Gastrointestinal Physiology: Intestinal Absorption of Antibodies AnS 536 Spring 2016

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Gastrointestinal Physiology: Intestinal Absorption
of Antibodies
AnS 536
Spring 2016
Outline for the day…
Mechanism of absorption of antibodies from
colostrum
 Closure of gut
 How failure of passive transfer affects future
performance

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
Non-selective Transfer of IgG

Occurs in calves and sheep
– IgG, IgM, and IgA absorbed in proportion to amounts in
colostrum

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 newborns
– 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 Newborn
(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 neonatal vaccines
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