Complement system Complement system - main humoral main humoral mechani mechani s s m m of nonspecific immunity of nonspecific immunity - - > > 40 glykoprot 40 glykoprot eins eins - - blood blood - - on the surface of immune on the surface of immune cells cells - Complement components Complement components inter-react be precise and inter-react be precise and regulated manner regulated manner to eliminate microbs, foreign cells or material. to eliminate microbs, foreign cells or material. - Charles Bordet 1896 Charles Bordet 1896 - - fresh serum of immunized animals fresh serum of immunized animals agglutinate agglutinate in in vitro vitro and lyse bacteria and lyse bacteria used for immunization used for immunization - s - s e e rum rum heated to heated to 60 60 o C a C a g g glutin glutin ate ate bacteria bacteria , , but do but do not lyse not lyse - - system responsible for lysis was named system responsible for lysis was named
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Complement system -main humoral mechanism of nonspecific immunity - > 40 glykoproteins - blood - blood - on the surface of immune cells - on the surface.
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Complement systemComplement system
-main humoral main humoral mechanimechanissmm of nonspecific immunity of nonspecific immunity
- - >> 40 glykoprot 40 glykoproteinseins - - bloodblood - - on the surface of immune cellson the surface of immune cells
- Complement componentsComplement components inter-react be precise and regulated manner inter-react be precise and regulated manner
to eliminate microbs, foreign cells or material. to eliminate microbs, foreign cells or material.
-Charles Bordet 1896Charles Bordet 1896 - - fresh serum of immunized animals agglutinate fresh serum of immunized animals agglutinate in in vitro vitro and lyse bacteria used for immunization and lyse bacteria used for immunization
- s- seerum rum heated to heated to 6060ooC aC aggglutinglutinate bacteriaate bacteria,, but do but do not lyse not lyse
- - system responsible for lysis was named system responsible for lysis was named alexalexiinn
Cascade system of activation Cascade system of activation – – active component serve as enzyme active component serve as enzyme and activate and activate ((splitsplit) ) following componentfollowing component
Activation of ComplementActivation of ComplementClassical pathwayClassical pathway
Activation signals:Activation signals:
1.1. Immune complexesImmune complexes ccomplex Ag + Ab (IgM, IgG3, IgG1)omplex Ag + Ab (IgM, IgG3, IgG1)
2.2. CRP – CRP – C-reactive proteinC-reactive protein During inflammation rise itsDuring inflammation rise its concentration concentration 100100 times. times.CRP binds polysaccharides of bacteriaCRP binds polysaccharides of bacteria,,fungi, parasites and viruses.fungi, parasites and viruses.Its binding to Its binding to AgAg is non specific is non specific
C1qC1q - 3 - 3 types of chainstypes of chains (A, B,C) (A, B,C) - - triplet of chains triplet of chains A+B+C A+B+C form subunit with binding site for form subunit with binding site for
- C- CHH2 2 domain domain IgGIgG
- C- CHH4 4 domaindomain IgM IgM
Activation signal Activation signal = = binding of binding of C1q C1q to immunocomplexto immunocomplex (( IgM,IgM, IgG + Ag)IgG + Ag)
Activation of ComplementActivation of ComplementClassical pathwayClassical pathway
Binding of Binding of C1q C1q to immune complex to immune complex auto-catalytic splitting of auto-catalytic splitting of proenzproenzymeyme C1r C1r for for active enzyme active enzyme C1r C1r conversion of conversion of C1s C1s for active for active serine protease serine protease C1sC1s splitting of splitting of C2 na C2a a C2bC2 na C2a a C2b and and C4 na C4a a C4bC4 na C4a a C4b C4b2a = C4b2a = C3 C3 cconvertonvertase – ase – split split C3 C3 for for C3a a C3bC3a a C3b C4b2a3b = C4b2a3b = C5 C5 cconvertonvertase – ase – split split C5 C5 C5a a C5bC5a a C5b
Activation of ComplementActivation of ComplementAlternative pathwayAlternative pathway
Activation signals :Activation signals : 1. 1. Aggregated Aggregated IgG4, IgA1, IgA2, IgE IgG4, IgA1, IgA2, IgE 2. 2. Polysaccharides Polysaccharides 3. LPS 3. LPS of bacteria (low content of sialic acid)of bacteria (low content of sialic acid) 4. 4. Various components of Various components of vviirusruseses, , fungifungi, , protozoaprotozoa, , cancer cellscancer cells
Spontaneous conversion of Spontaneous conversion of C3 C3 for for C3bC3b. . C3b C3b rapidly inactivatedrapidly inactivated ((HH factor factor)) binding to binding to sialsialc (typical for cells c (typical for cells MAOMAO))
Cells with low content of sialic acid Cells with low content of sialic acid (MIO) (MIO) cause low affinity of cause low affinity of H H factorfactorto to C3bC3b. C3b persist and binds . C3b persist and binds B B factor factor – – further further activation of activation of C3 C3 alternative pathway of activationalternative pathway of activation
Activation of ComplementActivation of ComplementLectin pathwayLectin pathway
Resemble of classical pathway Resemble of classical pathway – 2 – 2 differencesdifferences
A) A) C1q C1q is supplied by is supplied by MBP MBP ((mannose binding proteinmannose binding protein) – ) – strucrurally close to strucrurally close to C1qC1q
B)B) MASP MASP ( (MBP asssociated serine proteaseMBP asssociated serine protease) – ) – strucrurally close to strucrurally close to C1r a C1s C1r a C1s
After binding of After binding of MBP MBP to to manmannose or nose or N-acetylgluk N-acetylglukoseoseamamiinn – activation of – activation of MASP – MASP – splitting splitting C4 a C2C4 a C2
Activation of ComplementActivation of ComplementMACMAC