THE COMPLEMENT SYSTEM
complement activation needs to be carefully
LEARNING OUTCOMES:
After completing this topic, you should be able to:
1. Describe the roles of the complement system.
2. Differentiate between the classical, alternative,
and lectin pathways and indicate proteins and
activators involved in each.
3. Discuss the formation of the three principal units
of the classical pathway: recognition, activation,
and membrane attack units.
4. Describe how the initiation of the lectin pathway
occurs.
5. Explain how C3 plays a vital role in all pathways.
6. Describe regulators of the complement system and
their role in the complement system.
7. Discuss the complement-related kidney disorders
and applicable complement testing.
8. Relate biological manifestations of complement
activation to the generation of specific complement
products.
9. Describe the deficiencies of complement
components and the diseases they cause.
10. Differentiate tests for functional activity of
complement from the measurement of individual
complement components.
11. Analyze laboratory findings and indicate disease
implications in relation to complement
abnormalities.
INTRODUCTION / HISTORY:
▪ Jules Bordet was awarded the Nobel Prize in
1919 for his role in elucidating the nature of the
complement.
▪ The complement system is a complex series of more
than 30 proteins that play a significant part in
amplifying the inflammatory response to destroy
and clear foreign antigens—hence, their name
‘complement.’
o Complement was originally recognized in the
1890s; Paul Ehrlich coined the term
complement because the substance
‘complements’ the action of antibodies in
destroying microorganisms.
▪ Complement proteins are part of the innate
immune system and are composed of soluble and
cell-bound proteins.
▪ Complement is considered an acute-phase
reactant because levels rise during an infection.
▪ It also has the unique property of being easily
inactivated (i.e., heat-labile) by heating serum to
56°C for 30 minutes.
▪ They have the following essential roles:
o Membrane attack—lyse foreign cells (MAC).
o Phagocytosis—opsonize and tag the invaders
for clearance. C3b has the most important
opsonizing activity.
o Inflammation—complement proteins serve
as an important link between the innate and
adaptive immune responses (C3a, C4a, C5a):
▪ Ability to increase vascular permeability.
▪ Recruit monocytes and neutrophils to the
area of antigen concentration.
▪ Trigger the secretion of immunoregulatory
molecules that amplify the immune
response.
▪ Chronic activation can lead to inflammation and
tissue damage to the host.
▪ Because of its potential for far-reaching effects,
regulated.
▪ Any deficiencies to the complement system can
result in increased susceptibility to infection or the
accumulation of immune complexes resulting in
possible autoimmune disorders.
PROTEINS OF THE COMPLEMENT SYSTEM:
Complement proteins were named as they were
isolated before the sequence of activation was known—
hence the irregularity in the numbering system.
Proteins of the CLASSICAL PATHWAY (arranged
in their order of activation in the cascade):
1. The Recognition Unit: C1
▪ Molecular weight: 740,000 Daltons
▪ Consists of three subunits—C1q, C1r, and C1s
▪ Calcium-dependent (to maintain its structure)
▪ It is composed of one (1) C1q subunit and two
(2) each of C1r and C1s subunits.
a. C1q
▪ Molecular weight: 410,000 Daltons
▪ Concentration in serum: 150 µg/mL
▪ Structure: composed of six strands that
form six globular heads with a collagen-like
tail portion. This structure has been
likened to a bouquet of tulips with six
blossoms extending outward.
▪ Function: C1q “recognizes” the fragment
crystallizable (Fc) region of two adjacent
antibody molecules, but at least two of the
globular heads of C1q must be bound to
initiate the classical pathway.
b. C1r
▪ Molecular weight: 85,000 Daltons
▪ Concentration in serum: 50 µg/mL
▪ A serine protease enzyme, initially an
inactive proenzyme—becomes activated
once C1q is bound to the antibody
molecules.
▪ It activates the C1s subunit.
▪ Activated C1r is extremely specific—its
only known substrate is the C1s subunit.
c. C1s
▪ Molecular weight: 85,000 Daltons
▪ Concentration in serum: 50 µg/mL
▪ A serine protease enzyme, initially an
inactive proenzyme—becomes activated
once C1q is bound to the antibody
molecules.
▪ C1s subunit has a limited specificity, with
its only substrates being C4 and C2.
▪ Once the C1s subunit is activated, the
recognition stage ends.
2. The Activation Unit:
Phase two, the formation of the activation unit,
begins when C1s cleaves C4 and ends with the
production of the enzyme C5 convertase.
a. C4
▪ Second most abundant complement protein
▪ Molecular weight: 205,000 Daltons
▪ Concentration in serum: 300-600 µg/mL
▪ The cleavage of C4 represents the first
amplification step in the cascade
because, for every C1 attached,
approximately 30 molecules of C4 are split
and attached.
▪ Cleaved by C1s into 2 fragments:
