Fetal & Neonatal Immunity Flashcards
why is the fetus considered an “allograft”
it is a tissue transplant that contains MHC genes that are “non-self” relative to the mother
- has maternal and paternal MHC
how does the presence of non self MHC on the fetus not trigger an immune response by the mother
it is a site of immune privilege
has specialized cells that allow for the fetus to persist throughout gestation
trophoblasts
fetal cells that line the outermost layer of the placenta
major barrier between fetal compartment and maternal blood
how do trophoblasts prevent an immune response from the dam
do not express MHC II proteins
usually do not express MHC I proteins, but if they do it is non-classical
what is a risk of having the maternal-fetal interface be immune privileged
pathogens that are not cleared from the body are able to colonize the area due to low MHC expression
decidual NK cells (dNK)
largest population of maternal immune cells
involved in maintenance and tissue remodeling for fetal invasion during implantation
- NOT cytotoxic
- produce growth factors, angiogenic factors, and cytokines
decidual macrophages
primary APCs at the maternal-fetal interface
- anti-inflammatory: express IL-10
- promote vascular growth by producing VEGF and MMP9
- promote clean up and phagocytosis of apoptotic trophoblasts
- produce IDO to prevent T cell activation and dampen immune response
fetal-specific Treg cells
confer tolerance to fetal antigen and help maintain a homeostatic environment for fetal survival
recruited to and induced at the maternal-fetal interface
is the maternal immune system aware of the fetus or does the fetus evade it completely/go undetected
maternal immune system is AWARE and induces a tolerance response with Treg cells
dam is NOT immunosuppressed
what immune responses are altered in the dam during pregnancy
Th1: improves with pregnancy
Th2: worsens with pregnancy
how does gestation length impact immunocompetence of the neonate
longer gestation = born with fully developed immune system
shorter gestation = immune system still developing after birth
at what day in gestation does the fetus begin to produce its own antibodies
day 125
produces IgG
effect of infection with BVDV during early gestation (<125 days)
cow becomes immune
fetus becomes tolerant –> does NOT produce antibody against it
calf will be infected for life but is antibody negative –> becomes a continuous shedder
virus may mutate into a cytopathic form causing superinfection of calf and other viremic animals leading to fatal mucosal disease
effect of infection with BVDV in mid gestation (100-150 days)
calf has congenital malformations
effect of infection with BVDV in late gestation (>150 days)
calf is normal and has protective antibodies
epitheliochorial placentation
greatest number of layers between maternal and fetal blood supply
NO IgG transfer - relies 100% on colostrum
horses, pigs, ruminants
endotheliochorial placentation
some layers between maternal and fetal blood supply
minimal IgG transfer - relies majority on colostrum
dogs, cats
hemochorial placentation
minimal layers between maternal and fetal blood supply
abundant IgG transfer - does not rely on colostrum
humans, rabbits, rodents
what is IgG transfer from blood or GIT into fetal/neonatal circulation mediated by
Fc receptors
placental transfer of IgG
- maternal antibody gets endocytose into fetal endothelial cells
- acidic pH of endoscope causes IgG to bind Fc receptor present in the endosome
- crosses to basolateral side –> exocytosis –> basic pH of extracellular fluid causes dissociation of IgG from Fc receptor
occurs in hemochorial and partly in endotheliochorial placentas
colostrum transfer of IgG
- Fc receptors expressed on enterocytes bind antibody as milk passes through intestinal lumen
- IgG + receptor complex gets internalized into an endosome and crosses to basolateral side
- Fc receptor releases IgG into neonatal blood supply
is colostrum intake time dependent
yes - must be within 24 hours after birth (peak at 12 hours)
neonates have specialized enterocytes that indiscriminately absorb large particles (including Ig) through pinocytosis
- only remains “open” for 24 hours, then gets replaced by mature enterocytes
when should the full “dose” of colostrum be administered by (ideally)
12 hours post birth
how does the content of colostrum antibody change over time
after 24 hours:
- IgG decreases significantly
- IgA continues to be secreted for local benefits
how to measure for failure of passive transfer
SNAP tests
measures IgG concentration in neonates
can also use serum protein as a proxy for IgG (high serum protein indicates adequate colostrum intake)
when is the best time to test for failure of passive transfer
24 hours after birth (end of absorption period)
what are some reasons for failure of passive transfer to occur
- production failure by dam
- ingestion failure by neonate
- absorption failure
- management problems
what is the state of most animals’ immune systems at birth
immunocompetent
begin IgG production very early after birth
neonates develop their microbiome and associated T and B cell responses
window of susceptibility
time during which maternal antibodies are too low to be protective to the neonate, but neonatal antibodies are not sufficient to provide protection against pathogens
age of high disease susceptibility (6-8 weeks)
want to start serially vaccinating at this time
what are some characteristics of neonatal immunity
- poor C3 activation
- poor response to glycoproteins and polysaccharides
- macrophages and neutrophils can phagocytose but have decreased intracellular killing ability
- decreased integrins and selectins
- ILCs may or may not be present
- AMPs and opsonins are present at birth
