Active Immunity and Failure of Passive Transfer Emily Davis

Outline Review: neonatal immunity, colostrum importance, IgG, FPT Testing colostrum Management of colostrum Active vs. Passive Immunity

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 Placental type of cows Syndesmochorial cotelydonary

Colostrum and its Role First time neonate will receive antibodies from mother Stomach is porous at birth to allow absorption Absorption at max for first six hours post birth Can acquire antibodies for up to 24 hours, but transfer hindered Without adequate intake of colostrum, newborn will have less productive life Higher risk of morbidity, mortality, decreased growth rates and first lactation milk production in dairy calves (Fidler, et al. 2007)

Colostrum Components Immune factors Growth factors Immunoglobulins, cytokines, lysozymes, glycoproteins Growth factors IGF-1, IGF-2, epithelial growth factor Nutritional components Vitamins, minerals, amino acids Antibodies IgG IgA IgM

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 more than twice as likely to get sick as non-FPT calves NAHMS estimates suggest 22% of all calf deaths could be prevented by better colostrum management

Failure of Passive Transfer Low IgG levels in colostrum Decreased amount of colostrum Timing/route of ingestion Maternal vs. pooled vs. replacer

Changing Absorption of IgG Difructose anhydride III Indigestible disaccharide which promotes absorption of calcium and magnesium in intestines Improves absorption of IgG in newborns Feed colostrum in one feeding Heat treated colostrum Decreases microbial count while maintaining IgG levels

Changing Absorption of IgG Use of colostrum replacers Colostrum replacers (CR) had less transfer of passive immunity when compared to colostrum (Fidler, et al. 2011) However, the more CR the calves received, the better the transfer Feeding sodium bicarbonate NaHCO3 can increase IgG concentration up to a point (Cabral, et al. 2011)

Ig Deficiencies Hypogammaglobulinemia IgG deficiencies Lack or decrease of one or more types of antibodies Fetuses that don’t receive antibodies through the placenta fall into this category IgG deficiencies More susceptible to infections such as pneumonia, bronchitis and others Often occurs when there’s also a deficiency in IgA or IgM Cause unknown but has possible genetic ties

Testing Colostrum Quality Quantity <20-100mg/mL Colostrometer- room temperature Quantity By weight of calf 5-6% of body weight per feeding 50 mg/mL high quality 20-40 medium Under 20 – do not feed Colostrometer uses differences in specific gravity and converts that into the color scale to determine IgG concentration Just let it float in the vat of colostrum Best results with room temp – chill rest but use a small sample to test at room temp bc bacteria

Timing/Route of Ingestion Immediately after birth is optimal Decreases after 4-6 hours Route depends on management Bottle vs. Tube vs. Suckling Bacteria on or around dam By hour 24 there is basically none left that can be absorbed Route- Management of keeping cow and calf together vs immediately separating and for those calves Bottle, tube, nursing

Efficiency of Ig absorption Review slide- ask class why it’s important to give high quality colostrum immediately after birth

Management Styles 46% of calves left to suckle on dam did not drink 61%, 19%, 10% FPT rates from suckling, bottle, and tube (Weaver et al 2000) Maternal vs pooled Dystocia First bullet was in 6 hours total Maternal is best when tested and properly administered Pooled – generally poor colostrum has increased quantity but decreased quality and can lower the value and quality of the pool of good colostrum so as long as management tests the quality and quantity to maintain high quality pooled then it will work – STRESS THIS POINT pooled can provide even colostrum to all cows as well as provide farm specific immunity from all cows- very beneficial Dystocia increases the rate of FPT

Replacer vs. Maternal FPT rates by Smith et. al in 2007 Separate study 2 bags CR-95% 3 bags CR-76% hypothesized the care wasn’t taken to properly determine IgG levels in the replacer as well as not mixing the proper amount of replacer with water or even making the calves drink enough of the replacer to get passive transfer.

