Immunology for getting through to your clients (Proceedings)

Infectious conditions like respiratory diseases, reproductive diseases and neonatal diarrheas continue to "plague" animal owners! To combat these "plagues," there are three management options: 1) increase the resistance to the disease of the animal/herd (vaccination and nutrition), 2) prevent the access of the disease to the herd (biosecurity), and 3) treatment. This discussion will emphasize immunization in an approach that has been beneficial in keeping client:veterinarian:vaccination relationships viable and active.

The basis of immunologic resistance is the recognition and disposal of an invading "infectious organism" by the "immune system" to prevent the establishment of infection and the development of disease. Vaccines have been developed to maximize the natural mechanism(s) of animals to resist and combat infectious disease.

The mammalian immune system has two major components; 1) natural resistance and 2) acquired immunity. Immunization depends on the acquired immune system's ability to identify and dispose of foreign invaders through production of neutralizing chemicals—antibodies—or stimulation of specialized cells—T-cells. Natural resistances are those innate characteristics of mammals that prohibit access of an infectious agent to the host animal.

Natural resistance includes physical and physiological barriers and is a key factor in the survival of all animals. Physical barriers include intact skin and mucous membranes and motility of the intestinal tract and the mucocillary apparatus of the respiratory tract. Natural physiological barriers involve the pH and secretions of the various systems. Species resistance to various microorganisms is due to genetically defined receptors on the surface of the cells, i.e., IBR will not infect swine because the necessary cellular receptor is both host animal and virus specific.

Acquired immunity (immunization) involves complex molecular and cellular mechanisms which 1) recognize an invading foreign substance (ANTIGEN) and develop specific immune responses (ANTIBODIES and IMMUNE CELLS) to dispose of the invader and 2) develop specific memory (ANAMNESTIC RESPONSE) for each invading substance. Acquired immunity consists of several components.

• Antigen recognition: the interaction of the invading foreign antigen (protein) with specific cells and the subsequent stimulation of the appropriate component of the immune system.

• Immunity is the production of specific proteins (antibodies) that appear in the blood. Lymphocytic stem cells differentiate into the "B cell" series that produce specialized chemicals called immunoglobulins or antibodies. Antibodies are able to bind to the specific antigen and "neutralize" its activity.

o The major serum protective immunoglobulins are IgG, and IgM. IgM is the first immunoglobulin to develop in response (5-7days) to the antigen and is "broadly active" (less specific)." IgG develops within 7-14 days and is very specific to the antigen that simulated its production.

• Local immunity is the development of secretory IgA antibodies on the surface of the respiratory, urogenital and GI tracts. In this response, surface lymphocytes of the tracts process and produce IgA; specific epithelial cells in the tracts attach a "secretory protein" to the IgA molecule that makes the immonogloubulin resistant to extreme pH and various enzymes present in tract secretions.

• Cell mediated immunity is the production of specific cells that remove or kill infected cells. CMI results with stimulated stem cells produce "T cells," which recognize certain types of antigen within cells and destroy the "infected" cells before the microorganism, especially viruses, is released from the cell and infects other cells.

• Immunologic memory, or the anamnestic response, permits the humoral and cell-mediated immune systems to "remember previous encounters" and respond more rapidly and specifically when re-exposed to the invading agent--the premise for vaccination. Local immunity has little or no "memory" and must constantly be "reminded" by re-exposure or revaccination. The anamnestic response also recognized magnitudes lesser amounts of an antigen than was required to stimulate the primary response additionally, the memory response routinely results in more antibody production or more "T" cell production. Vaccination does not mean immunization! Vaccination and immunization programs require regular repetitive revisiting of immunization programs and immunology.

o Cell mediated immunity is the production of specific cells that remove or kill infected cells. CMI results with stimulated stem cells produce "T cells," which recognize certain types of antigen within cells and destroy the "infected" cells before the microorganism, especially viruses, is released from the cell and infects other cells.

Factors Affecting the Immune Response

The nature of an antigen has a direct effect on the response of the system to the antigen. Protein is the major stimulant or recognition factor for the immune response. The larger and the simpler the protein, the better the recognition; the more exposed or available to the protein is to the APC system, the better the response. Viruses usually are better antigens because their proteins are usually simple, abundant and unobscured. Bacteria associated with lipids (fat molecules) or carbohydrates (sugar) are poor stimulators of the immune response. Consequently, viral vaccines more reliably induce protective immunity that do bacterial vaccines.

In order for the immune system(s) to be stimulated, a specific amount of an antigen must be present before the system even realizes that a foreign antigen is present. The stimulating, or recognition, dose is called "antigenic mass." The antigenic mass amount is dependent upon the type of foreign substance present; those antigens, like bacteria, that are in association with fats or carbohydrates require more "mass" than simple proteins such as most viruses.

Killed or inactivated vaccines contain the appropriate antigenic mass in the inoculating dose to stimulate the "memory" of the immune system, however, these vaccines usually require two vaccinations 2-4week s to fully stimulate the immune system AND the memory response. The immunogenicity of modern vaccines may be enhanced by the presence of chemical additives called adjuvants. Adjuvants are non-specific enhancers of recognition and processing of antigens and are commonly used in killed vaccines. Unfortunately, adjuvants may also increase the incidence of adverse vaccine reactions especially with repeated vaccinations. Some killed vaccines can now immunize with one injection.

Live vaccines produce the antigenic mass by multiplying within the recipient. Living organisms stimulate both humoral and CMI immune responses and generally stimulate a higher level of immunity because they produce more antigen(s) through the replication/multiplication process. Immunization with living organism vaccines can be blocked by the presence of preformed antibodies such as colostral antibodies.

Route of administration can effect the immune response. Antigens that are presented to the immune system via intramuscular or subcutaneous inoculation stimulate the immune response at similar rates and levels. Oral, or intranasal immunization stimulates local immunity in the respiratory and GI tract while IM or SQ administration stimulates the humoral and CMI responses.

The immune system (both natural resistance and acquired immunity) requires the animal to be in an adequate nutritional state so all cellular and molecular functions are capable of recognizing and responding to limit the invading antigen (agent).

Stress has a major depressant factor on the immune response by the release of glucocorticoids which inhibit the molecular and cellular functions. Nutritional, physical and mental stresses have an adverse effect on the animal's ability to respond immunologically. Management of stress from environmental conditions and rough or improper handling and inadequate nutrition is significant in maximizing the immune response of cattle.

Under current management programs, immunization (vaccine) failure is associated with the sporadic incidence of disease in vaccinated animals. The most common management cause of vaccine failure is failure of administration—that cow that was missed in the chute! The most common biological cause of immunization failure is the inability of the animal to respond to the vaccine administered. It is reported that 5-30% of vaccine recipients fail to respond to an administered vaccine for reasons we cannot define albeit we usually try to blame failure on STRESS!.

Vaccine handling is a significant contributor to vaccine failures. All vaccines should be kept in a cool dark environment. Live product vaccines should also be utilized within 1-2 hours following preparation and delivery systems must be chemically and biologically clean. Lastly, products must not be mixed either in the bottle or in the animal.

References

Veterinary Immunology; An Introduction. 7th Ed. 2004. Ian R. Tizard. W.B. Saunders, Philadelphia.

Lecture Notes on Immunology. 3rd Ed. 1996. G. Reeves and Ian Todd. Blackwell Science, Cambridge, MA.

Fundamental Immunology. 2nd Ed. 1989. W. E. Paul. Raven Press, New York.