Complement System Regulation Mechanism

COMPLEMENT SYSTEM REGULATION MECHANISM Regulation of 2thepath: complement system activation process is generally carried out through (1) damage/lability of each component involved in certain stages, and (2) certain factors that can influence the course of the reaction. (1) In general, therewillis be damage to active complexes suchatasthe C3bBb, C4b2a and C4b2a3b, so there obstacles to system activation relevant stage. Apart from that, thereglycoprotein is a factor called DAF (decay acceleration factor)ofwhich is found as an integral in cell membranes. The distribution DAF is very wide, but issolution mainly found infound the membranes ofblood platelets, erythrocytes and leukocytes. The form is very low in plasma, saliva and urine. accelerates the breakdown oftheC3integration convertaseoffrom both pathways. It iscomponents veryDAF possible that its role is to inhibit the convertase rather thanof working to decompose the molecules that have been formed. The presence DAF in the membrane will prevent complement activation so that cell lysis does not occur. (2) Controlling substance: -Apart C1 esterase inhibitor istofound in serum with BMof105 kdandwith various functions. from functioning inhibit the activation Clr Cls, it can also inhibit the activation of enzymes in other biological systems such as plasmin, kallikrein and Hagemancomplement factor. So ifsystem there istoactivation of these systems itiswill also cause the classical become more active. This because the C1 inhibitor used by these systems will also cause the classical complement system towillbecome moretheactive. Thiscomplement is because thesystem C1 inhibitor usedmore by these systems also cause classical to become active. This is because the C1 inhibitor is used by these systems. -Factor FactorI Iisisaninvolved inthat thespecifically regulation ofbreaks C3/C5down convertase inC3b bothafter pathways. enzyme C4b and being assisted by a suitable cofactor. With the presence of factor I the conversion function inC3question isblood greatlybecause inhibited. These sufferers only haveof aC3bBb smallwill amount of in their the uncontrolled formation continue to break down C3.the Patients dothenotcomplement experience system problems in dealing with bacterial infections so that role of in the body becomes clearer. -binding Factor HC3bis asosingle chain glycoprotein with a BM of functions 150 kd which is capable of that it plays a regulatory role through related to C3b. The binding of Factor H toHC3b willinaccelerate the breakdown ofaC3bBb and C3bBbP in plasma. Factor found the membrane will act as C3b receptor on certainC5lymphocyte and macrophage cells.between Presumably Factor Hbonds. also Factor regulates convertase because it competes C3b and C5 Hbroken acts asdown a cofactor in the breakdown of c3b and Factor is into iC3b which is then broken downC3(H2O) into C3cbyand C3dI.byC3b enzymes. - C4b ‒ binding protein (C4bp) C4bp regulates theaffinity C3 convertase (C4b2a) fromphase the classical pathway through binding with high to C4b in the liquid or membrane-bound phase. Apart from inhibiting the formation of C3 convertase, if factor I is bound to C4bp, C4bp acts as a cofactor for factor I in breaking down C4b into C4c and C4d, there by accelerating the breakdown of C4b. C4bp is the largest complement component with a BM of 570 kd. The structure of human C4bp consists ofunited 7 identical chains, each of which has a BM of 71 kd. The seven chains are inendone‒ NH2of centerC4bp so thatcanwith aneach electron microscopeIt itis appears as aCb4p spider.is Seventh bind C4b molecule. known that regulated by genes on chromosome 1. C4bp deficiency disorders have never been reported. -C5b67 Proteincomplex S participates inchanging regulating the complement system by binding toresult, the thereby its ability to attach to membranes. As a no membrane damage occurs. Regulatory Proteins in Membranes Among thewhich regulatory substancesinto of the complement system, there are several proteins are categorized one group because these proteins are integral proteins of the membranes of certain cells. 1. Complement receptor Type 1 (CR1) CR1 is a glycoprotein foundneutrophils, in various types of cells suchandas:certain erythrocytes, monocytes, macrophages, B lymphocytes T lymphocytes and podocytes in the kidney. CR1 exhibits binding activation in the regulation of C4b and C3b, but its primary role is thought to lie in the clearance ability of immune complexes. After immune complex enveloped by C3b during complement activation, it will then be bound via CR1 to erythrocytes which in turn are cleared through the liver and spleen. C3b that has been used will be broken downwill andinterfere cleaned by factors H and I. So a lack of complexes. CR1 on the surface of erythrocytes with the clearance of immune This situation is found in SLE sufferers. 2. Complement receptor Type 2 (CR2) CR2 ishas alsoonly a glycoprotein molecule as an integral moleculecells in thein membrane, but it been found in B lymphocytes and dendritic the spleen.by CR2 may play a role in B lymphocyte activation. CR2 and CR1 are regulated the same gene on band 1q32 on chromosome 1. 3. Membrane cofactor protein (MCP) MCP isnotfound ononthethemembranes ofmembrane. monocytes,The platelets and Toflymphocytes, but is found erythrocyte main role MCP iscofactor thought toin be monitoring the destruction of C3 on the cell surface by acting as a the breakdown of C3b by factor I. 4. Destruction acceleration factor DAF or Decay acceleration factor the group of substances found on has the been surfacediscussed of cells.how it works, including in