Gordon King, Animal & Poultry Science, University of Guelph

For many centuries the prevailing belief was that disease represented divine retribution for sin and must be endured with patience and humility. The Reformation (17^th century) fostered alternate ideas so more attempts to treat, control or even to eradicate the most devastating problems began. The first effective use of vaccines in veterinary medicine started with the discoveries of Louis Pasteur during the latter half of the 19^th century and Paul Ehrlich in the late 19^th and early 20^th centuries, which established that living micro-organisms were the cause of specific diseases. Through concentrated effort involving research and its practical application, elimination of certain contagious diseases was possible in some regions. Such progress is still mainly limited to affluent countries possessing the ability to devote substantial resources towards surveillance and eradication activities by regulatory agencies. In addition, adequately trained and equipped veterinary practitioners are available for the treatment and prevention of disease in affluent societies with intensive livestock production. This is often not the situation in many developing regions where a substantial proportion of the world's livestock are forced to exist.

Any deviation from "normal" anatomical structure or physiological function represents disease. The cause might be non-infectious when resulting from injury, malnutrition, toxic substances or genetic anomalies; or infectious if produced by pathogenic viruses, bacteria or parasites. Acute and chronic diseases in livestock cause billions of dollars in production losses each year so disease prevention is an essential component of sound management. While maintaining animals in good health does not alone insure high production, any animals that must use some of their nutrients to overcome illness can never perform to their full genetic potential. Producers must work with veterinarians and other professional advisers to design and construct suitable physical conditions, to provide adequate amounts of a balanced ration always, to reduce exposure to disease-inducing agents through sanitation and to increase immunity to specific pathogens through vaccination.

The four main causes of death are injury, infection, malignancy or degenerative processes but it is the first two that cause almost all morbidity and mortality in younger animals. Any mechanism that reduces the incidence and severity of these conditions should substantially increase the productivity of livestock. The important body processes for accomplishing this are healing and immunity. Sound management, in addition to reducing the chance of injury or exposure to potential pathogens, provides conditions that enhance the animals' ability to build or acquire immunity to prevalent diseases.

Some terms that should be familiar to people working in animal health:

Acute disease - appears quickly and is soon resolved through either recovery, a progression to a chronic state or death.

Chronic disease - a condition that persists for weeks, months or even years.

Clinical disease - one in which obvious signs of abnormality are present.

Sub-clinical disease - an insidious condition with pathogenic organisms present in the body but overt signs of disease are absent.

Morbidity Rate - the incidence or prevalence of a disease in a population.

Mortality Rate - the death rate due to a disease.

The overall health of animals on any farm is regulated by management practices. The most effective routine procedures which can be used to maintain excellent health within any herd or flock are: 1) minimize exposure to potential disease causing agents and 2) promote resistance in animals that might be exposed to potentially infectious agents through good nutrition and active immunization.

Defensive Mechanisms

Injury or local infection usually provokes inflammation, a localized protective response characterized by classical signs of pain (dolor), heat (calor), redness (rubor) and swelling (tumor). Microscopically, inflammation involves a complex series of events including vascular and cellular changes. One initial event is increased blood flow, dilatation and permeability of blood vessels, resulting in the warmth associated with an inflammatory response. This is accompanied by the exudation of leukocytes, plasma proteins and other factors from capillaries throughout the affected area. The body's defense mechanisms attempt to minimize the extent of injury or infection and eventually to restore normal structure and function. Occasionally, the containment process fails and a systemic infection results.

One of the major challenges for any animal is differentiating between what is "self" or part of its own body, and what is "non-self" or foreign. The entire organism, through all of its physiological systems, attempts to preserve an environment in which "self" cells and tissues can function effectively. One of the essentials in maintaining this status is the rapid detection and elimination of "non-self" cells or other foreign material that gains entry into the body before it can interfere with normal function. All cell membranes contain a series of molecules, the Major Histocompatibility Complex (MHC), that are unique for each individual. Immune cells are conditioned not to respond to "self" but recognize and mount a response against any "non-self" material they encounter. Thus, immunity is concerned with the recognition and disposal of "non-self" materials that might gain entrance to the body. Foreign materials are usually in the form of infectious and often life-threatening micro-organisms or toxins. Several related mechanisms interact to resist the initial entry and persistence of foreign material and to ensure the removal of damaged host cells. These constitute the immune system.

