Microbiology Stories: Complement Activation

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Pathwayes of activation of complement

Complement protiens are soluble protiens present in all of our body fluids "except CSF & Urine".
It present in inactive forms, so needs activation to work proberly.
The activation process occures by diffrent pathways:
3 pathways actually:

Classical pathway.
Alternative pathway.
Lectin pathway.

These are many pictures showing the diffrent pathways of complement activation:

Let us to discuss each pathway ......

Classical pathway:

Assembly of C1 during the Classical Complement Pathway

The Fab of IgG or IgM bind to epitopes on an antigen. C1q, C1r, and C1s then assembles on the Fc portion of the antibodies to form C1, the first enzyme of the classical complement pathway. The enzyme C1 is able to cleave C4 into C4a and C4b, as well as C2 into C2a and C2b.

Formation of C3 Convertase during the Classical Complement Pathway

The enzyme C1 is able to cleave C4 into C4a and C4b. The C4b binds to adjacent proteins and carbohydrates on the surface of the antigen. C2 then binds to the C4b and C1 cleaves C2 into C2a and C2b. The C4b2a functions as a C3 convertase that can subsequently cleave hundreds of molecules of C3 into C3a and C3b.

Formation of C5 Convertase during the Classical Complement Pathway

The C4a2b functions as a C3 convertase that can subsequently cleave hundreds of molecules of C3 into C3a and C3b. Much of the C3b binds to adjacent proteins and carbohydrates on the antigen to participate in opsonization while C3a can stimulate inflammatory responses. Some of the C3b binds to C4b2a to form C4b2a3b, a C5 convertase that can cleave C5 into C5a and C5b.

The Membrane Attack Complex (MAC) Causing Cell Lysis

This C5b6789n, or membrane attack complex (MAC), puts pores into lipid bilayer membranes of human cells to which antibodies have bound. This results in cell lysis. MAC can also damage the envelope of enveloped viruses and put pores in the outer membrane and cytoplasmic membrane of gram-negative bacteria causing their lysis.

See these links:

http://student.ccbcmd.edu/courses/bio141/lecguide/unit4/innate/c1act_flash.html

http://student.ccbcmd.edu/courses/bio141/lecguide/unit4/innate/c3case_flash.html

http://student.ccbcmd.edu/courses/bio141/lecguide/unit4/innate/c5case_flash.html

http://student.ccbcmd.edu/courses/bio141/lecguide/unit4/innate/mac_flash.html

http://student.ccbcmd.edu/courses/bio141/lecguide/unit4/innate/cytogn.html

Lectin pathway:

Activation of the Lectin Pathway

Activation of the lectin pathway begins when mannose-binding protein (MBP) binds to the mannose groups of the carbohydrates on microorganisms. Two more lectin pathway proteins called MASP1 and MASP2 (equivalent to C1r and C1s of the classical pathway) now bind to the MBP. This forms an enzyme similar to C1 of the classical complement pathway that is able to cleave C4 and C2 to form C4bC2a, the C3 convertase that is able to enzymatically split hundreds of molecules of C3 into C3a and C3b.

See this link:

http://student.ccbcmd.edu/courses/bio141/lecguide/unit4/innate/lectin_flash.html

Alternative pathway:

Activation of the Alternative Complement Pathway and Formation of C3 Convertase

Activation of the alternative complement pathway begins when C3b (or C3i) binds to the cell wall and other surface components of microbes. Alternative pathway protein Factor B then combines with the cell-bound C3b to form C3bB. Factor D then splits the bound Factor B into Bb and Ba, forming C3bBb. A serum protein called properdin then binds to the Bb to form C3bBbP. C3bBbP functions as a C3 convertase that can enzymatically split hundreds of molecules of C3 into C3a and C3b.

Formation of C5 Convertase during the Alternative Complement Pathway

Some C3b binds to C3bBb to form C3bBb3b. C3bBb3b functions as a C5 convertase that can enzymatically split hundreds of molecules of C5 into C5a and C5b.

See this link:

http://student.ccbcmd.edu/courses/bio141/lecguide/unit4/innate/alternative_flash.html