Activation Mechanism Lecture Notes

Activation mechanism Activation of the complementproteins systemtois interact not a single event, but a dynamic process that allows its component to produce an integrated system. Activation of the classical pathway can be immunological because the activator is a complex immune or immunoglobulin aggregates. The immunoglobulin that can act as anactivators activatorcan is IgG1, IgG2, IgG3and IgM. of Meanwhile, non-immunological take the form of a number substances including DNA, C-reactive protein, certain cell membranes, for example lipopolysaccharide (LPS) and trypsin-like enzymes. As in the immune response process, theefferent complement reaction pathway is differentiated intoarm. the afferent arm and the arm. The activator will start in the afferent C1 : The C1bond component consists ofthe3 protein groups, each called C1q,the C1rbond, and C1s, which very tightly when C1 ion is present.++. To release itarrangement is enough toactually removeconsists the Ca ion++from the environment. The entire C1Cls of a C1q molecule, 1 C1r molecule and 4 molecules.The C1q molecule hasthea BM ofmolecule 400 kd with a structure similar to collagen fibers. In more detail, C1q consists of 18 polypeptide chains, each of which is differentiated into 3 structural parts. structures At the periphery, the 18 polypeptide chains combine into 6 bundles of globulin atandthe ends, while the 6 bundles of fibrillar structures move towards the center join rod-shapedfrom central The six globulin structures are able to bindinFcamolecules IgG structure. or IgM molecules. ThetheClractivator moleculeandis aC1--globulin with[Ac]C1 a BM ofcomplex 190 kd.isWhen a bond occurs between via C1q, the formed which rise to the abilityenzymatic activity of C1r so that C1s becomes active too. gives Integrity of macromolecules and enzymatic Ca ions++still needed forarises the binding. Clssingle is a -globulin with a BM of 97 kd. The activity of Cls when the peptide bondthein the Clsphase molecule is classical removedpathway by Cle. With thecomplement formation ofsystem the Cls enzyme, initial of the of the ends. Furthermore, substances suchplace, as activator, Clq and Clr areofnothelonger needed for the next process to take namely the formation enzyme [Ac] C4b2a on the surface of the activator. [Ac]C4b2a is formed from both large broken fragments of C2 and C4. C4 : The C4 component is a --globulin molecule withafter a BMeach of 206 kd. The formation of the bimolecular complex C4b2a occurs C4 and C2 molecule breaks apart. Cl cleaves molecules C4, which consists of 3 chains, becomes C4ahas molecule which is much than C4b. C4a which comes from the -the chain biological activity as ansmaller anaphylactoxin C2 : The C2into component is a molecules. molecule with alarger BM ofC2a 117has kd which can be broken down by Cl C2a and C2b The the ability to bind C4b to form a C42a complex if Mg++ ions are present. The molecular weight of the C4b2a 288 kd.binding Most ofpartthebefore C4 andthey C2 molecules reactioncomplex will loseis their succeed ininvolved attachingintothis each other onthat the surface of thethe cellnext or bacterial membrane. C4b2a is a proteolytic enzyme will continue process in activating the complement system, without the involvement of the previous components. This enzyme is also called the C3 convertase enzyme, because the substrate is the C3 component. The active part of the enzyme is in the C2a molecule. C3 : The C3 component is ofa molecule thatwith functions as185a substrate for11-4). the C4b2a enzyme, in the form -2-globulin a BM of kd (Figure When C3 isreleased broken-down by thelarger convertase enzyme, the bondsC3aat the end of the chain are becoming C3a and C3b molecules. has its own biological potential (Figure 11-8),thewhile the C3battachment molecule athasthethestart ability to attach to the membrane around activator of the reaction. The toC3C4b2a. gene isthe located on chromosome 17.Most of the C3 fragments failed to bind attachment of C3b to the membrane around the C4b2a molecule causes the formation of the C4b2a3b enzyme which will work on the C5 molecule as the substrate. C3b as a result of solving C3 is not only obtained via thepathways classicalwhich pathway asbedescribed above, but can11-1). also beBecause obtained via alternative will discussed later (Figure C3b has quite an important function, its presence is required in quite large quantities The provision route whichinisblood also plasma. an amplification system.of C3b is enlarged in an alternative