Natural Immunity. The body's first line of defense is its natural, innate or non-specific mechanisms that are present in all individuals and available at very short notice to protect from a foreign invader. These act against any non-self material without needing to wait for programming and proliferation of specially sensitized lymphocytes and, if successful, prevent initial entry or result in rapid removal from the body.

Natural mechanisms may be summarized as:

1. Physical Barriers a) skin and mucous membranes; b) secretions, sneezing, coughing, etc. that provide flow or movement carrying foreign particles out of the body orifices; c) soluble factors (pH, fatty acids, enzymes, lysozymes, interferons, cytokines) that may denature or immobilize foreign materials.
2. Phagocytes - Neutrophils and macrophages which engulf and degrade foreign particles. Much of the foreign material that manages to pass beyond the physical barriers is eventually disposed of by these cells.
3. Natural Killer Cells. A specialized subset of lymphocytes that kill by binding to target cells and releasing lytic particles. Tumor cells and virus-infected cells are believed to be their major targets.

Acquired Immunity. Acquired or active immunity is a specialized response that supplements the protection provided by natural immunity. The ability to mount an immune response to foreign protein or "non-self" cells is present at or shortly after birth in domesticated animals but is not exhibited until after exposure to specific foreign material. Initial contact with a foreign agent (antigen) initiates a chain of events (immunization) resulting in activation of certain lymphocytes (cellular response) and synthesis of antibodies (humoral response) with specific activity against the antigenic material.

Any acquired immune response has several general characteristics:

• Discrimination - the ability to recognize and respond to molecules that are "non-self" while avoiding response to "self" material.
• Adaptive - ability to respond to previously unseen molecules.
• Specificity - ability to differentiate between different molecules and to respond in required rather than random manner.
• Memory - ability to recall previous contact with particular "non-self" molecules and to respond in a more rapid and stronger manner.

The lymphocytes are major components in all immune responses. These small, usually spherical cells with very little cytoplasm, are found circulating in the blood and continually trafficking through all tissues of the body. In addition to the natural killer cells described above, the lymphocytes are further subdivided into T cells that function mainly in the cell mediated immunity, and B cells that can acquire the ability to form specific antibodies in the humoral immune process.

The Humoral Immune Response. Whenever material with foreign MHC is encountered by B lymphocytes, an association forms between the cell and the strange material. In most instances, this non-self substance contains components called antigens that act to stimulate defensive processes in the lymphocytes. Many of the motivated B cells transform into plasma cells which are prolific factories synthesizing and releasing large quantities of specialized protein called antibody. Each unique antibody (immunoglobulin) possesses the ability to bind with the specific antigen that stimulated its production. Through this binding process antibodies can neutralize toxins or viruses and immobilize, agglutinate or precipitate microorganisms and other foreign particles so these are more readily phagocytized.

Check the CELLS Alive site "How Lymphocytes Produce Antibodies" for illustrations of the cell-to-cell interactions involved in antibody production.

Immunoglobulin Types, Major Locations and Actions

IgG - distributed approximately equally between intravascular and extravascular spaces

- IgG is an opsonizing antibody that reacts with the surfaces of microorganisms so the foreign cells can be phagocytized more readily by macrophages and neutrophils

IgA - most found in secretions like mucus, saliva, tears and sweat

- IgA has anti-viral and anti-microbial properties so functions as the primary defense against infection of the respiratory and gastrointestinal tracts

IgM - present mainly in blood vessels

- IgM works with complement to agglutinate foreign particles

IgE - very low concentrations in serum

- IgE probably helps in overcoming infections by microorganisms and parasites

Following the initial invasion of foreign material and its interaction with B lymphocytes, it takes days or weeks before large quantities of antibody appear in the body. Some of the stimulated B cells, however, instead of differentiating into antibody producing plasma cells, persist as memory cells. If the original stimulating antigen is ever encountered again at some future time, the memory cells provide a much more rapid response and antibody appears almost immediately. This provides the animal with potential protection against the disease if repeated exposure occurs.

