Understanding Amyloid and Amyloidosis

A group of rare, serious conditions caused by a build-up of an abnormal protein called amyloid in organs and tissues throughout the body.

A pathologic proteinaceous substance deposited between cells in various tissues and organs of the body in a wide variety of clinical settings.

The deposition of various types of amyloid in tissues leads to organ malfunction.

Misfolded proteins are resistant to breakdown, aggregate, and form insoluble amyloid fibrils.

Diagnosis involves identifying amyloid deposits in biopsy specimens through staining and examination.

Congo red staining and apple green birefringence under polarized light.

1. Non-branching fibrils in a beta-pleated sheet conformation
2. Amyloid-associated proteins
3. Extracellular matrix components

1. FBC, LFTs
2. Renal function tests (creatinine, eGFR, 24hr proteinuria)
3. Cardiac tests (troponin, ECG, ECHO, MRI)
4. Serum protein electrophoresis (SPEP)
5. Bone marrow biopsy
6. Skeletal imaging
7. Genetic sequencing

Nonhereditary amyloidosis can be classified into two types: systemic and localized.

Primary amyloidosis is a rare disorder where the body produces abnormal amounts of amyloid protein due to an overproduction of immunoglobulin light chains from plasma cells.

Secondary amyloidosis is a complication of chronic inflammatory conditions, where the body produces an overproduction of acute phase proteins.

Localized amyloidosis affects only one organ, such as the heart or the kidney.

Hereditary amyloidosis is a rare condition caused by genetic mutations that lead to the production of abnormal amyloid proteins.

The most common type of amyloid fibril protein is AL, which is derived from immunoglobulin light chains produced by plasma cells.

AA amyloid is derived from serum amyloid A (SAA), a protein produced in the liver during inflammation.

An exaggerated response by the immune system to a drug or other substance, often seen in autoimmune diseases, allergies and other immunopathologies.

The first exposure initiates the sensitization process where antigen-presenting cells (APCs) present the antigen to naïve T cells, activating them into TH2 cells. These TH2 cells then produce IL-4 and IL-5. IL-4 stimulates naïve B cells to produce IgE, which binds to mast cells. IL-5 activates eosinophils, enhancing the inflammatory response.

The second exposure triggers a rapid and potent immunological reaction. The antigen binds to IgE on mast cells, cross-linking them, and leading to the release of histamine, which increases vascular permeability. This is the early, acute phase response. The late phase response, occurring 6-12 hours later, involves the recruitment of monocytes, eosinophils, and T cells, further prolonging the inflammatory response.

A genetic predisposition towards developing allergic diseases like allergic rhinitis, asthma, and atopic dermatitis (eczema). Atopic individuals are more prone to producing IgE.

Type I: Immediate hypersensitivity (IgE mediated) Type II: Antibody-mediated cytotoxicity Type III: Immune complex deposition Type IV: Delayed hypersensitivity (cellular)

1. Rhinitis (hay fever)
2. Asthma
3. Urticaria (hives)
4. Angioedema
5. Anaphylaxis
6. Eczema (atopic dermatitis)

The complement system is activated by the presence of IgM or IgG antibodies bound to antigen. This activation triggers a cascade of events that leads to the lysis of cells or the recruitment of inflammatory cells.

The body's immune response to environmental allergens, involving the release of chemicals like histamine, causing symptoms like sneezing, runny nose, and itching.

A protein complex that forms on the surface of cells targeted for destruction by the immune system, leading to cell lysis.

Substances that trigger an allergic response in the body, commonly found in inhaled, injected, ingested, or contacted materials.

A type of immune response where IgE antibodies attach to mast cells, causing the release of inflammatory mediators when exposed to the specific allergen.

The first exposure to an allergen, causing sensitization of the immune system.

The rapid response to an allergen after sensitization, characterized by the release of histamine and other inflammatory mediators.

The delayed response to an allergen, occurring hours after the initial exposure, characterized by the infiltration of immune cells into the affected tissues.

A type of hypersensitivity reaction where antibodies attack the body's own cells, causing cell lysis.

A type of hypersensitivity reaction where immune complexes (antigen-antibody aggregates) deposit in tissues, activating complement and causing inflammation.

The process of immune complexes depositing in tissues and activating the complement system, leading to inflammation and tissue damage.