Page 554 - Review of Medical Microbiology and Immunology ( PDFDrive )

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CHAPTER 63 Complement
543
Lectin
Alternative
Antigen–antibody
Microbial
Microbial surfaces
complexes
surfaces
(nonspecific activators
e.g., endotoxin)
Bind
Bind
Bind
Mannan-binding
C1
lectin
C3(H O) + B
C1
2
Protease
mebooksfree.com mebooksfree.com C4b,2b mebooksfree.com mebooksfree.com mebooksfree.com mebooksfree.com
cleaves C4 and C2
D (protease)
C2
C4
3
C
C
C3b,Bb
3
(C3 convertase)
(C3 convertase)
+
C2a,C4a
C3b,Bb,C3b
C4b,2b,3b
(C5 convertase)
+
+ C5 (C5 convertase)
C3a
C3a
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C5a + C5b
C6
C5b,6,7
C9
C8
C5b,6,7,8,9 (membrane attack complex)

Lysis, cytotoxicity
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mebooksfree.com mebooksfree.com mebooksfree.com REGULATION OF THE COMPLEMENT mebooksfree.com
FIGURE 63–1
The classic and alternative pathways of the complement system indicates that proteolytic cleavage of the molecule at the
tip of the arrow has occurred; a line over a complex indicates that it is enzymatically active. Note that all small fragments are labeled “a,” and all
large fragments are labeled “b.” Hence the C3 convertase is depicted as C4b,2b. Note that proteases associated with the mannan-binding lectin
cleave C4 as well as C2.
(2) In the lectin pathway, mannan-binding lectin (MBL)
(also known as mannose-binding protein) binds to the
SYSTEM
surface of microbes bearing mannan (a polymer of the
sugar, mannose). This activates proteases associated with
of the antibody itself. The complement-binding site on the
MBL that cleave C2 and C4 components of complement
and activate the classic pathway. Note that this process
heavy chain of IgM and IgG is unavailable to the C1 com-
ponent of complement if antigen is not bound to these
bypasses the antibody-requiring step and so is protective The first regulatory step in the classic pathway is at the level
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antibodies. This means that complement is not activated by
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early in infection before antibody is formed.
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(3) In the alternative pathway, many unrelated cell sur-
IgM and IgG despite being present in the blood at all times.
However, when antigen binds to its specific antibody, a
face substances (e.g., bacterial lipopolysaccharides [endo-
toxin], fungal cell walls, and viral envelopes) can initiate
bind and initiate the cascade.
the process by binding C3(H O) and factor B. This com-
2
plex is cleaved by a protease, factor D, to produce C3b, Bb.
Several serum proteins regulate the complement system
This acts as a C3 convertase to generate more C3b.
at different stages.

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