M1: Immunology of Pregnancy Flashcards
Maternal blood spurts from __________ into the placental _________ and bathes the outer _________. Allow exchange of gases, nutrients and other substances with fetal capillary blood within the villous core.
Uteroplacental vessels. Intervillous space. Syncitiotrophoblast.
Fetus is dependent on the ________ for pulmonary, hepatic and renal functions. Accomplished through unique anatomical relationship of the placenta and its uterine interface.
Placenta
Fetal & maternal blood are not mixed in the
Hemochorial placenta
There is a ______ system that links mother and fetus.
Paracrine
________ of the maternal decidua parietalis and the extraembryonic chorion laeve.
Juxtaposition
Plays a critical part at the maternal-fetal interface. Invasiveness for implantation, nutritional for conceptus & endocrine function for maternal physiological adaptations & pregnancy maintenance.
Trophoblast
Trophoblast: human placental formation begins with this which gives rise to a trophoblast cell layer encircling the blastocyst.
Trophectoderm
Trophoblast: trophectoderm appear at the _______ stage.
Morula
Trophoblast differentiation occurs when
8th day postfertilization
Trophoblast Differentiation: inner, mononucleated. Germinal cells from syncytium. Well demarcated cell border, single nucleus, undergoes DNA synthesis and mitosis.
Cytotrophoblast
Trophoblast Differentiation: outer, multinucleated. Has amorphous cytoplasm without cell borders, nuclei that are multiple and diverse in size & shape, and a continuous syncytial lining.
Syncitiotrophoblast
Trophoblast Differentiation: After implantation is complete, trophoblast further differentiate into two main pathways.
Extravillous & Villous trophoblasts
Trophoblast Differentiation: transports O2, nutrients and other compounds between the fetus and the mother.
Chorionic villi
Trophoblast Differentiation: gives rise to chorionic villi
Villous trophoblast
Trophoblast Differentiation: migrates into decidua and myometrium. Penetrates maternal vasculature, thus coming into contact with various maternal cell types. Further classified as ________ & _________.
Extravillous Trophoblast. Interstitial T. & Endovascular T.
Trophoblast Differentiation: Penetrates spiral artery lumen. Creates low resistance blood flow.
Endovascular trophoblast
Trophoblast Differentiation: invade the decidua and eventually penetrate the myometrium to form placental bed giant cells. Surrounds spiral arteries (do not invade)
Interstitial trophoblast
Early Trophoblast Invasion: Day wherein blastocyst become totally encased within the endometrium.
Day 10
Early Trophoblast Invasion: At ____ of development, the blastocyst wall facing the uterine lumen is a single layer of flattened cells. The opposite, thicker wall with two zones. _________ & the embryo-forming _________.
9 days. Trophoblast. Inner cell mass.
Early Trophoblast Invasion: As early as _______ postfertilization, the inner cell mass or _______ is differentiated into a thick plate of ________ and an underlying ________.
7 1/2 days. Embryonic disc. Primitive ectoderm. Endoderm.
Early Trophoblast Invasion: ________ appear between the embryonic disc and trophoblast and enclose a space that will become the _________.
Small cells. Amniotic cavity.
Early Trophoblast Invasion: _________ first appears as isolated cells within the blastocyst cavity.
Embryonic mesenchyme
Early Trophoblast Invasion: When the blastocyst cavity is completely lined with mesoderm, it is called _________. And its membrane is called _________ which is composed of mesenchyme & trophoblast.
Chorionic vesicle. Chorion.
Early Trophoblast Invasion: Some mesenchymal cells will condense to form the ________ which joins the embryo to the nutrient chorion and later develops into the _________.
Body stalk. Umbilical cord.
Early Trophoblast Invasion: ____ day. The syncitiotrophoblast is invaded by a system of intercommunicating channels called ________ which becomes filled with maternal blood.
12th day. Trophoblastic Lacunae.
Chorionic Villi: ______ 12th days postfertilization, extravillous cytotrophoblasts gives rise to __________ composed of cytotrophoblast core covered by __________.
Before. Solid primary villi. Syncitiotrophoblast.
Chorionic Villi: As the lacunae join, a complicated _______ is formed that is partitioned by solid cytotrophoblastic columns.