o C4b – bigger C4 fragment
▪ MW: 190,000 Daltons
▪ Interacts with the C2a fragment to
form the C3 convertase (C4b2a) of
the classical pathway.
▪ Must bind to protein or
carbohydrate within a few seconds
or it will react with water
molecules to form iC4b, which is
rapidly degraded.
o C4a – smaller C4 fragment
▪ MW: 9,000 Daltons
▪ Consists of 77 amino acids.
▪ An anaphylatoxin—is a small
peptide that causes increased
vascular permeability, contraction
of smooth muscle, and release of
histamine from basophils and mast
cells.
b. C2
▪ Closely related to Factor B of the
alternative pathway.
▪ Molecular weight: 102,000 Daltons
▪ Concentration in serum: 25 µg/mL
▪ When combined with C4b in the presence
of magnesium ions (Mg2+), C2 is cleaved
by C1s into two (2) fragments; an
exception to the rule of complement
protein nomenclature—C2a and C2b—the
bigger and smaller C2 fragments,
respectively.
o C2b – smaller C2 fragment
▪ MW: 34,000 Daltons
▪ Accelerates decay-dissociation of
the C3 convertase.
▪ Acts as a feedback inhibitor on the
activation of the classical pathway
of the complement system.
o C2a – bigger C2 fragment
▪ MW: 70,000 Daltons
▪ C2a interacts with the C4b
fragment to form the C3 convertase
(C4b2a) of the classical pathway.
▪ Provides the catalytic activity to
the C3 and C5 convertases of
classical and lectin pathways.
▪ C3 Convertase (C4b4a):
▪ The C3 convertase complex
(C4b2a) is not very stable.
▪ The half-life is estimated to be
between 15 seconds and 3 minutes,
so C3 must be bound quickly.
▪ If the binding does occur, C3 is
cleaved by the C3 convertase into
two fragments, C3a and C3b.
c. C3
▪ The major and central constituent of the
complement system—the key intermediate
in all three pathways of complement
activation.
▪ People with C3 deficiency are susceptible to
bacterial infection.
▪ Molecular weight: 190,000 Daltons
▪ Concentration in serum: 1,200 µg/mL
▪ The cleavage of C3 to C3b represents the
most significant step in the entire process
of complement activation.
▪ The cleavage of C3 represents a second
and major amplification step because
about 200 molecules of C3 are split for
every molecule of C3 convertase (C4b2a).
▪ Cleaved by the C3 convertase into 2
fragments:
o C3b – bigger C3 fragment
▪ MW: 180,000 Daltons
▪ C3b is potent in opsonization:
tagging pathogens, immune
complexes (antigen-antibody), and
apoptotic cells for clearance or
phagocytosis.
▪ Macrophages have specific
receptors for it.
▪ Glycoprotein composed of the
modified C3-α chain (α′) (MW:
105,000) and the intact C3-β chain
(MW: 75,000).
▪ If C3b is bound within 40-nm of the
C4b2a, this creates a new enzyme
known as the C5 convertase
(C4b2a3b).
o C3a – smaller C3 fragment
▪ MW: 10,000 Daltons
▪ An anaphylatoxin.
▪ C3a has a regulatory process and a
structure homologous to that of
complement component C5a.
▪ C3a formation is triggered by
pathogenic infection.
3. The Membrane Attack Complex (MAC):
The membrane attack complex (MAC) “punches” a
hole through the plasma membrane of the target
cell, killing the pathogen in the process. It is
composed of the following complement components:
a. C5
▪ Molecular weight: 190,000 Daltons
▪ Concentration in serum: 80 µg/mL
▪ Function: initiates the membrane attack
complex (MAC).
o The cleaving of C5 with deposition of
C5b at another site on the cell
membrane constitutes the beginning of
the MAC.
▪ Structure: C5 consists of two polypeptide
chains, α and β, which are linked by
disulfide bonds.
 ▪ C5 convertase (C4b2a3b) cleaves C5 into
two (2) fragments:
o C5b – bigger C3 fragment
▪ MW: 75,000 Daltons
▪ C5b attaches to the cell membrane,
forming the beginning of the MAC.
▪ C5b is extremely labile and rapidly
inactivated unless binding to C6
occurs.
▪ Once C6 is bound to C5b,
subsequent binding involves C7,
C8, and C9. None of these proteins
has enzymatic activity.
o C5a – smaller C2 fragment
▪ MW: 10,400 Daltons
▪ Released into the circulation (as an
anaphylatoxin – most potent).
b. C6
▪ Molecular weight: 110,000 Daltons
▪ Concentration in serum: 45 µg/mL
▪ Function: binds to C5b in MAC.
▪ It takes one IgM molecule attached to two
adjacent antigenic determinants to initiate
the classical cascade of activation.
o Immunoglobulin G (IgG):
▪ IgG1, IgG2, and IgG3, but not IgG4.
▪ Two (2) IgG molecules must attach to
antigen within 30 nm to 40 nm of each
other before complement can bind; it may
take at least 1,000 IgG molecules to ensure
that there are two, close enough to initiate
such binding.
▪ Some epitopes, notably the Rh group, are
too far apart on the cell for this to occur;
therefore, they are unable to fix
complement.
▪ Within the IgG group, IgG3 is the most
effective, followed by IgG1 and then IgG2.
▪ Triggering substances: In addition to antibodies,
a few substances can bind complement directly to
initiate the classical cascade. These include C-
reactive protein (CRP), several viruses,
mycoplasmas, some protozoa, and certain Gram-
negative bacteria such as Escherichia coli.

