Proteins of the Alternative Pathway

B was originally characterized as one of the serum factors required for C3 destruction by the zymosan-activated properdin system. It was 

B Properdin factor B, /32-glycoprotein II, heat-labile factor (HLF), C3 

C3b-INA C3b inactivator, factor C ( ), conglutinin-activating factor (KAF) C3b inactivator accelerator 

Properdin (from the Latin verb perdere—to destroy) was first recognized as a distinct serum protein related to complement by Pillemer and associates in the early 1950s (Pillemer et aL, 1954). It was shown to play an essential role in the then described properdin pathway, which was conceived as an alternative mechanism for the activation of the late-acting complement components not requiring antibody. Cl, C4, and C2. 

Activated properdin has an apparent affinity for C3 and its activation fragments. Under appropriate conditions of pH and ionic strength, and 

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Complement A term originally used to refer to the heat-labile factor in serum that causes immune cytolysis, the lysis of antibody-coated cells, and now referring to the entire functionally related system comprising at least 20 distinct serum proteins that is the effector not only of immune cytolysis but also of other biologic functions. Complement activation occurs by two different sequences, the classic and alternative pathways. The proteins of the classic pathway are termed components of complement and are designated by the symbols... 

Trach, K.A. Hoch, J.A. Multisensory activation of the phosphorelay initiating sporulation in Bacillus subtilis identification and sequence of the protein kinase of the alternate pathway. Mol. Microbiol., 8, 69-79 (1993)... 

After reviewing the previously obtained data, the hypothesis is advanced that when a normally primed synthetic material is exposed to blood, the air nuclei trapped in the surface roughness of the material activates the complement proteins by the alternative pathway and that the products of this activation process (i.e. at least C3a, and C5a) promote cellular adhesion to the synthetic material. The evidence in favor of this hypothesis includes the following. 

Figure 5.4 The Alternative Pathway of Complement Activation. C3 is spontaneously hydrolysed without cleavage of C3a, to become C3b (like). This has the ability to cleave factor B. Combination of C3b (like) with Bb forms a C3 convertase capable of cleaving further C3 into C3b and the anaphylotoxin C3a. Fluid phase C3b is unstable and rapidly inactivated by control proteins, but the availability of a suitable protective surface serves to bind and stabilise the C3b. Stabilisation results in activation of the alternative pathway and constitutes recognition of the protective surface as foreign. C3b can then cleave more factor B to form the true C3 convertase C3bBbP, itself stabilised by the enhancing control protein Properdin (P).

The complement system comprises twenty plasma proteins present in the blood and in most bodily fluids. They are normally present in an inactive form but become activated via two separate pathways the classical pathway, which requires antibody, and the alternative pathway, which does not. Once the initial components of complement are activated, a cascade reac-... 

The reactions that take place in the complement system can be initiated in several ways. During the early phase of infection, lipopoly-saccharides and other structures on the surface of the pathogens trigger the alternative pathway (right). If antibodies against the pathogens become available later, the antigen-antibody complexes formed activate the classic pathway (left). Acute-phase proteins (see p. 276) are also able to start the complement cascade lectin pathway, not shown). 

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