K.32 Komplemen 4 Nop2007

Komplemen(Complement)Dr.Edhie Djohan Utama, SpMKDr. Tetty Aman Nasution, M.Med.Sc

28 Oktober 2007

Jules Bordet (1870-1961), discoverer of complement National Library of Medicine Complement refers, historically, to fresh serum capable of lysing antibody (Ab)-coated cells.

This activity is destroyed (inactivated) by heating serum at 56 degrees C for 30 minutes. (Jules Bordet)+Complement in fresh serumCell lysis

KomplemenSalah satu sistem enzim serum yang berfungsi dalam inflamasi, opsonisasi partikel antigen, dan kerusakan membran sel2 yang terinfeksi.

Merupakan molekul sistem imun nonspesifik yang larut dan dalam keadaan tidak aktif.

Jika teraktivasi enzim utk reaksi berikut, enzim pengontrol, & bbp tanpa aktivitas enzim.

EFEK BIOLOGIK SISTEM KOMPLEMENAkibat aktivasi sistem komplemen :Reaksi inflammasiKemotaksis dan opsonisasi (mempermudah terjadinya phagositosis)Aktivitas sitolitik(Cell lysis : cell bacteria, allograft dan cell tumor.)4. Menghasilkan mediator (e.g. histamine)

REAKSI INFLAMASIReaksi tubuh terhadap masuknya benda asing, invasi mikroorganisme atau kerusakan jaringan.

Usaha pertama tubuh, mengerahkan elemen2 sistem imun ke tempat dimana benda asing dan mikroorganisme yang masuk tubuh atau jaringan yg rusak tsb

Proses inflamasi ada 3 hal :

Peningkatan persediaan darah ke tempat benda asing, mikroorganisme yang masuk atau jaringan yang rusak

Peningkatan permeabilitas kapiler (pengerutan sel endotel molekul yg lebih besar spt antibodi & fagosit bergerak keluar pembuluh darah) dan sampai di tempat tsb

Leukosit, terutama fagosit PMN dan makrofag dikerahkan dari sirkulasi dan bergerak ke tempat benda asing, mikroorganisme yang masuk atau jaringan yang rusak.

Mediator yg dilepas saat komplemen diaktifkanC1qrs meningkatkan permeabilitas vaskularC2 mengaktifkan kininC3a & C5a kemotaksis mengerahkan lekosit juga sbg anafilatoksin mempengaruhi mastositC3b opsonin & adherens imunC4b opsoninC 5-6-7 kemotaksisC 8-9 melepas sitolisin menghancurkan sel

InflammationanaphylotoxinsC5achemoattractionC3a, C4a----activationC3a, C4a---increasedvascular permeability

The acute inflammatory response is characterized by symptoms of redness, pain, swelling, and heat due to the action of C4a, C3a, C5a, and histamine. Inflammation's primary goal is to set into motion a series of events that result in the elimination of foreign and damaged cells. This response can be mediated by the anaphylatoxins and their byproducts.

The main activity of C3a and C5a is anaphylaxis. These cause histamine release from mast cells and basophils, which can affect the activity of smooth muscle. Spasmogenicity, accounts for the ability of these molecules to induce an anaphylactic response in animals. In addition to spasmogenicity, histamine release induced by the anaphylatoxins as effects on inflammation. The cellular responses of neutrophils and monocytes to C5a include (1) degranulation and lysosomal enzyme release, (2) cell adherence, and (3) chemotactic migration.

C3a dan C5a merupakan anafilatoksinANAFILATOKSIN : bahan dengan BM kecil degranulasi mastosit atau basofil, pelepasan histamin.Histamin = meningkatkan permeabilitas vaskular dan = kontraksi otot polos menimbulkan gejala2 lain pada reaksi Allergi, seperti asthmatis (serangan sesak napas)

Peningkatan permeabilitas vaskular menimbulkan oedem. Yaitu akumulasi cairan dalam jaringan yg mengandung lbh byk antibodi & komponen komplemen meningkatkan lagi pelepasan anafilatoksin memperluas reaksi.Dlm proses inflamasi, byk lekosit dihancurkan, kemudian makrofag lain memasuki daerah tsb mengakhiri reaksi inflamasi.

