Complement proteins/system activation pathways

The immunoisolative capabilities of the encapsulation motif are based upon a size-exclusion principle whereby antibodies (primarily IgM and IgG) and complement proteins of the immune system are unable to reach the implanted cells. In order to activate the complement pathway in which antibodies bind specific complement proteins and ultimately destroy the implanted cells through lysis, one IgM molecule (MW = 800 kDa 30 nm diameter) and one molecule of complement protein Clq (MW = 410 kDa, 30 nm diameter) must bind together. Alternatively, two IgG molecules (MW =150 kDa each, 20 nm total diameter) bind in concert with Clq to destroy the implant cells. Encapsulating cells in materials... 

Although complement pathways have not been extensively described in bivalves, there are several lines of evidence that support the presence of this defence mechanism in these organisms. The complement system is composed of more than 30 soluble plasma proteins that collaborate to distinguish and eliminate non-self particles. C3 is the central component system. In vertebrates, it is proteolyticaUy activated by a C3 convertase through the classic, lectins and alternative routes (Nonaka and Yoshizaki, 2004). In the classic activation route, immunoglobulins are recognised by the Cl protein, whereas activation is initiated by the recognition of membrane carbohydrates by lectins and ficolins in the lectin route (Nonaka and Kimura, 2006). 

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-... 

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... 

Herceptin attaches to the HER2/neu receptor and activates the complement system (a series of serum and cell-associated proteins involved in immune response) to destroy those cells expressing such receptors. Through this action, Herceptin disrupts the signaling pathway for breast cancer cell proliferation (refer to diagram below). 

Complement Some microorganisms produce proteins that bind to and inactivate components of the complement system and hence decrease activation of the cascade, e.g. the vaccinia virus secretes a protein that inhibits activation of both the classical and alternative pathways. Some bacteria produce a protein that mimics the action of an acceleration factor, which increases the rate of destruction of the active convertase this factor is normally produced by the host when the complement response is no longer required. 

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). 

The complement system consists of about 20 interacting soluble proteins that circulate in the blood and extracellular fluid. Immunoglobulin molecules bound to the surface of the microorganisms activate Cl, the first component of the complement pathway. The activation occurs through the Fc portion (see Topic D2) of the bound antibody. Only bound antibody can activate complement, soluble antibody not bound to an antigen has no such effect. 

The complement system has been reviewed151,152 it is composed of a series of proteins, C1-C9, present in normal human serum, that serve as important mediators in the host defense. The terminal components, C3-C9, are involved in the destruction of invading microorganisms, but, in order to achieve this, they have to be activated. This activation process can be divided into two pathways, the alternative pathway and the classical pathway, although both pathways can occur simultaneously in the host defense-mechanism. 

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