Immunopathology 4 By Dr. Mays - PowerPoint Presentation

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Immunopathology 4

By Dr. Mays

Ibraheem

Amyloidosis

is a disorder characterized by the extracellular deposits of

misfolded proteins that aggregate to form insoluble fibrils (beta-pleated sheet) conformation.Generally amyloid deposits cause tissue injury and impair normal function by causing pressure on cells and tissues but they do not evoke an inflammatory response.Common features of Amyloid:Individual subunit form β-pleated sheetsOn H&E stain- looks amorphous eosinophilic depositsOn Congo red stain- looks as red depositUnder polarized light- looks Apple green birefringence

Amyloidosis

Pathogenesis of Amyloidosis:

The deposition of proteins in amyloidosis may result from:

1- Excessive production of proteins that are prone to misfolding and aggregation; 2- Mutations produce proteins that cannot fold properly and tend to aggregate;3- Defective or incomplete proteolytic degradation of extracellular proteins.

Amyloid

light chain (AL):

Immunoglobulin light chainsDerived from plasma cells; lambda light chain amyloid occurs more often than kappa; associated with plasma cell tumors (e.g., multiple myeloma).Amyloid-associated (AA):Synthesized by hepatocytes as part of the “acute phase response”; AA amyloid is associated with chronic inflammatory states.β-Amyloid (Aβ):It derives from a transmembrane amyloid precursor protein, forms the core of cerebral plaques and deposits within cerebral vessel walls in Alzheimer disease.Transthyretin (TTR): A normal serum protein that binds and transports thyroxine and retinol. Excess amounts of normal TTR can deposit in geriatric hearts

β2-microglobulin:

Component of class I HLA molecules and a normal serum protein; complicates long-term hemodialysis.

Types of Amyloidosis

1

. Systemic (generalized), involving several organ systems, or

2. Localized, when deposits are limited to a single organ.Classification of Amyloidosis

is

associated with the following conditions

Primary amyloidosis:AL type of amyloid that form of fibrillary protein: kappa or lambda light chains e.g. is plasma cell disorder (multiple myeloma, and B cell lymphomaReactive systemic amyloidosis( secondary amyloidosis)AA type of amyloid in the form of serum amyloid SAA (acute phase reactant protein elevated with ongoing inflammation and neoplasia) e.g. are Rheumatoid arthritis , systemic lupus erythematosus, TB, cancer , etc.Familial Mediterranean fever AA type of amyloid in the form of SAA, it is an Autosomal recessive disease cause recurrent inflammation, fever, and neutrophil dysfunction.Hemodialysis associated amyloidosis:β2 microglobulin amyloid in patients on chronic hemodialysis. This cause carpel tunnel syndrome and joint disease

Systemic amyloidosis

Senile

cerebral amyloidosis( Alzheimer disease)

Aβ amyloid found in Alzhiemer plaque in cerebral vesselsSenile cardiac amyloidosis:TTR amyloid (transthyretin), men more than 70 years and may cause heart failureEndocrine type Occurs in tumors associated with hormone synthesis; example, thyroid medullary carcinoma making procalcitonin that deposit as amyloid fibrils.Localized type:

Kidney

:

Most commonly involved organ in the form of nephrotic syndromeHeart: Can cause restrictive cardiomyopathy and low voltage ECG with arrhythmias and congestive heart failureHepatosplenomegalyGastrointestinal tract: Present with tongue enlargement and malabsorptionDiagnosis of amyloidosis: by biopsy of the rectal mucosa, gingiva or the abdominal fat padClinical features

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