Fagositosis komponen penting pada inflamasiFAGOSITOSIS : proses menghancurkan patogen dalam sel tanpa kerusakan jaringan sekitarnya.Proses ini tjd bila neutrofil, monosit, makrofag, dan eosinofil kontak dgn sasaran inflamasi (bakteri, parasit, bahan asing, dsb)

Fagosit akhirnya memakan benda asing, mikroorganisme atau jaringan yg rusak. Selama proses tsb, enzim lisosom dilepas oleh makrofag ke luar sel shg dpt merusak jaringan sekitar. (phagolispspm)Akibat kerja sama sistem imun non spesifik dan spesifik dapat terjadi reaksi tubuh spt panas, bengkak, sakit dan kerusakan jaringan (tanda2 inflamasi)

Sel PMN lbh sering ditemukan pada inflamasi akut.

Proliferasi monosit ditemukan pada inflamasi kronik

Eosinofil kurang berfungsi sbg fagosit dibanding dg neutrofil. Sasaran eosinofil biasanya parasit ukuran besar.

KEMOTAKSIS DAN OPSONISASIKEMOTAKSIS : gerakan fagosit ke tempat infeksi respons thd berbagai faktor spt produk bakteri & faktor biokimiawi yg lepas pd aktivasi komplemen. Jaringan yg rusak atau mati dpt juga melepas faktor kemotaksis. Sel PMN bergerak cepat berada di tempat infeksi dalam 2-4 jamMonosit bergerak lbh lambat perlu waktu 7-8 jam untuk sampai di tujuanC3a, C5a dan C5-6-7 mempunyai efek kemotaksis

CHEMOTAXIS :Adalah pergerakan bakteri akibat ketarikannya (attraction) oleh bahan kimia yang terdapat didalam lingkungannya

Opsonization / PhagocytosisCR1, CR3, or CR4C3b or iC3bopsonized bacteria

OPSONIN : molekul yg dpt diikat oleh partikel yg hrs difagositir dan oleh reseptor fagosit.

Sehingga opsonin merupakan jembatan antara 2 protein reaktif tersebut di atas.

AKTIVITAS SITOLITIK

Eosinofil dan sel PMN mempunyai reseptor utk C3b dan IgG C3b dpt mengaktifkan sitotoksisitas sel efektor ADCC (Antibody Dependant Cellular Cytotoxicity) kerjanya bergantung pd IgG

Sel darah merah yg disensitisasi C3b dpt dihancurkan oleh makrofag tanpa fagositosis, disebut kerusakan kontak (contactual damage).

Akhir aktivasi komplemen, C8-9 merusak membran sebagai akibat lisis osmotik

Dapat mengaktifkan komplemen melalui jalur klasik :

kompleks imun (IgG dan IgM) agregat antibodi (IgG1,IgG2, IgG3) lipid A dari endotoxin protease kristal urat polinukleotide membran virus tertentu CRP

OPSONISASI : proses melapisi partikel antigen oleh antibodi dan/atau oleh komponen komplemen sehingga lebih mudah dan cepat dimakan sel fagosit.

Hal ini oleh karena ada reseptor pd fagosit utk fraksi Fc dr IgG, C3b dan CRP (C-Reaktif Protein) yg berfungsi sbg opsonin.

Opsonization.Facilitated phagocytosis is referred to as opsonization. In this process, C3b, which coats the particle, is known as an opsonin. This process occurs when cells, viruses, or immune complexes are made ready for enhanced phagocytosis by becoming coated with C3b or C4b. This leads to binding of bacteria to phagocyte C3 receptors and the subsequent clearance of the bacteria by phagocytosis. It can either take place in the presence or absence of antibodies.

