university of guelph genetic regulation of the bovine immune system professor bonnie a. mallard...
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University of Guelph
GENETIC REGULATION OF THE BOVINE IMMUNE SYSTEM
Professor Bonnie A. Mallard
PRACTICAL APPLICATION OF THE
HIGH IMMUNE RESPONSE TECHNOLOGY IN DAIRY HEALTH MANAGEMENT
Mastitis costs the dairy producer between $110 to $320 per case and 1 out of every 5 dairy quarters in Canada is infected with mastitis- causing pathogens
Canadian Bovine Mastitis Network, University of Montreal, Quebec, Canada
Emerging and re-emerging diseases, many of which are zoonotic;
Tomley and Shirley 2008. Phil. Trans. R. Soc. B. 364:2637
There are increasing restrictions on antibiotic use in livestock Berge et al., 2009. J.Dairy Sci. 92:4707
Several dairy support industry companies offer diagnostic, treatment or prevention solutions for specific diseases
However, there are No solutions available on the market for evaluating & predicting broad-based disease resistance
Current Challenges for Dairy Health
Genetic Selection for Better Health
Genetic selection by immune response is desirable and sustainable for reducing infectious disease
Kelm et al. 2001. Vet. Clin. North Am. Food Anim. Prac. 17:477Stear et. al., 2001. Res. Vet. Sci. 71:1
Genetic selection to improve immune response provides health and productivity advantages
Wilkie and Mallard. 1999. Vet. Immunol. Immunopath. 72:231
Mallard 2007. 40th Proc. Am. Assoc. Bovine Practitioners. Sept 20-21, Vancouver British Columbia, 40:1-7.
HIGH IMMUNE RESPONSE
The High Immune Response (HIR) concept was first developed in pigs
Mallard, B.A., B.N. Wilkie, B.W. Kennedy and M. Quinton
Use of estimated breeding values in a selection index to breed Yorkshire pigs for high and low immune and
innate resistance factors.
Anim. Biotech. 1992, 3:257-260.
GUIDING PRINCIPLE
Optimal Disease Resistance Should be a Function of Optimal Innate and Acquired Defence Mechanisms
Phenotype
What is HIR for Dairy Cattle?
The High Immune Response (HIR) is:
Simple immune response test Done once in an animal’s lifetime Helps producers identify their healthiest
animals HIR cows are at much less risk for disease Is a useful management tool to improve
health Is heritable - useful for breeding h2=0.2-0.3 Novel alternative to use with traditional
methods of infection control
THE HIR TEST PROTOCOL
DAY 14
- CMIR - Initiate skin thickness
test and take background
skin-fold measurements
- AMIR - Collect blood for ELISA
DAY 15- Final skin-fold measurements
24-48 hours
DAY 0
- Collect blood for
ELISA
- Immunize with type
1 & 2 antigens in
neck or rump
The HIR test is a 15 day test that requires 3 farm visits:
Ranking Animals using Estimated Breeding Values
1. Measure the IR phenotype
Phenotype = Genotype + Environment
2. Calculate a breeding value to rank animals
EBV = Phenotype – Environment
Integrating these quantitative genetic
methods is a useful way to rank
animals to enhance the immune system
and improve disease resistance
TWO IMMUNE TESTS ARE PERFORMED TO REPRESENT BROAD-BASED RESISTANCE
ANTIBODY MEDIATED
IMMUNE RESPONSE
(AMIR)
CELL-MEDIATED IMMUNE RESPONSE
(CMIR)
QuickTime™ and a decompressor
are needed to see this picture.
Photos and figures courtesy of Dr. B. Mallard
Wagter and Mallard et al. 2000 J. Dairy Sci. 83:488
Op
tica
l Den
sity
Val
ue
(OD
)
Week relative to calving
Sera AMIR Response to OVA
Immune Response Can Be Used to Rank Cattle
0
0.2
0.4
0.6
0.8
1
1.2
1.4
1.6
1.8
2
-8 -3 0 3 6
Group I
Group 2
Group 3
PM
c
cc
b
bb
c
b
a
aa
a
− High− Avg− Low− Mean
Combined EBVs for AMIR and CMIR of Holstein Cows in 58 Canadian Bovine Mastitis Research Network Cohort Herds
Day 14 – Primary Response Day 21 – Secondary Response
85
90
95
100
105
110
115
Low
Average
High
Time of immune response sampling
Breeding Values for IR in Canadian Herds
Thompson-Crispi et al 2011 Technical Report to the Genetic Evaluation Board, Canadian Dairy Network
7.50%
11.30%
14.40%
0.00%
2.00%
4.00%
6.00%
8.00%
10.00%
12.00%
14.00%
16.00%
% D
isea
se O
ccur
renc
e
High Average Low
Disease data from: Wagter et al. 2000 JDS 83:488 and De Lapaz, J. 2008 MSc Thesis, University of Florida.
