TISSUE

BE REJECTED
 NO REJECTION
B
A
B
Y

CAN DEVELOP
 MOTHER RHESUS - BABY RHESUS +
B
A
B
MOTHER ANTI RHESUS Y

BE REJECTED

SEMINAL PLASMA
ANTIBODY
 THE UTERUS AS THE SITE
FOR IMMUNE REACTIVITY
• IMMUNE RESPONSE ARE OPERATIVE IN THE REPRODUCTIVE
AREA.
• PLACEMENT OF EXPERIMENTAL ALLOGRAFT IN THE UTERUS
RESULTING IN THE REJECTION
• FOLLOWING INTERCOURSE  SPERMATOZOA  NOT
RECOGNIZED AS A FOREIGN ?
• IT IS POSSIBLE THAT IN THE SEMINAL PLASMA  HIGH
MOLECULAR WEIGHT COMPONENT  ACT AS
IMMUNOSUPRESSANT
 MUCOSAL IMMUNITY
Immuoglobulin A cotaining plasma cell in the lamina
propria.(Fallopian tube, endometrium, endoservix and
vagina)

Langerhans’ cell, dendritic cell, CD4 and CD8 T

lymphocytes, and plasma cells in fallopian tube, servix,
vagina and vulva.
The greatest number of Intraepithelial lymphocyte
(predominantly CD8) and subepithelial lymphocytes
(predominantly CD4) in the servical transitional zone.
IgG is serum-derived immunoglobulin and
IgA (anti viral) is locally produced
Serum IgG

UTERUS VAGINA

LOCAL PLASMA CELL

SECRETORY IgA

SERVIX/VAGINA
Superficial submucosal of the female genetal tract
(Macrophage, Langerhans’ cell, dendritic cell and T cell)

PATHOGEN SPERM
INVASION “INVASION”

IMMUNOLOGICAL IMMUNOLOGICAL
RESPON TOLERANCE

???
 Immunotolerance to sperm?
• Sperm factors?
The presence of immunosupressor in the ejaculate fluid.
• mucosal immunity of the servix and vagina is
tolerant to sperm antigens .
Antisperm antibody was found in 75% of men with oral
sex, only 1-12% of women with normal sex.
• Factor of partner?
Women with less sperm antigen exposure more
predisposed to develop preeclampsia.
Recurrent pregnancy loss with different partner
 OVULATION
• Residence macrophages are a mayor
component of interstitial compartement
of ovarium.
• Influx of leucocytes around the time of
ovulation.
• Numerous macrophage are observed in
the corpus luteum after follicle ruptur.
 OVULATION
In vitro study :
• TNFα inhibit secretion of steroid hormon by
ovarium granulosa cells.
• Interleukin 1β is cytotoxic to ovarium cells
dispersated.
Ovulation is inflammatory like reaction
with IL- 1β as its centerpieces.
Progestron
 IMPLANTATION
• At the time of implantation, decidua contains
numerous leucocytes, including macrophages
and T cells.
• The majority of T cells are γδT cells , which are
less capable than αβT cells
• The role of γδT cells in maintaining or
supporting pregnancy is not clear.
 T CELL DEVELOPMENTAL STAGES

BM Cortex of Thymus Medulla of Thmus Periphery

α ß α ß

TCR
α ß CD4+CD8-TCRαß Helper T cell
Pos/neg α ß α ß
selection
CD4 CD8
CD4-CD8+TCRαß CTL
γ δ γ δ γ δ