The Membrane Attack PathwayThe MAC is especially important for the immune response against Neisseria spp. Membrane proteins (CD59, HRF) prevent MAC formation on host cells.MAC

DefinitionOverviewClassical PathwayAlternative PathwayRegulationDeficienciesComplement (C) Definition :Group of 30 different serum proteins which exist normally in an inactive form. When activated, they can enhance aspects of innate immunity & some of the biological effects of antibodies.Complement Pokok bahasan / Key wordsSistem Komplemen terdiri atas lebih dari 25 protein yang secara normal dijumpai didalam plasma dan serum darah hewan dan manusia di produksi oleh jaringan yang berbeda, hepatocytes, macrophage dan epitel saluran pencernaan. Komponen dari komplemen 2 itu ditulis dengan huruf C1 C9 sesuai dengan penemuannya.

Complement system is composed of more than 25 different proteins produced by different tissues and cells including hepatocytes, macrophages and gut epithelial cells.

All components of the complement pathway are designated by letter C followed by a number (C1-C9). Numbered in the order of their discovery

Komplemen terdiri dari 9 komponen protein yang disebut C1 sampai dengan C9. C1 terdiri dari 3 fraksi yaitu C1q, C1r dan C1s. Faktor B (serine protease) dan D (plasma serine protease) serta Properdin

These proteins are activated by a variety of agents and their activation proceeds in a cascade fashion leading to lysis. Classical Pathway of Complement ActivationThe process of complement activation is a cascade of enzyme linked reactions

Complements Protein Sources := Hepatocytes= Tissue macrophages= Epithelial cells of the GI= Blood monocytesComplement :Heat Labile component of normal plasmaAugments opsonization of bacteria by abs.Allows some antibodies to kill bacteria

Activity was said to complement antibacterial activity of antibodiesConsequently, an absence of one of the components in the pathway can disrupt the cascade and terminate the reaction.

The effector functions of complement can be activated through 2 major pathways : = The Classical Pathway (Acquired Immunity)= The Alternative Pathway (Innate Immunity)

Antigen

3 Main Consequences of Complement Activation1. Opsonization of Pathogens: C3b2. Acute Inflammation: C3a, C5a 3. Killing of Pathogens: pore formation

AKTIVASI KOMPLEMENPada tahapan pengaktivan komponen itu dihasilkan satu enzim baru yang dapat melibatkan beberapa molekul substrat berikutnya, sehingga timbul reaksi yang cukup kuat untuk merusak dinding sel (sel lisis).

Aktivasinya memerlukan ion Ca dan Mg dan tergantung dari pH (7,2 7,4) dan suhu 30oC 37oC.

Antibodi yang dapat mengikat komplemen adalah IgG dan IgM, sedangkan antibody jenis lain tidak mengikat komplemen.

Komplek Ab dengan Ag : misalnya Ab dengan sel eritrosit berkemampuan untuk mengaktifkan beberapa komponen.

Efek dari komplemen Cell lysis : cell bacteria, allograft dan cell tumor.Opsonisasi : mempermudah phagositosisMenghasilkan mediator (e.g. histamine) Komplemen terutama dihasilkan oleh hati, heat labile yaitu dapat di- inaktivasi dengan memanaskan serum pada 56oC selama 30 menit. Sedangkan pada suhu ini immunoglobulin tidak di-inaktivasi (tdk rusak). Sebagian komplemen adalah proenzyme, yang bekerja menyebabkan aktivasi enzyme. Komplemen bisa diaktivasi oleh Ag-Ab kompleks (kompleks IgG atau IgM) atau oleh molekul yg nonimmunologic seperti endotoksin.