Labyrinth
Chorionic Villi: The trophoblast lined labyrinthine channels form the _________ and the solid cellular columns form the _________.
Intervillous space. Primary villous stalks.
Chorionic Villi: 12th day postfertilization, _______ is formed, invasion of _______ derived from extraembryonic mesoderm into the solid trophoblast column.
Secondary villi. Mesenchymal cords.
Chorionic Villi: ________ begins on the mesenchymal cords. ______ are formed.
Angiogenesis. Tertiary villi.
Chorionic Villi: Day wherein maternal arterial blood enter the intervillous space.
15th day
Chorionic Villi: Day wherein fetal blood vessels are functional.,placental circulation is established.
17th day
Chorionic Villi:Fetal placental circulation is completed when the __________ of the embryo connected with _________.
Blood vessels. Chorionic vessels.
Chorionic Villi: In some villi, angiogenesis fails from __________. It can be seen normally but exaggeration of the process is seen with __________.
Lack of circulation. Hydatidiform mole.
Chorionic Villi: Villi are covered by outer layer of _______ and inner layer of ______, which are also known as ________.
Syncytium. Cytotrophoblast. Langhans cells.
Chorionic Villi: Cytotrophoblast proliferation at the villous tips produces the trophoblastic cell columns that form _________ not invaded by fetal mesenchyme, anchored to the decidua at the basal plate.
Anchoring villi
Chorionic Villi: ________ consists of two layers of trophoblasts externally and fibrous mesoderm internally.
Chorionic plate
Chorionic Villi: The __________ is formed by 8-10 weeks as the amnionic and the primary chorionic plate mesenchyme fuse together.
Definitive chorionic plate
Chorionic Villi: _______ is formed by the fusion of connective stalk @ allantois.
Umbilical cord
Hemochrial placenta: _______ act to increase surface area in direct contact with maternal blood. Associated pinocytic vacuoles and vesicles are r/t absorptive and secretory placental functions.
Microvilli
Hemochrial placenta: more prominent during the first trimester of pregnancy; consists of inner layer of cytotrophoblastsn and associated basal lamina covered by syncytiotrophoblast.
Hemodichorial
Hemochrial placenta: later in pregnancy; inner layer of cytotrophoblasts are no longer continuous, only scattered cells are present; aids in nutrient and oxygen transport of the fetus.
Hemomonochorial
Chorion & Decidua Devt: chorionic villi in contact with the decidua basalis; fetal component of the placenta.
Chorion frondosum (leafy chorion)
Chorion & Decidua Devt: avascular fetal membrane; abuts the decidua parietalis. Until the near end of the third month, this is separated from the amnion by the exocoelomic cavity to form an avascular ________.
Chorion laeve (smooth chorion)
Chorion & Decidua Devt: is more translucent that amnion and rearely exceeds 1mm thickness. Both are important sites of molecular transfer and metabolic activity.
Chorion laevae
Maternal Regulation of TI & VG: During the first half of pregnancy, ___________ accumulate in the decidua and are found in direct contact with trophoblast.
Decidual Natural Killer Cells (dNK)
Maternal Regulation of TI & VG: dNK cells lack ___________ and are able to dampen inflammatory ______ cells.
Cytotoxic functions. T(H)17.
Maternal Regulation of TI & VG: Together with _________, prevent NK cells from recognizing and destroying fetal cells as foreign.
Decidual macrophages
Maternal Regulation of TI & VG: also have the ability to attract and promote trophoblast invasion into the decidua (IL-8 & interferon-inducible protein 10) and promote vascular growth (proangiogenic factors such as VEGF & PIGF)
dNK cells
Trophoblast invasion of the Endometrium: _________ of the first trimester of pregnancy are highly invasive & extends from the endometrium to the inner third of the myometrium. This process occurs under _________ conditions.
Extravillous trophoblast. Low oxygen.
Trophoblast invasion of the Endometrium: Invasive trophoblasts secrete _________ that digests ECM and activate ________ already present in the endometrium.
Proteolytic enzymes. Proteinases.
Trophoblast invasion of the Endometrium: Trophoblast also secrete ___________ which converts plasminogen to plasmin which degrades matrix proteins and activates matrix metalloproteases.
