Classical Complement Pathway
The complement system is part of the defense against invading cells and is composed of about twenty different proteins found in the plasma. When activated, complement proteins form a pathway of proteolytic reactions that culminates in the lysis of foreign cells. The complement system also stimulates phagocytosis of foreign cells and an inflammatory response. There are two different complement systems, the classical complement pathway initiated by antibody complexes on the cell surface, and an alternative complement pathway that is initiated without antibodies. The complement system proteins are named with a capital C followed by a number. A small letter after the number indicates that the protein is a smaller protein resulting from the cleavage of a larger precursor by a protease. In the classical pathway, the first step is the initiation of the pathway triggered by recognition by complement factor C1 of antigen-antibody complexes on the cell surface. When C1 complex interacts with aggregates of IgG with antigen on a cell's surface, two C1-associated proteases, C1r and C1s, are activated. Other factors like lipopolysaccharide also activate C1s. Once C1s is activated, it cleaves C4 to form C4b that then binds to the cell membrane of the cell being attacked. The proteolytic complement cascade is then amplified on the cell membrane through sequential cleavage of complement factors and recruitment of new factors until a cell surface complex containing C5b, C6, C7, and C8 is formed. The addition of a multiple C9 proteins creates the membrane attack complex results in a large pore that spans the membrane of the cell being attacked, allowing ions to flow freely between the cellular interior and exterior. Ions flow out, but large molecules stay in, causing water to flood into the cell and ultimately burst the cell from osmotic pressure.
Contributor: Kathy McGraw
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