Colostrum Management Pooled (Beam et al 2009) FPT rates were 2.2x higher on pooled farms Must account for management practices Measuring IgG concentrations Feed or chill in timely manner Proper sanitation of utensils Timing of colostrum feeding + route Measuring IgG will increase quality of samples- maybe the farm differences in management were all they needed to increase FPT rates in comparison with maternal colostrum at the unpooled farms

Longevity of Calves Overall FPT decreases value Decreased weaning weights Decreased health (increased cost) Decreased performance Decreased first lactation yield Increase in being culled after 1st lactation

Endogenous IgG Production IgG, IgM, and IgA concentrations begin to increase within a few days after birth in colostrum deprived calves In calves- IgM does not begin until 4 days, is not functional until 8 days after birth All reach appreciable levels for neonates by 32 days Half-life for IgG is antibody dependent 23-39 d in foals 16-50 d in calves Big windows with FPT calves for infections bc no colostrum to give antibodies until they are making it themselves which can take a lot longer to be functional than you would think

Active vs. Passive Immunity Direct transfer of antibodies actively formed by another person or animal “Borrowed” immunity Transfer of IgG from the mother to fetus across the placenta during gestation Ingestion of colostrum transfers IgA Antibodies are usually broken down before one month of age Antibody-synthesizing ability does not develop before one month of age

Active vs. Passive Immunity The production of antibodies as a result of exposure to an antigen Natural exposure Artificially acquired Vaccines contain modified antigens that initiate an immune response without causing the disease Initial response produces memory T lymphocytes or B lymphocytes T Cells- from thymus – cell mediated B cells – from bone marrow – humoral (antibodies)

B Cell Overview https://askabiologist.asu.edu/sites/default/files/resources/activities/body_depot/viral_attack/bcell_maturation.gif

T Cell Overview http://www.austincc.edu/apreview/NursingPics/ImmunoPics/activationofhelptertcells.jpg

Macrophage http://quest.nasa.gov/projects/flies/images/adaptive.jpg WBC that digests and engulfs cell debris so microbes etc In neonates Increases secretions of pro-inflammatory cytokines but a decrease in the ability to stimulate T cell proliferation

Natural Killer Cells Lymphocyte that Binds and attacks virus infected cells without needing an antigen stimulation Kills by inserting granules into the infected cell that contain perforin This binds to the membrane and basically creates holes in it resulting in lysis and death In neonates Higher percentage of NKC in blood than humans Decreased cytotoxicity and impaired ability to adhere to target cells Pic from http://breastcancerconqueror.com/wp-content/uploads/2014/12/NK-cells.jpg

Neutrophil The main WBC in circulation and type of phagocyte Primary to respond to inflammation Can go where other cells cannot, are recruited by chemotaxis by other cells IN NEONATES Slower response to bacterial infection but same amount of cells as adults they're just immature When the cells in neonates respond to chemotaxis they gave a harder time sticking to the endothelium walls to penetrate through to the tissues that need them so in general just weaker cells at birth http://1.bp.blogspot.com/-eTh5Yl9sV0g/UjgywzCnpuI/AAAAAAAAA90/B9F5m76cOBQ/s1600/neutroawesome.png

Cell Mediated Response https://www.youtube.com/watch?v=1tBOmG0QMbA

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 Maternal antibodies can stay in the calf until around 2 months Immune system isn’t matured until at least 5 months

Active Immunity Increased susceptibility through 40 days of life Decreased phagocytes Active immunity can take 2-4 weeks to become present and can keep growing up until puberty

Chase et al in 2008

Chase et al 2008

Chase et al 2008

Vaccines Limited for calves after birth Maternal antibodies still present Maternal vaccinations pre-partum (Dudek et al 2014) Challenged calves with respiratory infections Mothers were vaccinated in one group Calves from vaccinated mothers were protected Stimulated the immune system- was activated

Vaccines Maternal vaccinations (Cortese 2009) E. Coli, rotavirus, coronavirus All showed effective transfer through colostrum to calf and moderated diarrhea when challenged Consider with calf vaccinations Immune status of calf- colostrum program quality Specific antigen Presentation of the antigen

Cortese 2009 Cortese 2009

Questions?

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