The classical pathway is a part of the specific immune response. It is initiated either by the foreign cell membrane of a parasite or a surface antibody. The first chemical, C1, is a large complex of three molecules, C1q, C1r, and C1s. When the C1q subunit has recognized and bound to surface receptors on the membrane, the C1r subunit cleaves the C1s proenzyme, and an activated enzyme emerges. During amplification, the C1s enzyme has as its primary targets proenzymes C4 and C2. Through the enzyme's action, C4 is converted into C4a and C4b, and C2 is converted into C2a and C2b. C4b and C2a fragments remain attached as an enzyme, C3 convertase, whose substrate is factor C3. The cleaving of C3 yields subunits C3a and C3b. C3b has the property of binding strongly with the cell membrane in close association with the component C5, and it also forms an enzyme complex with C4b-C2b that convert C5 into 2 fragments C5a and C5b. C5b will form the nucleus for the membrane attack complex. This is the point at which the two pathways merge. From this point on, C5b reacts with C6 and C7 to form a stable complex inserted in the membrane. Addition of C8 to the complex causes the polymerization of several C9 molecules into a giant ring shaped membrane attack complex that bores ring-shaped holes in the membrane. If the target is a cell, this reaction causes it to disintegrate. If the target is an enveloped virus, the envelope is perforated and the virus inactivated.
The Alternative pathway, sometimes called the properdin pathway, is not specific to a particular microbe. It can initiated by a wide variety of microbes, tumors, and cell walls. It requires a different group of serum proteins- factors B, D, and P (properdin), C3b, and magnesium in the initiation and amplification phases rather than C1, C2, or C4 components. The remainder of the steps occur as in the classical pathway. The principle function of the alternative systems is to provide a slower but less specific means of lysing foreign cells (especially gram-negative bacteria) and viruses.
Properdin: pro-, before and -perdere, to detroy
You will notice that at many of the steps of the classical pathway, two molecules are given off. One of these continues in the formation of the membrane attack complex, and the other (C2a, C4a, C3a, or C5a) goes on to become a cytokine or stimulant of inflammation and other immune reactions. Complement components also behave as one type of opsonin that promotes phagocytosis. Complement can participate in inflammation and allergy by causing liberation of vasoactive substances from mast cells and basophils. C3a and C5a are so potent in this response that injecting only one quadrillion of a gram elicits an immediate flare-up at the site.
Reference: Foundation in Microbiology (Basic principle) by Kathleen Park talaro
Page: 441, Chapter 14: Nature of Host defenses
Page: 441, Chapter 14: Nature of Host defenses
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