COMPLEMENT SYSTEM

A defense mechanism that can be activated by both innate and acquired immune mechanisms

complement system

Consists of enzymatic pathways that cause specific proteins

to bind covalently to the surface of invading microbes

complement system

Inactive in healthy uninfected animals and activated by

either antigen bodies attached to surface of an organism or simply by the complex carbohydrates found on the surface of infectious agent

complement system

complement in liver

1. C3

2. C6

3. C8

4. B

complement in macrophages

1. C2

2. C3

3. C4

4. C5

5. B

6. D

7. P

8. I

complement in neutrophils

large quantities of

1. C6

2. C7

complement in alternative pathway

1. B

2. D

complement in terminal proteins

1. C5

2. C6

3. C7

4. C8

5. C9

3 different mechanism

1. classical pathway

2. terminal classical pathway

3. alternative pathway

Activated by antibodies bound to antigens (part

of acquired immunity)

Classical Pathway

Generates inflammatory mediators, opsonin for

phagocytosis of antigen and lytic complexes that

destroy cell

classical pathway

C1 molecule is activated and induces proteolytic

cascade involving multiple other complement

proteins

Classical Pathway

•Activated by anti

Bound C3b binds to C5 → C5b + C3b → binds to C6 and

C7 → forms C5b67 complex → insert itself into the

microbial cell membrane → bind to C8 and multiple C9

Terminal Classical Pathway

(C5b678 Complex) Formation of a tubular structure called

membrane attack complex

MAC inserts itself into a microbial cell membrane and

effectively punches a hole in the invader

Terminal Classical Pathway

Sufficient formation of MAC can cause osmotic lysis of

the microorganis

terminal classical pathway

Triggered by contact between microbial cell walls and

complement components

alternative pathway

Activated immediately when it comes into contact with blood thus a key component of innate immunity

Alternative Pathway

most important complement protein; synthesized by liver cells and macrophages and complement component of highest concentration in serum

C3

binds to microbial cell surface

c3b

Mediates inflammatory responses to infection as well as direct

lysis of microbes

alternative pathway

activated directly by microbial carbohydrates; also an innate defense mechanism

lectin pathway

most important lectin; can bind to the surface of bacteria, fungi, parasitic protozoa and viruses

mannose-binding lectin (MBL)

is the most important regulator

C1 inactivator (C1-INH)

Controls the assembly of C4b2b by blocking the

activities of active C1r and C1s

C1 inh

Decay accelerating factor

cd 55

Expressed on surface of red blood cells, neutrophils, lymphocytes , monocytes, platelets, endothelial cells

cd 55

Binds to convertases and accelerates their decay

cd55

Function is to protect normal body cells from complement attack

cd55

found in plasma

Factor H & C4-binding protein (C4BP)

found on cell membranes

CD35 and CD46

C3b bound to a microbial surface is a very potent and effective opsonin

opsonization

Major contributor to acute inflammation

chemotaxis

Activation of the complement generates several potent chemotactic peptides

chemotaxis

anaphylatoxins

c3a and c5a