Small Intestinal Development in Newborn
Ruminants – Absorption of Macromolecules
Dr. Howard Tyler
Department of Animal Science
Iowa State University
Neonatal Immunity
Human placenta transports IgG from maternal to
fetal circulation
– Babies born with IgG concentration approximately 89%
of adult values
No transport of immunoglobulins across placenta in
farm animals
– Offspring born with essentially no circulating IgG
– Colostrum provides IgG after birth
Classifications of Mammals Based on
Method for Obtaining Passive Immunity
•
GROUP I – Primates, Rabbits
•
•
•
GROUP II – Cats, Dogs, Rodents
•
•
•
Extensive transplacental transport of IgG
Limited or no postnatal absorption across small intestinal epithelium
Extensive transplacental transport of IgG
Some postnatal transport across small intestinal epithelium
GROUP III – Cattle, Sheep, Horses, Pigs
•
•
No transplacental transport of IgG
Extensive postnatal transport across small intestinal epithelium
Selective Transfer of IgG
Occurs in rats through binding of IgG to FC
receptors in the small intestine
Time dependent
–
–
–
–
Non-specific absorption after birth
By 3 d of age, IgG absorption favored
By 7 d of age, IgG absorption selection 20X greater
At 21 d of age, no intact proteins absorbed into
circulation
Non-selective Transfer of IgG
Occurs in calves and sheep
– IgG, IgM, and IgA absorbed in proportion to amounts in
colostrum
Pigs and foals selectively absorb IgG compared to
other macromolecules
– IgA and IgM found on enterocyte surface but not inside
the cell
Absorption rate decreases with increasing age
– Mean time to closure approximately 21 to 26 h of age
Absorption of Colostrum
Absorption in duodenum regulated by Fc receptors
– Minimal
Absorption in jejunum and ileum non-specific
– Accounts for most of Ig absorption
– Absorb anything presented to surface
• Ig’s, bacteria, viruses
Cells nearest tips have far more absorptive
capability than those nearest crypts
– Absorptive capability takes 3-4 days of cellular
differentiation
Absorptive Mechanism
Pinocytosis
– Absorbed via intermicrovillous spaces
• Absorption permitted by lack of terminal web in
microvilli
– Vacuole forms around absorbed material
– Vacuole expands as more material absorbed
– Vacuole fills cell
• Nucleus pushed down to basolateral membrane
Absorptive Mechanism
Filled vacuole pinches off at luminal end
Nucleus and vacuole change places
Vacuole merges with basolateral membrane
– Enhanced by large intercellular spaces in
neonatal intestine
Material in vacuole is “purged” into
intercellular spaces
After Absorption
Immunoglobulins are absorbed unchanged and
enter the lymphatics
– Lymphatics highly fenestrated immediately after birth
– Enter circulation via thoracic duct
– In circulation, IgG is distributed equally between extraand intravascular space
– Equilibrium reached in 51 h
IgG can be secreted back into the intestinal lumen
through the duodenal crypt cells
Intestinal Closure
Related to energy availability and intestinal
maturation
– Closure occurs at about 21 hours
• Appears to be later if calf not fed
Crypt cell mitosis rate is low in the fetus, and more
rapid at 1 d of age compared to 3 wk of age
– Migration from crypt to villous tip occurs in fetus takes 5-7
days
– Migration from crypt to villous tip occurs after birth takes
72 h
Efficiency of Ig absorption
40
35
30
25
20
15
10
5
0
0
4
8
12
16
20
24
Time (hours) relative to birth
Closure
Even after closure occurs, cells continue to
take up colostral material into vacuoles
Completed vacuoles do not exchange places
with nucleus or other cellular organelles
Cell migrates to tips of villi and are sloughed
off and excreted
Factors Affecting IgG Absorption
Rate of IgG absorption increases with
increasing amount of colostrum fed
Apparent efficiency of absorption (AEA)
decreases with increasing mass of antibody
in colostrum
– AEA is increased at higher concentrations when
mass is constant
Serum IgG (g/L) = IgG consumed x AEA (%) / serum volume (L)
AEA (%) = serum IgG (g/L) x serum volume (L) / igG ingested (g)
Failure of Passive Transfer (FPT)
Low IgG levels greatly increase risk for death
and disease
– 40% of calves classified as FPT (<10 g IgG/L)
– Colostrum-deprived calves 50-74 times more
likely to die before 3 weeks of age
– FPT calves are twice as likely to get sick as nonFPT calves
NAHMS estimates suggest 22% of all calf
deaths could be prevented by better
colostrum management
Endogenous IgG Production
IgG, IgM, and IgA concentrations begin to
increase within a few days after birth in
colostrum deprived calves
– Undetectable in foals until after 7 d of age
Half-life for IgG is antibody dependent
– 23-39 d in foals
– 16-50 d in calves
IgG Production by the Calf
(Active Immunity)
Not enough of a response to be effective in
preventing disease
– T- and B-cells less functional for first few months
after birth
– Poor response to vaccinations for first few
months
Also need to consider that maternal
antibodies (from colostrum) will inhibit
response to calfhood vaccines