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AA&P Module 5 exam 2
Immunologic and skin changes in pregnancy
36
Biology
Graduate
03/18/2013

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Term
Normal WBC count for non-pregnant woman
Definition
5-10K
Term
Normal WBC for pregnant woman
Definition
5-15K
Term
How do WBC's change in L&D and PP
Definition
L&D- increases up to 25-30K
PP- gradually returns to normal values by 4-7 days
Term
Which hormone probably causes the changes in the white blood cell count?
Definition
Estrogen
Term
What are the major changes in the the inflammatory response?
Definition
The maternal circulation is seeded w/ small particles from the trophoblast. These cell clusters function as antigens of fetal origin and stimulate a systemic inflammatory response. The point of direct maternal contact with the placenta is the junction with maternal endothelial cells in the uterine spiral arteries. This contact activates endothelial cells and initiates and inflammatory response.
Term
What are the major changes in the innate immune response?
Definition
Chemotaxis is decreased, which may delay initial maternal responses to infection.
Monocyte and granulocyte activity is enhanced, with faster and efficient phagocytosis. This helps protect mom so she does not mount a cell-mediated immune response to trophoblastic & fetal cells.
Systemic Natural killer (NK) cell activity is down-regulated d/t progesterone that forms a blocking factor to decrease lymphocyte proliferation & NK activity.
PMNs attachment, ingestion, & digestion of Candida albicans are increased d/t hCG. Even so, pg. women have higher rates of fungal infections d/t estrogen increased nutrient availability in the reproductive tract.
Term
What are the major changes in the complement system?
Definition
Overall activation of the complement system, but early immune response is actually delayed.
Does not result in fetus rejection despite activation.
Alterations begin @ 11 wks w/ an increase in serum complement and specific proteins.
Term
What are the major changes in the adaptive immunity?
Definition
Progesterone stimulates production of Th2 cytokines and decreases TH1.
This has a protective role in the maternal-fetal immune relationship.
If Th1 stays predominate, then inflammatory cytokine production increases, leading to spontaneous abortion, preeclampsia, preterm labor, and fetal growth restriction
Term
What are the major changes in cell-mediated immunity?
Definition
Somewhat depressed during pregnancy
Progesterone lessens the # of TH1 cytokines which may decrease maternal resistance to bacteria & viruses.
Because T-helper cells augment cytotoxic responses, decreased numbers help protect fetus from rejection by mom.
Corticosteroids suppress activation of T-cell lymphokines, phagocytic activity, & lymphokine responsiveness of macrophages.
AFP induces production of regulatory T lymphocytes.
PG, hPL, & AFP suppress immune system during pregnancy.
Term
What are the major changes in humoral immunity?
Definition
IgG: levels fall as gestation progresses, with decreases from 30-40% after 28 weeks. This relative decrease in Igg, along with alterations in the WBC population, may increase risk for strept.
IgA: decreases or remains stable.Slight decrease in serum may reflect increased levels found in saliva & other mucosal fluids.
IgM: decreases slightly or remains stable.
IgE: slight or no change.
IgD: increases to term. Role is unknown
Term
What is pregnancy zone protein (PZP)?
Definition
A glycoprotein that has an inhibitory effect on the inflammatory process.
Term
What does PZP do in pregnancy?
Definition
It inhibits phagocytosis and suppresses inflammatory responses and IL-2 function near the decidua-trophoblast interface.
Term
Why do maternal serum IgG levels decrease during pregnancy?
Definition
hemodilution of pregnancy
Enhanced loss of IgG in urine
Transfer of maternal IgG to fetus in last trimester.
Term
What are the functions of maternal antibody (IgG) in the fetus/neonate?
Definition
Passive immunity against pathogens
Epigenetic inheritance of immunologic memory
Immunological imprinting
Suppression of IgE responsiveness
Suppression of tumor development
Term
List the factors that are thought to help the mother's immune system accept the conceptus.
Definition
Exposure to paternal antigens on sperm and seminal fluid before preg may lead to decreased responsiveness.
Trophoblast HLA-G
Progesterone & progesterone induced-blocking factor which stimulates B cell production of asymmetric antibodies that cannot initiate complement or phagocytosis, but can combine with antigen. The result of this combination is an antigen-antibody complex that is univalent and functions as a “blocking antibody” that prevents further antigen-antibody interaction.
