Understanding Amyloid and Amyloidosis

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Questions and Answers

What is the primary source of the AL amyloid fibril protein?

Monoclonal B cell proliferation leading to immunoglobulin light chain overproduction (correct)

Renal cells undergoing atrophy

Liver hepatocytes during chronic inflammation

Cardiac myocytes in response to hemodynamic stress

Which organ is characterized by 'Sago' or 'lardaceous' appearance due to amyloid deposits?

Heart

Spleen (correct)

Kidney

Liver

Which of the following is a characteristic feature of renal amyloidosis?

Kidneys with pus-filled lesions

Shrunken and dark kidneys

Kidneys with significant calcification

Large, pale, grey, and firm kidneys with microscopic deposits in glomeruli (correct)

In which condition is AA amyloid protein primarily produced?

Chronic inflammatory states (B) Signup and view all the answers

Which of the following best describes the effect of amyloid deposits in the liver?

Massive enlargement with hepatocyte compression and atrophy (A) Signup and view all the answers

What is the effect of nonfibrillar pentagonal glycoprotein in amyloidosis?

It is derived from serum amyloid P (SAP) and is a component of amyloid deposits (B) Signup and view all the answers

What is a key differentiating factor between primary and secondary systemic amyloidosis?

Primary amyloidosis is caused by immunocyte dyscrasia, while secondary is a complication of an underlying condition. (A) Signup and view all the answers

What is a typical presentation of cardiac amyloidosis?

Mild to moderate enlargement with subendocardial elevations (B) Signup and view all the answers

What is the primary characteristic of amyloid that defines it as a pathological substance?

Its deposition as a proteinaceous substance between cells. (B) Signup and view all the answers

Which of the following is the main problem that occurs due to amyloid deposition in tissues?

Organ malfunction because of tissue damage. (C) Signup and view all the answers

What is the core issue that leads to the formation of amyloid?

The misfolding of proteins from their tertiary structure. (D) Signup and view all the answers

Why are amyloid fibrils so persistent in tissue?

They are resistant to proteolysis. (B) Signup and view all the answers

What does Congo red staining typically show when examining tissue with amyloid deposits?

Pink with apple-green birefringence. (B) Signup and view all the answers

Which of the following is NOT a typical investigational step in diagnosing amyloidosis?

Evaluation of the patient's diet. (A) Signup and view all the answers

What is true about the shape of the amyloid fibrils?

They form unbranched beta-pleated sheets. (A) Signup and view all the answers

How do both oligomers AND fibrils contribute to organ dysfunction in amyloidosis?

Oligomers are cytotoxic, and the fibrils distort tissue architecture. (B) Signup and view all the answers

Which of the following is a direct result of the Membrane Attack Complex (MAC)?

Cell lysis. (D) Signup and view all the answers

In Antibody-Dependent Cell-mediated Cytotoxicity (ADCC), which cells are activated by IgE?

Eosinophils (D) Signup and view all the answers

Which of the following is NOT a typical route of exposure to allergens?

Transfusion (B) Signup and view all the answers

What is the primary event that occurs during the sensitization phase of an IgE-mediated response?

First exposure to an allergen. (B) Signup and view all the answers

What is the result of autoantibodies binding to the TSH receptor in Graves' disease?

Overproduction of thyroid hormones (A) Signup and view all the answers

In Myasthenia Gravis, which of the following is directly blocked by antibodies?

The acetylcholine receptor (D) Signup and view all the answers

What is the key component of Type III hypersensitivity reactions?

Immune complex formation (C) Signup and view all the answers

Which event is a result of complement system activation in Type III hypersensitivity?

Inflammatory response and tissue damage (D) Signup and view all the answers

Which of the following best describes the role of IgG in Antibody-Dependent Cell-mediated Cytotoxicity (ADCC)?

Activate neutrophils and monocytes. (D) Signup and view all the answers

In the absence of a functioning complement system, how can cell lysis still occur in Type II hypersensitivity reactions?

Via the action of inflammatory mediators released by eosinophils, neutrophils and monocytes. (D) Signup and view all the answers

Which of the following best describes hypersensitivity?

An exaggerated immune response to a substance. (B) Signup and view all the answers

During the sensitization phase of a Type I hypersensitivity reaction, which of the following is NOT a direct step?

