4. Complements

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a note on complement, function and mechanism

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Jules Bordet (1890s)Sheep antiserum Lysis of Vibrio cholera cells Bacteriolytic activityHeating of Sheep antiserum Absence of bacteriolytic activity Intact Vibrio cholerae cellsHeated Sheep antiserum + fresh serum with no antibodies Bacteriolytic activity Lysis of Vibrio cholerae cells

Antibodies + heat-sensitive component responsible for the lytic activityThe complement system is the major effector of humoral immune respose

6Nomenclature of Complements

Complement components are designated by numerals (C1 C9), by letter symbols (E.g., factor D), or by trivial names (e.g., homologous restriction factor).

Complement fragmentationSequential activation of complement components occurs via one of three pathways :

The classical pathway is initiated when C1 binds to antigen-antibody complexes. The alternative pathway is initiated by binding of spontaneously generated C3b to activating surfaces such as microbial cell walls. The lectin pathway is initiated by binding of the serum protein MBL to the surface of a pathogen.

All three pathways generate C3 and C5 convertases and bound C5b, which is converted into a membrane attack complex (MAC) by a common sequence of terminal reactions.

Classical Pathway

The membrane attack complex forms a large channel through the membrane of the target cell, enabling ions and small molecules to diffuse freely across the membrane.All the complement reactions take place on the hydrophilic surface of membranes or on immune complexes in the fluid phase. As C5b6 binds to C7, the resulting complex undergoes a hydrophilic-amphiphilic structural transition that exposes hydrophobic regions, which serve as binding sites for membrane phospholipids.

The alternative pathway is Antibody independent