COMPLEMENT CASCADE Jalur klasik (classic pathway)

Jalur alternative (alternative pathway)

Jalur Lectin

Jalur Lytic (Membrane attack pathway)

ClassicAlternativeBindBindAntigen-Antibody compexesMicrobial surfaces ( nonspecific activators eg. Endotoxin)C1C1C4 C2C4b,2bC3C4b,2b,3bC5C3(H2O) + BD (protease)C3b,Bb ( C3 convertase )C3b,Bb,C3b( C5 covertase )( C3 convertase )+C2a,C4aC3a = anaphylatoxin+C3a = anaphylatoxin+C5a + C5bC3C5b,6,7C5b,6,7,8,9Lysis & cytotoxicityC6C7C8C9= Proteolytic cleavagediatas huruf = enzymatic activity( C5 covertase )Levinson & Jawetz, 2000, Ed.6th, page 381C1 (protease)

Pathways of Complement Activation

Jalur klasik (classic pathway)C1q, C1r dan C1s terikat satu dengan lainnya dengan perantaraan ion Ca (calcium). Setelah C1q terikat pada antibodi (Ig), maka fraksi C1s bersifat sebagai enzim protease yang mengaktipkan C4 dan C2 membentuk kompleks C4b2b (enzyme) .

Komplek C4b2b akan memecah C3 menjadi C3a dan C3b

C3a adalah anafilatoksin. C3b membentuk kompleks C4b2b3b yang menghasilkan enzim baru yang merupakan convertase C5 (C4b2b3b) yang memecah C5 menjadi C5a dan C5b (C5a adalah anafilatoksin & faktor khemotaksis).

C5b terikat pada C6 dan C7 membentuk kompleks yang berinteraksi dengan C8 dan C9 dan membentuk MAC = membrane attack complex (C5b6789) yang menyebabkan sel lisis, karena terjadi pori pori (lubang2) pada membrane sel sehingga sel lisis sebab kehilangan air.

C3b yang terikat pada kompleks antibody dan menempel pada dinding sel.

Classical Pathway Component cleavageEnzymatic act.Component asemb.

CLASSICAL PATHWAYClassical pathway normally requires a suitable Ab bound to antigen (Ag), complement components 1, 4, 2 and 3 and Ca++ and Mg++ cations.

C1 activation Binding of C1qrs (a calcium-dependent complex), present in normal serum, to Ag-Ab complexes results in autocatalysis of C1r. The altered C1r cleaves C1s and this cleaved C1s becomes an enzyme (C4-C2 convertase) capable of cleaving both C4 and C2.

C4 and C2 activation (generation of C3 convertase) Activated C1s enzymatically cleaves C4 into C4a and C4b. C4b binds to the Ag-bearing particle or cell membrane while C4a remains a biologically active peptide at the reaction site. C4b binds C2 which becomes susceptible to C1s and is cleaved into C2a and C2b. C2a remains complexed with C4b whereas C2b is released in the micro environment. C4b2a complex, is known as C3 convertase in which C2a is the enzymatic moiety.

C3 activation (generation of C5 convertase) C3 convertase, in the presence of Mg++, cleaves C3 into C3a and C3b. C3b binds to the membrane to form C4b2a3b complex whereas C3a remains in the micro environment. C4b2a3b complex functions as C5 convertase which cleaves C5 into C5a and C5b. Generation of C5 convertase marks the end of the classical pathway.

Components of the Classical PathwayC1(q,r,s)C1qBinds to antibody that has bound antigen, activates C1r.C1rCleaves C1s to activate protease function.C1sCleaves C2 and C4.C2C2aUnknown.C2bActive enzyme of classical pathway; cleaves C3 and C5.C3C3aMediates inflammation; anaphylatoxin.C3bBinds C5 for cleavage by C2b. Binds cell surfaces for opsonization and activation of alternate pathway.C4C4aMediates inflammation.C4bBinds C2 for cleavage by C1s. Binds cell surfaces for opsonization.

