1. Active Immunity and Failure of Passive Transfer
Emily Davis

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

3. 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

4. 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)

5. 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

6. 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 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

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

8. 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

9. 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)

10. 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

11. 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

12. 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

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

14. 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

15. 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.

16. 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

17. 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

18. 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

19. 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

20. 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)

21. B Cell Overview

22. T Cell Overview

23. 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

24. 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

25. 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

26. Cell Mediated Response

27. 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

28. 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

29. Chase et al in 2008

30. Chase et al 2008

31. Chase et al 2008

32. 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

33. 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

34. Cortese 2009
Cortese 2009

35. Questions?

36. References
Batista, Camila F., Maiara G. Blagitz, Heloisa G. Bertagnon, Renata C. Gomes, Kamila R. Santos, and Alice M.m.p. Della Libera. "Evolution of Phagocytic Function in Monocytes and Neutrophils Blood Cells of Healthy Calves." Journal of Dairy Science (2015): Web.
Beam, A.l., J.e. Lombard, C.a. Kopral, L.p. Garber, A.l. Winter, J.a. Hicks, and J.l. Schlater. "Prevalence of Failure of Passive Transfer of Immunity in Newborn Heifer Calves and Associated Management Practices on US Dairy Operations." Journal of Dairy Science 92.8 (2009): Web
Besser TE, Gay CC, Pritchett L. Comparison of three methods of feeding colostrum to dairy calves. J Am Vet Med Assoc 1991;198:419–422.
Chase, Christopher C.l., David J. Hurley, and Adrian J. Reber. "Neonatal Immune Development in the Calf and Its Impact on Vaccine Response." Veterinary Clinics of North America: Food Animal Practice 24.1 (2008): Web.
Cortese, Victor S. "Neonatal Immunity." Vet Clin Food Animal 25 (2009): Web.
Dudek, Katarzyna, Dariusz Bednarek, Roger D. Ayling, and Ewelina Szacawa. "Stimulation and Analysis of the Immune Response in Calves from Vaccinated Pregnant Cows." Research in Veterinary Science 97.1 (2014): Web.
Filteau V., Bouchard E., Fecteau G., Dutil L., DuTremblay D. “Health Status and Risk Factors Associated with Failure of Passive Transfer of Immunity in Newborn Beef Calves in Quebec.” Canadian Veterinary Journal 2003; 44:
Fulton, Robert W., Robert E. Briggs, Mark E. Payton, Anthony W. Confer, Jeremiah T. Saliki, Julia F. Ridpath, Lurinda J. Burge, and Glenn C. Duff. "Maternally Derived Humoral Immunity to Bovine Viral Diarrhea Virus (BVDV) 1a, BVDV1b, BVDV2, Bovine Herpesvirus-1, Parainfluenza-3 Virus Bovine Respiratory Syncytial Virus, Mannheimia Haemolytica and Pasteurella Multocida in Beef Calves, Antibody Decline by Half-life Studies and Effect on Response to Vaccination." Vaccine (2004): Web.
Smith, G.w., and D.m. Foster. "Short Communication: Absorption of Protein and Immunoglobulin G in Calves Fed a Colostrum Replacer." Journal of Dairy Science 90.6 (2007): Web.
Swan, H., S. Godden, R. Bey, S. Wells, J. Fetrow, and H. Chester-Jones. "Passive Transfer of Immunoglobulin G and Preweaning Health in Holstein Calves Fed a Commercial Colostrum Replacer." Journal of Dairy Science 90.8 (2007): Web.
Trotz-Williams, L.a., K.e. Leslie, and A.s. Peregrine. "Passive Immunity in Ontario Dairy Calves and Investigation of Its Association with Calf Management Practices." Journal of Dairy Science (2008): Web.
Weaver, Dusty M., Jeff W. Tyler, David C. Vanmetre, Douglas E. Hostetler, and George M. Barrington. "Passive Transfer of Colostral Immunoglobulins in Calves." Journal of Veterinary Internal Medicine J Vet Int Med 14.6 (2000): 569. Web.