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Issue 11, July 2002
About this Newsletter


Researchers Investigate Immunity in Pigs

Producers want to safeguard their investment by having the best pigs possible. They want healthy pigs that recover quickly from infections without costly therapeutic drug treatments. Consumers want safe pork products that contain less drug residues.

Some pigs are naturally healthier than others. They seem to have heightened abilities to fight off infections. ARS researchers are interested in finding out why some pigs in a population respond better to infections. Identifying genes that endow resistance to each of the large number of pathogen infections that impact swine is nearly impossible. Instead of finding beneficial genes for each disease, it might be more useful to find pigs that are better at fighting off pathogens in general.

When invaded by foreign agents, the immune system responds to a complex array of antigens and initiates cell-mediated responses, either type 1 immunity (responding to intracellular infections) or type 2 immunity (responding to extracellular infections and allergens). The type of response that dominates is the one best equipped to combat a particular type of pathogen. Cells in the immune system communicate with each other through hormone-like proteins called cytokines. Cytokines are secreted by cells for each type of response and can suppress the activity of the other. So, the way in which an immune system initially reacts to a pathogen is critical to a pig's health.

Most health problems facing today's pigs are respiratory in nature. USDA's Swine 2000 Survey states that 39.1 percent of deaths in grower/finisher pigs were due to respiratory diseases. Indoor-reared pigs expressing type 1 immunity should be better suited to face health challenges encountered in these production conditions, according to immunogeneticist Joan Lunney, the research leader of ARS' Immunology and Disease Resistance Laboratory (IDRL) in Beltsville, Md.

In cell-mediated immunity, T cells (lymphocytes) respond to invaders by binding to the surface of other cells that display antigens. The cytokine interleukin-12 (IL-12) usually has the primary role in enabling macrophages and T cells to attack invaders using type 1 immunity. IL-12 induces the expression of the cytokine interferon-gamma (IFN-gamma), the main force behind the type 1 immune response. Therefore, a high level of IFN-gamma in a pig after infection may be a good predictor that the animal has developed a strong protective immune response against a virus, although it may not be true for all viruses.

The development of protective immunity in pigs is poorly understood. Gloria Solano-Aguilar, working in Lunney's lab, recently showed that swine responses to IL-12 are lower than in cows. Unlike in other animals, IL-12 does not cause high IFN-gamma responses in uninfected swine. So, there must be other cytokine signals to induce an IFN-gamma dominated response.

Because IL-12 seems to stimulate less of a response in pigs, ARS scientists want to know how IFN-gamma is generated. They want to define which genes control type 1 immune responses in pigs and how they do it. A better understanding of the role that different types of immune effector mechanisms have in mediating protective immunity against pig viral diseases is key to developing effective vaccines.

What Makes A Pig Healthy?

In the coming years, Beltsville researchers hope to find new cytokines and cytokine receptors and identify several new genes, including ones that determine a type 1 response and others that may prevent it. They are cooperating with other researchers to examine the genetics and breeding results of pigs that respond well to IFN-gamma.

Their research has been aimed at defining immune properties that result in pigs with improved production traits and better abilities to respond to diseases and survive. They want to identify and select pigs predisposed to develop a strong type 1 response to viral antigens so they can develop genetic markers for this trait.

Harry Dawson and Joseph Urban of the Nutrient Requirements and Functions Laboratory (NRFL)--part of the Beltsville Human Nutrition Research Center--have led the effort to develop sensitive molecular tests for pig cytokine genes and receptors predicted to be involved in both type 1 and type 2 immune responses. They have collaborated with IDRL researchers Lunney, Dante S. Zarlenga, Ethiopia Beshah and Sandra Nishi to answer the question of which pathogens cause one or the other type of gene expression profile.

Using these tests should also help them identify genes that are believed to play a role in some pigs' ability to resist infection with Toxoplasma gondii, a protozoan parasite that is present in some pigs but usually causes little harm to them. T. gondii is more of a food safety issue because it can cause birth defects when a pregnant woman becomes infected. It can also cause serious problems in AIDS patients or others with weakened immune systems. This team of swine researchers expects to identify pig genes responsible for genetic differences in the ability among pigs to prevent T. gondii from taking hold, and in doing that, identify genes that stimulate type 1 immunity in general. This development would help swine breeders also select for more viral disease-resistant stock.

Researchers at IDRL are collaborating with Kelly M. Lager and Juergen Richt at the National Animal Disease Center (NADC) in Ames, Iowa, to examine a major pathogen impacting pig production. They are looking at responses to respiratory infections caused by swine influenza virus (SIV). They hope to apply their results to Mycoplasma hyopneumoniae, the organism that triggers mycoplasmal pneumonia. M. hyopneumoniae, SIV and porcine reproductive respiratory syndrome virus (PRRSV) are associated with the porcine respiratory distress complex (PRDC). Because pathogens are better able to overcome immune defenses when they work in combination with each other, M. hyopneumoniae can weaken the immune system and encourage secondary infections.