c. C7 Classical Pathway of Complement Activation:

▪ Molecular weight: 100,000 Daltons
▪ Concentration in serum: 90 µg/mL (1) IgM or (2) IgG
▪ Function: binds to C5bC6 in MAC. C1qrs complex C1qrs complex

d. C8
▪ Molecular weight: 150,000 Daltons
C1qrs
▪ Concentration in serum: 55 µg/mL C4 C4a + C4b
▪ Function: binds to C5bC67 in MAC; starts
the pore formation on the membrane.
C1qrs
e. C9 C2 C2a + C2b
▪ Molecular weight: 70,000 Daltons
▪ Concentration in serum: 60 µg/mL
▪ Function: multiple C9 molecules bind to C4b + C2a C4b2a (C3 convertase)
the C5bC678 complex and polymerize to
form a transmembrane channel, the
membrane attack complex (MAC), which
C4b2a
causes lysis of the cell. C3 C3a + C3b
▪ If the complex is soluble in circulation, it is
known as sC5b–9.
▪ Measurement of the level of sC5b–9 is an C4b2a + C3b C4b2a3b (C5 convertase)
indicator of the amount of terminal
pathway activation that is occurring.
C4b2a3b
C5 C5a + C5b
PATHWAYS OF THE COMPLEMENT SYSTEM:

The complement system can be activated in three (3) C5b + C6 + C7 + C8 C5bC678

different ways:
1. Classical pathway
2. Alternative pathway C5bC678 + C9 molecules
3. Lectin pathway

CLASSICAL PATHWAY: C5b–9 (Membrane Attack Complex)

