Host Immunity 2 Flashcards
What are the three complement pathways?
classical, alternative, and lectin
What is the common key product of the complement pathways?
C3b
What are the end effects of the complement pathways?
- cell lysis
- inflammation
- opsonization
- interact with other pathways
What activates the classical pathway of complement fixation?
C1 binding to C-reactive protein on the pathogen surface
also called binding of Ab to Ag
What are the steps involved in the classical complement pathway?
- > C1 binds to C-reactive protein on the pathogen surface
- > C1s cleaves C4 into C4b which binds to C1
- > C2 binds to C4b and is cleaved by C1s into C2a, which binds to the complex, and another fragment, C2b.
- > the combination of C4b2a (C3 convertase) cleaves C3 into C3b which binds to the complex and also releases fragment C3a
- When acted on by C3 convertase, C3 is cleaved into C3b which binds to C4b2a and a small fragment, C3a is released. The complex of C4b2a3b forms C5 convertase
What do bacteria induce macrophages to produce and what does it do?
IL-6 which acts on hepatocytes to induce synthesis of acute-phase proteins
What is IL-6?
a pro-inflammatory cytokine produced by macrophages and induces hepatocytes to synthesize acute-phase proteins
What does the liver (hepatocytes) produce in response to IL-6 specifically?
C-reactive protein, fibrinogen, mannose-binding lectin
What does C-reactive protein bind to and do?
binds to phosphorylcholine on bacterial surfaces, acting as an opsonin and as a complement activator
What does mannose-binding lectin bind to and do?
binds to residues on bacterial surfaces, acting as an opsonin and as a complement activator
What are the initial complement components of the classical pathway?
- C1q, C1r, C1s, C4, C2
What makes up C3 convertase in the classical pathway?
C4bC2b
What makes up C5 convertase in the classical pathway?
C4bC2bC3b
What is the activator of the lectin pathway?
mannan binding lectin (MBL), MBL-associated serine protease-2 (MASP-2)
What is the initial complement component of the lectin pathway?
C4, C2
What are the steps involved in the Alternative pathway ‘tick over’ phase?
- Fluid phase C3 and H2O creates C3i
- C3i acts with factor B and Mg2+ to create C3iB
- C3iB is acted on by factor D to create C3iBb and Ba
- C3iBb acts on C3 to create C3b and C3a
- C3b binds to normal cell surface or is hydrolyzed and inactivated in fluid phase
What are the steps involved in the activation phase of the alternative pathway?
- The spontaneous hydrolysis of C3 to C3b and the binding of C3b to microbial surfaces initiates the alternative pathway
- Factor B binds to C3b and factivates factor D
- When factor D acts on bound Factor B, the latter is cleaved into the fragments Ba and Bb;Bb binds to the complex, forming C3bBb (C3 convertase)
- This complex is then stabilized by the binding of properdin
- When acted on by C3 convertase, C3 is cleaved into C3b which binds to C4b2a and a small fragment, C3a is released. The complex of C4b2a3b forms C5 convertase
What is the activator of the alternative pathway?
contact of microbial cell wall with C3
What is the initial complement component of the alternative pathway?
C3
What makes up C3 convertase in the alternative pathway?
C3bBb