Immunological Implications of Pregnancy Flashcards

1
Q

EVT

A

Extravillous Trophoblasts

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2
Q

ST

A

Syncytiotrophoblasts

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3
Q

EVT and ST both function as ____ immune cells

A

Innate

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4
Q

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

A

EVT and ST

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5
Q

3 major functions of STs?

A
  1. Fused cells = no leaks
  2. Shed extracellular vesicles for crosstalk between cells in decidua
  3. FcRn-IgG transport from maternal circulation
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6
Q

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

A

Invasion of bacteria

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7
Q

What cell is the FcRn-IgG transport seen in?

A

STs - Syncytiotrophoblasts

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8
Q

Describe the FcRn-IgG transport seen in STs

A

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

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9
Q

Why is it important to get IgG into fetal circulation?

A

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

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10
Q

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

A

NO

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11
Q

EV

A

Syncytiotrophoblastic vesicles

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12
Q

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

A

Exosomes

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13
Q

What are the 3 functions of the STs shedding vesicles?

A
  1. Downregulate adaptive immune responses
  2. Stimulate innate inflammatory responses
  3. Regulate metabolism and vascular responses
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14
Q

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

A

INCREASE

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15
Q

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

A

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

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16
Q

EVTs secrete IL-15 to?

A

Reduce cytotoxicity of dNKs

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17
Q

EVTs secrete IL-10 to?

A

Support M2 differentiation

18
Q

EVTs secrete TGF-beta to?

A

Support Treg differentiation

19
Q

What cell releases HLA-G?

A

EVTs

20
Q

What is the function of HLA-G?

A

Influences phenotype of immunes responses in decidua

= Maintenance of peripheral tolerance to fetus

21
Q

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

A

DECREASE

22
Q

Main function of Decidual NK cells (dNKs)?

A

Surround trophoblasts after implantation and support their development

23
Q

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

A

dNKs

24
Q

Main function of CD4+TReg cells?

A

SUPPRESS adaptive immune response and Ag presentation in the decidua

25
Q

What do all CD4+TReg cells express?

A

CTLA-4

26
Q

What does CTLA-4 bind to?

A

B7 (CD80)

27
Q

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

A

Induces Aenergy so APCs do NOT activate naive T cells

28
Q

What cells express CTLA-4?

A

CD4+TReg cells

29
Q

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

A

Suppressor cell

30
Q

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

A
  • Support TRegs

- Support dNKs

31
Q

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

A

Myeloid

32
Q

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

A

Plasmacytoid

33
Q

Main jobs of dDCs?

A

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

34
Q

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

A

Attachment and implantation of blastocyst!!

35
Q

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

A

Maternal blood supply to the fetus

36
Q

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

A

Developmental failure of the fetus

37
Q

When during gestation do pro-inflammatory mediators dominate?

A

Early in pregnancy and late in pregnancy

- Implantation and Parturition!!

38
Q

When during gestation do anti-inflammatory mediators dominate?

A

Middle of pregnancy

- Fetal growth

39
Q

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

A
M1
Neutrophils
IL-6
IL-10
Th17
40
Q

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

A
M2
TREG
IL-10
TGF-beta
IDO
41
Q

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

A

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

42
Q

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

A

12 hours before parturition