunes responses in decidua

= Maintenance of peripheral tolerance to fetus

Question 21

____ levels of HLA-G were seen to involved pregnancy complications

Answer 21

DECREASE

Question 22

Main function of Decidual NK cells (dNKs)?

Answer 22

Surround trophoblasts after implantation and support their development

Question 23

What decidual cell is vital for spiral artery development at the placenta?

Answer 23

dNKs

Question 24

Main function of CD4+TReg cells?

Answer 24

SUPPRESS adaptive immune response and Ag presentation in the decidua

Question 25

What do all CD4+TReg cells express?

Answer 25

CTLA-4

Question 26

What does CTLA-4 bind to?

Answer 26

B7 (CD80)

Question 27

What does the binding of CTLA-4 to B7(CD80) do?

Answer 27

Induces Aenergy so APCs do NOT activate naive T cells

Question 28

What cells express CTLA-4?

Answer 28

CD4+TReg cells

Question 29

Decidual macrophages (dmacrophages) transition to M2 early in pregnancy. Main job?

Answer 29

Suppressor cell

Question 30

dmacrophages secrete IL-10 and IL-15. What are the jobs respectively?

Answer 30

- Support TRegs | - Support dNKs

Question 31

During the first 2 trimesters, most of the decidual dendritic cells (dDCs) are what type?

Answer 31

Myeloid

Question 32

Late in the 3rd trimester, most of the dDCs are what type?

Answer 32

Plasmacytoid

Question 33

Main jobs of dDCs?

Answer 33

Maintain self tolerance, decrease antigen presentation and induce immune responses to pathogens

Question 34

Acute phase cytokines are extremely important for what stages of pregnancy?

Answer 34

Attachment and implantation of blastocyst!!

Question 35

Acute phase cytokines are extremely important for establishment of what blood supply?

Answer 35

Maternal blood supply to the fetus

Question 36

Too little or too much expression of the acute phase cytokines can cause what?

Answer 36

Developmental failure of the fetus

Question 37

When during gestation do pro-inflammatory mediators dominate?

Answer 37

Early in pregnancy and late in pregnancy | - Implantation and Parturition!!

Question 38

When during gestation do anti-inflammatory mediators dominate?

Answer 38

Middle of pregnancy | - Fetal growth

Question 39

Give a few examples of pro-inflammatory mediators seen in the beginning and very end of pregnancy

Answer 39

``` M1 Neutrophils IL-6 IL-10 Th17 ```

Question 40

Give a few examples of anti-inflammatory mediators seen in the middle of pregnancy

Answer 40

``` M2 TREG IL-10 TGF-beta IDO ```

Question 41

Why are pro-inflammatory mediators necessary for successful blastocyst implantation?

Answer 41

Disrupts the mucous barrier and promotes adhesion molecule expression to make the endometrium "sticky" for implantation

Question 42

When will there be a large increase of pro-inflammatory mediators leading up to parturition?

Answer 42

12 hours before parturition