Immunological Implications Of Pregnancy Flashcards
How is the mom tolerant to the fetus
Mom is exposed to some of fetus H and Igs and gets tolerant
What cytokines are part of early phase pregnancy
IL1, 6, 17, TNF, LIF, PGE, Neutrophils, Macrophage, DC,ILC3
*acute inflammatory response
Reason we have acute inflammatory response
- NK, macrophage, Neutrophils: make the endometrium rough
= exposed adhesion molecules on the endometrium for blastocyst - Also priming of foreign semen proteins starts
What are some acute phase cytokines
IL 1, 6, 8, 12, TNF, INF-g
What macrophage and cytokines is in pre-pregnancy
What macrophage is in implantation
their function
M1 and IL-1
M1+M2, and IL-10, TGF-B
* to clean up debris around spiral arteries , when trophoblast invade
* sustain CL
Decidual Dendritic Cells
Maintain dTreg cells, promote Th2 cells
IL15 —> NK
dNK and uNK cells
Implantation
Support development of trophoblasts after its implanted
- help spiral arteries develop
- most important
- inhibitory receptor to HLA C,E,G
Trophoblasts are part of what immune system
Innate
How does the trophoblast function as part of the immune system
- Recruits immune cells, Tregs, M2, uNK cells
- Trains them
- Has TLR receptors to see PAMPS, DAMPS, -> tissues damage, infection
What cytokines is needed to train
uNK cells
Tregs
M2
IL15, TGF-B
TGF-B
IL10, M-CSF
Syncytiotrophoblasts in innate immunity
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
Fc Receptors do what
Transport IgG into fetus through endocytosis
Rh - and Rh +
TX : rhogam
Type 2 hypersensitivity
Father is + , Rh - females
What does the Syncytiotrophoblasts give off to the maternal circulation
Sheds off vesicles with proteins that allow ST to regulate local and systemic mechanisms
- Downregulate adaptive, upregulate innate
- Vascular response, metabolism regulation
Syncytiotrophoblasts vesicles/exosomes can lead to what
Since they regulate metabolism, there is drastically more vesicles in patients with
- pre-eclampsia, gestational diabetes, pre-term birth
What do the syncytiotrophoblasts exosomes have as receptors on their surface
- FasL
- TRA/L
* suppress active immune, apoptosis - HLA-G
* downregulate Ag presentation
Immune function of Extravillous Trophoblasts
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)
HLA -G
Class 1,
*——I active immune response (TOLERANCE)
+ maintain peripheral fetal tolerance
- preeclampsia have low HLA-G
Acute phase cytokines
Needed for
- implantation (blastocyst to attach)
- villi and spiral artery development (mom supply to fetus)
- Also in delivery and labor
Some acute phase cytokines
IFN-g/a (Brian), TNF-a, IL-6, IL-17, IL1B
During Pregnancy Week 13-27, which immune cells
M2, dNK, dM, dDC
dNK during pregnancy
Helper cells, not cytotoxic
Around the extravillous trophoblast to help invade and angiogenesis
promotes Treg (IL10, INF-g) can still attack if needed
dM (macrophage) in during pregnancy
Primarily M2 (second trimester) Suppressor cell : IL 10 (Treg) IL15 (dNK) HLA-G —I t-cell presentation
dDC during pregnancy
From myeloid line
1st 2 trimesters
Self tolerance + immune response to foreign
IL10, TGF-B
HLA _G
*low during late preg. (HIGH plasmacytoid DCs)
