The Complement cascade - Abcam

The Complement cascade

The complement system is a heat labile component of blood that confers bactericidal properties. The functions of complement include the attraction of inflammatory cells, opsinization to promote phagocytosis, immune complex clearance and direct microbial killing through the formation of the membrane attack complex (MAC). Three pathways lead to complement activation; the classical pathway initiated by antibodies bound to the surface of foreign bodies and the alternative and lectin pathways that provide an antibody independent mechanism for complement activation induced by the presence of bacteria and other micro-organisms.

The classical pathway (in light-blue): C1 the first molecule in the classical complement cascade comprises C1q and two molecules of C1r and C1s. C1q binds target bound antibody leading to the activation of C1s. C1s cleaves C4 present in the plasma releasing C4a and C4b. C4b binds C2, which is subsequently cleaved by C1s. This results in the release of C2b and C2a. C2a remains associated with C4b to form the classical pathway C3 convertase (C4b2a). C2a in the convertase complex cleaves C3 releasing C3a and C3b. The latter binds to the C3 convertase complex to form C4b2a3b, the classical pathway C5 convertase. This complex cleaves C5 leading to the release of C5a and C5b.

The lectin pathway (in white): Mannan-binding lectin (MBL) and MBL-associated serine proteases (MASPs) are involved in the initial step of the lectin pathway of complement activation. The binding of MBL to mannose and N-acetyl glucosamine in micro-organisms leads to the activation of MASPs, which subsequently cleave C4 and C2. Following these cleavage events, complement pathway activation continues as in the classical pathway.

The alternative pathway (in dark-blue): The alternative pathway of complement activation is in a constant state of low-level activation (known as tickover). C3 is hydrolysed in the plasma to C3i, which has many of the properties of C3b. C3i then binds the plasma protein, Factor B. Bound Factor B is cleaved by Factor D to produce Ba and Bb. Ba is released and the remaining complex comprised of C3iBb forms the alternative pathway C3 convertase. Most of the C3b generated by the convertase is hydrolysed. However, if C3b comes into contact with an invading micro-organism it binds and amplification of the alternative pathway is promoted by the binding of C3b to Factor B. The plasma protein, properdin stabilizes the C3 convertase to prolong activity. C3b produced in this pathway also yields the C5 convertase, C3bBb3b, which leads to the production of C5a and C5b. Note, C3b generated in the classical pathway feeds into the alternative pathway to amplify the activation of complement.

Inhibitors of the complement system (in yellow): The complement system is regulated to protect the host. Complement inhibitors include the plasma serine proteinase inhibitor serpin (C1 inhibitor). The plasma proteins, Factor I and C4 binding protein (C4-bp), inhibit the activity of the classical C3 convertase. Classical pathway activation is also inhibited by the surface bound proteins, decay accelerating factor (DAF), CR1 and membrane co-factor protein (MCP). The alternative pathway is regulated by Factor H, DAF and CR1, which inhibit the C3 convertase of the alternative pathway. Factor I promotes the catabolism of C3i and C3b (Factor H and MCP act as co-factors).



C1qr2s2

Serpin (C1 inhibitor)

C4

Pathway activation

C4b

C2

C2b

Opsonin

MBL/MASPs

C3

Serpin

C4a

Pathway activation

C3 convertase

C2a

C4b2a

C3b

C4bp, Factor I, MCP, DAF and CRI

Hydrolyzed

C3

`Tickover'

C3i + Factor B

Pathway

C5

cross-talk

Factor I, MCP

C3iB

Ba

Factor D

Factor H DAF and CR1

C3iBb

C3 convertase

Stabilized by invading micro-organisims

C3

C3b

C3bBb3b

C5 Convertase

C3a

Factor I

Carboxypeptidase

C3a

C5 convertase

C4b2a3b

Chemotaxis and activation of inflammatory cells, inducing cytokine production, and mast cell degranulation, which results in enhanced vascular permeability and local blood flow.

Vitronectin, clusterin (plasma proteins) and CD59 on host cells.

Membrane attack complex

C5b

+ C6 + C7 + C8 + C9

Compromised bacterial

C5a

function due to pore formation

Bacterial lysis

C7 C5b C8

C6

C9

Opsinization (C3bi breakdown product is also an opsonin), Clearance of immune complexes and B cell priming.

Complement antibodies from Abcam:

Product

Clonality Applications

Host

Crossreactivity

Datasheet ab...

