Membrane-attack complex

The classical pathway can become activated by immune complexes, bacteria, viruses, and F-XIIa. Binding occurs to the complement C1 q, a part of complement factor 1 (Cl). This initiates a cascade of activations, first of Clr, Cls, then of C4. This C4 activates C2, after which C3 becomes activated. Activated C3 initiates a cascade of activations, which are in common with the alternative pathway and which end up in activated C5-9, a membrane attack complex that lyses the target. 

The alternative pathway may become activated by lipopolysaccharides, endotoxin (sepsis), virus, fungi, immunoglobulin A-antigen (IgA-Ag) immunocom-plexes, and foreign material. These activate C3, after which the common pathway of complement activation takes place (Fig. 4). There are also a number of inhibitors that regulate and control complement activation. The most important are the Cl-esterase inhibitor (Cl-Inh) and the membrane attack complex inhibitor factor (MACIF CD59). In sepsis a relative deficiency of Cl-Inh has been reported. Administration of Cl-Inh to patients with septic shock attenuates complement acti-... 

Fig. 4. The classical and alternative pathway cascade of complement activation. activation Cl-inh., Cl-esterase inhibitor MACIF, membrane attack complex inhibiting factor (—CD59).

ApoJ is another protein component of HDL which is highly expressed by the RPE and neural retina, especially under oxidative stress conditions (Wong et al., 2000, 2001). It can act as a complement regulatory protein, which by binding to and inactivating the membrane-attack complex can prevent cytolysis (Bartl et al., 2001). ApoJ accumulation was identified in drusen in AMD patients (Sakaguchi et al., 2002 Wong et al., 2000). 

MACPF Conserved domain in membrane attack complex proteins and perforin E(MP)B 0(0) 0(0) ... 

Proteolytic cleavage of factor C3 provides two components with different effects. The reaction exposes a highly reactive thioester group in C3b, which reacts with hydroxyl or amino groups. This allows C3b to bind covalently to molecules on the bacterial surface (opsonization, right). In addition, C3b initiates a chain of reactions leading to the formation of the membrane attack complex (see below). Together with C4a and C5a (see below), the smaller product C3a promotes the inflammatory reaction and has chemotactic effects. 

The late factors C5 to C9 are responsible for the development of the membrane attack complex (bottom). They create an ion-permeable pore in the bacterial membrane, which leads to lysis of the pathogen. This reaction is triggered by C5 convertase [2]. Depending on the type of complement activation, this enzyme has the structure C4b2o3b or C3bBb3b, and it cleaves C5 into C5a and C5b. The complex of C5b and C6 allows deposition of C7 in the bacterial membrane. C8 and numerous C9 molecules—which form the actual pore—then bind to this core. 

About 20 different proteins are included in the complement system Proteins C1-C9, factors B and D, and a series of regulatory proteins. All these proteins are made in the liver, and they circulate freely in the blood and extracellular fluid. Activation of the complement system involves a cascade of proteolytic reactions. In addition to forming membrane attack complexes, the proteolytic fragments released during the activation process promote dilation of blood vessels and the accumulation of phagocytes at the site of infection. 

Deng, J., Gold, D., LoVerde, P.T. and Fishelson, Z. (2003) Inhibition of the complement membrane attack complex by Schistosoma mansoni paramyosin. Infection and Immunity 71, 6402-641 0. 

Type II hypersensitivity results from the formation of antigen-antibody complexes between foreign antigen and IgM or IgG immunoglobulins. One example of this type of hypersensitivity is a blood transfusion reaction that can occur if blood is not cross-matched properly. Preformed antibodies bind to red blood cell membrane antigens that activate the complement cascade, generating a membrane attack complex that destroys the transfused red blood cells. In hemolytic disease of the newborn, anti-Rh IgG antibodies produced by an Rh-negative mother cross the placenta, bind to red... 

C11. Cybulsky, A. V., Rennke, H. G., Feintzeig, I. D., and Salant, D. J., Complement-induced glomerular epithelial cell injury The role of the membrane attack complex in rat membranous nephropathy. J. Clin. Invest. 11, 1096-1107 (1986). 

Antibodies bound to an invading microorganism activate the complement system via the classical pathway. This consists of a cascade of proteolytic reactions leading to the formation of membrane attack complexes on the plasma membrane of the microorganism that cause its lysis. Polysaccharides on the surface of infecting microorganisms can also activate complement directly in the absence of antibody via the alternative pathway. 

B8. Biesecker, G., Lavin, L., Ziskind, M., and Koffler, D., Cutaneous localization of the membrane attack complex in discoid and systemic lupus erythematosus. N. Engl. J. Med. 306, 264-270 (1982). 

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