Complement System In Immunology

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Complement System In Immunology Essay.

The firstly disocovered pathway was the classical pathway. It is the most a distinctive pathway as its initiation begins with a pair of antibodies attached to antigens.(Lodish et al. 1007) The antigens may include proteins and polysaccharide membranes.These attached antibodies activate compliment C1. Complement C1 is made of a molecule of C1q bound to two molecules of C1r and two molecules of C1s. This C1 complex is activated then it attaches to the IgM or IgG which then cleaves complement c2 and c4 into c2a and c2b + c4a and c4b. (chen et al 2009)Complement System In Immunology Essay.


Together C2a and C4b forms and enzyme (C3 convertase C4b2b) which this enzyme cleaves C3 into C3a and C3b. C3 covertase is the central complement to all 3 pathways, C3b attaches to C3 convertase forming a C5 complex whereas C3a is released during the cleavage of C3 by C3 convertase

The alternate pathway is activated the complement proteins named factor B, D and P. (Janeway et al. 2005). These proteins are attracted to the surfaces of the bacterium; such surfaces include lipid carbohydrate complexes of particular bacteria. The process with this pathway involves the cleaving of the complement 3 into its fragments (C3a and C3b) likewise in the classical pathway, where at this point the C3b may conjoin with C3 convertase forming a C5 convertase, and with the c5 convertase it converts complement C5 into components C5a and C5b continuning to form an membrane attack complex, and c5a aiding in the area of inflammation.(Cummings. 2007) However more recent studies suggest that the initiation of the alternative pathway involves the hydrolysis of C3 forming a C3h20 complex which binds to factor B. In addition factor D binds forming the C3(h20)Bb complex which then cleaves C3 to C3a and C3b.(chen et al 2010) + (hannigan 2009). However in hindsight it is significant to exemplify that studies are always being conducted which improve the understanding of these complex mechanisms however to have a basic understanding is most valuable.

The lectin pathway was the last type of complement pathway activation discovered. Macrophages ingest particular materials through phagocytosis. In doing this they release certain types of chemicals which aids in the formation of Mannon-binding lectin.(pearson 2007) Mannan binding lectin(MBL) binds to the microbial surfaces, this binding brings forth MBL- associated serine proteases named MASP-1 and MASP -2. This complex like the classical pathway acts as the C1 complex where it cleaves c2 and c4 forming the fragments which are also evident in the alternate and classical pathway, where the c3 convertase is formed constituting the cascade of complement activation. (Hannigan et al. 2009)

Evidently the three pathways following from the formation of the C3 convertase follow the same path where C3a and C3b are formed. The significant aspect is the way in which they activate the complement system as its the only way in which they differ. However all three pathways lead up to the inflamation response, production of the oposonins and the membrane attack complex.Complement System In Immunology Essay.

The membrane attack complex involves Cb3 joining onto a C5 complement protein forming a c5 convertase which activates the remaining complements leading to the formation of the membrane attack complex (Lodish et al 2008). The membrane attack complex is a group of the post C complements exceeding complement 5 where C5b activates Complement 6, 7, 8 and several complement 9 proteins forming a ring type complex. This MAC complex can insert itself into the lipid bilayer of the target cell causing a disruption in the hydrophobic interactions causing a transmembrane channel to be formed in the cell. This causes ions to move out of the cells, and water plus sodium to flow in destroying the cell, this is also known as cytolysis. (Hannigan et al. 09) (Roitt.1997)

Other important responses due to the complement system is chemotaxis and inflammation. C5a and C3a are responsible for this area with C3a and C5a acting as chemotaxic factors attracting phagocytes to the site of infection. These two proteins are also are responsible for mediating inflammation with C5a acting as the stronger complment factor and C3a as a weak type. They increase vascular permeability and cause adhesion by acting upon the endothelial cells lining the blood vessels. They can attach to mast cells causing a release of histamine causing the more fluid to gather in a specific area to which antibodies, phagocytes and complement to the area of infection. C5a also can cause neutrophils and monocytes to adhere more easily to vessel walls; this aids the migration towards the antigens, ingesting them. (Janeway et al. 2005)

C3b also may act on its own as an opsonin, which it attaches covalently to the pathogen causing opsonisation, where phagocytic cells which have an attraction to the particular receptors on the C3b protein and are more easily able to ingest the cell. (Janeway et al. 2005)

The complement system is regulated by certain factors to control excessive amount of inflammation and cell lysis. If complement activation was constantly initiated it can cause damage to the body’s own tissues and cells. Complement control proteins exist in order to maintain the complement system. Such inhibitors are abundant such as the C1 inhibitor restricting the initiation of the classical pathway and it does this by inhibiting C1r and C1s from commencing protease activity. (Hannigan et al. 2009)Complement System In Immunology Essay.

Other type of regulation include the expression of proteins upon the surfaces of the host cells that interact with complement proteins and during this interaction it has the ability to either activate or degrade the complement proteins. These factors are specific in reducing the activation of C3 and C5. Another means of inhibiton decay accelerating factor ‘DAF’ is useful in that it induces the decay of C3 convertase of both alternate and classical pathways. (Hannigan et al.2009)Complement System In Immunology Essay.