immunopathy V

Question 1

describe amyloidosis

Answer 1

• diverse group of disorders characterized by extracellular deposition and accumulation of abnormal, MISFOLDED protein material generically termed amyloid
• deposits may occur locally in one organ or tissue or systemically in many organs
• amyloid can be seen in the context of cell injury or immunolgoical disease

Question 2

How is amyloid distinguished

Answer 2

• macroscopic starch-like staining reaction with iodine
• microscopic extracellular distribution with special staining (CONGO RED) and optical properties (fluorescence under polarized light)
• protein fibril structure demonstrated by electron microscopy and x-ray crystallography

Question 3

describe the contents of deposits of amyloid

Answer 3

Consist of 2 components

• Amyloid protein FIBRILS (95%) = have the capacity to fold into a Beta-pleated sheet configuration with binding sites for congo red
• Pentagonal component (5%) = glyco-protein related to the normal serum protein from which the amyloid protein is derived

Question 4

describe the pathogenesis of amyloids

Answer 4

• Amyloid proteins are derived from the conversion of SOLUBLE CIRCULATING PROTEIN PRECURSORES into INSOLUBLE (FIBRILLAR) forms
• amyloid fibril types are designated by two letters
• -> A for amyloid followed by letters for the chemical type

Question 5

describe Amyloid light chain type (AL)

Answer 5

• composed of Ig light chains, often gamma, derived from abnormal clones of Ig-secreting plasma cells (B cells)
• 5-15% of casses secondary to multiple myeloma or some other monoclonal disorder of B-cells
• most common is the primary
• usually generalized but involves heart, GI, peripheral nerves, skin and tongue

Question 6

describe Amyloid associated chain type (AA)

Answer 6

• Amyloid associated occurs with INFLAMMATORY or INFECTIOUS STATES (called reactive or secondary amyloidosis)
• fibrils are related to non-immunoglobulin AA protein and its serum precursor (SAA)
• -> acute phase reactant synthesized by hepatic cells stimulated by IL-1 and IL-6 released from activated macrophages
• occurs with chronic cell breakdown (RA, IBD, renal cell CA, hodgkins lymphoma, drug abuse)
• Systemic distribution but tend to involve kidney, liver, spleen, lymph nodes, adrenals

Question 7

describe ATTR

Answer 7

• autosomal dominant depositon of mutant form of transthyretin (serum transport protein for transport thyroxin and retinol)
• in peripheral nerves causes polyneruopathy
• local ATTR deposits also occur in senile systemic amyloidosis

Question 8

describe A-beta 2-microglobulin

Answer 8

• deposition in synovium, joints and tendon sheaths complicates long-term dialysis in patients which chronic renal failure because protein does NOT pass through conventional dialysis membranes

Question 9

describe A-beta protein

Answer 9

• deposited in the cerebral blood vessels and plaques of patients with senile cerebral amyloidosis and alzheimer’s disease; blood vessel deposits may be associated with hemorrhagic cerebrovascular accidents

Question 10

describe the clinical features of amyloidosis

Answer 10

• variable (minimal to life threatening) based on extend of deposits, organ affected
• frequent, severe renal deposits
• cardiac lesions cause CHF, conduction disorders
• GIT lesions cause macroglossia, dysphagia
• localized inovlement cause nodular masses that cause obstruction or mimic tumor
• systemic involvement cause poor prognosis unless good control of etiology (reactive type)