13. Immunity in the Fetus

and Newborn

王家鑫，MD. Prof.

School of Veterinary Medicine

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 postcon

ception.

• The bone marrow and spleen appear at 55d.

B cells work?

• Lymph nodes are found at 60d, but Peyer’s patc

hes 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 receptor

s 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 s

ac 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 wee

ks of age and CD8+T cells at 4 weeks.

• IgM+B cells can be found in blood by day 50 duri

ng the conception.

• NK cells don’t develop until several weeks after

birth.

• B cells can be found in the thymus of newbor

n piglets!!!

• The VDJ rearrangement is first seen in the fetal l

iver at 30d.

• IgM, IgA, and IgG transcripts are present at 50d.

Uptake and transport of maternal IgG by enterocytes of the gut of the newborn piglet.

Near absence of enterocytes containing IgG 24 h postpartum determined using the same technology as in A

Synthesis (arrow) and epithelial transport (arrow) of IgA by crypt epithelial cells in the gut of 5 week old conventional piglets.

Detection of a few IgM producing cells in the lamina propria of conventional 4-week-old piglets and evidence for IgM transport into the gut lumen by crypt epithelial cells.

Changes in immunoglobulin levels during reproduction.

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 com

monly employed in the modern poultry industry.

• The major vaccine employed is against the Mare

k’s disease herpesvirus.

13-1-1 Development of Phagocytic Capability

• Neutrophils are fully capable of phagocytosing bac

teria in the fetal pig at 90 days postconception.

• Poor bactericidal activity lasts until 100 days of pre

gnancy.

• Near birth, the phagocytic and bactericidal capacit

y of neutrophils declines as a result of fetal steroid

levels.

• After birth, macrophages have depressed chemo

tactic responsiveness, and they are also able to

support the growth of some viruses.

• Newborn piglets is deficient in some complemen

ts.

• There are very few pulmonary macrophages in n

ewborn piglets. They appear predominantly a fe

w 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 brucell

a abortus.

• Fetal infections commonly trigger an immu

ne response and elevated Ig levels.

• The presence of any Ig in the serum of a n

ewborn, unsuckled animal suggests infecti

on 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 neonat

al animals respond rapidly to an ingested

antigen.

• Calves orally vaccinated with coronavirus

vaccines at birth are resistant to virulent c

oronavirus within 3 to 9 days.

• Piglets vaccinated orally 3 days after birth w

ith transmissible gastroenteritis virus (TGE)

vaccines develop neutralizing antibodies in t

he intestine 5-14 days later.

• There is an early intestinal IgM response th

at 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 res

ponses 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 epito

pes on vaccine antigens and so prevent th

eir 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 respon

d well to pseudorabies virus by 2 days after bi

rth.

• If piglets suckled colostrum, antibody producti

on does not begin until 5 to 6 weeks after birt

h.

• Colostrun-deprived lambs generate IgG1 a

t 1 week and IgG2 by 3 to 4 weeks.

• In colostrum-fed lambs, IgG2 synthesis do

es 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 o

f the newborn to mount its own immune respons

es.

• Very young animals are unable to respond to act

ive immunization using vaccines.

• Such an inhibition is B-cell specific and T cell res

ponses 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 l

ast for 6 months, and antibodies to equine arterit

is virus for as long as 8 months.

• Antibodies to bovine virus diarrhea may persist f

or up to 9 months in calves.

• The half-lives of maternal antibodies against equ

ine influenza and equine arteritis virus antigens i

n 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 envir

onment of the egg and require temporary immuno

logical assistance.

• Serum immunoglobulins are actively transported f

rom the hen’s serum to the yolk while the egg is s

till 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 abs

orbs the yolk IgY, which then appears in its

circulation.

• IgM and IgA from the albumin diffuse into t

he amniotic fluid and are swallowed by the

embryo.

• A newly hatched bird has IgY in serum an

d, IgM and IgA in its intestine.

• The maternal antibodies effectively preven

t successful vaccination until they disappe

ar between 10 to 20 days after hatching.

Take good care of our babies.

Thank You!