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Department of Medicine and Epedimiology, School of Veterinary Medicine
University of California
The following excerps are based on notes used in the teaching of clinical immunology to veterinary students.
Host cells are rendered foreign when specific foreign antigens are elaborated on their
surfaces, and are thus rendered targets for attack by specific T-cells and activated
macrophages. Malignant cells may express new antigens on their surface; these antigens
may be unique to the body or were expressed only during embryogenesis and prior to the
time that self-tolerance is induced. Cells that are infected with microbes are also rendered
foreign. Foreign proteins produced within the cells by the microbe are transported to the
cell surface and expressed on the major histocompatibility complex-I (MHC-I). Host cells
may also be rendered foreign when their surface antigens are chemically altered, as in the
case of contact hypersensitivities to plastics, drugs, or other substances. In rare cases,normal cells can come under attack by killer T-cells by mechanisms that are identical to
those described for autoantibody responses (Wucherpfennig et al., 1995). These various
mechanisms are amply illustrated by the number and variety of immune disorders of dogs
that have a type IV immune etiology.
It must be stressed that immune diseases are not due to a distinct and pathologic type of immune response; rather, they are the result of normal types of immune responses that occur in a dysregulated fashion, for an excess duration, in an abnormal location, or against antigens that are not normally considered to be foreign. Type I (allergic) diseases are associated with the IgE system, which is one of the primary defenses against parasite attacks. Type II (auto- and allo-antibody reactions) involve the formation of antibodies that react against self-antigens. Type III reactions involve the deposition and clearance of immune complexes, which are essential features of normal immune responses. Type IV diseases involve cellular immunity, which is the most important immune defense against pathogens or pathogenic states involving cells. Type V diseases involve excessive production of immunoglobulins or parts of immunoglobulins, while Type VI diseases occur when something impedes normal immune defense mechanisms, either innate or adaptive.
There are six general factors that underlie most immune diseases of dogs. The foremost is genetic susceptibility. About 60% of dogs are now purebred, and purebreeding always involves inbreeding. Because of the great diversity of immune mechanisms, and hence the genetic complexity of its development and regulation, it is understandable how inbreeding can result in a spectrum of disorders ranging from dysregulation of the immune system and autoimmunity at one extreme to cancers at the other. Although it may be oversimplistic, the susceptibility to autoimmune diseases is thought to be controlled by the interplay of environmental and heritable factors; the latter involving genes of the major histocompatibility complex (MHC) (Campbell and Milner, 1993).
The gender of the dog is the second most common cofactor (Quimby et al., 1980); intact females have the highest incidence of immune diseases and intact males the lowest, as has been observed in humans. The gender bias is not nearly as obvious with widespread spaying and castration. Ovariohysterectomy reduces the incidence, while castration increases the incidence, thus tending to equalize gender effects in neutered animals.
The third most common factor underlying immune diseases is the presence of other immunologic disorders. If a certain breed or bloodline of dogs suffers from one immune disease, they will also have an increased incidence of a wide range of other immunologic disorders, as demonstrated in a study of the Old English sheepdog (Day and Penhale, 1992). Plasmacytic/lymphocytic thyroiditis and hypothyroidism is a common occurrence among dogs that develop other types of immune diseases. Dogs with systemic lupus erythematosus may also present with autoantibody associated cytopenias.
The fourth most common cofactor is infectious diseases. Infections can trigger allergies, the formation of autoantibodies (Adachi et al., 1992), immune complex diseases, cell-mediated pathologies, gammopathies, or immunodeficiencies. 22.214.171.124. Perianal adenitis and perianal fistulae. Inflammation of the circumanal apocrine sweat glands, leading to severe perianal fistulae, occurs predominantly in German Shepherd Dogs, and to a lesser degree, Irish Setters (Killingsworth et al., 1988). The incidence is higher in males than females and is greater in intact as compared to neutered animals. The perianal abnormalities have been associated with histological evidence of colitis as well (Harkin et al., 1996). Perianal lesions vary greatly, even in the same dog, in degrees of fibrosis, severity of inflammatory response and depth of sinus tracts (Killingsworth et al., 1988). Lesions tend to be in the zona cutanea, and hidradenitis with formation of epithelial-lined sinus tracts is apparent in over one-half of the biopsies examined. In another study dealing with anatomic predisposition, the only predisposing cause between German shepherds and other non-affected breeds was in the greater number of apocrine sweat glands in the zona cuneata (Budsberg et al., 1985). Secondary bacterial infection, with a number of different bacteria, is inevitably present (Killingsworth et al., 1988).
Before the immunologic nature of the disease was discovered, the treatment of choice was often surgical excision of the fistulous tissues, or Glucocorticoids and special diets (Ellison, 1995; Harkin et al., 1996; Holt, 1985; Viehoff and van Slujis, 1993). The accepted treatment is now cyclosporine (Matthews and Sukhiani, 1997; Matthews et al., 1997).
The development of allergies is also influenced by genetics (Huang and Marsh, 1993). If both parents have atopy, 75% of their children will be atopic. If one parent has atopy, the chances are 50%. Similar genetic predispositions have been seen in animals, especially among purebreds.
The most effective control of systemic allergic reactions is to avoid re-exposure to the offending allergen. This is easily done when drugs are the offenders, because alternative products are usually available that are not allergenic. However, vaccines, which are the most common cause of such reactions, are more problematic for veterinarians. Many veterinarians believe that booster vaccinations are absolutely essential and are unwilling to forego their use even when they have previously evoked an allergic reaction. If systemic allergic reactions to vaccination are life-threatening (i.e., anaphylactic shock), the risk of subsequent immunizations will far out-weigh the negligible benefits provided by booster vaccinations. The chances of an older and well-vaccinated dog getting potentially fatal infections like canine distemper, infectious canine hepatitis, parvovirus enteritis, leptospirosis or rabies are extremely low, and the other vaccinatable diseases, such as kennel cough, parinfluenza, Lyme borreliosis, and coronavirus enteritis are of limited clinical relevance in the general dog population. Even concern about the legal requirement for rabies boosters should not override common sense; a waiver can usually be obtained for rabies vaccinations when the use of such vaccine is life threatening. If systemic allergic reactions to vaccines are severe, but not life threatening (hives, angioneurotic edema), pretreat the animal 1 h before immunization with antihistamine and prednisolone. Give 1/10th the vaccine dose; if no adverse reaction is seen in 10± 20 min, administer the remainder. Changing brands or types of vaccine will seldom prevent the problem, because most vaccines contain similar offending allergens. However, leptospirosis bacterin is the worst offender and the least essential vaccine, and can easily be left out of the vaccination regimen.