CD4-CD8-TCRγδ ? function
 IMPLANTATION CYTOKINES
• EGF stimulates blastocytes development (Blastocytes
express EGF receptor)
• Colony stimulating factor family (GM-CSF, CSF-1,IL-3)
and c-fms receptor for CSF-1 have been identified in
decidua and placenta.
• Leukemia inhibitory factor (LIF) is needed for
endometrial implantation of blastocyte
• IL-1β inhibits blastocytes attachment but enhances
trophoblast outgrowth.
• IFNγ inhibits trophoblast outgrowth and cause
degenerative change of trophoblast
 PLACENTA
• Trophoblast produces protrein and steroid hormon.
• Acts as lung, kidney, liver and intestine of the foetus.
• Syncytiotrophoblast as barrier for foetus from
maternal immune effector mechanisms,
• Trophoblast produces Cytokines which are also
produced by mononuclear phagocytes. (CSF-1 dan
reseptornya c-fms, IL-3, GM-CSF, IL-10)
 PLACENTA
• Trophoblast express high level of LIF
receptors.
• Trophoblast has ability to phagocytosis
(syncytialization).
• Trophoblast is responsive to TNFα, IL-1, TGFβ
dan IL-6 by producing IL-10.
 THE PLACENTA AS AN IMMUNE
ORGAN
• Trophoblast express high level of LIF
receptors.
• Trophoblast has ability to phagocytosis
(syncytialization).
• Trophoblast is responsive to TNFα, IL-1, TGFβ
dan IL-6 by producing IL-10.
 THE PLACENTA AS AN IMMUNE ORGAN
• Trophoblast express HLA G (No expression of
Class I and Class II HLA)
• HLA G can interact with CD8.
• HLA G is associated with β microglobulin and
has only a limited number of polymorphisms
in contrast with classic HLA I and II.
• HLA G Inhibits activation of of NK cells, Thus,
it may play a key role as a survival factor
during early pregnancy
 Immunity in pregnany:
• Intracellular bacteria, virus, fungi, protozoa and
helminths have greater virulence during
pregnancy,(weakness in CMI )
• Pregnant women are much more likely to suffer
more serious diseases compare with nonpregnant
women. (Poliomyelitis, Viral hepatitis , Influenza,
malaria, tbc, leprosy.)
• Decrease function of CMI maybe an immunologic
tolerance against foetus
• There is no change in humoral immunity during
pregnancy
Pregnant mice infected with Listeria monocytogens

CMI eliminated this Maternal-fetal interface

intracellular parasit, of placenta
effectively..

Maternal decisua shows Fetal spongiotrophoblast show

numerous number of the present of listeria but no
inflamatory cells. inflamatory cells :
 PLACENTAL STEROID HORMON

• The placenta secretes high level of estrogens

and progesterone.
• Steroid hormones inhibit CMI
• Hydrocortisone inhibis IL-2 production and
enhances IL-4 production.,
• Activated T cells, in the presence DHEA
(dehydro- epiandrosterone) in physiologic
concentration will produce greater
concentarions of IL-2.
 PLACENTAL STEROID HORMONE