▪ Antibody-directed mechanism for triggering the
complement activation.
▪ The classical pathway, so-called because it was
discovered first, uses a plasma protein called C1q
to detect antibodies bound to the surface of a
microbe or other structure.
▪ However, not all immunoglobulins are able to
activate this pathway:
o Immunoglobulin M (IgM):
▪ Most efficient in complement fixation
because of its multiple binding sites.
ALTERNATIVE PATHWAY:
▪ First described by Pillemer and his associates in
the early 1950s.
▪ It was originally named for the protein properdin,
a constituent of normal serum with a concentration
of approximately 5 to 15 μg/mL.
▪ In addition to properdin, the serum proteins
Factor B and Factor D are unique to this
pathway.
▪ C3 is a key component of this pathway as well as
the two other pathways (classical and lectin). The
conversion of C3 is the first step in this pathway.
▪ Triggering substances for the alternative
pathway include bacterial cell walls, especially
those containing teichoic acid, zymosan, and
lipopolysaccharide (LPS); fungal cell walls, yeast;
viruses, virally infected cells; tumor cell lines; and
some parasites, especially trypanosomes.
Proteins of the ALTERNATIVE PATHWAY:
1. Factor B
▪ Molecular weight: 93,000 Daltons
▪ Concentration in serum: 200 μg/mL
▪ Function: Bb fragment binds to C3b to form
the C3 convertase (C3bBb).
▪ Once bound to C3b, Factor B can be cleaved by
Factor D.
▪ The role of Factor B is thus analogous to that
of C2 in the classical pathway because it forms
an integral part of a C3 convertase.
5. C5 Convertase (C3bBb3bP)
▪ If, however, some of the C3b produced remains
bound to the C3 convertase, the enzyme is
altered to form C3bBb3bP, which has a high
affinity for C5 and exhibits C5 convertase
activity.
Alternative Pathway of Complement Activation:
1. C3 is hydrolyzed by water to produce C3b, which
binds Factor B and together they attach to the
target cell surface.
2. B is cleaved by Factor D into the fragments Ba and
Bb. Bb combines with C3b to form C3bBb, an
enzyme with C3 convertase activity.
3. More C3 is cleaved, forming more C3bBb. This
enzyme is stabilized by properdin, and it continues
to cleave additional C3.
4. If a molecule of C3 remains attached to the C3bBbP
enzyme, the convertase now has the capability to
cleave C5. The C5 convertase thus consists of
C3bBbP3b. After C5 is cleaved, the pathway is
identical to the classical pathway.

2. Factor D
▪ Molecular weight: 24,000 Daltons
▪ Concentration in serum: 2 μg/mL (lowest
concentration in the plasma)
▪ Function: a serine protease that cleaves its
only substrate, Factor B, into two (2)
fragments—Ba and Bb.