Figure details. Once the components of the active immune system are programmed by any specific antigen, memory cells remain long after the initial response is terminated and circulating antibodies have declined to very low concentrations. If the same antigen is ever encountered by the immune system at some future date, no programming or learning phase is necessary so antibody production begins at once and the response is greater and persists for a longer period.

Cell Mediated Immune Response. T lymphocytes also have receptors that respond to "non-self" and the T cells are attracted towards any foreign (antigenic) material that gains entry into the body. There are several different sub-populations of T cells whose functions after being stimulated include:

• helper T cells that cooperate with B cells to enhance antibody production;
• cytotoxic T cells that contact foreign cells directly and attempt to kill them;
• inflammatory T cells which produce and release certain lymphokines that attract macrophages and neutrophils towards foreign materials ;
• suppressor T cells that modulate activity of other cells.

As is the case with B lymphocytes, the T lymphocytes are activated and become specific in their response to particular antigens. Also, after the first stimulation, a clone of memory cells remain so response to a second challenge with the same antigen results in a much faster response.

Although the humoral and cellular components of the immune system have been considered separately, they work very closely together and with the natural immune system, attempting to protect and ensure survival of the host.

While it is focused primarily on human information, the Virtual Explorer provides an excellent overview of the modern principals of immunology.

Immunoprophylaxis

Immunoprophylaxis represents one of the most significant accomplishments of scientific research.

Active Immunity. Just as immunity to an infectious disease is induced by exposure and usually remains in an infected animal after recovery, resistance can be induced through administration of the appropriate antigen by vaccination (immunization). The antigen that is injected, usually in the form of a toxin, microorganisms, viruses or some component of these, must be inactivated (attenuated) in some way so that it is no longer capable of causing the disease. A second or booster injection of the antigen produces an anamnestic response in just the same manner that a subsequent infection would.

One active and very promising research area is the development of engineered vaccines. Whenever whole microorganisms, either killed or attenuated, are injected into an animals body, side-effects resulting from the multitude of potential antigens or even toxins present in the original preparation are always a potential problem. Molecular immunologists are now attempting to isolate individual antigenic components (subunits) from bacterial cell membranes or virus particles and selecting only those most capable of stimulating a protective response. These are then produced in quantity for use in vaccines. Some of the methods involved are:

Recombinant DNA technology. DNA containing the desired genomic sequence is isolated from the pathogenic organism and inserted into appropriate expression vector (i.e.. tissue cultures, plasmids, nonpathogenic organisms, bacteriophage, etc.). The vector then is induced to manufacture large quantities of the antigen for use in vaccines. In some instances, the vector itself might be injected into an animal to stimulate an immune response.

Synthetic Products. The amino acid sequence of individual antigens is determined and the critical peptide length is synthesized through appropriate chemical reactions.

Monoclonal Antibodies. Under special conditions in vitro, B lymphocytes with the ability to make a specific antibody can be induced to fuse with myeloma cells. This produces hybridoma cells which, like the neoplastic myeloma cells, can survive and replicate in culture and, like the contributing B cell, produce immunoglobulin. Continued culture of the hybridoma cells results in large quantities of the antibody which can be purified for therapeutic or diagnostic use.

Passive Immunity. This results when antibody collected from an actively immunized animal is administered to a second, non-sensitized animal. The protection persists only as long as the administered antibody remains in the recipient animal and there is no associated memory to protect against subsequent exposures.

If a dam has immunity to any specific antigen, she will usually confer passive immunity to her offspring. Thus, active immunization of the mother provides an effective means of providing newborn animals with passive protection that lasts for a few weeks or months. Many animals receive maternal antibodies through the placenta prior to birth. Unfortunately, the domesticated mammalian species commonly found on livestock farms have placentas that do not allow transfer of large protein molecules like antibodies. The immunoglobulins can, however, also be passed through the mammary tissue and into the milk. Thus, the first milk (colostrum) contains elevated concentrations of IgG's and this persists for a few days. Provided colostrum is ingested soon after birth, it can confer passive protection to the offspring.

