January 23, 2013

Inherited and Acquired Immune Deficiencies

While the immune system is designed to function perfectly, a lot of things can go awry.

Animals can inherit immune deficiencies as a predisposition to certain diseases. Or they acquire immune deficiencies by virtue of excessive vaccination, poorly balanced diet, hormonal changes, insufficient nutrition, over-use of corticosteroids and other drugs, as well as virus and diseases. Moreover, they can inherit or develop auto-immune disease, which has to be the unkindest cut of all.

In auto-immune dysfunction, the immune system identifies parts of its own body as foreign and attacks them.At other times, the immune system overreacts to foreign invaders by producing too many antibodies or other chemicals (known as hypersensitivity or allergic reactions). Sometimes the immune system does not react at all (immunosuppression) or cannot generate an appropriate immune response. The malfunctions are called immune-mediated disorders.

Auto-immune disorders are classified in four types.

Type I Reactions (Anaphylaxis) Anaphylaxis is a life-threatening, immediate allergic reaction to something that has been ingested or injected. In a healthy immune system, the binding of an antigen to an antibody activates various cells, which produce chemicals such as histamines. In anaphylaxis, the body activates an excessive number of cells, resulting in the production of very large numbers of histamines and other chemicals. These chemicals can affect various organs such as the blood vessels and muscles. The severity of the reaction depends on the type of antigen, the amount of antibodies produced, the amount of antigen, and the route of exposure. Agents that can cause anaphylactic and allergic reactions include biting insects, vaccines, drugs, food, and blood products. The most common signs include restlessness, excitement, drooling, vomiting, abdominal pain, diarrhea, shock, collapse, convulsions and death.

In a Type I reaction, the animal has been previously exposed to an antigen and produces an excess of antibodies. If this antigen appears in the blood, the result can be either anaphylactic shock or more localized reactions (such as itchy patches on the skin). If the antigen enters through the skin, the more localized reaction is typical.

Type I Disorders

  • Anaphylactic Shock
  • Hives (urticaria) and Swelling
  • Allergic Rhinitis (Seasonal Nasal Allergies)
  • Chronic Allergic Bronchitis
  • PIE Syndrome (Pulmonary Infiltration with Eosinophilia)
  • Food Allergies
  • Skin Allergies

Type II Reactions (Antibody-mediated Cytotoxic Reactions) occur when an antibody binds to an antigen present at the surface of its own cells. This antibody–antigen complex then activates a cell-killing series of proteins called complement, resulting in cell death and tissue damage. It is unclear what triggers this antibody-mediated cell killing but, as with all immune-mediated diseases, the combination of both external factors and an infection can lead to the development of this type of reaction. It has been suggested that some viral infections as well as overuse of antibiotics and cortisteroids can lead to changes in regulation of the immune system. This can either trigger an overreaction of the immune system or convert protective immunity into a disease.

Signs of Type II hypersensitivity vary depending on the organ in which the reaction is occurring. Signs can include fever, kidney failure, vomiting, diarrhea, abdominal pain or joint swelling. Hypersensitivity is diagnosed by physical examination and by biopsies of the damaged organ.

Type II Disorders 

  • Immune-mediated Hemolytic Anemia (IMHA) 
  • Immune-mediated Thrombocytopenia (IMT)
  • Autoimmune Skin Disorders 
    • Pemphigus foliaceus
    • Pemphigus vulgaris
    • Bullous pemphigoid 
  • Myasthenia Gravis

IMHA and IMT are life-threatening conditions and require immediate veterinary treatment often including blood transfusions. Autoimmune skin disorders are unsightly and painful. They are treated with immune-suppressing drugs. Even with treatment, prognosis is poor for animals that inherit or develop Type II Antibody-Mediated Reactions.Some humans and dogs diagnosed with myasthenia gravis do well with supportive treatment.

Type III Reactions (Immune Complex Disease) occur when a large number of antigen–antibody complexes lodge in certain organs, causing damage to blood vessels. There are many possible reasons for the continuous presence of antigens, including persistent infections caused by viruses, bacteria, fungi or parasites. In addition, antibody responses to certain drugs can occur, particularly in the case of long-acting drugs or drugs that are given continually over a long period of time. Some animals can react and produce antibodies against self antigens. However, in many cases, the cause of the disease is unidentifiable.

The most commonly affected sites include the joints, skin, kidneys, lungs and brain. Signs vary and may include fever, lameness that shifts from leg to leg, painful or swollen joints, behavioral changes, vomiting, diarrhea and abdominal pain. An immune-complex disease is usually diagnosed with blood tests.

Type III Disorders

  • Glomerulonephritis
  • Systemic Lupus Erythematosus (Lupus)
  • Vasculitis
  • Anterior Uveitis
  • Immune-mediated Arthritis
    • Canine rheumatoid arthritis
    • Plasmacytic-lymphocytic synovitis
    • Idiopathic polyarthritis
  • Immune-mediated Meningitis

Type IV Reactions (Cell-mediated Reactions) or delayed hypersensitivity occurs more than 24 hours after the body was exposed to an antigen. The antigens usually responsible for the development of Type IV reactions include bacteria, parasites, viruses, chemicals and certain cell antigens.This type of reaction can occur in any organ. For this reason the signs will vary. The reaction is diagnosed based on excluding other causes for organ-specific diseases and by laboratory tests on the tissue. The goals of treatment are to provide support based on the organ-specific disease process, to identify (if possible) and eliminate the source of the antigen causing the reaction and to relieve inflammation and immune suppression.