Urokinase Type Plasminogen Activator
Trophoblast invasion of the Endometrium: critical for human trophoblast invasion
MMP-9
Trophoblast invasion of the Endometrium: the degree of trophoblast invasion is controlled by ______________ and by factors that cause trophoblast migration.
Matrix degradation regulation
Trophoblast invasion of the Endometrium: Trophoblast secrete _______ which acts in an autocrine manner, promotes invasion into endometrium.
IGF 2
Trophoblast invasion of the Endometrium: secreten insulin like growth factor binding protein type 4 which blocks autocrine loop.
Decidual cells
Trophoblast invasion of the Endometrium: Low ______ levels are critical for trophoblast invasion and remodeling of the spiral arteries.
Estradiol
Trophoblast invasion of the Endometrium: As the pregnancy advances, increasing estradiol levels repress & control the extent of uterine vessel transformation via _______ & ________ expression.
VEGF. Integrin Receptor.
Invasion of Spiral Arteries: extensive modification of vasculature by
Trophoblast
Occur in the first half of pregnancy, important in uteroplacental blood flow. Also integral in some pathological conditions such as preeclampsia,fetal growth restriction & preterm birth.
Invasion of Spiral Arteries
Invasion of Spiral Arteries: two extravillous trophoblasts
Imterstitial & Endovascular
Invasion of Spiral Arteries: Uteroplacental vessel devt proceeds in ____ waves or stages.
Two
Invasion of Spiral Arteries: 1. Occurs _________ postfertilization. Invasion & modification of spiral arteries up to the border between the decidua & myometrium.
Before 12 weeks
Invasion of Spiral Arteries: 2. Between ___________. Invasion of the intramyometrial segments of spiral arteries.
12 & 16 weeks
Invasion of Spiral Arteries: narrow lumen, muscular spiral arteries, dilated, low resistance uteroplacental vessels.
Remodelling
Invasion of Spiral Arteries: In ________, trophoblast invasion is incomplete resulting to narrower and less distensible blood vessels.
Preeclampsia
Approximately ________ after conception, maternal blood enters the intervillous space in fountain-like bursts from the spiral arteries.
One month
Placental Growth: PG is more rapid than that of the fetus
First trimester
Placental Growth: _____ postmenstrual weeks. Placental & fetal weights are approximately equal.
17
Placental Growth: Term. Placental weight is approximately _____ of fetal weight.
1/6
Placental Growth: Lobes, slightly elevated convex areas; c
Varies fro 10-38, incompletely separated by grooves that overlie the __________.
Placental septa
Placental Growth: functional units of the placenta
Lobule or Cotyledons
Placental Maturation: As the villi continue to branch and the terminal ramifications become more numerous and smaller, the volume and prominence of cytotrophoblasts _____.
Decrease
Placental Maturation: As the _________ thins, the fetal vessels become more prominent and lie closer to the surface.
Syncytium
Placental Maturation: In early pregnancy, the branching connective-tissue cells are separated by an abundant loose intercellular matrix. Later the _________ becomes denser and the cells are more spindly @ more closely packed.
Villous stroma
Placental Maturation: Stromal infiltration of ________ (fetal macrophages) phagocytic, immunosuppressive, cytokine production, paracrine regulation of trophoblast functions.
Hofbauer cells
Fetal Circulation: Deoxygenated venous-like fetal blood flows to the placenta through ___________.
Two umbilical arteries
Fetal Circulation: Blood with significantly higher oxygen content returns from the placenta via a single _________ to the fetus. AVA.
Umbilical vein
Fetal Circulation: branches of umbilical vessels that traverse along the fetal surface of the placenta in the chorionic plate, responsive to vasoactive substances.
Placental surface or chorionic vessels
Fetal Circulation: chorionic arteries always _________ chorionic veins.
Cross over
Fetal Circulation: ____% of the placenta. Chorionic arteries form a fine network of supplying the ________.
- Cotyledons.
Fetal Circulation: ____% of the placenta. The arteries radiate to the edge without narrowing.
35
Fetal Circulation: perforating branches of surface arteries that pass through the chorionic plate.
Truncal arteries
Fetal Circulation: Each trunchal artery supplies one main stem ______ & thus one ______.