Jalur alternative (alternative pathway)Komplemen aktivasi juga terjadi melalui jalur alternatip dimana terjadi by pass dan untuk menstimulasi jalur ini reaksi antigen antibody tidak perlu. Properdin, suatu serum protein, berfungsi dalam proses ini.

Jalur alternatip diinisiasi (diawali) oleh berbagai bahan (substances) seperti lipopolisakarida bakteri (endotoksin), dinding fungi, dan envelope virus. Diawali dengan terikat C3(H2O) & faktor B.

Kompleks ini menjadi C3bBb oleh enzim protease, seperti konvertase yang memecah C3 dan membentuk C3b & C3a.

C3 : C3b terikat pada permukaan mikroba, berfungsi sebagai opsonin dan sebagai komponen dari C3 dan C5 convertase.Factor B : Bb adalah serine protease dan mengaktipkan C3 dan C5 convertase.Factor D : Plasma serine protease, memecah (cleaves) faktor B dan terikat pada C3b.Properdin : menstabilkan C3 covertase (C3bBb) pada permukaan mikroba.Proteins of the Alternative Pathway

ClassicAlternativeBindBindAntigen-Antibody compexesMicrobial surfaces ( nonspecific activators eg. Endotoxin)C1C1 (protease)C4 C2C4b,2bC3C4b,2b,3bC5C3(H2O) + BD (protease)C3b,Bb ( C3 convertase )C3b,Bb,C3b( C5 covertase )( C3 convertase )+C2a,C4aC3a+C3a+C5a + C5bC3C5b,6,7C5b,6,7,8,9Lysis & cytotoxicityC6C7C8C9= Proteolytic cleavagediatas huruf = enzymatic activity( C5 covertase )Levinson & Jawetz, Ed.6th,2000, page 381

Alternate Pathway

Components of the Alternate PathwayC3C3aMediates inflammation; anaphylatoxin.C3bBinds cell surfaces for opsonization and activation of alternate pathway.Factor BBBinds membrane bound C3b. Cleaved by Factor D.BaUnknown.BbCleaved form stabilized by P produces C3 convertase.Factor DDCleaves Factor B when bound to C3b.ProperdinPBinds and stabilizes membrane bound C3bBb.

LECTIN PATHWAY C4 activation can be achieved without antibody and C1 participation by the lectin pathway.

This pathway is initiated by three proteins: a mannan-binding lectin (MBL), also known as mannan-binding protein (MBP) which interacts with two mannan-binding lectin-associated serine proteases (MASP and MADSP2), analogous to C1r and C1s.

This interaction generates a complex analogous to C1qrs and leads to antibody -independent activation of the classical pathway.

C1q can also bind to a number of agents including some retroviruses, mycoplasma, poly-inosinic acid and aggregated IgG, and initiate the classical pathway.

Roitt et al. Immunology (5th ed.), chapter 4

Table 1. Proteins of the Complement systemClassical PathwayLectin PathwayAlternative PathwayLytic PathwayActivation Proteins:C1qrs, C2, C3, C4Control Proteins:C1-INH, C4-BPMannan binding protein (MBP), mannan-asociated serine protease (MASP, MASP2)

(Mannan = Mannose)C3, Factors B & D*, ProperdinFactors I* & H, DAF, CR1, etc.C5, C6, C7, C8, C9Protein SComponents underlined acquire enzymatic activity when activated.Components marked with an asterisk have enzymatic activity in their native form.

LYTIC PATHWAY The lytic (membrane attack) pathway involves the C5-9 components.

C5 convertase generated by the classical or alternative pathway cleaves C5 into C5a and C5b. C5b binds C6 and subsequently C7 to yield a hydrophobic C5b67 complex which attaches quickly to the plasma membrane (slide 22, 23 & 24).

Subsequently, C8 binds to this complex and causes the insertion of several C9 molecules. bind to this complex and lead to formation of a hole in the membrane resulting in cell lysis.

