Lecture 24 (Neonatal Immunity) Flashcards
why is a fetus considered a foreign antigen?
the sire has MHC molecules that are foreign and the dam is receiving those
what are the 4 maternal mechanisms for achieving maternal-fetal tolerance
- progesterone
- increased complement regulatory proteins
- TH2 response dominates (lower chance for TH1 mediated cytolysis of fetal tissues)
- high levels of Tregs
T-regulatory cells [heighten/dampen] your immune response
dampen
is a TH2 response humoral immunity or cell-mediated immunity?
humoral immunity
what are the 3 fetal mechanisms for achieving maternal-fetal tolerance
- fetal cells down regulate MHC I (lowers expression of self-antigens)
- TH2 cytokines are expressed
- inhibit T-cells (progesterone & other cytokines)
[MCH I/MHC II] is expressed on all nucleated cells
MHC I
t/f: the adult is less able to combat infections than a fetus
false - the fetus is less able to combat infections than an adult
reduced or absent adaptive immunity [decreases/increases] with fetal age
increases
despite early population of lymphoid tissues, the adaptive response is limited at birth…why?
there is limited antibody and T-cell diversity, no memory cells, and reduced cytokines (haven’t flushed out the system with exposure to antigens yet)
neonates have a slow and weak [innate/adaptive] response
adaptive
since the fetus has a reduced adaptive response, that means it relies on what three things?
-innate immunity
-passive immunity
-physical barriers
the adaptive immune response requires population of primary and secondary lymphoid organs in the ________ trimester
1st
when does the adaptive immune response start to increase in the fetus?
after population of lymphoid organs
due to reduced adaptive immunity, the fetus relies on what two things?
-its own innate immunity
-passive immunity from the dam
the fetal innate response and developing adaptive response can be passively supplemented by maternal _________
antibodies
placenta type where maternal epithelium is in contact with fetal tissues (fetal endothelium, CT, and epithelium)
a) epitheliochorial
b) endothelialchorial
c) hemochorial
a) epitheliochorial
placental type where there is no maternal epithelium, and instead the endothelium is in contact with fetal tissues (fetal endothelium, CT, and epithelium)
a) epitheliochorial
b) endothelialchorial
c) hemochorial
b) endothelialchorial
placental type where the fetal tissues (fetal endothelium, CT, epithelium) are in direct contact with maternal blood
a) epitheliochorial
b) endothelialchorial
c) hemochorial
c) hemochorial
what type of placenta do horses, swine, and ruminants have?
a) epitheliochorial
b) endothelialchorial
c) hemochorial
a) epitheliochorial
what type of placenta do dogs & cats have?
a) epitheliochorial
b) endothelialchorial
c) hemochorial
b) endothelialchorial
what type of placenta do humans, primates, and rodents have?
a) epitheliochorial
b) endothelialchorial
c) hemochorial
c) hemochorial
t/f: antibodies cannot pass through multiple layers of the placenta
true
any species that maintains all 6 of the placental layers are completely dependent on _____________ for transfer of their passive immunity
colostrum
what layers are lost in an epitheliochorial placenta?
none
*no maternal layers are lost
what layers are lost in an endotheliochorial placenta?
-maternal epithelial cells
-maternal connective tissue
what layers are lost in a hemochorial placenta?
all three maternal layers:
-maternal epithelial cells
-maternal connective tissue
-maternal endothelial cells
which placental type allows for complete transfer of colostrum?
a) epitheliochorial
b) endothelialchorial
c) hemochorial
c) hemochorial
which placental type allows for partial transfer of colostrum?
a) epitheliochorial
b) endothelialchorial
c) hemochorial
b) endotheliochorial
what percentage of total neonate serum IgG is transferred via the placenta in cats and dogs
~5-10%
fetal humans, rabbits, and rodents have complete transfer of which immunoglobulin via the placenta?
IgG
in addition to placental transfer, all species can receive maternal antibodies post-fetally via ______________
colostrum
what is colostrum?
milk produced late in gestation and early postpartum that is high in antibody content
the maximum amount of colostrum that can be absorbed is within the first ___ hours in foals and calves and then rapidly declines
6 hours
which immunoglobulin is the only one to pass through the placenta?
