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23 Cards in this Set

  • Front
  • Back
What three general actions does complement cause to occur?
1) inflammation
2) Ag phagocytosis
3) directly lyse cells
Zymogen
inactive form of complement protein made in liver until cleaved, then are proteases
protease
the active form of the complement protein
Every complement pathway results in C3b covalently bound to surface components of pathogens. This causes three things to happen. What are they?
1) MAC (membrane attack complex) perforates the Ag membrane
2) Opsonization of pathogens, facilitating uptake and killing by phagocytes
3)Recruitment of inflammatory cells by anaphylatoxins
Describe the 2 steps in activation of the classical complement pathway.
1) pathway activated by C1q binding Rc region of Ab, which causes C1r and C1s activation
2) IgM (pentameric) or IgG binds the pathogen, the C1 binds to a single IgM molecule or C1q binds to two or more IgG molecules
What happens after the classical complement pathway is activated?
C3 convertase is formed by the following steps:
1) C1s binds and cleaves C4
2) C4b covalently binds to the pathogens surface
3) C1s binds and cleaves C2
4) C2a binds to the C4b fragment bound to th epathogen's surface forming the classical C3 convertase
5) Classical C3 convertase cleaves C3
6) C3b will bind to the pathogen's surface in the same vicinity as the C3 convertase
After the C3 convertase is made, what happens?
The C5 convertase is formed.
1) C3b attaches to the pathogen surface acting as an opsonin
2) C3 convertase and C3b combine to form the C5 convertase
3) C5 convertase cleaves C5
4) C5b functions in initiating the formation of the membrane-attack complex (MAC)
What is opsonization?
When a delicious coating, a relish if you will, coats an antigen or pathogen, much like the C3b does with pathogen.
What happens after the C5 convertase is formed in the complement pathway?
The MAC is created
1) C5b binds to C6 and C7
2) Complex will insert into lipid bilayer of Ag
3) C8 then binds C5b exposing hydrophobic site to insertion and polymerization of the C9 component that forms membrane pores
What are the "leftovers" of the classical complement pathway?
Anaphylatoxins C3a, C4a, C5a increase inflammation locally by the following actions.
What do anaphylatoxins do?
increase inflammation by:
1) all act on blood vessels to increase vascular permeability which causes 2) and 3)
2) extravasation of Ab and complement
3) cell migration of macrophage, neutrophils, lymphocytes from blood to tissue
what do you need to know about complement receptors?
1) CR1(CD35) that binds C3b producing phagocytosis
2) CR2 (CD21) that is a coreceptor for B cell receptor on the cell surface
How is the classic complement pathway regulated?
C1 inhibitor - C1INH
DAF, C4BP, CR1, MCP, Factor H
How do self-cells not get hit by the complement actions?
CD59 is a host cell membrane bound protein that disrupts the MAC. Phew.
How is the lectin pathway different from the Classic Complement Pathway?
1) Mannose-Binding Lectin (MBL) practically replaces C1q, r, s as it binds Ag, itself.
2) MASP subunits of MBL are activated
3) MASP does all the initial C2, 3, 4 conversions
How is the alternative complement pathway different?
There is no Ab involvement
What are the step in the alternative complement pathway?
1) C3 sponateously hydrolyzes in plasma to C3(H2O)
2) C3(H2O) binds to Factor B enabling factor D to cleave factor B into Ba and Bb
3) C2(H2O)Bb complex is the C3 convertase of the alternative pathway, and it cleaves C3 to C3a and C3b
4) C3b binds to cells surface immediately
5) membrance bound C3b binds factor B and is cleaved by Factor D to Bb forming membrane-bound C3 convertase
Describe hereditary edema and how it relates to the complement pathway.
Defect in C1INH, producing excess cleaved fragments of C1, C2, C2b -> C2-kinin -> excessive swelling.
Dangerous because can cause trachea swelling suffocation.
Recall all these extras will produce a lot of anaphlatoxins
What deficiencies can be problematic in regard to complement?
1) C3b convertase component deficiencies: C1, C2, C4
2) Factor B, D deficiencies
3) C3 deficiency
4) terminal pathway: C5 - C9 deficiency
What is the significance of a C3b convertase component (C1, C2, C4) deficiency?
looks like systemic lupus erythematosus (SLE) because you can see dposition of immune complexes in kidneys, skin, and blood vessels
What is the significance of C3 deficiency?
early childhood presentation of recurrent bacterial infections
What is the significance of Factor B and D deficiencies?
susceptibility to bacterial infections and recurrent infections of pyogenic (pus-forming) bacteria
what is the significance of C5 - C9 (terminal pathway) deficiencies?
MAC doesn't form. Gram (-) bacterial Neisseria infection common with these deficiencies.