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 The immune responses.immune cells exist within the decidua to combat infection. The immunology of the maternal-fetal interface from the perspective of these diverse sets of demands, which, may not always be compatible with one another.

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 SPECIFICITY AND TRAFFICKING
 INFECTIOUS DISEASE CONTROL
 PERSPECTIVE VIEW
 CONCLUSION

3. pregnancy
complications
preeclampsia
congenital
infections
IUGR
abortion,
 Interface :-
INTRODUCTION
 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
d NK cells,
Dendritic cells
Macrophages,
T cells

4. HISTORICAL PERSPECTIVE AND
SIGNIFICANCE
? 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.
Preeclampsia (5-7%)
(Impaired activation of d
NK cells)
Uterine
vasculature
remodeling
in gestation
Reproductive
success in placental
(eutherian)
mammals
Placenta Uterus

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. MATERNAL IMMUNE CELLS
d NK cells,
Dendritic cells
Macrophages,
T cells
Placental Development and
function
 Minimise chance of placenta
being attacked.
 To combat infection
Trophoblast
(PLACENTA)
Decidualization Uterine Mucosa

9. NATURAL KILLER CELLS (D NK CELLS)
FUNCTIONS
1.Transforming spiral arteriole in decidua
Replacing endothelium by trophoblast
First phase
 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
Second phase
d NK cell
Hypoxia
2. Role in I/U inflammation & Abortion
d NK cell Cytotoxic granules (perforin and granzyme) (Manaster, 2010)

10. 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)
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

11. MACROPHAGES
 2nd most abundant : 20% ( 50-100 cells/mm² in first trimester)
Remodelling
Pathogen sensors
Immune effector cell
macrophage
 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

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

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

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

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. ANTIGEN SPECIFICITY 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)
Activated T cell accumilate at
inflammatory site: chronic
deciduitis, chronic
chorioamnionitis and VUE.
Naive maternal CD8+ T cells fail to
encounter Ag and differentiation into
Th1 cells and CTLs (Reinchart et al, 2003)
 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.

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

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

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

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

23. CONCLUSION
 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.

24. REFERENCES
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