Thompson-Crispi, K. et al., 2011 Technical Report to the Genetic Evaluation Board, Canadian Dairy Network
HIR Benefit #1 – Lower Disease Occurrence
Disease by Combined AMIR/CMIR RankOdds Ratios for High vs Average Cows:
2x less mastitis
4x less metritis
1.4x less ketosis
1.3x less retained placenta
HIR Benefit #2 – Better Response to Commercial Vaccines
0
0.2
0.4
0.6
0.8
1
1.2
-8 -3 0 3 6
Group 1
Group 2
Group 3
PM
a
bb
a
aa
a
b
ab
a
b
ab
a
c
b
Ref – Wagter & Mallard et al 2000 JDS 83:488
LsMEANS OF SERUM ANTIBODY TO J5 E. coli VACCINE
HIR Benefit #3 – Greater Amount of Antibody in Colostrum
HIGH RANK FOR SERUM ANTIBODY ALSO MEANS THE HIGHEST RANK FOR WHEY ANTIBODY
0
0.5
1
1.5
2
2.5
3
0 2 3 4 6
Group 1
Group 2
Group 3
PM
a
b
ab
a
b
ab
c
b
a
a
c
b
Ref – Wagter & Mallard et al 2000 JDS 83:488
HIR Benefit #4 – Cost Benefit for HIR Cattle
There is a 3-FOLD benefit in terms of reduced disease/treatment costs relative to the predicted cost of test in the first year
– Reduced disease costs were calculated based on a comparison of risk for disease between HIR and AVG cows
– Costs calculated using the Odd Ratios and current available economic cost estimates
Increase to a 12-FOLD return on investment by the fourth year
Bringing HIR to the Marketplace
1000 dairy producers were sent a letter to participateN=128 producers participated in survey
116 on line (Survey Monkey) and 12 by mailProducers were asked about their operation,
management priorities and attitudes towards health and interest in HIR
Survey and analysis completed by Agri-Studies, an agricultural marketing firm in Guelph, Ontario
Quantitative Market Assessment
Determining Disease Prone Animals
Do some animals seem to be more prone to disease problems
than others?
67%
33%
Yes No
Determining which animals are more prone to disease problems
1%
44%
38%
25%
90%
0% 20% 40% 60% 80% 100%
GeneticTests
HerdRecords
DHIReports
VetReports
VisualInspection
% of Respondents
Dealing with Disease Prone Animals
What do you do with disease prone animals?
45%
22%
33%
0% 5% 10% 15% 20% 25% 30% 35% 40% 45% 50%
Cull them
Treat themdifferently than other
animals
Treat them the sameas other animals
% of Respondents
Producers were Read an HIR Concept Statement
“Researchers have developed a new testing process for dairy cows that allows you to determine which cows in your herd have a greater ability to resist a variety of common diseases like mastitis, ketosis, milk fever and Johne’s disease...
And then asked some further questions
Producers Identify Benefits of HIR
2
2.4
2.4
2.6
2.8
2.8
2.9
2.9
3.1
3.1
3.5
0 0.5 1 1.5 2 2.5 3 3.5 4
Facilitate grouping animals by health and dealing withgroups in different ways
Help in buying new animals that are resistant todisease
Provide information on which animals to push harder
Get a higher price on animals you sell if they havehigher immune ratings
Reduce feed costs
Provide guidance in using vaccines to treat animalsmost likely to have disease problems
Reduce the number of vet visits
Allow me to spend more time with healthy animals
Reduce the use of antibiotics
Provide early identification of animals for culling
Lead to a more productive herd with higherperformance
Importance Mean
Producer Interest in HIR
11%
69%
20%
0% 10% 20% 30% 40% 50% 60% 70% 80%
Very Little Interest
ModeratelyInterested
Highly Interested
% of Respondent
Potential Uses of HIR
6%
31%
4%
59%
0% 10% 20% 30% 40% 50% 60% 70%
Try on at leastsome animals
Use it on milkingcows only
Use it on youngcalves only
Use it on entireherd
% of Respondents
0.00
20.00
40.00
60.00
80.00
100.00
120.00
140.00
160.00
-0.2
0
0.2
0.4
0.6
0.8
1
1.2
1.4
1.6
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15
% In
crea
se in
Ski
n Th
ickn
ess
OD
Val
ue (
1/50
+ 1
/200
)
Sire
Corrected Ab % Skin Thickness
Sire Can Also Be HIR Tested
No adverse reactions and no cross-reactivity were found before and after HIR testing protocol
Summary
Producers are Interested in HIR as a management tool
Cattle (cows, calves and sires) may be ranked by immune response based on animal variation (EBV)
Antibody response in sera is highly correlated in whey
HIR testing in sires demonstrates variability in immune response, with no adverse effects or cross-reactivity
Beta-testing and evaluation of knowledge transfer of HIR will help to improve interest and the adoption of HIR by the dairy industry
AcknowledgementsStudents and PDFsLauri Wagter-LesperanceKathleen Thompson-CrispiArmando HernandezDoug HodginsBrad Hine Maria Nino-Soto
Industry CollaboratorsCDNCanWestDHIGencorSemex AllianceAgri-Studies
Technical SupportShannon Cartwright Laura CainSophia Lim
Funding Support NSERC OMAFRADairyGenBusiness Development Office, U of G
CollaboratorBruce WilkieFilippo MigliorKen LeslieJack Dekkers
