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