Preg protein 13 that help hide trophoblastic antigens from maternal immune system.
Term
Explain the inflammatory process at implantation and during the third trimester.
Definition
Invasion of trophoblast and implantation yield strong inflammatory response.
Quiet anti-inflammatory state while fetus grows.
Strong inflammatory response to cause contractions and birth/rejection of placenta.
Term
Describe the role of HLA-G in the prevention of rejection of the conceptus.
Definition
The cytotrophoblast has a unique nonclassical surface antigen, HLA-G, which does not stimulate the classic cytotoxic T-cell response.
HLA-G has a Fas/Fas ligand pathway for killing activated T cells and may help prevent maternal rejection of the fetus by inducing apoptosis of activated maternal t cells.
HLA-G inhibits NK cell cytotoxicity and dendritic cell maturation.
Term
What are the consequences of decreased expression of HLA-G and sHLA-G on the trophoblast?
Definition
HLA-G= altered conversion of spiral arteries leading to recurrent abortion and preeclampsia.
sHLA-G= placental abruption, miscarriage, and preeclampsia.
Term
Differentiate systemic Natural Killer Cells (NK) and decidual NK. Which one is critical for pregnancy maintenance?
Definition
Systemic NK cells are highly cytotoxic.
Decidual NK cells produce cytokines that are beneficial for trophoblastic invasion and are critical for pregnancy maintenance.
Term
Failure of Th2 responses to increase or for Th1 responses to decrease will cause an
Definition
increased risk for spontaneous abortion
Term
How does progesterone act to protect against pre-term birth?
Definition
Progesterone may up-regulate TLR-4 and suppress TLR-2 to protect against preterm labor.
Term
Toll-like receptors (TLR)
Definition
Molecules on phagocytes and other cells that recognize the patterns of microbial products and generate signals to activate an innate immune response.
TLRs are expressed in the placenta and help the trophoblast to recognize microorganisms.
Term
Hofbaurer cells
Definition
Macrophage that is the primary placental defense.
Screens organisims as they try to pass from maternal blood flow to fetal.
Term
List the immunologic properties of human milk.
Definition
Leukocytes (monocytic macrophages and lymphocytes) transport immunoglobulins and protect against necrotizing enterocolitis, Staph areus, E coli, and candida albicans.
High B & T cell concentrations which produce IgG, IgA,& IgM as well as protect against gram neg. organisims.
Term
Which of the immunoglobulins is most abundant in breast milk?
Definition
Secretory IgA (secretory protects from digestion in babys GI tract)
Term
What is lysozyme and what does it do?
Definition
Lysozyme is a bactericidal enzyme that lyses the cell walls of many bacteria and enhances Lactobacillus growth.
Levels of lysozyme in human milk are several hundred times higher than in cow’s milk.
Lysozyme also acts with other substances to destroy E. coli and some strains of Salmonella.
Term
List the immunologic factors that may cause spontaneous abortion.
Definition
•Immune response to infection: chlamydia, listeriosis, parvovirus B10, toxoplasmosis
•Exaggerated maternal response to trophoblastic invasion: predominance of Th1, instead of Th2
•Cytokine-induced failure of ovary to produce enough progesterone
•Presence of autoimmune antibodies such as antiphospholipid antibodies that interfere with implant
•Decreased expression of HLA-G on extravillous trophoblast
•Decreased sHLA-G (maternal)
•Decreased Treg cells in decidua
•Increased peripheral T-cell activation
Term
List the alterations in the immune system that will increase the risks for viral, bacterial, and fungal infections in pregnant women.
Definition
•Suppression of maternal Th1 cell-mediated immunity
•Genetic polymorphisms in genes that encode modulators of innate mucosal immunity (IL-6 & 8, & TNF-a) may alter vaginal microflora
•Alterations in neutrophil chemotaxis & function
•Urinary statis d/t anatomic alterations of pg
•Greater reduction in TCD4 cells
•Increased adherence of Candida to vaginal mucous membrans
•Increased glycogen in vagina
•Enhanced proliferation of Candida d/t estrogen
•Alterations in cell-mediated immunity
Term
Describe how infection and inflammation can cause pre-term labor.
