Effector mechanisms of humoral immunity

The Complement System

(C’)

Activation pathwaysEffector functions

Regulation of complement activation

Jules Bordet(1870-1961)

1919.

Nobel prize

For complement-mediated bacteriolysis

Complement system(complements i.e. assists functions of antibody)

Consists of serum and cell surface proteins involved in defense against pathogens and tissue damage mediated by antibodies

Effector mechanism of both innate and adaptive humoral immunity

Complement system

Over 30 serum and cell surface proteins:

- Complement components (in serum inactive, activated sequentially as a cascade)

- Complement receptors(cell surface, recognize activated components)

- Regulatory proteins of complement(both in serum and cell surface, inhibit activated

components)

Complement system

Pathways of activation

- Classical

- Alternative

- Lectin

Complement system

Activation and functions

of complement (overview)

Classical

Lectin

Alternatve

C1, C4, C2

Early steps Late steps

MBL, C4, C2

C3, B, D (P)

C3, C5, C6, C7, C8, C9

C3, C5, C6, C7, C8, C9

C3, C5, C6, C7, C8, C9

Activationpathway

Classical

Lectin

Effector functions(elimination of pathogen)

C3 convertase

Alternatve

Ag-Ab complex(microorganism and IgG or IgM Ab)

microorganism

microorganism

C5 convertase

b

a

Early steps Late steps

C1

MBL

C3

C4

C2

D

B

Early steps of

complement activation

D

B

P

MASP MBL

Late steps of complement activation

C1C1Activated

C4b2b

C3 CONVERTASE

C5

C9C8C7C6

Bacterium

IgG

IgM

C4 C2C4a C4bC2b C2a

C3

C3aC3b

C4b2b3b

C5 CONVERTASE

C5a C5bLysis

MEMBRANE ATTACK

COMPLEX

C5-C9 MAC

C4b2b

C3 CONVERTASE

C5

C9C8C7C6

Bacterium

C4 C2C4a C4bC2b C2a

C3

C3aC3b

C4b2b3b

C5 CONVERTASE

C5a C5bLysis

MEMBRANE ATTACK

COMPLEX

C5-C9 MAC

MASP

MBL

C3 C3b

C5

C6C7C8C9

Bacterium Factor D

Ba Bb

C3

C3a C3b

C3bBb3b

Alternative C5 convertase

C5b

C5a

Lysis

MEMBRANE ATTACK

COMPLEX

C5-C9 MAC

Factor B

C3bB C3bBb

Alternative C3 convertase

Properdin

Effector functions of activated complement

- Cytolysis (MAC)

Cytolysis (MAC)

Effector functions of activated complement

- Cytolysis (MAC)

- Opsonization (C3b, C4b)

Opsonization and phagocytosis (C3b, C4b)

Effector functions of activated complement

- Cytolysis (MAC)

- Opsonization (C3b, C4b)

- Stimulation of inflammation (C5a, C3a, C4a)

Stimulation of inflammatory rections

(C5a, C3a, C4a) Activation of mast cells and neutrophils

(anaphylatoxins)

Effector functions of activated complement

- Cytolysis (MAC)

- Opsonization (C3b, C4b)

- Stimulation of inflammation (C5a, C3a, C4a)

- Stimulation of humoral response (C3d)

Stimulation of humoralimmunity (B cells)

Effector functions of activated complement

- Cytolysis (MAC)

- Opsonization (C3b, C4b)

- Stimulation of inflammation (C5a, C3a, C4a)

- Stimulation of humoral response (C3d)

- Immune complex clearance (C3b)

Immune complex clearance (C3b)

Immune complex clearance (C3b)

Regulatory proteins of complement

Regulatory proteins of complement

http://highered.mcgraw-hill.com/sites/0072556781/student_view0/chapter31/animation_quiz_1.html

Complement system(animation)

Laboratory tests for complement assesment

Quantification of compoments (C3, C4, MBL - RID, nephelometry)

- concentration: g/L (mg/ml)

Functional testsfor classical and alternative pathway of activation

10.____9.____8.____7.____5._____4._____3._____2._____

C3a, C4a and C5aj.Osmotic lysis of microbes are mediated by10.

C3bi.Inflammatory reactions are induced by9.

MACh.Important opsonin is8.

C3 componentg.Proteins involved in early steps of classical pathway are

7.

IgM and IgG bound to antigenf.Components of alternative pathway are6.

C1, C4, C2e.Activators of classical pathway are 5.

classical, alternative and lectind.First component in lectin pathway is4.

factor B, factor D, properdinc.Central role in complement activation belongs to

3.

effector mechanism of innate and adaptive immunity

b.Complement activation pathways are2.

mannose binding lectin (MBL)a.Activation of complement system is1.

1._____ 6.____d g a f c e i jb h