• Glucocorticoids inhibit production of cytokines

(Antiinflammation effect)
• Circulating glucocorticoid concentrations
increase during pregnancy .This alterations
may be one mechanism in which systemic
immunity is regulated during pregnancy.
 PLACENTAL PROTEIN
• HCG is produced by trophoblast, increases
during th 1st trimester and decreases through
the remainder of pregnancy.
• AFP (alpha-fetoprotein) is secreted by the
fetal liver into fetal serum and amnion fluid in
high level during the 2nd trimester and then
plateaus.
• Physiologic levels of AFP can depress
proliferative T cell responses.
 Decrease Lymphocytes Reactivity in
Pregnancy.
• Depressed CMI during pregnancy is
indisputable, opinion differs regarding in
change T cell number, distribution and
reactivity during gestation.
• CD4 T cells decrease but CD8 T cells increase
in number
• Cytotoxic activities of NK cells is said to be
defective.
 Decrease Lymphocytes Reactivity in
Pregnancy
• Tymic incolution has been observed in rodents
during the latter half of gestation
• No consistent or significant changes in
humoral immunity during pregnancy
 Survival of normal pregnancy
• To establish normal pregnancy, Th2 type
reponse s must be induced by maternal
immune system in materna-foetus interface.
• Th2 will induced maternal antibody
production and not in destructive CMI that
could damage trophoblast.
• Antibody will promote trophoblast
implantation and endometrial remodeling.i
 Survival of normal pregnancy
• Adaptive Immune repons during pregnancy
are permissive rather the critical.
• Pregnancy is characterized by marked change
in immunoregulation with enhanced innate
immunity and supressed adaptive immunity.
(Pregnancy is not an immunosupressive
condition)
 INFERTILITY
• Antisperm antibody (IgG in blood and
lymphatic fluid, IgiA in vaginal secretion)
(problrm for infertility but solution for family
planning)
• Antisperm antibody are found in 1-12%
fertile women and in 10-20% of women with
unexplained infertility.
• In the male, Antisperm antibody are found in
seminal plasma and blood of men
undergoingvasectomy.
 NATURAL IMMUNITY TO
SPERMATOZOA
• Sera obtained from normal fertile
animalrabbit,mouse and human  contain
antibodies  reacts to sperm of their own
species
• Spermatozoa recovered from reproductive
tract of female rabbit have immunoglobulins
on the head region.
• Vigorously moving sperm did not have
immunoglobulins
Immotile sperm  immunoglobulins positif
 Etiolgy of autoimmunity to
spermatozoa
• The expressions of antigens on sperm
central consideration of their
immungenicity auto or alloimmunity
• Development of autoimmunity:
1.Genital tract infection
2.Trauma to the testis  granuloma in
the testis.
 RECURRENT SPONTANEOUS ABORTION
• The cause of abortion can be found in majority
cases (60%)
• Fie couple with unexplained cause of recurrent
abortion, 60% will eventually carry a pregnancy
succesfully without specific therapoitic
intervention,
• If 1st abortion occcured in 1st trimester and 2nd
abortion in 2nd trimester, it is maybe immunologic
cause
• Antiphospholipid syndrome (Prolonged bleeding
time, recurrent pregnancy loss).
IMMUNE THERAPIES FOR INFERTILITY
• Condom therapy for the presence of
antisperm antibody
• Intrauterine insemination
• Corticosteroid therapy
• In vitro fertilzation..
• Gamet intrafalopian transfer.
 IMMUNOTHERAPY
• One half of women with recurrent abortus
without gynaecological abnormality may be
due to immunologic needs immunotherapy.
• HLA homozygocity (sharing between partner)
cause decreasing production of maternal
blocking antibody.which may appear in all
succesful pregnancies,
 WAS DONE FIRST BY
PROF.PANCOAST
DI PHILADELPIA 1884
ARTIFICIAL INSEMINATION
IN VITRO FERTILIZATION
(IVF)
 ???

LUPUS ANTICOAGULANT ANTICARDIOPILIN ANTIBODY

Interact with thrombogenic adhesion

molecules on endothelium
(negatively charged phospholipid)
Prolonged bleeding time
(Prolonged of phopholpid Maternal thrombosis and
dependent in vitro placental infarction
coagulation test)

ABORTION

ANTIPHOSPHOLIPID SYNDOMES
 INTRAUTERINE INFECTION
• Bactrial vaginosis (anaerobic bacteria and group B
streptococcus).
• Proinflamatory cytokines (IL-1β, TNFα,IL-6 an IL-8)
dapat diproduksi oleh gestational tissue sebaai respon
terhadap infeksi bakteri.
• Proinfmatory cytokine ditemukan dalam cairan amnion
ibu yg terinfeksi bakteri.
• Preterm labor reflect an intrauterine inflammatory
syndrome.
• Maternal and fetal inflammatory respons uterotonic
production (arachidonic metabolic).
 PATHOGNSIS ECLAMPSIA
????

ENDOTHELIAL ACTIVATION, DYSFUNCTION AND DAMAGE

LOST OF ENDOTHLIAL CELL INTEGRITY

TRANSUDATION GLOMERULAR DAMAGE

VASOSPASME

EDEMA HYPERTENSION PROTEINURIE

 Postulated PATHOGENESIS OF ECLAMPSIA

• Poor trophoblast invasion.

- Na rrowing of placental blood vessels,
- Inflammation(atherosclerosis ?).
• Immunological cause
- 1st pregnancy.
- Immunological tolerance against seminal
antigens (Low risk for multiparitas ).
- Th1 respon environment (IL-12 ). CMI