o Bb
▪ MW: 60,000 Daltons
▪ Bb remains attached to C3b, forming
the initial C3 convertase of the
alternative pathway (C3bBb).
▪ Bb is rapidly inactivated unless it
becomes bound to a site on one of the
triggering cellular antigens.
▪ Some C3b attaches to cellular surfaces
and acts as a binding site for more
Factor B, resulting in an amplification
loop.
o Ba
▪ MW: 33,000 Daltons
3. Properdin
▪ Molecular weight: 55,000 Daltons
▪ Concentration in serum: 15-25 μg/mL
▪ Function: Properdin (P) stabilizes the C3
convertase. The binding of properdin
increases the half-life of C3bBb from 90
seconds to several minutes.
4. C3 Convertase (C3bBb)
▪ As the alternative pathway convertase,
C3bBb is then capable of cleaving
additional C3 into C3a and C3b.
▪ C3bBb can also cleave C5, but it is much
more efficient at cleaving C3.
LECTIN PATHWAY:
▪ Instead of activation through antibody binding, the
lectin pathway is activated by recognition of surface
moieties that are found on pathogens.
o This pathway is initiated by the binding of
mannose-binding lectin (MBL), collectin 11
(CL-K1), and ficolins (Ficolin-1, Ficolin-2, and
Ficolin-3) to microbial surface oligosaccharides
and acetylated residues, respectively.
▪ It involves non-specific (non-selective) recognition of
carbohydrates that are common constituents of
microbial cell walls and that are distinct from those
found on human cell surfaces.
▪ The lectin pathway plays an important role as a
defense mechanism in infancy (innate immune
response), during the interval between the loss of
maternal antibody and the acquisition of a full-
fledged antibody response to pathogens.
▪ Once C4 and C2 are cleaved, the rest of the pathway
is identical to the classical pathway.
Proteins of the LECTIN PATHWAY:
1. Mannose-Binding Lectin (MBL)
▪ Another term: mannan-binding lectin
▪ Molecular weight: 200,000 to 60,000 Daltons
▪ Concentration in serum: 0.0002 to 10 μg/mL
▪ Function:
o As the name implies, it binds to mannose
or related sugars in a calcium-dependent
manner to initiate this pathway.
o It is considered an acute-phase protein
because it is produced in the liver and is
normally present in the serum but
increases during the initial inflammatory
response.
The enzymatic role played by C1r and C1s in the
classical pathway is played in the lectin pathway by
serine proteases called MBL-associated serine
proteases (MASPs).
2. MASP-1
▪ Molecular weight: 93,000 Daltons
▪ Concentration in serum: 1.5 to 1.2 μg/mL
▪ Function:
o MASP-1 is synthesized as a zymogen (an
inactive form of the enzyme) and is
activated when it complexes with the
pathogen recognition molecules of the
lectin pathway, the mannose-binding
lectin, and the ficolins.
o This protein is not directly involved in
complement activation but may play a role
as an amplifier of complement activation by
cleaving complement C2 or by activating
another complement serine protease,
MASP-2.
3. MASP-2
▪ Molecular weight: 76,000 Daltons
▪ Concentration in serum: unknown
▪ Function:
o MASP-2 is very similar to the C1s
molecule, of the classical complement
pathway—it cleaves C4 and C2
o When the carbohydrate-recognizing heads
of MBL bind to specifically arranged
mannose residues on the surface of a
pathogen, MASP-2 is activated to cleave
complement components C4 and C2 into
C4a, C4b, C2a, and C2b, respectively.
SYSTEM CONTROLS:
Activation of complement could cause tissue damage
and have devastating systemic effects if it were allowed
to proceed uncontrolled.
1. C1 Inhibitor (C1-INH)
▪ Molecular weight: 105,000 Daltons
▪ Concentration in serum: 240 μg/mL
▪ Function:
o C1 inhibitor (C1-INH) inhibits activation
at the first stages of both the classical and
lectin pathways.
o Its main role is to inactivate C1 by binding
to the active sites of C1r and C1s.
o C1-INH also inactivates MASP-2 binding
to the MBL-MASP complex, thus halting
the lectin pathway.
Further formation of C3 convertase in the classical
and lectin pathways is inhibited by four main
regulators: soluble C4-binding protein (C4BP) and
three cell-bound receptors, complement receptor type 1
(CR1), membrane cofactor protein (MCP), and decay-
accelerating factor (DAF).
2. Factor I
▪ Molecular weight: 88,000 Daltons
▪ Concentration in serum: 35 μg/mL
▪ Function:
o Cleaves C3b and C4b
o For the regulation of the classical and
lectin pathways
o All of the C3 convertase regulators
mentioned above act in concert with
Factor I, a serine protease that inactivates
C3b and C4b when bound to one of these
regulators.
3. Factor H
▪ Molecular weight: 150,000 Daltons
▪ Concentration in serum: 300 to 450 μg/mL
▪ Function:
o Principal soluble regulator of the
alternative pathway.
o It acts by binding to C3b, preventing the
binding of Factor B.
o Factor H also accelerates the dissociation of
the C3bBb complex on cell surfaces.
o When Factor H binds to C3bBb, Bb
becomes displaced.
o Additionally, Factor H acts as a cofactor
that allows Factor I to break down C3b.
4. C4-Binding Protein (C4BP)
▪ Molecular weight: 520,000 Daltons
▪ Concentration in serum: 250 μg/mL
▪ It is abundant in plasma
▪ Function:
o Acts as a cofactor with Factor I to
inactivate C4b.
o If C4BP attaches to cell-bound C4b, it can
dissociate it from C4b2a complexes
(classical pathway C3 convertase), causing
the cessation of the classical pathway.
5. S Protein (Vitronectin)
▪ Molecular weight: 84,000 Daltons
▪ Concentration in serum: 500 μg/mL
▪ Function:
o S protein is a soluble control protein that
acts at a deeper level of complement
activation (the terminal components).
o Also known as vitronectin, S protein
interacts with the C5b-7 complex as it
forms in the fluid phase and prevents it
from binding to cell membranes.
o Binding of C8 and C9 still proceeds, but
polymerization of C9 does not occur;
therefore, the complex is unable to insert
itself into the cell membrane or to produce
lysis.
Other Regulatory Proteins or Receptors: COMPLEMENT COMPONENT
ABNORMALITIES
6. Complement Receptor 1 (CR1)
▪ Also known as CD35 Deficiencies of complement components can place an
▪ Ligand: C3b, iC3b, and C4b individual at risk for certain infections. Missing or
▪ Molecular weight: 165,000–280,000 Daltons deficient regulators are the cause of diseases such as
▪ It is found mainly on peripheral blood cells, paroxysmal nocturnal hemoglobinuria and hereditary
including neutrophils, monocytes, angioedema.
macrophages, erythrocytes, eosinophils, B
lymphocytes, some T lymphocytes, and
follicular dendritic cells.
▪ Function:
o A main function of CR1 is as a receptor on
platelets and red blood cells (RBCs), which
helps to mediate transport of C3b-coated
immune complexes to the liver and spleen.
o It binds C3b and C4b but has the greatest
affinity for C3b.
o Once bound to CR1, both C4b and C3b can
then be degraded by Factor I.