IDRL researchers want to determine how genes develop strong type 1 immune response in pigs by looking at two different viruses and comparing a weak type 1 immunity response to a strong one. With their NADC collaborators, they will compare pigs infected with T. gondii to pigs infected with SIV and PRRSV and examine their unique immune gene expression profiles.

Lunney said a whole series of genes are known to change expression during parasitic and viral infections. She said the Beltsville team is interested in finding out if other pathogens stimulate additional genes, besides those already known about. Additionally, the NRFL scientists are developing the pig as an improved model for human nutrition studies. Urban, Dawson and Solano-Aguilar (now at NRFL) plan to use these gene expression assays to determine the effect of different nutrients on immune functions.

For more information on swine immunity research, contact:

Joan K. Lunney, (301) 504-8201

Joseph Urban, (301) 504-5528

Kelly M. Lager, (515) 663-7371

Research Briefs

ARS' National Animal Germplasm Program has officially added swine to its collection. This will help provide breeders with the genetic tools necessary to develop animals with disease resistance and other important traits. Researchers have also started a national breed survey and developed software to sample breeds. They are also working to improve germplasm cryopreservation.
Harvey Blackburn
(970) 495-3268

Scientists are developing a database known as the Feed Information Technology (FIT) expert system. Through a cooperative agreement with industry, ARS and their partners will identify, define and evaluate relationships between a plant's growing conditions and its nutritional value. The information collected on the chemical composition of forage could help boost a herd's productivity. It could also help the environment by reducing excess nutrients in livestock manure.
David Mertens
(608) 264-5288, Richard Muck
(608) 264-5245

A two-year cooperative study to produce new vaccines for foot-and-mouth disease (FMD) recently began between ARS and a veterinary institute in South Africa. The cooperating scientists are using genetic engineering to develop better vaccines that respond to constant mutation by the FMD virus. Limiting the presence of FMD overseas helps protect U.S. livestock.
Plum Island Animal Disease Center
(631) 323-3202

ARS researchers and collaborators developed a test to help identify sexually active mature sheep. Between 15 and 25 percent of all male sheep in the United States may ignore ewe's mating overtures. The new test is based on the premise that libido is closely linked to the ability to secrete testosterone. Breeders prefer to let their flocks breed naturally and artificial insemination involves high labor costs.
John Stellflug
(208) 374-5306

A new test measures the blood concentrations of a previously little-understood protein to evaluate the health of poultry. Because ovotransferrin (OTF) increases in chickens with infections, ARS researchers believe a better understanding of it, and other acute phase proteins (APPs), could lead to new approaches for improving natural disease resistance in poultry.
Narayan Rath
(479) 575-6189

An ARS researcher is investigating nitrated protein measurement as a biomarker of stress or injury. The naturally occurring proteins may serve as an early warning system and identify an animal recovering from an illness or potentially yielding unsafe meat or milk.
Ted Elsasser
(301) 504-8281

A new system developed by an ARS scientist uses an electrostatic charge to trap airborne dust that harbors Salmonella and other pathogenic bacteria. The system sterilizes pathogens in poultry houses. It reduced Salmonella transmission and other airborne pathogens by 80 to 95 percent in experimental and commercial hatching cabinets.
Bailey Mitchell
(706) 546-3443




Awards

These ARS researchers were honored recently at ARS' annual recognition ceremony:

Donald P. Knowles, Animal Disease Research Unit, was named ARS' "Distinguished Senior Research Scientist of the Year", for his leadership in developing new methods to diagnose animal diseases, such as new diagnostic tools to detect infections in cattle by Anaplasma marginale

The following were among seven individuals recognized by ARS as "Early Career Research Scientists" for their respective areas:

Mitchell V. Palmer, Bacterial Diseases of Livestock Research Unit, National Animal Disease Center, for research leading to the diagnosis and control of tuberculosis in cattle, white-tailed deer and other wildlife.

Timothy P. Smith, Production Systems Research Unit, Roman L. Hruska U.S. Meat Animal Research Center, for research to develop and use genetic maps for cattle and swine in support of the livestock industry.

Tad S. Sonstegard, Gene Evaluation and Mapping Laboratory, for bovine genome research and molecular genetic tools leading to a better understanding of livestock reproduction and lactation physiology.

The following researchers were among eleven ARS scientists honored as winners of 2002 Federal Laboratory Consortium (FLC) Awards for Excellence In Technology Transfer:

Mark C. Jenkins, Parasite Biology, Epidemiology and Systematics Laboratory, for leading his research unit in developing therapeutic methods for people and animals afflicted with cryptosporidiosis. Three biotechnology companies have been licensed to develop vaccines based on his lab's research.

William R. Wolters, Geoffrey C. Waldbieser, and Brian G. Bosworth, Catfish Genetics Research Unit, and Jeffrey T. Silverstein, National Center for Cool and Cold Water Aquaculture Research, for developing an improved catfish line that consumes more and grows faster, reaching market weight sooner than other catfish.

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