The lysis of target cell by C5b6789 complex is nonenzymatic and is believed to be due to a physical change in the plasma membrane. C5b67 can bind indiscriminately to any cell membrane leading to cell lysis.

Such an indiscriminate damage to by-standing cells is prevented by protein S (vitronectin) which binds to C5b67 complex and blocks its indiscriminate binding to cells other than the primary target.

ClassicAlternativeBindBindAntigen-Antibody compexesMicrobial surfaces ( nonspecific activators eg. Endotoxin)C1C1 (protease)C4 C2C4b,2bC3C4b,2b,3bC5C3(H2O) + BD (protease)C3b,Bb ( C3 convertase )C3b,Bb,C3b( C5 covertase )( C3 convertase )+C2a,C4aC3a+C3a+C5a + C5bC3C5b,6,7C5b,6,7,8,9Lysis & cytotoxicityC6C7C8C9= Proteolytic cleavagediatas huruf = enzymatic activity( C5 covertase )Levinson & Jawetz, Ed.6th,2000, page 381LYTIC PATHWAYMAC

Components of the Membrane-Attack ComplexNative componentActive component(s)Function(s)C5C5aMediates inflammation; anaphylatoxin, chemotaxin.C5bInitiates assembly of the membrane-attack complex (MAC).C6C6Binds C5b, forms acceptor for C7.C7C7Binds C5b6, inserts into membrane, forms acceptor for C8.C8C8Binds C5b67, initiates C9 polymerization.C9C9nPolymerizes around C5b678 to form channel that causes cell lysis.

Classical Pathway Component cleavageEnzymatic act.Component asemb.Lytic Pathway

Alternate Pathway Lytic Pathway

The complement system. Activation of either wing of the system leads to the formation of peptide fragments that function on leukocytes and forms the membrane attack complex.

Late Steps of Complement Activation

Hereditary C Deficiencies

C3 Deficiencyrecurrent bacterial infectionsdescribed in canines (Brittany spaniel colony)

Porcine factor H deficiencyInhibits binding of C3b to Bb failure to thriveDie of renal failure

BIOLOGICALLY ACTIVE PRODUCTS OF COMPLEMENT ACTIVATION (1)Activation of complement results in the production of several biologically active molecules which contribute to resistance, anaphylaxis and inflammation.

Kinin production C2b generated during the classical pathway of C activation is a prokinin which becomes biologically active following enzymatic alteration by plasmin. Excess C2b production is prevented by limiting C2 activation by C1 inhibitor (C1-INH) also known as serpin which displaces C1rs from the C1qrs complex.

A genetic deficiency of C1-INH results in an overproduction of C2b and is the cause of hereditary angioneurotic edema. This condition can be treated with Danazol which promotes C1-INH production or with -amino caproic acid which decreases plasmin activity.

BIOLOGICALLY ACTIVE PRODUCTS OF COMPLEMENT ACTIVATION (2)Anaphylotoxins C4a, C3a and C5a (in increasing order of activity) are all Anaphylotoxins which cause basophil/mast cell degranulation and smooth muscle contraction. Undesirable effects of these peptides are controlled by carboxypeptidase B (C3a-INA).

Chemotactic Factors C5a and MAC (C5b67) are both chemotactic. C5a is also a potent activator of neutrophils, basophils and macrophages and causes induction of adhesion molecules on vascular endothelial cells.

Opsonins C3b and C4b in the surface of microorganisms attach to C-receptor (CR1) on phagocytic cells and promote phagocytosis.

Other Biologically active products of C activation Degradation products of C3 (iC3b, C3d and C3e) also bind to different cells by distinct receptors and modulate their functions.

The main activity of C3a and C5a is anaphylaxis. These cause histamine release from mast cells and basophils, which can affect the activity of smooth muscle. Spasmogenicity, accounts for the ability of these molecules to induce an anaphylactic response in animals. In addition to spasmogenicity, histamine release induced by the anaphylatoxins as effects on inflammation. The cellular responses of neutrophils and monocytes to C5a include (1) degranulation and lysosomal enzyme release, (2) cell adherence, and (3) chemotactic migration.

