Viviparity is a unique characteristic of mammals. Gestational outcomes avoiding fetal defects or loss, maternal infection, or morbidity are contingent upon an intimate association between mother and developing fetus that nurtures the fetus without provoking maternal immune responses. Therefore the maintenance of optimal immunity is necessary for the successful gestation.

1. IMMUNOLOGY OF THE MATERNAL – FETAL
INTERFACE
Asha Ann Philip
MVSc Scholar
Division of Pathology (VPL)
IVRI,Izatnagar, UP-243122

2. OVERVIEW
 INTRODUCTION
 HISTORICAL PERSPECTIVE AND SIGNIFICANCE
 PREGNANCY –MOUSE Vs HUMAN
 MATERNAL FETAL INTERFACE
 IMMUNE CELLS (d NK cells, Macrophages, DC, T
cells )
 ANTIGEN SPECIFICITYAND TRAFFICKING
 INFECTIOUS DISEASE CONTROL
 PERSPECTIVE VIEW
 CONCLUSION

3. pregnancy
complications
preeclampsia
congenital
infections
IUGR
abortion,
 Interface :-
 Composition and functions vary locally- Uterine decidua
(NK cells, Dendritic cells, Macrophages, T cells)
 Immune cells play a role in pregnancy /failure
 Mouse and human studies
 Pathogenesis of pregnancy complications
INTRODUCTION
d NK cells,
Dendritic cells
Macrophages,
T cells

4. ? Paternal histocompatibility by fetus
should provoke tissue rejection
response (Medawar ,1953)
? Unusual kind of decidual NK ( d NK )
cells perform key developmental role in
human and mice .
? Immunological lesions underlying
pregnancy complication.
Uterine
vasculature
remodeling
in gestation
Preeclampsia (5-7%)
(Impaired activation of d
NK cells)
Reproductive
success in placental
(eutherian)
mammals
Placenta Uterus
HISTORICALPERSPECTIVEAND
SIGNIFICANCE

5. PREGNANCY –MOUSE VS HUMAN
•20 days
•Placental trophoblast do not
invade deep in decidual
arteriole.
•Preeclampsia and IUGR rare
•Decidualisation only at
implantation
• 9 months
• Trophoblast temporarily replace
maternal endothelial cells
• Common
• Decidualisation at
Secretory phase and implantation
•Haemochorial placentation
•Decidual accumilation of NK cells (Moffett,2006) and (Maltepe et al,
2010)

6. MATERNAL FETAL INTERFACE
Flow cytometry and
Immuno staining
(Bulmer et al, 2010)
NK Cells- 70%
Macrophages- 20%
T cells - 10-20%
DC & B cells- rare
Cellular constituents in first trimester of human decidua

8. MATERNALIMMUNECELLS
d NK cells,
Dendritic cells
Macrophages,
T cells
Placental Development and
function
 Minimise chance of placenta
being attacked.
 To combat infection
Trophoblast
(PLACENTA)
Uterine MucosaDecidualization

9. NATURAL KILLER CELLS (D NK CELLS)
1.Transforming spiral arteriole in decidua
Replacing endothelium by trophoblast
 Incomplete spiral transformation and failure of trophoblast
Preeclampsia & IUGR (Khong et al, 1986)
 Role of IFN γ in Remodelling of spiral arteriole (Apps et al, 2011)
 Preeclampsia: KIR lack Tel-B for HLA-C.
 Inhibitory signal to d NK Cell RSA & IUGR (Hiby et al, 2010)
 No mice shows gestational hypertension
Trophoblast endovascular migration
FUNCTIONS
Second phase
First phase
d NK cell
Hypoxia
2. Role in I/U inflammation & Abortion
d NK cell Cytotoxic granules (perforin and granzyme) (Manaster, 2010)

10. Why d NK cell do not threaten fetal survival?
 d NK cell cytolytic action is low at base line
 Non classical MHC I molecule interaction (HLA-E, HLA-G)
on trophoblast cell (App et al, 2008) ( Chazara et al, 2011)
D NK cell is embryotoxic at certain circumstances
 IL-10 TNF- α , IL-6: Embryo resorption
Appear in secretory endometrium prior to implantation.( CD 56 bright,
CD16-) (Koopman et al, 2003)
Pregnancy specific functions :TGF-β, IL-15 (Keskin et al, 2007)

11. MACROPHAGES
 2nd most abundant : 20% ( 50-100 cells/mm² in first trimester)
 Marker : CD 14 , CD 209 (IL-10 level)
 Remodelling: (fibronectin, collagen components, matrix
metalloproteinase-9, C1q)
d macrophage in 3rd trimester: Preeclampsia
 Role in parturition:Pro inflammatory mediators (IL-6, TNF- α )
 PAMPs Acute chorio amnionitis preterm birth
Remodelling
Pathogen sensors
Immune effector cell
macrophage