The digestive system of almost all animals is populated by numerous micro-organisms that contribute to digestion of ingested food material. Under normal conditions this is a symbiotic balanced relationship with a very high proportion of beneficial organisms and very few potential pathogens. Newborn animals, however, have no intestinal flora but must obtain these from the environment during the first few days or weeks after birth. This is a critical stage since the balance of micro-organisms is easily disrupted and the immune system may not be fully developed. Any excessive stress that might be inflicted through nutritional deficiencies, environmental problems or excessive exposure to potential pathogens could induce imbalance, resulting in intestinal inflammation, poor digestion, impaired absorption and diarrhea. Such intestinal disorders, along with pneumonia, are the major causes of neonatal mortality under all livestock management systems.

Breeding for Health

The results obtained from some recent research investigations indicates that conventional genetic selection procedures combined with appropriate testing can produce animals with better or worse than average immune responses to antigenic challenge. Further development could enable breeders to develope commercial lines with increased resistance to disease.

Controlling Disease Incidence

The health (disease) status of any herd, flock, band or group of livestock depends on the degree of exposure to potential disease causing agents and the animals ability to resist these. The following figure illustrates these two aspects and the major factors affecting them.

The overall health of animals on any farm is regulated by management practices. The most effective routine procedures which can be used to maintain excellent health within any herd or flock are: 1) minimize exposure to potential disease causing agents and 2) promote resistance in animals that might be exposed to potentially infectious agents through good nutrition and active immunization. Most people keeping domesticated animals realize that bacteria, viruses and other micro-organisms are responsible for diseases and that livestock must be protected from infectious agents or treated whenever signs of illness appear. Unfortunately, many are not aware of the importance of proper nutrition and an environment that minimizes stress in promoting animal health.

Minimizing exposure involves detecting and removing any objects or agents that might induce physical injury. This should be combined with controlling the entry of animals, people, equipment, feed, bedding materials, supplies and especially pets, rodents or birds that might introduce infection. A reduction in exposure to infectious agents already present in the environment can be accomplished through cleanliness and sanitation, reducing direct animal to animal contact by avoiding mixing of groups, all-in all-out management and isolation of sick stock. Increased resistance to infection is obtained through disease prevention programs which promote active immunity to specific diseases in young animals and maintain this in older stock.

Detecting Unhealthy Animals.

The early detection and treatment of diseased animals is extremely important aspect of sound health management. Early signs of illness are:

• lethargy, dullness or droopiness
• Staying apart from herd or flock mates
• abnormal behavior or posture
• loss of appetite
• coughing, sneezing, wheezing, etc.
• abnormal excreta

The physiological values fluctuate considerably within these normal ranges. Generally, values are higher in younger animals and following exercise or excitement. Any pathological condition beyond the most minor diseases usually produce persistent values outside the normal ranges.

General Recommendations for Minimizing the Incidence of Disease in Livestock Units

• Provide an appropriate facility and adequate space for all animals.
• Always maintain very young animals within their comfort zones.
• Avoid any temperature extremes and sudden changes for all ages.
• Insure adequate ventilation in all confinement units. Usually about four air changes per hour in winter but considerably more in summer.
• Practice good sanitation at all times. Manure should be removed as often as practical.
• Obtain replacement animals from sources that maintain excellent health status.
• Isolate all new introductions for a sufficient period before allowing full entry into your facility.
• Follow an all-in all-our system whenever possible.
• Thoroughly clean and disinfect the premises between departure of one group and the introduction of the next.
• Ensure that animals always have adequate amounts of an appropriately balanced ration
• Provide ample, potable water.
• Protect feed and water from fecal contamination.
• Test feed ingredients for nutrient content and for the presence of spoilage or toxins. If inferior materials must be feed, always mix these with quality feeds to minimize any effects.
• Supervise parturitions and provide assistance if required.
• Ensure that neonates receive colostrum soon after birth.
• Immunize young animals against endemic diseases and provide booster treatments for older animals as appropriate.
• Do not mix species.
• Keep different age groups separate.
• Control internal and external parasites.
• Observe all stock regularly for abnormal behavior or other signs of disease.
• Begin treatment quickly whenever diseases are detected.
• Isolate sick animals.
  

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