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Effector mechanisms of humoral immunity. The Complement System (C’) Activation pathways Effector functions Regulation of complement activation. Jules Bordet (1870-1961) 1919. Nobel prize For complement-mediated bacteriolysis. Complement system.

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Effector mechanisms of humoral immunity

Effector mechanisms of humoral immunity

The Complement System (C’)

Activation pathways

Effector 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)


Complement system

Consists of serum and cell surfaceproteins 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



Activation

pathway

Early steps

Late steps

Classical

C1, C4, C2

C3, C5, C6, C7, C8, C9

C3, C5, C6, C7, C8, C9

MBL, C4, C2

Lectin

Alternatve

C3, B, D (P)

C3, C5, C6, C7, C8, C9


Ag-Ab complex

(microorganism and IgG or IgM Ab)

a

C1

Classical

C4

b

C2

Lectin

MBL

C3 convertase

C5 convertase

microorganism

D

B

Effector functions

(elimination of pathogen)

Alternatve

C3

microorganism

Early steps

Late steps


Early steps of

complement activation

B

D

MBL

MASP

P



MEMBRANE ATTACK COMPLEX

C6

C7

C8

C9

IgG

IgM

Lysis

C5-C9 MAC

Bacterium

C5a

C5b

C5

Activated

C1

C2

C4

C3 CONVERTASE

C4b2b3b

C4a

C4b

C2b

C2a

C4b2b

C5 CONVERTASE

C3

C3b

C3a

C1


MEMBRANE ATTACK COMPLEX

C6

C7

C8

C9

Lysis

C5-C9 MAC

Bacterium

C5a

C5b

C5

C2

C4

C3 CONVERTASE

C4b2b3b

C4a

C4b

C2b

C2a

C4b2b

C5 CONVERTASE

C3

C3b

C3a

MBL

MASP


C3a

C3b

C3

Alternative C5 convertase

Ba

Bb

C3bB

C3bBb

C3b

C3bBb3b

Alternative C3 convertase

Factor B

Factor D

Bacterium

C5-C9 MAC

C5b

C5

C5a

MEMBRANE ATTACK COMPLEX

C9

C8

C7

C6

C3

Properdin

Lysis







Stimulation of inflammatory rections

(C5a, C3a, C4a)

Activation of mast cells and neutrophils (anaphylatoxins)



Stimulation of humoral

immunity (B cells)







Complement system

(animation)

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


Laboratory tests for complement assesment
Laboratory tests for complement assesment

Quantification of compoments

(C3, C4, MBL - RID, nephelometry)

- concentration: g/L (mg/ml)

Functional tests

for classical and alternative pathway of activation


1.

Activation of complement system is

a.

mannose binding lectin (MBL)

2.

Complement activation pathways are

b.

effector mechanism of innate and adaptive immunity

3.

Central role in complement activation belongs to

c.

factor B, factor D, properdin

4.

First component in lectin pathway is

d.

classical, alternative and lectin

5.

Activators of classical pathway are

e.

C1, C4, C2

6.

Components of alternative pathway are

f.

IgM and IgG bound to antigen

7.

Proteins involved in early steps of classical pathway are

g.

C3 component

Important opsonin is

h.

MAC

8.

9.

Inflammatory reactions are induced by

i.

C3b

10.

Osmotic lysis of microbes are mediated by

j.

C3a, C4a and C5a

1._____

b

2._____

d

3._____

g

4._____

a

5._____

f

6.____

c

7.____

e

8.____

i

9.____

j

10.____

h


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