Amyloidosis and Basic Complement System CIS Flashcards
Describe the pathway that leads to amyloidosis.
Inflammation leads to hepatic production of SAA protein. Inadequate breakdown and/or excessive accumulation leads to to amyloidosis.
What results from a renal biopsy would lead one to suspect the presence of amyloids?
Pink deposits identified on microscopic examination. Nuclei not evenly dispersed.
What is the clinical indication that would lead one to suspect amyloidosis, leading to a kidney biopsy?
LE edema. Proteinuria leads to fluids leaking out of blood vessels and accumulate in tissues.
How is the Congo red stain used to test for amyloidosis?
If amyloids are suspected, Congo Red stain can be applied. A polarized light filter will glow “apple-green” if amyloid is present.
How can mutant forms of amyloid become harder to degrade?
By the inclusion of more beta pleated sheets.
Explain how the alternate complement pathway is initiated.
Autoactivation via spontaneous splitting of C3a to C3b. C3b cleaves Factor B into Ba and Bb. Bb combines with C3b and C3 convertase is formed.
What serum protein enhances the successive proteolytic steps of C3bBb (C3 convertase)?
Properdin
Describe the lectin complement pathway.
Mannose-binding lectin (MBL) recognizes terminal mannose residues on bacteria. This activates MASP1 and MASP2 (mannose-associated serine protease). They act similarly to C1 and triggers downstream effects identical to classical pathway.
How does membrane cofactor protein (MCP) limit complement activity?
By cleaving C3b and C4b (factor 1 mediated)
How does decay-accelerating factor (DAF) limit complement activity?
By destabilizing C3/C5 convertase of the CP and AP
How does complement receptor type 1 (CR1) limit complement activity?
Decay accelerating activity and cleavage of C3b and C4b (factor 1 mediated).
How does CD59 limit complement activity?
By preventing the formation of MAC.
How can the complement system contribute to Glomerulonephritis?
Can result from deposition of immune complexes or antibodies binding to antigens in kidney, activating the classical pathway of complement. Leads to protease release, RO intermediates, and inflammatory cytokines.
How can the complement system contribute to Vasculitis?
Complement can be mistakenly activated by immune complex deposition or direct antibody interaction. Leads to classical pathway.
How can defects in the complement system cause hereditary angioedema (HAE)?
Mutation in C1 inhibitor. Leads to continuous activation of plasma complement. C1 inhibitor also inactivates kallikrein, leading to an increase in bradykinin, causing swelling.
