Transcript Section 18 Immunity in the Fetus and Newborn

13 Immunity in the Fetus
and Newborn
13-1 Development of the Immune System
• The thymus is the first immune organ to develop.
• The development of secondary immune organs.
• B cells appear soon after the development of the
spleen and lymph node, but antibodies are not
usually found until late in fetal life.
• The ability of the fetus to respond to
antigens develops very rapidly after the
immune organs appear, but all antigens are
not equally capable of stimulating fetal
response.
• The ability to mount cell-mediated immune
responses develops almost simultaneously
as antibody production.
Calf
• The gestation period of the cow is 280d.
• The fetal thymus is recognizable by 40d
postconception.
• The bone marrow and spleen appear at 55d.
B cells work?
• Lymph nodes are found at 60d, but Peyer’s
patches don’t appear until 175d.
Lamb
• The gestation period of the ewe is about 145d.
• MHC class I positive cells can be detected by
19d after sex service.
• MHC class II positive cells can be found by 25d.
• The thymus and lymph nodes are recognizable
by 35d and 50d, respectively. CD4+ and CD8+
cells appear in the thymus by 35 to 38d.
Lamb
• Blood lymphocytes are seen by 32d.
• B cells are detectable at 48d in the spleen.
• The Peyer’s patches appear only at 60d.
• C3 receptors appear by 120d, but Fc
receptors don’t appear until the animal is
born.
Piglet
• The gestation period of the sow is about 115d.
• The first leukocyte can be found in the yolk
sac and liver at 17d.
• The thymus develops by 40d postconception.
• The intestinal lymphoid tissues are devoid of
T cells at birth.
• CD4+T cell appear in the intestine at two
weeks of age and CD8+T cells at 4 weeks.
• IgM+B cells can be found in blood by day 50
during the conception.
• NK cells don’t develop until several weeks after
birth.
• B cells can be found in the thymus of
newborn piglets!!!
• The VDJ rearrangement is first seen in the fetal
liver at 30d.
• IgM, IgA, and IgG transcripts are present at 50d.
Chick
• 21-day of hatching eggs.
• Stem cells arise in the yolk sac membrane and
migrate to the thymus and bursa at 5 to 7 days
of incubation.
• IgM+ lymphocytes are detected in the bursa by
day 14. Antibodies are produced by 16 and 18d.
• IgY+ lymphocytes develop on day 21 around the
time of hatching.
• IgA+ lymphocytes first appear in the intestine 3
to 7 days after hatching.
• Vaccination of 18-day embryonated eggs is
commonly employed in the modern poultry
industry.
• The major vaccine employed is against the
Marek’s disease herpesvirus.
13-1-1 Development of Phagocytic Capability
• Neutrophils are fully capable of phagocytosing
bacteria in the fetal pig at 90 days postconception.
• Poor bactericidal activity lasts until 100 days of
pregnancy.
• Near birth, the phagocytic and bactericidal
capacity of neutrophils declines as a result of fetal
steroid levels.
• After birth, macrophages have depressed
chemotactic responsiveness, and they are also
able to support the growth of some viruses.
• Newborn piglets is deficient in some
complements.
• There are very few pulmonary macrophages in
newborn piglets. They appear predominantly a
few days later.
13-1-2 The Immune System and
Intrauterine Infection
• The fetal immune system is less capable of
combating infection.
• The acquired immune system is not fully
functional.
• Some infections may be sever or lethal in the
fetus.
Bluetonge, infectious bovine rhinotracheitis,
porcine parvovirus, bovine virus diarrhea, and
brucella abortus.
• Fetal infections commonly trigger an
immune response and elevated Ig levels.
• The presence of any Ig in the serum of a
newborn, unsuckled animal suggests
infection in utero.
The effects of bovine viral diarrhea virus infection on
development of the fetal calf depend on the time of infection
• Since they are specifically tolerant to BVD,
persistently infected calves shed large quantities
of virus in their body secretions and excretions
and so act as the major source of BVD for other
animals in a herd.
• The persistently infected calves grow slowly and
often die of opportunistic infections, such as
pneumonia before reaching adulthood.
13-2 Immune Response of Newborn Animals
• Situation: mammals are born into an
environment rich in microorganisms after
developing in the sterile environment in the
uterus.
• The young of domestic animals are capable of
mounting both innate and acquired immune
responses at birth.
• The acquired immune system is in progress.
• The newborn animals tend to produce immune
responses skewed toward a Th2 rather than Th1
cytokine pattern.
• Over the first months of life, the immune
responses usually revert to the balanced adult
pattern.
• Unless immunological assistance is provided,
newborn animals may be killed by organisms
that present little threat to an adult.
13-3 Transfer of Immunity from
Mother to Offspring
• The rout by which maternal antibodies reach the
fetus is determined by the structure of the
placenta.