Villus. Cotyledon.
Maternal Circulation: Maternal blood enters through the _______ and is driven high up toward the ________ by arterial pressure before laterally dispersing.
Basal plate. Chorionic plate.
Maternal Circulation: After bathing the external microvillous surface of the chorionic villi, maternal blood drains back through the venous orifices in the basal plate and enters the __________.
Uterine veins
Maternal Circulation: Maternal blood traverses the placenta randomnly without _________.
Preformed channels
Maternal Circulation: Spiral arteries are ______ to but veins are ______ to the uterine wall. Aids in closure of veins during uterine contraction and prevents exit of maternal blood from the intervillous space.
Perpendicular. Parallel.
Maternal Circulation: There are about _____ spiral arterial entries into the intervillous space at term.
120
Maternal Circulation: After the _____ week, a prominent venous plexus separates the ________ from the myometrium and thus participates in providing a cleavage plane for placental separation.
30th. Decidua basalis
Immunological consideration: are the only fetal-derived cells in direct contact with maternal tissues.
Trophoblasts
Immunological consideration: act to control the invasion of trophoblast, which have adapted to survive immunologically hostile environment.
Maternal Natural Killer Cells
Immunological consideration: Model of trophoblast invasion & maternal vascular remodeling. Decidual NK cells work in concert with _________. They mediate angiogenesis through production of proangiogenic factors such as ______ and control trophoblast chemoattractiom toward spiral arteries by production of IL-8 & Interferon inducible protein 10.
Stromal cells. VEGF.
Immunogenecity of Trophoblast: is considered immunologically inert and therefore unable to create maternal immune response.
Placenta
Immunogenecity of Trophoblast: are absent from villous trophoblast, which appear to be immunologically inert at all gestational ages.
MHC Class I & II Antigens
Immunogenecity of Trophoblast: do express MHC Class I molecules.
Invasive Extravillous Trophoblasts
Immunogenecity of Trophoblast: Normal implantation depends on controlled ________ of the maternal EM-decidia and spiral arteries.
Trophoblastic invasion
Immunogenecity of Trophoblast: permit then limit trophoblast invasion
dNK cells + HLA class 1 genes
Are the products of multiple genetic loci of MHC located within the short arm of chromosome 6
HLA genes
Encode the major class I (class Ia) transplantation antigen.
HLA-A, HLA-B & HLA-C (classical genes)
Encode class Ib HLA antigens
HLA-E & HLA-G
Combine with unique expression of 3 specific HLA Class I genes im extravillous cytotrophoblast act in concert to permit and subsequently limit trophoblast invasion.
Uterine dNK cells
Originate in the bone marrow and belong to the natural killer cell lineage. Predominant population of leukocyte present in mid-luteal phase endometrium at the expected time of implementation. Has distinct phenotype characterized by a high surface density of ______ or neural cell adhesion molecule.
Uterine Natural Killer Cells. CD56.
uNKC: Filtration is increased by ________ and by stromal cells production of ______ and decidual _______.
Progesterone. IL-15. Prolactin.
uNKC: nuclei of the uNK cell begin to disintegrate near the end of ________ of nonfertile ovulatory cycles.
Luteal phase
uNKC: If implantation proceeds. It persists in large numbers in ________ during early pregnancy.
Decidua
uNKC: 1st trimester Decidua, many uNK cells in close proximity to __________ where they serve regulate trophoblast invasion.
Extravillous trophoblasts
uNKC: At term, ____ uNK cells in the deciduas.
Few
uNKC: uNK cells secrete large amounts of ____________ activated state. May function primarily to forestall trophoblast apoptosis and not to promote trophoblast replication.m
Granulocyte-Macrophage-Colony-Stimulating factor (GM-CSF)
uNKC: suggest a role in decidual vascular remodeling
Expression of angiogenic factors by uNK cells
uNKC: primary responsible for decidual immuno surveillance
uNK cells
Expressed only in humans specifically in cytotrophoblast. Has a high restricted tissue distribution. Identified only in extravillous cytotrophoblast in the decidua basalis and in the chorion laeve. During pregnancy, a soluble major isoform ________ is increased.
HLA-G expression in Trophoblasts. HLA-G2.