Definition
Mechanisms such as intrauterine infection, utero-placental ischemia or hemorrhage, uterine overdistention, cervical disease, stress, endocrine disorders all lead to inflammation. Inflammation can trigger the onset of labor.
Both acute & chronic infections are associated with preterm labor.
Intrauterine infection leads to activation of the innate immune system. inflammatory chemokines and cytokines increase PG production and release of matrix metalloproteases that lead to cervical ripening, fetal membrane, rupture, and increased myometrial contractility.
UTIs have also been associated w/ preterm labor. Fever can lead to dehydration which increases uterine activity & may result in labor initiation.
Acute infections w/ hi temps may lead to release of catecholamines and corticotropin-releasing hormone & increases uterine irritability.
Term
List the factors that demonstrate that preeclampsia is caused by immunologic events.
Definition
•Increased incidence of the disorder in primigravidas
•In multiparas, a pg w/ a new partner or different sperm donor
•Increase in pregnancies w/ a large placental mass or hydatidiform mole
•Decreased incidence in repeat pregnancies
•Decrease w/ longer cohabitation w/ the father before pg (and thus exposure to paternal antigens in semen)
•Presence of pathologic changes in the uterine vessels near the placental site that are similar to those w/ allograft rejection
Term
List the specific alterations in the immune system that have been observed in women with pre-eclampsia
Definition
•Reduction of NK cell activity w/ increased peripheral & decreased decidual NK cells
•Altered macrophage activation
•More Tcytotoxic cells
•More antibody-antigen complexes
•Increased levels of fibronectin
•Decreased IDO activity
•Alterations in complement
•Th1 predominates instead of Th2 like usual in pg
•Increased levels of inflammatory cytokines (TNF-a, IL-2, 6, & 8)
•Increased expression of TLRs by interstitial trophoblast or alterations in TLR signal transduction
•Abnormal cytokine levels
•Decreased placental HLA-G & sHLA-G expression
All of the above lead to vascular endothelial injury, which is the primary underlying mechanism.
Term
Discuss PP13 and preeclampsia
Definition
placental protein (PP13) will divert the mother's immune system so that the fetus is accepted and grows. PP13 comes from the placenta where the father's gene expression dominates. The placenta is responsible for keeping the fetus alive and when it senses a decrease in blood flow to the placenta, it will cause the B/P of the mother to go up in an effort to save the fetus. This is part of what we see in pre-eclampsia. When there is not enough PP13 to divert the immune system of the mother, then there is an incomplete dilation of the uterine arteries. This will decrease blood flow to the fetus and result in increased blood pressure for mother.
Term
Why do women with rheumatoid arthritis experience improvement in symptoms during pregnancy?
Definition
RA is associated with increased Th1 mediators and Th1 is decreased in pregnancy. Followed by a relapse within the first 3 months postpartum.
Changes in plasma levels of maternal humoral factors
Depression of cell-mediated immunity
Suppression of inflammatory reactions
Term
Can Graves Disease or Myasthenia Gravis be transmitted to the fetus? Explain.
Definition
Maternal Graves’ disease may involve transplacental passage of a thyroid-stimulating immunoglobulin resulting in transient neonatal hyperthyroidism in 1% of offspring that can persist up to 2-6 months.
Myasthenia gravis is associated w/ passage of maternal IgG a/ acetylcholine receptors, resulting in transient myasthenia gravis in 10-20% of offspinrg. Symptoms can last form a few hours to up to 3 months.
Term
Rh incompatibility
Definition
The Rh system involves a group of at least 45 RBC surface antigens controlled by Rh proteins. D antigens are the ones usually involved in incompatibility between mom and baby.

You know how this works....
Term
ABO incompatibility
Definition
3x more likely than RH incompat. is less severe.
Previous exposure and immunizations are not necessary b/c mom already has naturally occuring antibodies against fetal RBC antigens.
Most common is O mom/A baby, next is O mom/B baby. may happen with AB baby but NEVER with O baby.
This is a mild d/o compared to Rh incomp b/c the antibodies of the ABO system are primarily IgM, which does nto cross the pacenta.
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