IMMUNOLOGY IN

PREGNANCY
IMMUNOLOGY OF PREGNANCY
One tissue that is repeatedly grafted
and repeatedly tolerated is the fetus. The
mysterious mechanism of the immune
system that prevents rejection of fetus
remains unknown.
 The immune system is generally divided into
Innate and Adaptive.
Innate immune system
The innate immune system is the
(a) First line of host defense against infection.
(b) It works fast once it recognizes the
pathogens.
(c) It cannot identify the self vs non-self
(nonspecific).
 The immune cells involved are : phagocytic
(neutrophils, monocytes and macrophages) cells,
natural killer cells (NK cells), eosinophils and
basophils.
 The phagocytic cells ingest and digest
microorganisms with lysosomal enzyme.
 The NK cells can recognize and distinguish
between normal cells and cells infected with a
virus or tumor.
Adaptive Immune System:
 It works as a second line defense against
infection
 It has delayed response
 It can discriminate ‘self’ from ‘non-self’
 It prevents re-infection through
‘immunological memory’.
(Lymphocytes (B and T lymphocytes)
and antigen presenting cells (APC).)
 T lymphocytes are classified into T
helper (Th) and T cytotoxic (Tc) cells.
 Th cells have two subtypes– Th 1 and
Th 2.
 Th 1 cells activate macrophages and
are involved in cell mediated
immunity.
 Th 2 cells activate B cell differentiation
and are involved in humoral immunity.
 Major Histocompatibility Complex (MHC) is a
complex of genes with multiple loci. It is
located on the chromosome 6.
 MHC encodes two types of membrane proteins.
 Those are known as Human Leukocyte
Antigens (HLA) Class I and Class II.
 The process of graft rejection generally
involves recognition of foreign MHC molecules
by host T 1 hymphocytes.
IMMUNOLOGY IN PREGNANCY
 Pregnancy is not an immunodeficient state.
Women are able to respond to both humoral and
cell mediated immunity against the paternal
antigen.
 Specific types of NK cells (large granular
lymphocytes) are present in the decidua mainly at
the site of implantation. These NK cells (Uterine
NK cells) are different from blood NK cells.
 These U-NK cells control the trophoblast
proliferation, invasion when they interact
with the trophoblast HLA(Human
Leukocyte Antigens) Class I molecule.
 U-NK cells contribute to maternal tolerance
of the fetus and maintenance of pregnancy.
 Trophoblast cells are derived from the
fetal tissue and invade the decidua.
 These trophoblast cells (placenta) form
the interface between the fetus and the
mother.
 Thus the placenta forms an efficient
barrier against the transmission of
immuno-competent cells between the
fetus and the mother.
 The trophoblast covering the chorionic
villi (villous trophoblasts) comes in
contact with the maternal blood in the
intervillous space and interacts with
maternal systemic immune response.
 It does not express HLA Class I or Class II
molecules
 The trophoblast in contact with the
decidua (extravillous trophoblast)
expresses HLA Class I molecules but
not HLA Class II molecule.
 This interacts with maternal local
uterine immune response.
 Placenta presents no immuno-
competent cells due to lack of HLA
antigens.
 Placenta acts as an efficient
immunological barrier.
 During pregnancy, maternal immune
response is shifted (immunomodulation)
from Th 1 (cell mediated) to Th 2 (humoral
mediated) type. Th 2 type response is
beneficial due to the production of anti-
inflammatory cytokines.
 Immunomodulation results in improvement
of woman with rheumatoid arthritis in
pregnancy.
 During pregnancy there is production of
antibodies of paternal antigens.
 These are anti–HLA antibodies and
antibodies against sensitized T cells.
 These antibodies have no major effect on
pregnancy outcome.
 Immunological mechanisms involved in
pregnancy are not the same as that of
organ transplantation.
 Immunological tolerance through
complement and cytokines regulation is
protective for pregnancy.
MATERNAL FETAL CELL TRAFFICKING
AND MICROCHIMERISM :
 Maternal tolerance of fetus is due to
bidirectional cell trafficking between the
mother and fetus.
 Cell free fetal DNA (Cff DNA) and also infant
fetal cells are detected in maternal
circulation during entire pregnancy.
 The existence of two cell populations in a
single person is known as microchimerism.
It is likely that microchimerism may have
beneficial effects.
 Immunosuppressive factors that operate
in pregnancy are: estradiol, progesterone,
hCG and prolactin.
 Fetal tolerance is probably due to the
presence of alpha fetoprotein.
 A number of pregnancy associated
glycoproteins, e.g. α2 macroglobulin and
placental interferon have
immunosuppressive properties.
 Amniotic fluid is rich in immunosuppressive
phospholipids.
IMMUNE TOLERANCE:
 Immune tolerance of normal pregnancy at the
maternal-fetal interface is maintained by the
interaction of HLA-G with uterine NK cells.
 This effect predominates in a normal
pregnancy.
 The levels of complements and cytokines
(proinflammatory factors) are often raised
during pregnancy.
 Inhibition of such complements and cytokines
by the placenta reduces the immune mediated
pregnancy complications.
 ABO HEMOLYTIC DISEASE OF THE
NEWBORN
 Jaundice in newborn infants within 24 hours of
birth may be due to ABO isoimmunization of the
mother.
 The incidence is higher in group ‘O’ mothers
carrying group
 It is postulated that IgG anti-A/anti-B are
formed more commonly in group ‘O’ mothers.
 IgM anti-A/ anti-B maternal antibodies are also
known to play some role in bringing about ABO
hemolytic diseases of the newborn.
RH-ISOIMMUNIZATION
1. Entry of fetal blood in maternal
circulation(0.1 mL of Rh-positive fetal )
2. Fetal RhD positive red cells enters the
circulation of Rh-negative mother
3. IgG forms and crosses the placental
barrier
4. Agglutination and hemolysis of fetal RBC
5. It may lead to complications like
hydrops fetalis, kernicterus etc
PREECLAMPSIA/ECLAMPSIA:
 In preeclampsia the abnormal
immunological response develop in two
stages;

