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MLSCI 475 > Immunology of Pregnancy > Flashcards

Immunology of Pregnancy Flashcards

1
Q

T or F. Synctiotrophoblast is a single cell layer

A

T,
no cell borders so lymphocytes can’t get through = physical barrier?

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2
Q

Is the ST barrier effective against pathogens?

A

Supposedly, but TORCH
= associated with congenital anomalies
- toxoplasmosis
other = syphilis, varicella-zoster, parvovirus, B19, Zika
- Rubella
- CMV
- Herpes

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3
Q

first time infection of CMV transmission rate

A

40%

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4
Q

microchimerism

A
  • bi-directional trafficking of fetal and maternal cells
  • low levels (1 fetal cell per 1 mill maternal cells)
  • cells are detected decades after delivery and likely persist for a lifetime
  • highly conserved across species
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5
Q

maternal positive effects of microchimerism

A
  • existing Tregs may enhance fetal protection in the next pregnancy
  • pluripotent fetal microchimeric cells may differentiate into and replace diseased cells in maternal tissues (eg. islet cells)
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6
Q

where is IDO expressed?

A

normally in circulating monocytes, macrophages, and dendritic cells

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7
Q

IDO

A

intracellular heme containing enzyme
indoleamine dioxygenase

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8
Q

what does IDO do?

A
  • catalyzes first step in tryptophan catablism
  • suppresses T cell proliferation
  • increased by infection and inflammatory cytokines
  • constitutively expressed at maternal-fetal interface in pregnancy
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9
Q

function of the placenta

A
  • oxygen and nutrient exchange
  • removal of waste
  • barrier against maternal immune response and infections
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10
Q

routes of congenital infections

A

villous placental (through free villus)

extravillous placental

across the membranes

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11
Q

routes of transplacental infections

A

A: passive diffusion of HCMV through ST and TBM

B: IgG-bound HCMV transported through ST

C: infection via basal release from HCMV infected ST

D:infection via infected maternal monocytes migrating through damaged ST

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12
Q

offspring positive effects of microchimerism

A
  • protection against fetal wastage in next generation pregnancies under conditions that interrupt fetal tolerance mechanisms
  • may contribute to immune response maturity in fetus/nb
  • increased Tregs may dampen inflammation from microbial colonization = training neonatal immune response
    -reduced rejection of transplants
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13
Q

negative effects of microchimerism

A

autoimmunity
- the more # of male cells in women, the more likely for MS

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14
Q

protective physiology of placenta towards fetus

A
  • no killing by maternal T cells (no MHCI/II expression)
  • expression of non-classical MHC I (-G, -E, -C) and polymorphic HLA-C = no killing by maternal uterine or peripheral NK cells
  • ST expresses Fas ligand = kills maternal immune response that tries to attack placenta
    > IDO depletes tryptophan
    > inhibits T cell proliferation
    > decidual IL-10 and TGFB inhibit T cell responses
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15
Q

normal function of Tryptophan in T cell activation

A

released by APCs to proliferate T cells

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16
Q

normal feedback mechanism to reduce T cell activation by IDO

A

IFNy (from T cell) shuts down tryptophan by producing IDO in APC = pulls tryptophan from the environment into cell

IDO degrades tryptophan to reduce amount in the environment to shut down T cell response

17
Q

constitutive action of IDO in trophoblasts

A

Constitutive activity of IDO in trophoblasts = but no interaction

IDO pulls tryptophan in all the time = creates an environment where cells are prevented from proliferating = protection against activation

18
Q

Mellor/Munn experiment

A

found that using an IDO inhibitor (1-methyl-tryptophan) to block IDO-unduced tryptophan degradation matters if pregnancy is allogeneic (mom and dad different MHC)

if IDO blocked = no protection for fetus = unviable pregnancy

SO pregnancy turns off rejection in MHC-specific manner

19
Q

during pregnancy, these cells predominate in the decidua

A

Th2 cells
( lower number since ratio expressed as Th1/Th2)

20
Q

T or F. Pregnant mice fail to resist Leishmania major infections in a study

A

T, mor effective in clearing gut worms more efficiently

NOTE: reduced = NOT GONE; still have ability for CMI (cell-mediated immune response

21
Q

T or F. Type 1 response (CMI) is better in pregnant women for autoimmune disease states

A

T

22
Q

T or F. Pregnant women can deal better with intracellular pathogens (CMI/type 1 response)

A

F! poor response

23
Q

T or F. The higher the MHC matches among couples, the higher the chance of pregnancy loss

A

T
There needs to be some mismatching at the beginning of pregnancy to have higher chances of survival

24
Q

T or F. There is evidence of harmful adaptive immune responses against paternal MHC antigens

A

F! opposite is true

25
Q

25% of the T cells in th pregnant uterus are these

A

T reg cells (CD4+25+Foxp3+)
= maintains tolerance to the fetus

26
Q

beneficial effects of sperm/seminal plasma in pregnancy

A

less contact with partner’s seminal plasma (less sexual cohabitation, less use of oral contraceptives, younger women, more barrier methods, knew partners for less time = more likely to develop preeclampsia

27
Q

T or F. Women with greater and longer exposure to seminal plasma from same partner are at reduced risk for preeclampsia

A

T

28
Q

role of NF-kb

A

drives inflammation cytokine production
drives immune suppressors down

29
Q

T regs are lower in the following three conditions:

A

spontaneous abortion compared to induced

infertility

preeclampsia

30
Q

peripheral vs decidual/uterine NK cells

A
  • pNK kill cells that do NOT express HLA antigens
  • dNK inhibited from killing because invading placental cells express non-poly HLA antigens (ex. -G)
  • dNK promote vascular growth of decidua by producing pro-angiogenic factors
  • dNK cells produce chemoattractant that encourage placental cell invasion = remodels maternal spinal arteries
31
Q

pro-angiogenic factors

A

VEGF
TGF-B1
IL-6
IL-8

31
Q

inhibitory ligand for KIR2DL4 receptor found on all NK cells

A

HLA-G
- shuts off cytotoxic effects
- produces proangiogenic factors for uterine remodelling
- preg disorders = reduced HLA-G expression

31
Q

CD16-dim/CD56+bright

A

decidual/uterine NK cells (dNK)

32
Q

CD16+, 56+

A

peripheral NK cells (pNK)

33
Q

what is the spiral artery?

A

allow blood flow into where placenta is; embedded in uterine wall

33
Q

NK cells attract these to help anchor decidua to the uterine wall

A

trophoblasts

34
Q

T or F. dNK have the capacity to be cytotoxic

A

T!

MLSCI 475 (22 decks)

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