Chapter 20. AUTOIMMUNE DISEASES & IMMUNODEFICIENCY DISEASES PG.REDDY

 

20.1 Summary of Major Objectives

This chapter is intended to give a basic understanding on the concept and etiology of autoimmune diseases with some examples of autoimmune diseases in domestic animals. More extensive discussion on organ-specific autoimmune diseases of domestic animals will be made in Spring Semester (Microbiology 202). Treatment strategies in general for some diseases are also discussed.

This chapter also deals with immunodeficiency disorders with some examples for animals. Students are expected to answer questions on the etiology, consequences, and treatment of some of these disorders.

 20.2 Introduction

Ability to discriminate between self and nonself is an essential and primary function of the immune system. Autoreactive lymphocyte clones exist normally and may be accompanied by low levels of autoantibody. Homeostasis is maintained by intrinsic regulatory controls which prevent an abnormal increase in effecter cells and antibodies that may cause autoimmune disease.

Autoimmune disease is caused by abnormal or excessive activity on the part of immune effecter cells. The defect may be due to the effecter cells, the regulatory system or the genetic apparatus or combinations of any of these. While the exact mechanism is not clearly known, it is likely that the major histo-compatibility complex is an important component.

20.2.1 Mechanisms of autoimmunity:

• 1. Release of sequestered antigens: certain tissues (lens of the eye, sperm, central nervous system) are normally sequestered from immune system. When these tissue antigens enter circulation autoimmunity may occur causing endopthalmitis, aspermatogenesis, or encephalitis.
• 2. Tolerance may be terminated by cross-reactions (host response to streptococcal antigens that cross-react with heart tissue antigens - Rheumatic fever.
• 3. Diminished suppressor T cell function - Suppressor T cells may limit immune response to self antigens. A decrease in suppressor T cell function may cause formation of antibodies to self antigens (autoantibodies against normal IgG - resulting in rheumatoid arthritis).
• 4. Viral infections may induce autoimmunity - Viruses, particularly those that infect lymphoid tissue, may interfere with normal immunological control mechanisms resulting in autoimmunity.

  As a result of induction of autoimmunity, the mechanisms of tissue damaging action can be by Type 1, 2, 3 and 4 Coombs-Gell reactions and augmented by means of lymphokines and the humoral system components, i.e., complement, coagulation, kinin and fibrinolytic systems.

  20.2.2 Examples of some autoimmune diseases in domestic animals:

• Involving Type I hypersensitivity: Milk allergy in cattle - delayed milking may increase intrammary pressure and force alpha casein into circulation - affected cows may show acute systemic anaphylaxis.
• Type II hypersensitivity: autoimmune hemolytic anemia, myasthenia gravis, Grave's disease etc.
• Type III hypersensitivity: Membranous glomerulonephritis, rheumatoid arthritis.
• Type IV hypersensitivity: Experimental allergic encephalitis, juvenile diabetes mellitus.

  AUTOIMMUNE DISEASE AUTOANTIBODIES DIRECTED AGAINST

• Autoimmune thyroiditis Thyroglobulin, thyroid colloid antigen
• Type I diabetes mellitus Pancreatic islet cells
• Autoimmune skin diseases Intercellular cement in the skin
• (Pemphigus foliaceous,
• pemphigus vulgaris)
• Autoimmune hemolytic anemia Erythrocytes
• Autoimmune thrombocytopenia Platelets
• Sjogren's syndrome Lacrimal and salivary glands
• Myasthenia gravis Acetyl-choline receptors
• Rheumatoid arthritis IgG
• Systemic lupus erythematosus Nucleus and DNA
• Grave's Disease Thyroid stimulating hormone receptors

20.3 Immunodeficiency Diseases

An immunodeficiency disease is the result of an immune defect either due to a single cause or in combination with the following defense mechanisms: cell-mediated immunity, humoral immunity, complement reaction and phagocytosis. The defect may be congenital or acquired and may be secondary to an embryological abnormality or of unknown etiology.

Recognition of immunodeficiency diseases in patients: chronic and/or recurring infections; unusual infectious agents (opportunists), and incomplete response to treatment.

Examples:

1. Chediak-Higashi Syndrome: observed in cats, mice, mink, cattle, man, white tigers, and killer whales. Characterized by abnormally large granules in PMN, monocytes, and eosinophils and defective chemotactic responsiveness and reduced capacity for intracellular killing. Further, the NK cells have reduced ability to kill targets. Affected animals suffer from recurrent infections and lymphoid tumors.

2. Canine spinal muscular atrophy: observed in Brittany spaniels that are homozygously deficient in C3. The third component of complement is opsonic, chemotactic and activates of the lytic sequence. These dogs have an increased susceptibility to bacterial sepsis or local bacterial infections.

3. Canine Granulocytopathy Syndrome: PMN have defective killing ability but are morphologically normal. Commonly seen in Irish setters. Affected dogs suffer from recurrent bacterial infections, gingivitis, and lymphadenopathy. Autosomal recessive condition.

4. Mac-1 deficiency: Mac-1 is a glycoprotein found on surface of phagocytic cells and acts as a complement receptor. Deficiency has been demonstrated in Irish setters.

5. Gray Collie Syndrome: Genetically determined defective function of PMN seen in collie dogs.

Several other inherited deficiency diseases occur in animals. The most important is the combined immunodeficiency syndrome in Arabian foals. Affected foals fail to produce functional T or B cells. Foals that suckle thrive for 2-3 months because of the maternal Ig but eventually die in 4-6 months as a result of overwhelming infections.

STUDY QUESTIONS

1. Define immunological tolerance. Distinguish tolerance from the immuno-suppressive effects of drug treatment.

2. How can autoimmune diseases be artificially induced in animal models?

3. What is an opportunistic infection? List several agents.

4. What is the role of T suppressor cells in regulation of immunity?

5. Distinguish between a poylclonal and monoclonal gammopathy.

REFERENCES

1. Veterinary Immunology, Chapters 24 and 26 (Tizard).

2. Veterinary Clinical Immunology, Chapter 20 (Halliwell & Gorman).