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45 Cards in this Set
- Front
- Back
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What is the complement system?
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A collection of circulating and cell-membrane proteins
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What immunity does complement play a critical role in?
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-Innate
-Humoral |
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How does complement change an immune response?
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It amplifies it
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What are many complement proteins?
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Proteolytic enzymes
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What are the 3 complement pathways?
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1. Alternative
2. Classical 3. Lectin |
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What triggers the classical complement pathway?
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When IgM and some IgG subclasses bind microbial surface antigens, and their Fc receptors then bind C1
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What does C1 binding of 2 Fc regions of antibodies trigger?
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Cleavage of C4 and C2 into C4b-2b
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What is the other name for C4b-2b?
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C3 convertase
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What does C3 convertase do?
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Cleaves C3 into C3a and C3b
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What does C3b do?
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Binds microbial surface antigens and the C4b-2b complex to make C5 convertase
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What does C5 convertase do?
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Cleaves C5 into C5a and C5b
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What does C5b do?
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Gets polymerized with C6, C7, C8, and C9, which forms the MAC complex and creates a pore in the microbe cell membrane; lysis
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How is the lectin pathway different from the classical complement pathway?
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Instead of C1 being the initial trigger, it is Mannose; all else is the same.
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So what does C3 convertase consist of in the Lectin pathway?
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Mannose-C4b-2b
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What triggers the alternative pathway?
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C3b coating microbe wall
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What generates the C3b that triggers the alternative pathway?
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Spontaneous hydrolysis of C3 due to its short half life.
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What forms C3 convertase in the alternative pathway?
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C3b-Bb
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What is the source of Bb in the alternative pathway?
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Factor B, which is cleaved by Factor D when Factor B binds C3b
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What does C3 convertase do?
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cleaves C3 into more C3b which coats the microbe and joins with C3 convertase
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What is C3b-Bb-C3b?
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C5 convertase
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And what does C5 convertase do?
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Cleaves C5 into C5b, which is then polymerized and forms MAC.
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What is the trigger of the lectin pathway again?
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Mannose binding lectin which binds to Mannose on microbial surface
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What complement proteins are anaphylatoxins?
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C3a, C4a, and C5a
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What do anaphylatoxins do?
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Phagocytes have receptors to anaphylatoxins; when bound, it stimulates inflammation to sustain the cellmediated response.
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So to summarize, what are 3 ways that complement kills microbes?
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1. Complement-mediated cell lysis
2. Opsonization 3. Inflammation recruitment of phagocytes |
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What is the complement protein that achieves C'-mediated cell lysis?
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MAC attack complex
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Which complement protein serves as the major opsonin?
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C3b (and C4b)
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Which complement proteins are the inflammatory mediators?
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C3a, C4a, and C5a.
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So we see that complement plays an important role in which types of immunity?
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Both innate AND adaptive!
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What role does complement play in adaptive immunity?
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REMEMBER! C3d binding to CR2 receptors on Bcells is majorly important!!! It is the 2nd signal for Bcell activation!!!
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What is the function of C1 inhibitor?
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Inhibits C1 from activating the classical cascade
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What is the function of Factor I?
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Proteolysis C3b and C4b
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What is the function of Factor H?
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Dissociates the C3 convertase of the alternative pathway
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What dissociates the C3 convertase of the classical pathway?
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C4 binding protein
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What is Membrane cofactor protein?
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A cofactor for Factor-I mediated dissociation of C4b and C3b
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What causes nonspecific dissociation of C3 convertase?
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DAF - decay accelerating factor
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What blocks C9 binding and prevents MAC formation?
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CD59
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What else causes dissociation of C3 convertase?
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Type I Complement receptor
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What does an inherited deficiency of C3 lead to?
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Susceptibility to infections
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What is the usual result of C3 deficiency?
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Death early in life
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What is the result of C2/C4 deficiency?
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No deficit
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What is the result of C9 and MAC deficiency?
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Susceptibility to Neisseria infection
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What is the result of C1 inhibitor deficiency?
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Overactivity of the classical C' cascade
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What is a symptom of excessive Complement activation?
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Edema of the larynx and tissues
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What is the excessive edema in C1 inhibitor deficiency called?
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Hereditary Angioneurotic Edema
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