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Vol.18, No. 9September 1996Continuing Education Article
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FOCAL POINTKEY FACTS
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Commercial vaccines arenot available for all importantinfectious agents.
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The humoral (antibody) andcell-mediated systems can bestimulated by vaccination.
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The immune response is furtherseparated into systemic andmucosal compartments.
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Passive immunity (maternalantibody) can interfere withactive immunization.
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Disease prevalence, housingstressors, population density,and exposure to other animalsinfluence selection of avaccination protocol.
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Veterinarians must understandthe strengths and limitations ofavailable vaccines and know thetypes of protection needed todefend animals againstpathogenic organisms.
ImmunologicPrinciples andImmunization Strategy 
Bradley Animal Hospital Abilene, KansasLawrence, Kansas
Robert L. Larson, DVM, PhD, ACTJohn S. Bradley, DVM
C
ontrolling infectious disease is a primary concern for practicing veteri-narians. Proper nutrition, environment enhancement, stress reduction,minimization of exposure to pathogens, and use of effective vaccinesare all important for the control of infectious disease.Numerous vaccines have been developed for controlling infectious agentsthat cause disease in animals. For the vaccines to produce an optimum im-mune response and decrease the risk of disease, they must be used in accor-dance with the principles of immunology. This article reviews basic immuno-logic principles that affect the development of protection against infectiousagents and considers how to apply these principles when developing an immu-nization program.
BASIC IMMUNOLOGIC PRINCIPLES
Immunization implies that after vaccination, the animal develops a protec-tive immune response against the invading pathogen. A proper vaccinationprotocol must select the correct antigen and deliver it in an optimum fashionand at the correct time to elicit a response that can protect the animal. In gen-eral, a successful immune response should produce the same humoral and cel-lular response that results from natural infection. To achieve this goal, the de-livery system should place the vaccine in association with lymphoid cells in thetarget tissue.
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Effectiveness of vaccination is influenced by the age, nutrition,immune status, and overall health of the recipient. When selecting diseases to include in a vaccination program, immunization with every available vaccine may be wasteful and unjustifiable (see Some Ques-tions to Consider). Some vaccines that have been manufactured for controllingcertain infectious agents are not efficacious. Other diseases for which vaccinesare available are not a primary concern in all geographic areas. The vaccines se-lected should be limited to those that produce protective immunity and for which there is a risk of disease.
 
Humoral Immune System
Two parts of an animal’s defense mechanism can bestimulated by vaccination: the humoral (antibody) sys-tem and the cell-mediated system. The humoral systemconsists of B lym-phocytes (non–thy-mus-derived lym-phocytes); plasmacells; and immuno-globulins (antibod-ies)—that is, IgG,IgM, IgA, and IgE.For an antigen tostimulate immuno-globulin production,the antigen must beprocessed (primarily by macrophages) andpresented to B lym-phocytes. In thepresence of antigen,specific lymphocytesare transformed intolymphoblasts thatrapidly increase innumber. These acti-vated B cells eitherdifferentiate into im-munoglobulin-pro-ducing plasma cellsor remain as memo-ry B cells. Each plas-ma cell producesonly one class-specif-ic immunoglobulinto a specific antigen. Approximately 80% of immuno-globulin activity inserum is IgG. IgGbinds to and op-sonizes antigen. The resultant complex activates thecomplement cascade.
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IgM, which is effective in com-plement fixation and opsonization, is the first im-munoglobulin produced in an immune response.
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Lym-phoid tissue located near mucosal surfaces producesIgA. IgA does not activate complement or opsonizebacteria but acts to prevent antigens from binding tomucosal surfaces. IgE is associated with tissue mastcells. When IgE binds to an antigen, the mast cells re-lease vasoactive agents such as histamine. The vasoac-tive agents cause a local inflammatory response thatfloods the tissue with immunoglobulins and phagocyticcells.
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IgE also plays a primary role in the immune re-sponse to helminth parasites.Immunoglobulin against surface antigens on bacteriamay confer protection from disease. Examples includeantigens from the flagellum, pilus, capsule, or cell wall.Conversely, a humoral immune response to antigensfrom inside living bacteria is unlikely to be protectivebecause internal antigens are inaccessible to im-munoglobulins. These internal antigens include cyto-plasmic antigens as well as certain cell-wall and mem-brane antigens.Similarly, immunoglobulins against external viralantigens (e.g., envelope and capsid antigens) may pro-vide protective immunity from viruses. Immunoglobu-lins against internal viral antigens (e.g., core proteinantigens) do not provide protective humoral immunity from viral pathogens.
Nonspecific Immune System
 Assisting the humoral system is the nonspecific im-mune system, which includes phagocytic cells (granu-locytes and macrophages), natural lymphocyte killercells, and complement. The nonspecific immune sys-tem is not directly affected by either vaccination orprevious exposure to an infectious agent. This systemcan respond to an infectious agent almost immediately and is crucial in the initial control of infection. Thehumoral and cell-mediated systems require 2 weeks toreach optimum function after the first exposure to anantigen. On second exposure to the same antigen, theresponse is rapid. This anamnestic response is the pro-tective principle on which vaccination is based. Theanamnestic response is the result of immunologicmemory provided by special classes of lymphocytes(memory cells).Immunoglobulin molecules alone cannot destroy in-fectious agents but do activate the nonspecific defensemechanisms and improve their efficiency. Im-munoglobulins may coat infectious agents, thereby minimizing the likelihood that the agents will attach tohost cells. Immunoglobulins may agglutinate infectiousagents (thus reducing their infectivity) and directly bind to and neutralize toxins. Immunoglobulins alsoact by working with other cells or effector molecules by binding to and marking an antigen so that phagocyticcells, cytotoxic cells, or complement destroys the infec-tious agent.