12. CD 14
Monocytes
CSF
IL-10
d Macrophage
D stromal cells
dNK cell
glandular epithelial cells
F4/80+MHCII hi (CD 209-)
F4/80+ MHCII lo (CD 209 +)
Growing myometrium
CSF
dNK cell

13. DENDRITICCELLS
Adaptive immune responses
D C are scarce at Interface (1-5 cells)
(Tagliani,2011)
Decidualisation : fall of DC cells 9/mm²
to 2/mm²
DC ENTRAPMENT Mouse endometrium lack
lymphatic vessel (Collins et al, 2009)
Inflammation
pathogen
DENDRITIC CELLS
Lymphatic vessel
Lymph node

14. FUNCTIONS
Dendritic cell as decidua
Tissue
remodelling
Uterine
mucosa to
survey
pathogen
T cell
immunosti
mulation

15. T CELLS
 10-20% of leucocytes in first trimester is CD3 TCR
10-20% T
cell
CD4
(30-45 %)
50%
Memory
5% Regul
CD8
(45-75%)
40%
Memory
Th2
Th 17
Th1
•5%
•2 %
•Spontaneous
Abortion
•5-30%
•RSA
Spontaneous Abortion
Preeclampsia
T Reg
Th 17

16. Activated T cell accumilate at
inflammatory site: chronic
deciduitis, chronic
chorioamnionitis and VUE.
ANTIGENSPECIFICITY AND TRAFFICKING
 How many T cells have fetal/ placental specificity?
 Human: CD 25 ( activated/ memory) CD4+ T cell in pregnancy is
elevated (10%) if mismatch in fetal-matetnal HLA-C allele (Tilburgs et al,
2009)
 Differentiating decidual stromal cells silences expression of the key
Th1/CTL-attracting chemokines (CXCL9 ,CXCL10 ,CXCL11 and CCL5)
 Loss of chemokine silencing: Late pregnancy complications.
Naive maternal CD8+ T cells fail to
encounter Ag and differentiation into
Th1 cells and CTLs (Reinchart et al, 2003)

17. INFECTIOUS DISEASE CONTROL
 Organisms infect placenta and amniotic membrane.
Preterm birth
IUGR
Still birth
Congenital Abnormalities
P.falciparum
Maternal
blood
Villous
tree
Other
organisms
Decidua Placenta
Decidua is GROUND
ZERO for avoiding
immunological assault
& infection

19. CYTOMEGALOVIRUS
Haemopoitic
progenitor
Mononuclear
phagocytes
Stromal
cells
(MICE)
RESERVOIR
Humoral immunity is the only defense.
Placental infection -vely corelated by Maternal IgG Titres
( Mc Donagh eta l, 2004)
CMV DNA detected in 89% of first trimester
Elective termination : +ve for i/c Staining Decidual biopsy
Immunocompetant host: Controlled by Memory T cells
organ transplant patients HIV patients
Latent infection: 30-70% population (Gandhi & Khanna, 2004)

20. LISTERIA MONOCYTOGENES
EXTRAVILLOUS TROPHOBLAST anchoring villi
PLACENTA
Organism carried by extravasating Leucocytes
Immunoprivilaged environment (T cells):
Survival
Decidua not at mercy of pathogen
Controlled by T cells
MACROPHAGES
NEUTROPHILS
TROPHOBLAST

21. ACUTE CHORIOAMNIONITIS
IL-8
TLR
d stromal cell
Trophoblasts
Amniotic epithelial cells
Neutrophils
IL-17 (T Cell)
IL-22 ( lymphoid cell)
G-CSF
 Ascending bacterial infection from cervix.
 Cause Pre term birth
 Neutrophils are recruited

22. Decidua
IL-15 NK CELL
CSF Macrophage
Chemokine silencing Th1/ CTL
Decidua resisted homing of Th1
and CTLs
Artificial decidual reaction
Restrict immune cells (T cell, DC, B cell )
Specialisation of leucocytes (NK, macrophage)
dNK cell accumulation
T cell exclusion as true decidua
loss of macrophage and DCdensity
PERSPECTIVE VIEW

23.  Trophoblast - d NK cell interaction is essential for success of
pregnancy
 Threat in reproductive success is due to pro inflammatory
molecules of macrophages (IL-6, TNF- α )
 Decidual macrophage exposure to CSF-1 is a major
mechanism for local monocyte recruitment & constant at gestation.
 Paucity of DCs limit adaptive T cell responses & minimizing
immunogenic responses to fetal/placental antigens
 Impaired activation of Immune cells lead to pregnancy
complications ( Preeclampsia, IUGR, Abortion)
 Decidua is GROUND ZERO for avoiding immunological assault
& during infection.
CONCLUSION

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