Complement System Flashcards
Define the Complement System
- a defensive system consisting of over 30 serum & membrane-expressed proteins
Describe complement activation
- its a cascade
- works within minutes
What are the main components of the complement system ?
- hepatocytes
- epithelial cells of the gut
- blood - monocytes
- tissue macrophages/dendritic cells
What are the 3 complement pathways ?
- classical pathway
- Lectin pathway
- alternative pathway
Are the pathways innate or acquired ?
- classical pathway = acquired
- lectin pathway = innate
- alternative pathway = innate
What are the main activators of the alternative pathway ?
any foreign substance in the absence of specific Ab;
- lipopolysaccharides from the cell walls of gram-negative bacteria
- cell walls of some yeasts
- viruses
- aggregated Abs
- necrotic cells
What is the most abundant complement protein ?
C3
Describe the initiation of the alternative pathway
- C3 contains unstable thioester bond
- this unstable bond makes C3 subject to slow spontaneous hydrolysis to C3b & C3a
- C3b is able to bind to foreign surface Ags
- deposition of C3b on cell surface initiates the alternative pathway
What are the main activators of the Lectin Pathway ?
- Gram-positive bacteria
- gram-negative bacteria
- fungi
Describe the Lectin Pathway Activation
- MBL bind to residue (Ags) on the surface of a microbe
- MBL-associated serine proteases (MASP 1 & 2) bind to MBL that already bound to microbe
- MASP proteins complex function is similar to C1qrs and cleaves ;
C2 –> C2a & C2b
C4 –> C4a & C4b - C3 convertase and thereafter C5 convertase are formed
What are the main activators in the classical pathway ?
- Ag/Ab complexes
- some viruses = HIV
- necrotic cells
- aggregated Abs
- C-reactive protein (CRP)
Describe the classical pathway activation
- formation of an Ab/Ag complex
- induces changes in Fc portion of the Ab molecule revealing binding site for complement
- C1 binds to exposed C1q-binding sites in the CH2 domain of the IgG1-IgG3
- C1 becomes activated when it binds to the ends of Abs
Describe MAC formation
- acts as a channel in which cytoplasm can rush out & water rushes in
- cell/bacterium’s inner integrity is compromised & it dies
What does MAC stand for ?
Membrane Attack Complex
How is the complement system activated ?
- molecules present on the surface of the cells
or - molecules in the serum that regulate the activity