The acute inflammatory response is characterized by symptoms of redness, pain, swelling, and heat due to the action of C4a, C3a, C5a, and histamine. Inflammation's primary goal is to set into motion a series of events that result in the elimination of foreign and damaged cells. This response can be mediated by the anaphylatoxins and their byproducts.

Opsonization.Facilitated phagocytosis is referred to as opsonization. In this process, C3b, which coats the particle, is known as an opsonin. This process occurs when cells, viruses, or immune complexes are made ready for enhanced phagocytosis by becoming coated with C3b or C4b. This leads to binding of bacteria to phagocyte C3 receptors and the subsequent clearance of the bacteria by phagocytosis. It can either take place in the presence or absence of antibodies.

In summary, the complement system takes part in both specific and non-specific resistance and generates a number of products of biological and pathophysiological significance.

There are known genetic deficiencies of most individual C complement components, but C3 deficiency is most serious and fatal.

Complement deficiencies also occur in :immune complex diseases (e.g., SLE) and acute and chronic bacterial, viral and parasitic infections.

Biological Properties of C Activation Products and their Regulatory Molecules

Biological Properties of C Activation Products and their Regulatory Molecules

ComponentBiological activityEffect ControlsC5a (anaphylatoxin; Chemotactic factor) Basophil & mast cell activation; enhanced vascular permeability; smooth muscle contraction. Anaphylaxis Inflammation

C3a INA Chemotaxis; neutrophil aggregation; Oxidative metabolism stimulationStimulation of leukotriene releaseDelayed anaphylaxisInduction of helper T-cells.ImmunoregulationC5b67 Chemotaxis; attachment to other cell membranes. Inflammation; lysis of bystander cells. Protein-S

Table 1 : Proteins of the Classical Pathway of ComplementAbbas & Lichtman : Cellular and Molecular Immunology,2003, Ed. 5th page 331

Table 2 : Proteins of the Alternative Pathway Abbas & Lichtman : Cellular and Molecular Immunology,2003, Ed. 5th page 331

ProteinStructureSerum conc. (ug/ml)FunctionC3185 kD (alpha subunit, 110 kD & beta subunit 75 kD)1000-1200C3b terikat pada permukaan mikroba, berfungsi sebagai opsonin dan sebagai komponen dari C3 dan C5 cinvertase.C3a menstimulasi inflamasi (anaphylatoxin)Factor B 93 kD monomer200Bb adalah serine protease dan mengaktipkan C3 dan C5 convertase.Factor D 25 kD monomer1-2Plasma serine protease, memecah (cleaves) faktor B dan terikat pada C3bProperdinTerdiri dari 4 buah 56 kD subunit25menstabilkan C3 covertase (C3bBb) pada permukaan mikroba.

Table 3 : Proteins of the Late Step of Complement ActivationAbbas & Lichtman : Cellular and Molecular Immunology. 2003, Ed. 5th page 331

ProteinStructureSerum conc. (ug/ml)FunctionC5190-kD dimer80C5b initiates assembly of the MACC5a stimulates inflammation (anaphylatoxin)C6110-kD monomer45Component of the MAC : binds to C5b and accepts C7C7100-kD monomer90Component of the MAC : binds to C5b,6 and inserts into lipid membranesC8155-kD trimer of 64-, 64-, and 22 kD chains60Component of the MAC : binds to C5b,6,7 and inisiates the binding and polymerization of C9.C979-kD monomer60Component of the MAC : binds to C5b,6,7,8 and polymerizes to form membrane pores.

Regulation of Complement Activation

Extracellular neutralization of virus by antibody. Antibody can reduce the number of infectious particles by linking virions and thereby causing aggregation. Antibody alone or with complement can also inactivate viruses.

C