Immuno Complement System

How many serum proteins

30

Serum proteins function

Interact in a complex reaction sequences

Complement cascade result

inflammation, phagocytosis, foreign cell lysis

C3 cleaved into

C3b/a

C3b/a degradation products have direct

opsonizing, chemotactic, and inflammatory effects

Lytic pathway activation involves

C5-9

C3a and C5a function

To mast cells/basophils to release inflammatory mediators

C3b function

Large granular lymphocytes and phagocyte activation

Immune complex transport via erythrocytes

C5a function

Chemotaxis via neutrophils and macrophages

C3b, C4b, and iC3b function

bacteria opsonization via phagocytic cells

C5b-9 function

Cell lysis

Classical pathway proteins

C1-9

Alternative pathway proteins

C3, C5-9, factor B/D

Ag:Ab complex activates the

classical pathway

bacteria and fungi cell-wall polysaccharides activate the

alternative pathway

C3 cleavage is seen in

classical and alternative

C3a and C3b initiate

cytolysis, inflammation, opsonization

Complement C1 consists of

C1q, C1r, and C1s

Staple form

When pentameric IgM binds to antigens

C1 binds to

A single IgM or 2+ IgG

Classical C4 cleavage

exposes a reactive thioester bond that covalently attaches the C4b fragment to the pathogen surface

Classical C4 cleaved by

activated C1

Classical Activated C1 cleaves

C4 and C2

Classical C3 convertase

C4b2a

Classical Cleaved C4 and C2 produces

C4b and C2a

Classical C3 convertase cleaves

C3

Classical C3 cleaves into

C3a/b

Alternative C3b bind to

Factor B

Alternative Factor D binds to

Factor B and cleaves it

Alternative Factor B cleaved products

Bb and Ba

Alternative C3 convertase

C3bBb

Alternative C3 convertase binds

C3

Alternative C3 cleaves into

C3a/b

Classical activation is amplified by

Alternative pathway C3 convertase

Cytolysis

Damage to the cell membrane to the point where cellular contents leak out

MAC

Membrane attack complex

MAC consists of

C5-9

MAC function

Produces transmembrane channels aka a big hole through the cell membrane so that contents come out

Histamine function

Increases blood vessel permeability

C1q

hexamer

C1r

dimer

C1s

dimer

Classical C1 activation

C1q binding to C1q-specific receptors on Fc portions of adjacent Abs

Abs without C1q-specific receptors

IgG4, IgA, IgE

Abs with C1q-specific receptors function

bind/fix complement

Classical C1q-specific receptors binding

activates C1r

Classical C1r activates

C1s

Classical C1s activates

C4

Classical C4b function

Binds to the cell membrane near the Ag:Ab complex

Classical after C4b is bound

it binds C2a

Classical C2 cleaved by

C4b and C1s

Classical C2 cleaved into

C2a/b

How many C3 molecules can C3 convertase activate

hundreds to amplify the cascade by providing large amounts of C3b/a

C3a is an

anaphylatoxin

C3b is an

opsonin

Classical C5 convertase

C4b2a3b

Classical C5 convertase function

activates C5

Alternative C5 convertase

C3b2Bb

C5 convertase cleaves

C5

C5 cleaves into

C5a/b

C5b binds

C6/7

C5b-C6-C7 complex attaches to

the target cell membrane surface

C8 binds to

C5b-C6-C7 complex

C5b-C6-C7-C8 complex function

Forms small pores in the target cell membrane

C9 complement polymerization

enhances C5b-C6-C7-C8 complex by forming transmembrane channels

Complement system defends against

Extracellular bacteria

Phagocyte and inflammatory reaction activation via complement protects

before and after Ab response develops