1. Abnormal placentation and spiral artery

remodeling:

2. preeclampsia
ABNORMAL PLACENTATION AND
SPIRAL ARTERY REMODELING:
 There is failure of extravillous trophoblasts
invasion and spiral artery remodeling.
 This is due to failure of interaction of
extravillous trophoblasts with uterine NK cells
and HLA-C receptors.
 PREECLAMPSIA
 It is associated with widespread systemic
inflammation and endothelial dysfunction.
The immune dysfunction in preeclampsia
are
 There is decrease in regulatory T cells
both in number and function.
 There is insufficient shift from Th-1 to Th-
2 as opposed to normal pregnancy.
 There is a higher level of cytokine
abnormalities with increased
concentration of Tumor Necrosis Factor
alpha, IL-6, IL-1b, IL-8 and lower
concentration of IL-10.
SPORADIC AND RECURRENT MISCARRIAGE:

In cases with sporadic and recurrent

miscarriages.
 Cytokines are immune molecules. Th-1 cells
produce PROINFLAMMATORY cytokines
whereas Th-2 cells produce ANTI-
INFLAMMATORY cytokines.
 In a normal pregnancy there is a shift of Th-1
response to Th-2 response.
 Progesterone has an immunomodulatory role
to induce a pregnancy protective shift from
Th-1 cytokine response to more favorable Th-
2 cytokine response.
 Women with recurrent miscarriage produce
low levels of Th 2 cytokines (IL–4 and IL–
10).
 Women with recurrent miscarriage have a
decreased population of NK cells in the
decidua. This indicates an altered immune
environment within the decidua.
ANTIPHOSPHOLIPID
SYNDROME:
 In SLE there is antiphospholipid antibodies,
e.g. lupus anticoagulant β2 glycoprotein, and
anticardiolipin
 These antibodies act by dysregulation of
coagulation pathways.
 This causes thrombosis of uteroplacental
vessels and poor placental perfusion.
MATERNAL AUTOIMMUNE DISEASE
AND FETUS
 Incidence of neonatal thyrotoxicosis is
higher in babies born of a thyrotoxic mother.
 A baby born to a mother with IMMUNE
THROMBOCYTOPENIA will suffer from the
same disease through transplacental
transfer of antiplatelet antibodies.
 Myasthenia gravis also has some such
relationship due to transplacental transfer
of acetylcholine-blocking factor.
IMMUNOLOGICAL CONTROL
OF FERTILITY
 Placental hormones— anti HCG vaccine
 Human sperm antigen– anti lactate
dehydrogenase–X(LDH-X) reduction of viable
sperm and improper implantation of ovum.
 ZONA pellucida- anti sera to ZP Blocks the sperm
penetration
 Anti sperm antibodies(IgG, IgM or IgA) binds with the
sperm surface antigen and affects the sperm motility.