Immunology of Pregnancy

Question 1

T or F. Synctiotrophoblast is a single cell layer

Answer 1

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

Question 2

Is the ST barrier effective against pathogens?

Answer 2

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

Question 3

first time infection of CMV transmission rate

Answer 3

40%

Question 4

microchimerism

Answer 4

• 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

Question 5

maternal positive effects of microchimerism

Answer 5

• 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)

Question 6

where is IDO expressed?

Answer 6

normally in circulating monocytes, macrophages, and dendritic cells

Question 7

IDO

Answer 7

intracellular heme containing enzyme
indoleamine dioxygenase

Question 8

what does IDO do?

Answer 8

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

Question 9

function of the placenta

Answer 9

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

Question 10

routes of congenital infections

Answer 10

villous placental (through free villus)

extravillous placental

across the membranes

Question 11

routes of transplacental infections

Answer 11

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

Question 12

offspring positive effects of microchimerism

Answer 12

• 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

Question 13

negative effects of microchimerism

Answer 13

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

Question 14

protective physiology of placenta towards fetus

Answer 14

• 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

Question 15

normal function of Tryptophan in T cell activation

Answer 15

released by APCs to proliferate T cells

Question 16

normal feedback mechanism to reduce T cell activation by IDO

Answer 16

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

Question 17

constitutive action of IDO in trophoblasts

Answer 17

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

Question 18

Mellor/Munn experiment

Answer 18

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

Question 19

during pregnancy, these cells predominate in the decidua

Answer 19

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

Question 20

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

Answer 20

T, mor effective in clearing gut worms more efficiently

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

Question 21

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

Answer 21

T

Question 22

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

Answer 22

F! poor response

Question 23

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

Answer 23

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

Question 24

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

Answer 24

F! opposite is true

Question 25

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

Answer 25

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

Question 26

beneficial effects of sperm/seminal plasma in pregnancy

Answer 26

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

Question 27

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

Answer 27

T

Question 28

role of NF-kb

Answer 28

drives inflammation cytokine production drives immune suppressors down

Question 29

T regs are lower in the following three conditions:

Answer 29

spontaneous abortion compared to induced infertility preeclampsia

Question 30

peripheral vs decidual/uterine NK cells

Answer 30

- 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

Question 31

pro-angiogenic factors

Answer 31

VEGF TGF-B1 IL-6 IL-8

Question 31

inhibitory ligand for KIR2DL4 receptor found on all NK cells

Answer 31

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

Question 31

CD16-dim/CD56+bright

Answer 31

decidual/uterine NK cells (dNK)

Question 32

CD16+, 56+

Answer 32

peripheral NK cells (pNK)

Question 33

what is the spiral artery?

Answer 33

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

Question 33

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

Answer 33

trophoblasts

Question 34

T or F. dNK have the capacity to be cytotoxic

Answer 34

T!