Granulomatous Reactions
  • Old Dog Encephalitis
  • Contact Hypersensitivity
  • Autoimmune Thyroiditis
  • Autoimmune Adrenalitis
  • Dry Eye (Keratoconjunctivitis Sicca)

Immunoglobulin Deficiency is a failure of the body to produce antibodies (immunoglobulins). This deficiency can be acquired (caused by other diseases) or congenital (present at birth). Congenital deficiencies of one type of immunoglobulin (immunoglobulin A, or IgA) have occurred in Beagles, German Shepherds and Chinese Shar-Peis, leading to respiratory infections, digestive system disorders, skin disease or allergies.

Acquired deficiencies occur in puppies that do not receive adequate maternal antibodies when nursing during the first several days of life. For older animals the cause is often a decrease in antibody production.

Combined Immunodeficiency Disease involves a defect in both cell-mediated immunity and antibody production. Affected animals lack both T and B cells, which makes it impossible for the body to fight foreign invaders. Cases have been seen in Bassett Hounds, Toy Poodles, Rottweilers and mixed-breed puppies. Affected dogs are healthy during the first several months of life but become progressively more susceptible to bacterial infections as the antibodies they received during nursing disappear. No treatment is available and the longterm outlook is poor.

Selective Immunodeficiencies Rottweiler puppies have a predisposition for severe and often fatal canine parvovirus infections. Their resistance to other diseases is essentially normal. The basis of this selective immunodeficiency is unknown. Localized and whole-body fungal infections affect certain types of dogs. Long-nosed breeds, in particular German Shepherds and shepherd mixes, are more likely to develop fungal infections in their nasal passages. Whole-body aspergillosis (a type of fungal infection) is seen almost exclusively in German Shepherds and occurs more commonly in western Australia than in other areas. Signs of this disease include infection of the kidneys, bones and the discs between the vertebrae of the spinal cord.

Immunodeficiencies Caused by Viruses These types of diseases can be caused by a number of viruses in animals. In dogs, distemper virus causes a profound immunodeficiency in infected puppies. The infection is associated with a progressive decline in levels of antibodies and an increased susceptibility to bacterial infections that are normally controlled by the immune system. Parvovirus infection in dogs causes a huge decrease in the number of white blood cells and a weakened immune response to bacterial and fungal infections.

Lymphoma - Immune System Tumors Cancer occurs when cells grow out of control. This can happen with the cells of the immune system. The normal immune system requires a rapid increase in the growth of lymphocytes to fight foreign invaders. On occasion however, this increase in the growth of lymphocytes may be uncontrolled, which causes a tumor called "lymphoma". Lymphoma is one of the most common tumors in dogs. Boxers, Basset Hounds and Rottweilers are predisposed to developing lymphomas, which primarily affect middle-aged and older dogs. Lymphomas can occur in the lymph nodes, spleen, liver and other organs.

Gammopathies in Dogs are conditions in which there is a dramatic rise in the production of the antibodies. There are two general types. In polyclonal gammopathies, levels of all the major immunoglobulins are increased. In monoclonal gammopathies, the levels of only a single type of immunoglobulin are increased.

  • Polyclonal gammopathies may occur when a dog has long-term skin disease or long-term viral, bacterial or fungal infections. Some long-term parasitic infections, rickettsial diseases and immunologic diseases (for example, rheumatoid arthritis) may also cause polyclonal gammopathies.  
  • Monoclonal gammopathies may be either benign and associated with no known cause or potentially associated with immunoglobulin-secreting cancers. Doberman Pinschers are predisposed to monoclonal gammopathies. The signs of monoclonal gammopathies vary depending on the location and severity of the source tumor(s). For example, tumors frequently develop in the cavities of flat bones in the skull, ribs,pelvis and in the spinal cord. Fractures of diseased bones can lead to central nervous system problems, spinal disorders, pain and lameness. Signs can also be caused by the presence of the monoclonal antibodies themselves. In about 20 percent of dogs with monoclonal gammopathies, blood changes occur that can cause blood clots, bleeding problems, depression, blindness and other nervous system signs. In some conditions, the animals develop gangrene and lose portions of the ear tips, eyelids, toes or tail tip.

The tumors that produce immunoglobulins can be treated with several medications. Remission may occur after treatment, but the overall outlook is poor and relapse is common after 6 to 12 months.
Clearly there's a lot that can go wrong in an animal's immune system. In almost every instance, conventional wisdom is to suppress it with drugs or surgically remove it.

Here's the rub.

Allergy symptoms are the body's expression of imbalance. Suppressing them does not move the body toward health; it simply silences the "sounds" of dysfunction. Yet the very symptoms we want to suppress are required for healing. Suppressing symptoms either drives the disease deeper or brings it back with a vengeance when the suppressive effects of the drug's action subside.

Could it be that we need a broader view of health in order to prevent immune damage in our companion animals or support the immune system in the direction of health (homeostasis) for those whose immunity is already damaged?

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