13-3-1 Secretion and Composition
of Colostrum and Milk
13-3-2 Absorption of Colostrum
• In pig, IgG and IgM are preferentially
absorbed.
• In ruminants, all immunoglobulin classes are
absorbed in the intestine.
• Permeability is highest immediately after
birth and declines after about 6 hours.
• In piglets, the ability of absorbing
immunoglobulins may be retained for up to
4 days.
• The amount of IgA in the intestine can be
large, a 3-week-old piglet may receive
1.6g daily from sow’s milk.
13-4 Development of Acquired
Immunity in Neonatal Animals
Local Immunity
• The intestinal lymphoid tissues of
neonatal animals respond rapidly to an
ingested antigen.
• Calves orally vaccinated with coronavirus
vaccines at birth are resistant to virulent
coronavirus within 3 to 9 days.
• Piglets vaccinated orally 3 days after birth
with transmissible gastroenteritis virus (TGE)
vaccines develop neutralizing antibodies in
the intestine 5-14 days later.
• There is an early intestinal IgM response
that switch to IgA by 2 weeks.
Systemic Immunity
• The maternal antibodies inhibit the ability of the
newborn to mount its own immune response.
• Such an inhibition is B cell-specific and T cell
responses are usually unaffected.
• One of the simplest is the rapid neutralization of
live vaccines by the maternal antibody.
• The inhibition results from antibodies binding to
B-cell Fc receptors and blocking BCR signaling.
• Maternal antibodies simply mask the
epitopes on vaccine antigens and so
prevent their recognition by B cells.
• An immune response can be elicited only
when maternal antibody titers fall below a
critical threshold.
• Calves begin to generate their own
antibodies by about 1 week of age if they
fail to suckle.
• If calves suckled and thus possess
maternal antibodies, antibody synthesis
does not commence until about 4 weeks of
age.
• In piglets, colostrum-deprived animals
respond well to pseudorabies virus by 2 days
after birth.
• If piglets suckled colostrum, antibody
production does not begin until 5 to 6 weeks
after birth.
• Colostrun-deprived lambs generate IgG1
at 1 week and IgG2 by 3 to 4 weeks.
• In colostrum-fed lambs, IgG2 synthesis
does not occur until 5 to 6 weeks old.
Effect of the presence of maternal antibodies
• The antibodies acquired by a young animal from
its mother is called maternal antibody(母源抗体).
• Maternal antibodies is able to inhibit the ability
of the newborn to mount its own immune
responses.
• Very young animals are unable to respond to
active immunization using vaccines.
• Such an inhibition is B-cell specific and T cell
responses are largely unaffected.
13-5 Vaccination of Young Animals
• Inhibition of maternal antibodies usually
persists for a few months.
• Maternal antibodies absorbed from the
puppy’s intestine reach maximal levels in
serum by 12 to 24 hours after birth.
• The catabolic rate of the proteins is
exponential and is expressed as a half-life.
• The half-life of antibodies to canine
infectious hepatitis is 8.4 days.
• Very few newborn puppies can be
successfully vaccinated.
• Maternal antibodies to tetanus toxin in foals can
last for 6 months, and antibodies to equine
arteritis virus for as long as 8 months.
• Antibodies to bovine virus diarrhea may persist
for up to 9 months in calves.
• The half-lives of maternal antibodies against
equine influenza and equine arteritis virus
antigens in the foals are 32 to 39 days.
• Maternal antibodies effectively block immune
response in young foals and calves, even at low
levels, leading to ineffectiveness of premature
vaccination.
• The effectiveness of vaccines increases
progressively after the first 6 months of life.
BHV: Bovine herpesvirus
BVDV: Bovine virus diarrhea virus
• A safe rule is that calves and foals should be
vaccinated no earlier than 3 to 4 months of age
followed by one or two revaccinations at 4-week
intervals.
• The precise schedule will depend on the vaccine
used and the species to be vaccinated.
• Animals vaccinated before 6 months of age
should always be revaccinated at 6 months or
after weaning to ensure protection.
13-6 Passive Immunity in the Chick
• Newly hatched birds emerge from the sterile
environment of the egg and require temporary
immunological assistance.
• Serum immunoglobulins are actively transported
from the hen’s serum to the yolk while the egg is
still in the ovary.
• IgM and IgA are acquired from oviduct secretions
as the fertilized ovum pass down the oviduct.
• As the chick embryo develops in ovo it
absorbs the yolk IgY, which then appears in
its circulation.
• IgM and IgA from the albumin diffuse into
the amniotic fluid and are swallowed by the
embryo.
• A newly hatched bird has IgY in serum and,
IgM and IgA in its intestine.
• The maternal antibodies effectively
prevent successful vaccination until they
disappear between 10 to 20 days after
hatching.
Take good care of our babies.
Thank You!