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CHAPTER 5 Disorders of the Immune System AUTOIMMUNE DISEASES - aka "collagen vascular diseases.

" They may be specific for one organ system or multiorgan diseases. (Table 5-1) SLE - the quintessential autoimmune disease (type III hypersensitivity) (Table 5-8) A multi-organ system disease. 10 times more common in females. Incidence varies; but, it is common (roughly 1 in 3,000), and more common and more severe in black Americans. Table 5-9 illustrates diagnostic features of common autoimmune diseases. While ANA is positive in a large number of persons with SLE, it is also present in a very large percent of patients with other autoimmune diseases (false positive for SLE). It is a sensitive test but not selective. The two most reliable tests for SLE are the Smith antigen and antibodies to double-stranded DNA. Both tests are highly specific (almost no one else was positive) but not very sensitive (many with the disease tested negative - false negative). Of interest is androgens seem to protect from SLE and there may be a genetic predisposition for it (higher than normal occurrence in monozygous twins). Ten year survival about 70%. Renal failure and infections frequent causes of death.

System Sclerosis (SS) - aka scleroderma. Skin primary organ involved but it is also a multi-organ system disease. May be diffuse (more severe form) or limited (localized, less severe). The marker for the diffuse form of the disease is antibodies to DNA topoisomerase I (ScI-70), seen in 70% of patients. In the limited (local) form, anticentromere antibodies are pretty selective., seen in 90% of patients. IMMUNODEFICIENCIES : PRIMARY: Brutons Disease/ X-linked agammaglobulinemia An inherited condition that deals with the failure of pre-B cells to mature into functional B-cells. Due to a lack of the enzyme Bruton tyrosine kinase. Therefore, the number of B-cells in the circulation and the levels of all antibody classes are reduced or absent. There is also depletion of plasma cells. T-cell levels are normal. The disease becomes apparent about 6 months after birth when maternal antibodies wane. Clinical problems are usually due to bacterial infections---sinusitis, ear infections, etc. Administration of pooled human serum is helpful.

Isolated Ig-A Deficiency: This is the most common primary immunodeficiency disease. Many people are asymptomatic. Weakened mucosal defenses lead to sinusitis and chronic diarrhea. The problem is with terminal differentiation of Ig-A secreting B-cells into plasma cells.

Rheumatoid arthritis (RA) - May involve more than joints (and usually does). Four or five times more common in females. About 1% of population affected. Unlike some other forms of arthritis, RA is usually symmetrical affecting smaller joints first (where as osteoarthritis affects large weight bearing joints). Characteristic features include pannus formation, deformity, fibrosis or anyklosis, and rheumatoid nodules. See Figure 5-23. After 15-20 years, persons may be incapacitated. Life span reduced by 5-10 years.

Thymic Hypoplasia (DiGeorge Syndrome) Results from congenital maldevelopment of the thymus, and, therefore, T-cell development. T-cells absent in the peripheral blood but B-cell numbers and antibody production are normal. People are susceptible to infection with intracellular bacteria, viruses and fungi.

Sjgren syndrome - aka sicca syndrome. Frequently seen with RA. CD4 cells attack salivary and lacrimal glands. Most specific tests are the SS-A (Ro) and SS-B (La) (Sjgren specific antibody "A" and "B").

Severe Combined Immunodeficiency Disease: A group of genetic syndromes that have defects in both humoral and cellular immunity. Infants are susceptible to severe infections from a wide variety of pathogens. One of the most common forms of the disease is caused by the enzyme deficiency adenosine deaminase (ADA). The thymus and lymph nodes are undeveloped. Usually treated with bone marrow transplant.

C1 Esterase Inhibitor Deficiency: C1 esterase is involved in activating the first component of complement. A hereditary defect in the inhibitor for C1 esterase allows for uncontrolled inflammation and edema. Oral-facial tissues swell from the edema. The condition is called angioedema.

AMYLOIDOSIS Amyloidosis is a multi-disease process (more than one disease can produce amyloid, a predominantly protein product). Amyloid has a structure that is made up of protein fibrils ordered in a pattern known as a ! -pleated sheet. A pleated sheet is one of several structural proteins. Amyloid deposition occurs outside of the cells (between the cells). It is especially common about blood vessels. There are two major groups of amyloid, one comprised of immunoglobulin light chains proteins (AL - amyloid light chain) and the other comprised of non-immunoglobulin proteins (AA amyloid associated protein). Immunocytic dyscrasias with amyloidosis(primary amyloidosis) - Malignant proliferations of B cells in bone marrow typically produce quantities of immunoglobulins and light chain components of immunoglobulins. It is this light chain production that leads to the formation of AL seen in primary amyloidosis. This is the most common form of amyloidosis. These light chains also form what is known as Bence-Jones protein, a protein product excreted in the urine of affected individuals. Multiple myeloma (MM) is a bone marrow malignancy of plasma cell (transformed B cells). They also produce light chains and immunoglobulins. Patients with MM do get amyloidosis, but much less frequently (about 10%) than those with primary amyloidosis. About 70% of patients with MM also have elevated light chains and is diagnostic for MM. Also, patients with MM get multiple "punched-out" radiolucent lesions in bones (and may include the jaws). Consequences - Most common outcome of systemic amyloidosis is renal failure and heart failure due to accumulation of amyloid impairing function.