7. Membrane Cofactor Protein (MCP)

▪ Also known as CD46
▪ Ligand: C3b and C4b
▪ Molecular weight: 50,000–70,000 Daltons
▪ It is found on virtually all epithelial and
endothelial cells, except erythrocytes (RBCs).
▪ MCP is the most efficient cofactor for Factor I-
mediated cleavage of C3b.
▪ It can serve as a cofactor for cleavage of C4b,
but it is not as effective as C4BP.
▪ MCP also helps to control the alternative
pathway because binding of Factor B to C3b is
inhibited

8. Decay Accelerating Factor (DAF)

▪ Also known as CD55
▪ Molecular weight: 70,000 Daltons
▪ Third main receptor and has a wide tissue
distribution.
▪ It is found on peripheral blood cells, on
endothelial cells and fibroblasts, and on
numerous types of epithelial cells.
▪ Ligand: C3b and C4b
▪ Function:
o DAF is capable of dissociating both
classical and alternative pathway C3
convertases.
o It can bind to both C3b and C4b in a
manner similar to CR1.
o The presence of DAF on host cells protects
them from bystander lysis. It is one of the
main mechanisms used in discrimination of
self from non-self because foreign cells do
not possess this substance.

9. Membrane Inhibitor of Reactive Lysis (MIRL)

▪ Also known as CD59
▪ Ligand: C8
▪ MIRL also acts to block formation of the MAC.
▪ MIRL is widely distributed on the cell
membranes of all circulating blood cells,
including RBCs, and on endothelial, epithelial,
and many other types of cells.
LABORATORY DETECTION OF
COMPLEMENT ABNORMALITIES
Techniques to determine complement abnormalities
generally fall into two (2) categories:
(1) Measurement of components as antigens in serum
▪ Measurement of C3 and C4 levels – routinely
measured by nephelometry or turbidimetry
▪ Measurement of C1-INH, C3bBbP, or C3bP –
measured by enzyme-linked immunosorbent
assay (ELISA)
▪ Radial immunodiffusion (RID)—uses
agarose gel into which specific antibody is
incorporated. Serum serves as the antigen and
is placed in wells that are cut in the gel.
Diffusion of the antigen from the well occurs in
a circular pattern. The radius of the resulting
circle can be related to antigen concentration.
ASSAY FOR THE ALTERNATIVE PATHWAY:
Hemolytic Titration (AH50) Assay:
▪ An AH50 can be performed in the same manner
as the CH50, except magnesium chloride and
ethylene glycol tetraacetic acid (EGTA) are
added to the buffer and calcium is left out.
▪ This buffer chelates calcium, which blocks
classical pathway activation.
▪ RABBIT RBCs are used as the indicator
because they provide an ideal surface for
alternative pathway activation.
Enzyme-Linked Immunosorbent Assay:
▪ An additional means of testing for alternative
pathway function is via ELISA.
▪ One such test can detect C3bBbP or C3bP
complexes in very small quantities.
▪ Microtiter wells are typically coated with
bacterial polysaccharide to trigger activation of
the alternative pathway.

(2) Measurement of functional activity

The hemolytic titration or CH50 assay is a

measure of lysis, the end point of complement
activation in the classical pathway. The AH50
assay is a similar test for measuring the activity of
the alternative pathway

ASSAY FOR THE CLASSICAL PATHWAY:

Hemolytic Titration (CH50) Assay:

▪ This assay measures the amount of patient
serum required to lyse 50% of a standardized
concentration of antibody-sensitized SHEEP
erythrocytes.
▪ Because all proteins from C1 to C9 are
necessary for this to occur, absence of any one
component will result in an abnormal CH50,
essentially reducing this number to zero
▪ The titer is expressed in CH50 units, which is
the reciprocal of the dilution that is able to lyse
50% of the sensitized cells.
▪ The 50% point is used because this is when the
change in lytic activity per unit change in
complement is at maximum.