THE IMMUNOLOGICAL PARADOX

OF PREGNANCY

Triyana Sari

Department of Biology
Faculty of Medicine Tarumanagara University
 A Strain Injected with CBA
spleen cells

CBA Strain

CBA skin
CBA skin
A Strain (+CBA)
(offspring)

C57 skin A Strain (-CBA)

(Control)

Medawar, 1953
C57 Strain
Immune System
 three lines of defense
 The physical barrier—first line
 The innate immune system—second line
 The adaptive immune system—third line
THE PHYSICAL BARRIER
 plays a critical role in the defense against
infection
 comprises an extensive surface area
approximately 400 m2
 the skin, covering approximately 2 m2 in the adult,
 mucous membranes (digestive, reproductive and
respiratory systems)
 INNATE IMMUNE SYSTEM
 consisting of the following constituents:
 Soluble elements (complement, acute phase
proteins, interferon)
 Professional phagocytes (macrophages, neutrophils)
 Natural killer cells
 The essential characteristic of the innate
immune system:
 response to any given pathogen is not affected by
previous exposure
 same magnitude each time the system is challenged
by pathogens
ADAPTIVE IMMUNE SYSTEM

 T and B lymphocytes, antibodies, receptors,

etc.,
 four fundamental :
 memory
 specificity
 diversity and
 tolerance to ‘self’
HLA genes
Harm Immune responses

Allergic disease Autoimmune Transplant

disease rejection
Innocuous Self-antigen Non-self
antigen antigen
PLACENTA
PLACENTA

No expression

HLA-C, HLA-G, HLA-E

HLA-C, HLA-G, HLA-E

Potential immunological
confrontation
 Immunity to sperm and seminal fluid;
 How the preimplantation embryo evades the
maternal immune system;
 Implantation and placentation: the nature of the
maternofetal immunological interface;
 Maternal immunocompetence during pregnancy;
 Maternal immune responses to fetal antigens;
 Whether recurrent miscarriage represents failure
of ill-defined immunoregulatory mechanisms that
normally sustain successful pregnancy.
Sperm and seminal plasma

Antigenicity of spermatozoa
 Once sperm leave the epididymis, they become
coated with seminal plasma components
including lactoferrin, which reduces their
immunogenicity
 low concentrations of seminal plasma in vitro can
inhibit the generation of cytotoxicT cells, the
cytotoxic effect of natural killer (NK) cells, the
phagocytic activity of macrophages and
neutrophils and the generation and activity of
antibodies
 The preimplantation embryo
Protection depends primarily on the following:
 Paternal antigens are not expressed at the two-cell
stage, but become apparent on the surface from the
six-to-eight-cell stage;
 Although the expression of these antigens increases
with cellular division, major histocompatibility antigens
are thought not to be present at this stage in human
pregnancy;
 Some research points to the existence of hormone-
dependent non-specific suppressor cells in secretory-
phase human endometrium. Supernatants from
cultured explants of endometrium, which include these
cells, have immunosuppressive effects. Thus, significant
immunological problems are, therefore, not posed by
the conceptus before implantation.
Immunology of implantation and
placentation
the immunological problem exists because of
the intimate juxtaposition of maternal and
fetally derived tissue, which is at least partially
foreign (semiallogeneic) to the mother.
 nature of the maternofetal immunological
relationship:
 the anatomy of the maternofetal interface;
 control of trophoblast growth;
 antigen expression by trophoblast; and
 immunology of the endometrium and decidua.
Anatomy of the maternofetal
interface
Antigen expression by
trophoblast

 HLA-G
 Erythrocyte antigenic systems
 Placental alkaline phosphatase
 Complement regulatory proteins on
trophoblast
 Antigens shared by trophoblast
Immunology of the endometrium and
decidua

No expression

HLA-C, HLA-G, HLA-E

HLA-C, HLA-G, HLA-E

 NK cells in
pregnancy

Tillery KM et al. Immunology of Normal Pregnancy. Seminars in Fetal & Neonatal Medicine (2006) 11, 279-295
J. Exp. Med.The Rockefeller University Press • 0022-1007/2004/10/951/5 $8.00 Volume 200, Number 8, October 18, 2004
951–955 http://www.jem.org/cgi/doi/10.1084/jem.20041783
How does the fetus survive?
Maternal-fetal Maternal immune

Fetus (Semi-allogeneic)
interface system
Ts
CD95L – induce T
Th2
cell apoptosis

Th
IDO – inhibition of T
TR
cell proliferation
NK

HLA-G – inhibition
of NK cell
B

HORMONAL CHANGES ? Aluvihare VR., et al. J Mol Med. 2005;83:88

Thank You