VPP 211: General Veterinary Pathology (1+1)

AUTOIMMUNE DISEASES

Definition

The animal reacts to its own tissue (endogenous antigen) to incite production of antibodies or sensitized lymphocytes. There is breakage of tolerance to the self-proteins.

• Autoimmune diseases are prevented by elimination of sensitized T and B lymphocytes by the process of apoptosis in the thymus and bone marrow during development (Central tolerance; clonal deletion), in the peripheral tissues (Peripheral tolerance) and clonal anergy (Clonal avoidance) by defective presentation of cells.
• The tolerance of CD4+ T_H cells is critical in preventing autoimmunity. Two major autoimmune diseases are thyroiditis and haemolytic anemia. Other conditions are rare in animals.

Autoimmune thyroiditis

Causes

• Genetic predisposition (Doberman dogs)
• Autoantibodies
• Lymphocyte mediated mechanisms

Pathogenesis

• Exact mechanism is not known. There is involvement of T lymphocytes.
• Microscopically, thyroid shows interstitial lymphoplasmacytic infiltration with germinal centres. The thyroid follicular epithelial cells are destroyed by T cells in dogs, causing hypothyroidism.
• Signs: Obesity, lethargy, alopecia, hyperlipidosis and pyoderma in dogs.

Autoimmune haemolytic anaemia

• The disease is characterized by severe haemolytic anaemia and thrombocytopenia, regenerative anaemia with high reticulocyte counts. Erythrocytolysis occurs following antigen-antibody attachment to the surface membrane of erythtocytes or by removal of such cells by the splenic macrophages. There will be low haemoglobin with spherocytosis and direct Coombs test (antiglobulin) is positive.
• Cryopathic autoimmune haemolytic anaemia (Cold haemagglutinin disease in dogs and horses): The dog is anaemic. Anaemia is observed only when the animal is having IgM auto-antibodies or exposed to cold.
• Grossly, lesion is seen in the nose, ears and extremities in dogs.
• Microscopically, capillary stasis, agglutination and lysis of erythrocytes are seen.

Myasthenia gravis

• The autoantibodies bind to acetylcholine receptors at motor endplates resulting in progressive muscular weakness and low exercise tolerance.
• Lymphocytic infiltration in synaptic clefts occurs at a later stage interfering with release of acetylcholine and diminishing the total area of postsynaptic contents. Congenital disease occurs in Jack Russell and smooth fox terrier dogs.

Pemphigus

• It is characterized by bullae formation in the skin and mucous membrane of dogs and humans.
• Oral mucosa is affected in dogs with loss of epithelial cell coherence and acantholysis. Autoantibodies are produced against epithelial cell glycopoteins. The variant of pemphigus is known as pemphigus foliaceous in which painful skin disease develops in the face and ears.
• The bullae form under the stratum corneum progressing to scabs and alopecia. Footpad lesions are common e.g. Bearded collies.
• In autoimmune pemphigoid, antiglycocalyx antibodies are produced against keratinocytes which affect basement membrane of epithelium.

Idiopathic polyradiculoneuritis

• It is a group of diseases of inflammation of peripheral nerves, nerve roots and ganglia, characterized by mononuclear cell infiltration, axonal degeneration and axonal reactions in lower motor nerves

Idiopathic polyneuritis in dogs (Coonhound paralysis)

• There is ascending symmetrical paralysis beginning 7-14 days after scratches or bites of raccoons, progressed to tetraparesis. The animals are alert and show initial signs of weakness to flaccid symmetric quadriplegia and may be segmental demyelination with perivenular lymphoid infiltration in the ventral nerve roots of spinal cord and some peripheral nerves.

Neuritis of the cauda equine

• Neuritis of the cauda equine (Guillain-Barre syndrome-idiopathic polyneuritis, a postinfectious paralytic disease that typically follows Influenza infection) in which segmental demyelimation is seen in spinal nerve roots of horses. Disintegration of myelin and infiltration of mononuclear phagocytes and macrophages into the sacral intradural rootlets, resulting in paralysis of tail and urinary and anal sphincters.

Systemic autoimmune diseases

• Canine lupus erythematosus: A rare disease in which progressive haemolytic anaemia, thrombocytopenic purpura, proteinuria and polyarthritis are seen. Renal failure causes death due to glomerulonephritis and plasma cell infiltrations.
• Thymus shows medullary lymphoid follicular development. Lymphocytic infiltration is seen around the dermal blood vessels of dogs. The anaemia is acute with severe haemolysis and positive antiglobulin (Coombs) test.
• Platelet destruction (autoantibodies to platelets) leading to thrombocytopenic purpura is manifested as haematuria, epistaxis, petechiae and ecchymoses in the skin and mucous membrane.