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45 Cards in this Set

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