Immunological Implications Of Pregnancy

Question 1

How is the mom tolerant to the fetus

Answer 1

Mom is exposed to some of fetus H and Igs and gets tolerant

Question 2

What cytokines are part of early phase pregnancy

Answer 2

IL1, 6, 17, TNF, LIF, PGE, Neutrophils, Macrophage, DC,ILC3

*acute inflammatory response

Question 3

Reason we have acute inflammatory response

Answer 3

1. NK, macrophage, Neutrophils: make the endometrium rough
   = exposed adhesion molecules on the endometrium for blastocyst
2. Also priming of foreign semen proteins starts

Question 4

What are some acute phase cytokines

Answer 4

IL 1, 6, 8, 12, TNF, INF-g

Question 5

What macrophage and cytokines is in pre-pregnancy
What macrophage is in implantation
their function

Answer 5

M1 and IL-1
M1+M2, and IL-10, TGF-B
* to clean up debris around spiral arteries , when trophoblast invade
* sustain CL

Question 6

Decidual Dendritic Cells

Answer 6

Maintain dTreg cells, promote Th2 cells

IL15 —> NK

Question 7

dNK and uNK cells

Implantation

Answer 7

Support development of trophoblasts after its implanted

• help spiral arteries develop
• most important
• inhibitory receptor to HLA C,E,G

Question 8

Trophoblasts are part of what immune system

Answer 8

Innate

Question 9

How does the trophoblast function as part of the immune system

Answer 9

1. Recruits immune cells, Tregs, M2, uNK cells
2. Trains them
3. Has TLR receptors to see PAMPS, DAMPS, -> tissues damage, infection

Question 10

What cytokines is needed to train
uNK cells
Tregs
M2

Answer 10

IL15, TGF-B
TGF-B
IL10, M-CSF

Question 11

Syncytiotrophoblasts in innate immunity

Answer 11

Have firm layer, secrete cytokines to bring immune cells to train then

• have Fc receptors to bring in Ig from mom to fetus
• TLR receptors
• secretion of IFN= anti-viral
• dense actin cytoskeleton to keep bacteria out

Question 12

Fc Receptors do what

Answer 12

Transport IgG into fetus through endocytosis

Question 13

Rh - and Rh +

Answer 13

TX : rhogam
Type 2 hypersensitivity
Father is + , Rh - females

Question 14

What does the Syncytiotrophoblasts give off to the maternal circulation

Answer 14

Sheds off vesicles with proteins that allow ST to regulate local and systemic mechanisms

1. Downregulate adaptive, upregulate innate
2. Vascular response, metabolism regulation

Question 15

Syncytiotrophoblasts vesicles/exosomes can lead to what

Answer 15

Since they regulate metabolism, there is drastically more vesicles in patients with
- pre-eclampsia, gestational diabetes, pre-term birth

Question 16

What do the syncytiotrophoblasts exosomes have as receptors on their surface

Answer 16

1. FasL
2. TRA/L
   * suppress active immune, apoptosis
3. HLA-G
   * downregulate Ag presentation

Question 17

Immune function of Extravillous Trophoblasts

Answer 17

Secrete IL15, CCL2, TGF-B (Treg) , IL10(M2), IFN Type1, HLA -G

• vascular remodeling ,
• reduce dNK (IL15) + (HLA-G)
• express PD-1 : —I T cell to bind to CD28
• M2 secretes IDO : —I T-cells, debris
• IL8 receptors (Neutrophils)

Question 18

HLA -G

Answer 18

Class 1,
*——I active immune response (TOLERANCE)
+ maintain peripheral fetal tolerance
- preeclampsia have low HLA-G

Question 19

Acute phase cytokines

Needed for

Answer 19

• implantation (blastocyst to attach)
• villi and spiral artery development (mom supply to fetus)
• Also in delivery and labor

Question 20

Some acute phase cytokines

Answer 20

IFN-g/a (Brian), TNF-a, IL-6, IL-17, IL1B

Question 21

During Pregnancy Week 13-27, which immune cells

Answer 21

M2, dNK, dM, dDC

Question 22

dNK during pregnancy

Answer 22

Helper cells, not cytotoxic
Around the extravillous trophoblast to help invade and angiogenesis
promotes Treg (IL10, INF-g) can still attack if needed

Question 23

dM (macrophage) in during pregnancy

Answer 23

Primarily M2 (second trimester)
Suppressor cell : 
IL 10 (Treg)
IL15 (dNK)
HLA-G —I t-cell presentation

Question 24

dDC during pregnancy

Answer 24

From myeloid line
1st 2 trimesters
Self tolerance + immune response to foreign
IL10, TGF-B
HLA _G
*low during late preg. (HIGH plasmacytoid DCs)

Question 25

Tregs are induced by

Answer 25

EVTs (HLA-C, HLA-G) and dM
——I immune responses
* other similar cell is PD-1 and TIGHT

Question 26

Tregs have what receptors

Answer 26

CTLA-4 —> B7 (CD80) to anergy of APC:

1. M2 ——> IDO —I Tcells
2. DC ——> IDO —I Tcells

Question 27

When fo Tregs increase dramatically

Answer 27

After implantation

Question 28

Which T-cells does the decidua have

Answer 28

1. Th2 : IL4,5,10,13
2. g/d Tcells : recognize Ag with no APC (IL10, TGF-B, IFN-g)

Th1/Th17 + CD8+ are VERY LOW

Question 29

Which immune cells are present during the delivery/parturition phase

Answer 29

Th17, T-cells, Neutrophils, M1, IL1,6,17,8

DAMPS, prostaglandins

Question 30

What causes the increase immune system response during delivery phase (3rd trimester)

Answer 30

trophoblasts release DAMPS and damages DNA

Question 31

What does the increased immune response cause

Answer 31

Ripen cervix and initiate labor

Question 32

Which cytokines is there within 12hrs before delivery

Answer 32

pro-inflammatory cytokines peak here
(IL1,6,8) (IFN-g, TNF-a)
Also prostaglandins and lipid modulators

Question 33

What Ig is in the breast milk

And function

Answer 33

IgA

*GI and Upper respiratory immune protection