Classical pathway C1q [7H8]

C1r C1s C2 C3 / C3b [755] C3 [11H9] C3a / C3a des Arg [013-16] C3a Receptor [hC3aRZ1] C3c (FITC)

C3d C4 [16D2] C4a [99-H7] C4b C4c / C4b (FITC) C4c C4d C5 / C5a C5 C5/C5b C5a / C5a des Arg [2952] C5b-9 [aE11] C5R1 [P12/1] GC1q R [60.11]

M ELISA, Flow Cyt, IHC-FoFr,

IHC-Fr, IP, WB

Rat

P DID, Ie, RID, RIe

Shp

P DID, Ie, RID

Shp

P ELISA, WB

Rb

M IP, WB

Mm

M Flow Cyt, IHC-Fr, IP, WB

Rat

M ELISA, WB

Mm

M Flow Cyt, IHC-Fr

Mm

P Flow Cyt, IHC-Fr

Rb

P ELISA, ICC, IHC-P

Rb

M Flow Cyt, IHC-Fr, IP, WB

Rat

M ELISA, WB

Mm

P ELISA, WB

Chk

P IHC-Fr

Rb

P ID, WB

Chk

P Flow Cyt, ICC/IF, IHC-Fr, IHC-P, WB Rb

P WB

Rb

P IHC-Fr, WB

Rb

P WB

Rb

M ELISA, WB

Mm

M ELISA, IHC-Fr, WB

Mm

M Flow Cyt, IHC-Fr, WB

Mm

M ELISA, Flow Cyt, IP, WB

Mm

Ms

11861

Hu

8781

Hu

8782

Hu, Ms, Rat, Dog and Zfsh 58389

Hu

11871

Ms

11862

Hu

36385

Hu

59554

Hu, Ms, Rat, Gt, Cow, Dog, Pig,

Pig, Sh, Cat, Gpig, Mink and Kg 4212

Hu

15981

Ms

11863

Hu

63796

Hu

48582

Hu

4216

Hu

61965

Hu

36075

Hu

46168

Ms

11898

Hu

46153

Hu

11878

Hu, Bb and Pig

15984

Hu and RhMk

33212

Hu, Ms and Rat

24733

Lectin Pathway

Mannan Binding Lectin A [2B4] M

Mannan Binding Lectin

[HYB 131-01]

M

MASP1

P

MASP1/3

P

MASP2

P

IA, WB

ELISA, IHC-Fr, IHC-P, WB WB WB WB

Rat Ms

Mm Hu Rb Hu Rb Hu Rb Hu

36670

23457 65891 65887 65895

Mannan Binding Lectin antibody [HYB 131-01] (ab23457)

Clonality Applications M ELISA, IHC-Fr, IHC-P, WB

Host Mm

Species cross reactivity Hu

Mannan Binding Lectin, MBL, belongs to the C-type family of collectins. It functions as an opsonin which activates the complement system on binding to microbial polysaccharides. This image shows Mannan Binding Lectin staining in formalin fixed and PFA-fixed paraffin embedded human liver, using ab23457

See more products at: immunology

Product

Clonality Applications

Host

Crossreactivity

Datasheet ab...

Alternative pathway

Factor B

P IHC-Fr

Factor D [008-01]

M ELISA, WB

Factor P [10-18]

M ELISA, FuncS, IHC-Fr

Properdin, B factor [008-02] M ELISA, WB

SC5b9 [3R2/0]

M ELISA, Flow Cyt, IHC-Fr, WB

Shp Hu Mm Hu Mm Hu Mm Hu Mm Hu

Regulatory / Inhibitors C4 binding protein CD59 [MEM-43]

Clusterin (Apolipoprotein J) Complement Receptor 1

(CR1) (CD35) [RLB25] Decay Accelerating Factor

(DAF) (CD55) [BRIC110] ECT Factor H

P IHC-Fr

Shp

M Flow Cyt, FuncS, ICC/IF, IHC-Fr,

IHC-P, IP, WB

Mm

P WB

Rb

M IHC-Fr, IHC-P

Mm

M Flow Cyt, ICC/IF

Mm

P WB

Rb

P DID, Flow Cyt, Ie, RID, RIe

Shp

Factor I [061-01]

M ELISA, WB

Mm

Membrane Co-Factor Protein

(MCP) (CD46) [MEM-258] M Flow Cyt, IP, WB

Mm

Properdin [HYB 039-06]

M AP, ELISA, WB

Mm

Serpin (C1 Inactivator)

M IHC-P, WB

Mm

Vitronectin [EP873Y]

M ICC/IF, IHC-P, WB

Rb

Hu

Hu Hu

Hu

Hu Hu, Ms and Mk Hu, Ms, Rat, Hrs, Dog, Cat and Gpig Hu

Cow and Hu Hu Hu Hu, Ms and Rat

Membrane Attack Complex (MAC)

C6

P IHC-Fr, WB

C7

P DID, Ie, RID

C8 [056B-373]

M ELISA, Flow Cyt, IHC-Fr, WB

C9

P ELISA, ID, IHC-Fr, IHC-P

Rb Ms Shp Hu Mm Hu Shp Hu

And many more...

64515 36383 58984 17932 59024

53894

9182 42673

49520

53353 15053

8842 52244

789 25850 54898 45139

11899 8791

59140 53896

C5R1 [P12/1] antibody (ab33212)

Clonality Applications

M

Flow Cyt, IHC-Fr, WB

Host Mm

Species cross reactivity Hu and RhMk

All cellular responses to C5a are specifically mediated by interactions with the membrane bound C5a receptor, a seven transmembrane GTP binding coupled receptor that belongs to the rhodopsin supergene family. C5a receptor 1 expression has been reported in myeloid blood cells, brain, liver, lung, spleen, heart, kidney, and intestinal tract. This image shows FACS analysis of C5R1 expressing cells in human peripheral blood granulocytes, using ab33212.

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