HLA-G: embryos used for in vitro fertilization do not implant if they do not express _________.
HLA-G Isoform
HLA-G: causes an abnormality in HLA-G expression
Pre eclampsia
At term it is a tough and tenacious but pliable membrane. It is an innermost avascular fetal membrane filled with amniotic fluid. Provides almost all tensile strength of the fetal membranes. It’s reliance to rupture.
Amnion
Is the relatively acellular zona spongiosa (contiguous with the second fetal membrane, chorion leave)
Outermost amnion layer
Lacks smooth muscle cells, nerves, lymphatics and importantly blood vessels.
Human amnion
Precursors of amnionic epithelium that line the inner surface of trophoblasts
Amniogenic cells
The amnion is first identifiable _______ day of embryo development. It is initially a minute vesicle.
7th or 8th
Becomes in contact with interior surface of the chorion leave.
Amniotic sac distention
_______ of chorion laeve and amnion cause an obliteration of extraembryonic coelem.
Apposition
Covers the placental surface
Placental amnion
Covers the umbilical cord
Umbilical amnion
Derivation fibroblast like mesenchymal cell layer
Embryonic mesoderm
Interstitial collagens are deposited between two cell layers (epithelial & mesenchymal cells) which marks the formation of ___________ which separates the two layers of amnion cells.
Amnion Compact Layer
At ________ amniotic sac expands to line the placenta and chorion frondosum, result to reduction and sparse distribution of mesenchymal cells.
10-14 weeks
Early in pregnancy, __________ replicates at a rate appreciably faster than mesenchymal cells.
Amniotic epithelium
At term, _________ are widely dispersed with the appearance of long slender fibrils.
Mesenchymal cells
The apical surface of replete with highly developed microvilli. Function as a major site of transfer between amnionic fluid and amnion.
Amnion Epithelial cells
Produce in the epithelia but functions in mesenchymal cells. It promotes synthesis of MMPs.
Fibronectin
Breaks down the strength-bearing collagens and increases PG synthesis to prompt uterine contractions and cervical ripening.
MMPs
Regulates the amnion tensile strength
Collagen 7
Major interstitial collagen in tissues characterized by great tensile strength
Collagen I
Contribute to tissue integrity and provides both tissue extensibility and tensile strength
Collagen III
Provide amnion extensibility
Elastin microfibrils
Regulates amnion tensile strength. Promote tissue strength.
Decorin
At term average amniotic fluid volume is
1000mL
What week does the amniotic fluid become a clear fluid that collects within the amniotic cavity increases as pregnancy progresses them decreases.
34 weeks
Umbilical cord develops in the
Yolk sac & umbilical vessels
Month in which the expanding amnion obliterates the exocoelom, fuses with the chorion laeve, and covers the bulging placental disc and the lateral surface of the body stalk, umbilical cord or funis.
Middle third of the month
Disappears early during fetal development leaving only the original left vein
Righ umbilical
Umbilical vesicle lined by a single layer of
Flattened or cuboidal epithelium
It is a glycoprotein with biological activity similar to LH.
HCG
In what week does hCG expressed in both syncytiotrophoblast & cytotrophoblast
Before 5 weeks
Complete hCG secretion (maximum)
8-10weeks
Plasma levels decline at what weeks
10-12 weeks
Both GnRH and its receptor are expressed by
Cyto & Syncytio
Elevates circulating hCG levels
GnRH administration
Inhibits GnRH & hCG production
Inhibin
Stimulates GnRH & hCG production
Activin
Promote uterine vascular dilatation and myometrial smooth-muscle relaxation
hCG
Ectopic pregnancy & early pregnancy wastage
Low HCG
Multifetal pregnancy, erythroblastosis fetalis, gestational trophoblastic dse & levels of this are seen in midtrimester with fetus with down syndrome
High HCG
Has a potent lactogenic growth hormone like bioactivity and immunochemical resemblance to human growth hormone. Concentrated in syncytiotrophoblast. Detected in the 2nd or 3rd week after fertilization.
HPL
Promotes maternal lipolysis with increased circulating free fatty acid levels. Inhibits leptin secretion, favors protein synthesis and provides a readily available AA source of the fetus.
HPL