Binding of IgE to Fcε receptors on mast cells. (A) Signup and view all the answers

What differentiates type I hypersensitivity from other types of hypersensitivity?

It is mediated by IgE antibodies. (C) Signup and view all the answers

Which of these conditions is NOT an IgE-mediated disease?

Type II hypersensitivity (D) Signup and view all the answers

What is the primary mechanism by which mast cells contribute to the immediate phase of a Type I hypersensitivity reaction?

Release of histamine upon cross-linking of IgE (B) Signup and view all the answers

In the late phase of a Type I hypersensitivity reaction, what is the role of eosinophils?

To prolong the inflammatory response. (B) Signup and view all the answers

Which of the following statements best describes the concept of Atopy?

A genetic predisposition to generate IgE-mediated allergic responses. (C) Signup and view all the answers

Which of the following is a characteristic of Type II hypersensitivity?

It's a complement-mediated, antibody dependent response. (A) Signup and view all the answers

What is the function of IL-4 in Type I hypersensitivity reactions?

Activation of naive B cells to secrete IgE (C) Signup and view all the answers

In a second exposure to an allergen, what directly causes the release of histamine from mast cells?

Cross-linking of IgE bound to mast-cell receptors. (A) Signup and view all the answers

Study Notes

Amyloid Definition

Amyloid is a protein deposit in tissues and organs
It occurs in various clinical settings
Causes organ malfunction

Amyloidosis

A group of rare, serious diseases
Caused by abnormal protein buildup (amyloid)
Affects organs and tissues throughout the body
Leads to organ malfunction

Detecting Amyloid

Misfolding of proteins is a core issue in amyloidosis
Abnormal proteins cannot clear; they interfere with cell function.
Proteins pathologically misfold and create linear sheets (beta-pleated)
These proteins resist breakdown (proteolysis)
Accumulate into oligomers, forming insoluble fibrils
The fibrils damage tissue architecture which damages organs
Diagnosis involves biopsy of affected areas (histopathology)
Directly examining the organ or an abdominal fat pad

Amyloid Staining

Congo red staining plus "apple green" birefringence indicates amyloid
Additional tests might include:
- Complete Blood Count (FBC) and Liver Function Tests (LFTs)
- Renal function tests (creatinine, eGFR, 24h proteinuria)
- Cardiac tests (Troponin, ECG, ECHO, MRI)
- Serum protein electrophoresis (SPEP) and light chain quantification
- Bone marrow biopsy
- Skeletal imaging
- Genetic sequencing

Amyloid Components

Non-branching fibrils in beta-pleated sheet conformation
Nonfibrillar pentagonal glycoprotein (Amyloid P component) derived from serum amyloid P (SAP)
Proteoglycans

Amyloid Types

Amyloid light chain (AL) is 90% of cases.
It results from immunoglobulin light chains from plasma cells
Amyloid-associated (AA) is caused by acute phase proteins in chronic inflammation
Derived from SAA
Influenced by cytokines (IL-6 and IL-1)
Transthyretin (ATTR) is another type, associated with heart, lung, tenosynovium, ligaments
Aß amyloid is found in the cerebral lesions of Alzheimer disease

Organ Involvement in Amyloid

Kidneys: Proteinuria, large pale, grey, firm, glomerular deposits.
Spleen: Moderate enlargement, pale, grey, waxy, “Sago” or “lardaceous” deposits.
Liver: Massive enlargement, deposits in space of Disse
Heart: Mild to moderate enlargement, Subendocardial deposits.
Other organs that may be involved include the endocrine system (adrenals, thyroid, pituitary, pancreas), gastrointestinal tract (GIT), tongue, synovial tissue (carpal tunnel), and skin.

Classifications of Amyloidosis

Nonhereditary: primary amyloidosis (systemic, multiple organs involved) and secondary amyloidosis (complication of chronic inflammation or tissue destruction)
Hereditary amyloidosis (often with a specific systemic pattern)

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Description

This quiz covers the definition of amyloid, its role in amyloidosis, and the methods used for detection and diagnosis of this condition. Learn about how abnormal protein buildup affects organs and tissues and the various clinical settings in which amyloidosis occurs.