Complement Flashcards
What are the major functions of complement?
Lysis
Opsonization
Chemotaxis
At which locations can complement act on microbes?
Blood & tissue
How does complement directly lyse pathogens?
Through formation of a membrane attack complex (MAC) that forms pores in the membrane.
What are the pathways for complement activation?
Classical, alternative, & lectin pathways
What enzyme breaks down C3 into C3a and C3b?
C3 convertase
What is the central complement component at which all activation pathways converge?
C3b
What is the function of C3b?
Deposited on the pathogen as an opsonin
What complement component is an important neutrophil chemotactic factor?
C5a
What complement components function in inflammation and chemotactic factors?
C3a & C5a
What is the function of C5b?
Binds to the pathogen surface and is essential for completion of the complement cascade
What are the early complement proteins?
C1, C2, C4, C3
How is the alternative pathway activated?
Spontaneous hydrolysis of C3 on all surfaces. This goes on to activate the C3 convertase, cleavage of C3, and formation of the C5 convertase
How is the lectin complement pathway activated?
Lectin in the blood binds to mannose on microbes. C4b & C2a bind to the MBL to form the C3 convertase, cleaving C3
How is the classical complement pathway activated?
The process is triggered by antibody binding to an antigen. C1 complex binds the antibody followed by C2a and C4b binding to the C1 complex. This leads to formation of the C3 convertase and cleavage of C3.
What complement components make up the membrane attack complex?
C5b, C6, C7, C8, & C9
Describe formation of the membrane attack complex (MAC).
C5b initaties assemply of tghe MAC. C6 binds to C5b and accepts C7. C7 inserts into the lipid membrane. C8 binds C5b, 6, 7 and iniates binding and polymerization of C9. C9 binds C5b, 6, 7, 8 and polymerized to form membrane pores.
Are G+ or G- bacteria more susceptible to killing by the MAC? Why?
G- bactera are more susceptible to the MAC because they lack the thick peptidoglycan layer found in G+ bacteria. While G+ bacteria are less susceptible to the MAC, they are still opsonized and killed via phagocytosis.
How are opsonized pathogens recognized for phaogcytosis?
Phagocytes express complement receptors on their surface that recognize complement proteins bound to microbes.
What protein regulates the classical pathway? How?
C1INH (C1 inhibitor) prevents assembly of the C1 complex
What protein regulates activity of the C3 convertase for all complement pathways?
Decay acceleration factor (DAC) / CD55 prevents formation of the C3 convertase
What regulates formation of the MAC?
CD59/protectin blocks C9 binding and formation of the MAC