IgG
what explains why absorption of colostral Abs is time sensitive?
a) IgG is only produced by dams
b) IgG is known to degrade within 6 hours
c) FcR receptor expression falls off after 6 hours
c) FcR receptor expression falls off after 6 hours
which immunoglobulin is predominant in ruminant milk?
IgG
which immunoglobulin is predominant in non-ruminant milk?
IgA
when is the maximum amount of colostrum absorbed from the neonatal intestine?
-first 6 hours in foals and calves
-within the first 12-24 hrs in other species
t/f: colostrum has low lymphocyte count
false - has high lymphocyte count
why is it important to consider the timing of when to vaccinate neonates?
-maternal antibodies can inhibit neonate Ig production (FcγRIIB)
-maternal antibodies can bind the vaccine antigen and block immune response (epitope masking, neutralization of live-attenuated viruses)
when should you start vaccinating puppies and kittens?
6 wks of age then every 3 wks x3
when should you start vaccinating foals and calves?
3-4 months of age then every 4 wks x3
what are the negative aspects of passive immunity?
-maternal antibody may impair neonatal adaptive immune response
-FcγRIIB receptor engagement reduces BCR activation → masks antigens; may bind epitopes and prevent appropriate response to neonatal vaccines
-maternal antibodies may also recognize neonatal tissue (neonatal isoerythrolysis; Rh disease)
what is neonatal isoerythrolysis?
when the mother has antibodies against the blood type of the newborn
*when the newborn ingests colostrum, it has antibodies against it’s own blood, causing destruction of RBCs
what can you give to prevent neonatal isoerythrolysis?
artificial colostrum
neonatal immunodeficiency can occur due to:
-can occur due to developmental failure
examples:
-innate response defects → trapped neutrophil syndrome (Border Collies)
-adaptive response → RAG-1/2 mutations
-can also occur due to failure of passive immunity transfer (vast majority)
what is the most common source of immunodeficiency?
failure of passive immunity transfer (FPT)
what is the major source of passive immunity?
maternal antibody transfer
what are the 3 specific groups of causes of immunodeficiency?
-production failure → maternal (does not make antibodies)
-ingestion failure → placental or neonatal
-absorption failure → neonatal (major cause is lack of colostral transfer)
discuss avian neonate immunity
-passive mechanisms of immunity transfer differ due to lack of placenta and lack of colostrum
-hen actively transfers IgY (=IgG) from serum to yolk → contents absorbed into bloodstream of developing chick
-IgM and IgA are secreted into the albumin in the oviduct (diffuse into amniotic fluid and swallowed by chick) → IgM and IgA in intestine (mucosal immunity)
which of the following features promotes maternal-fetal tolerance?
a) high maternal levels of estrogen
b) high maternal complement expression
c) high maternal levels of progesterone
d) Th1 predominant immune response
c) high maternal levels of progesterone
after maximum immunoglobulin consumption via colostrum, does the dam still provide immunity to the neonate?
yes, the dam continues to put immunoglobulin in colostrum (IgA) for mucosal immunity in the neonate
in what species is failure of passive transfer most common?
horses
list the 3 types of placenta
-epitheliochorial
-endotheliochorial
-hemochorial
this receptor binds IgG at birth, protecting it from digestion and bringing it to circulation in neonate blood
fetal Fc receptor
this receptor has high levels at birth and rapidly declines in number nearing 0 left by 24 hours
fetal Fc receptor
t/f: you vaccinate an animal as maternal antibodies decrease and young animal’s adaptive immunity response begins to develop
true
fescue hay having an endophyte that potentially causes a failure to produce colostrum is an example of which type of failure of passive immunity transfer?
production failure
this type of FPT can be placental (abnormal placenta that precludes normal transfer) or neonatal (foal that won’t stand to nurse)
ingestion failure
this type of FPT is mainly a cause of lack of colostral transfer such as taking in colostrum too late
absorption failure
Hens actively transfer this antibody from serum to yolk that is equivalent to IgG
IgY
_____ and ____ are two antibodies that are secreted into albumin in oviduct and diffuse into amniotic fluid and swallowed by the chick, ending up in the intestine
IgM and IgA