Cell-Mediated Immune System
The cell-mediated system consists of macrophages,lymphocytes, lymphokines, and monokines. The sys-tem is organized by thymus-matured lymphocytes (Tlymphocytes) that recognize specific antigens.
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 When
Small Animal
The Compendium 
September 1996
IMMUNE SYSTEMS
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IMMUNOGLOBULINS
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ANAMNESTIC RESPONSE
Some Questions to Consider
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Is it likely that sufficientimmunity to protect theanimal against a givendisease is already present?
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Could immunity already bepresent and thus inactivatethe vaccine?
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What is the nutritional statusof the animal?
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What is the health status ofthe animal?
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Does the animal havepossible immunosuppressionattributable to physiologicstressors or pharmacologicintervention?
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What is the level of exposurethat the animal is likely toencounter for the disease(s)being considered forvaccination?
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If cost is a factor for theclient, which veterinaryservice (vaccinations ordiagnostic screeningprocedures) is moreappropriate?
 
an animal is exposed to a disease or a vaccine that in-duces cell-mediated immunity, the T lymphocytes thatrecognize the antigen respond by replicating themselvesthrough mitosis. With reexposure to the same antigen,a large number of T lymphocytes (T memory cells) rec-ognize it and replicate. The T lymphocytes attempt todestroy the infectious agent directly and by secretinglymphokines. Lymphokines are proteins that direct andencourage other white blood cells to attack and destroy the agent.Cell-mediated immunity is particularly important forprotection against facultative intracellular viral and bac-terial pathogens. The cell-mediated system can destroy infected cells, thereby releasing the invading organismso that it can be destroyed by phagocytic or killer cells.Internal antigens as well as external and secreted anti-gens can induce a protective cell-mediated response.This response differs from the humoral response be-cause antigen processing and presentation of internalantigens by an antigen-presenting cell can induce a cell-mediated response that can destroy invaded host cells.The cell-mediated system may recognize antigens thatremain on the surface of host cells after viral penetra-tion, viral antigens synthesized by the host cells and ex-pressed on the cell surface, or processed antigens associ-ated with major histocompatibility complex (MHC)class I molecules.
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Cytotoxic T lymphocytes may destroy cells that ex-press viral antigens associated with MHC class Imolecules; such destruction is believed to be importantin protective immunity against many viral diseases.
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The T-helper lymphocytes responding to antigens asso-ciated with MHC class II molecules may mediate pro-tection from viral disease through secretion of lym-phokines. Lymphokines may make cells resistant toviral infection, damage viral infected cells, and enhanceactivity of cytotoxic cells (e.g., macrophages, neu-trophils, and natural killer cells).
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Systemic and Mucosal Immune Systems
The immune response is further separated into twodistinct compartments: systemic and mucosal. Systemicimmunity derives from cells in the spleen or lymphnodes, whereas mucosal immune responses are generat-ed by lymphoid tissue associated with mucosal surfacesor the associated draining lymph nodes.
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It is especially difficult for the immune system to protect animalsagainst infection on mucosal surfaces, such as the in-testinal, reproductive, and respiratory tracts.
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Most of the antibody classes responsible for humoral immunity as well as the white blood cells responsible for cell-me-diated immunity are not found on mucosal surfaces.Parenteral antigens usually result in a systemic im-mune response, whereas antigens transferred across amucosal surface induce mucosal immunity.
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 Whetherparenteral or local immunization is necessary for pro-tection depends on the pathogenesis of the disease.Mucosal immunity is particularly beneficial when theroute of exposure of a pathogen is the same as that of the target tissue. Examples of local immune stimulationare the intranasal use of attenuated infectious bovinerhinotracheitis (IBR) virus vaccine against respiratory disease in calves, intranasal use of 
Bordetella 
and
Parainfluenza 
vaccines for control of infectious tracheo-bronchitis in dogs, and intraocular or intranasal use of vaccine to control calicivirus infection in cats. The in-tranasal route has the advantage of inducing systemicimmunity as well as local antibody and cell-mediatedimmunity in the respiratory tract.
Protective Responses
The type of immune response that protects an ani-mal against infectious disease varies between pathogensand depends on the route of introduction and site of replication of particular organisms. Protection may re-sult from the presence of circulating immunoglobulins(humoral immunity), sensitized T lymphocytes (cell-mediated immunity), immunoglobulins on mucosalsurfaces, or a combination of these factors.
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Humoral immunity is important for protectionagainst extracellular phases of systemic viral and bacte-rial infection and for protection against endotoxin- andexotoxin-induced diseases.
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Cell-mediated immunity isimportant in combating facultative intracellular bacte-rial pathogens (e.g.,
Brucella 
), intracellular viral infec-tion (e.g., herpesvirus), fungal disease, and protozoaldisease.
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ANIMAL FACTORS OF IMMUNOLOGY
Numerous factors can influence an animal’s defensemechanisms and thus affect the immune response tovaccination. Factors important to an effective vaccina-tion program include the blocking effect of colostralantibody, the age and nutritional condition of the ani-mal, and the effect of concurrent infection. All of thesefactors affect an individual’s immune status.One of the most common problems associated withvaccination is interference of passive immunity (mater-nal antibody) with active immunization.
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For example,immunization of puppies against canine parvovirus 2 iscommonly prevented or delayed because of maternalinterference. The interference probably occurs whenpassively derived maternal antibody binds to the vac-cine antigen, thus resulting in clearance of the vaccineantigen from the body before it stimulates an immuneresponse.
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The level of maternal antibody that can in-
The Compendium 
September 1996Small Animal
CELL-MEDIATED IMMUNITY
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PARENTERAL ANTIGENS
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INTERFERENCE
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