THE COMPLEMENT SYSTEM

Opzonization – Deposition of opsonins on an

antigen, thereby promoting a stable adhesive
INNATE SYSTEM is the FIRST LINE: Whatever our contact with and appropriate phagocytic cell
body would sense that is foreign, it is something (macrophages).
that your innate immunity will be readily
Opsonin – a substance (e.g., an antibody or C3b)
available to attack.
that promotes the phagocytosis of antigens by
COMPLEMENT SYSTEM belongs to the INNATE binding to them.
IMMUNITY

- The complement system, particularly

the complement pathway, will be there
to sense.

 The phagocyte will have appropriate

receptor. It will now attach to the
receptor, then it will be eaten up by your
phagocytic cell.

BAINO, GWYNETH C. | DEN222

MICROBIOLOGY
COMPLEMENT - The three pathways will diverge to still have a
complement activation.
- Bacteriolytic activity requires two
different substances (opsonization, - all pathways promote complement activation
killing of bacteria)
THE COMPLEMENT COMPONENTS
- Heat-labile: not heat stable
- Augments opsonization and killing of - Mainly produced in the liver
bacteria by antibodies (The major - Most circulate in the serum in
effector of the humoral branch of the functionally inactive forms as
immune system.) proenzymes (zymogens).
- Evolved as part of the innate immune - Designated by numbers, by letter
system. symbols, or by trivial names.
- Peptide fragments formed by activation
HUMORAL – part of adaptive immunity namely
of a componenet
your antibodies (immunoglobulins)
 The larger fragments: bind to
By virtue of its definition it will always be the the target near the site of
complement system part of innate immune activation
system.  The smaller fragments: local
inflammation
- Complexes with enzymatic activity are
designated by a bar over the number or
symbol.

THE CLASSICAL PATHWAY

- Antigen antibody complex starts at C1 

activated C1  together with C2, C4,
and C3 convertase  C4b2a  activated

*memorize the diagram! Important daw*

- The three pathways are different from the start

or the signal that will cascade or activate the
specific pathways.
upon the major amplification step (C3)
 C3b, C4b2a  C4b2a3b  acted

BAINO, GWYNETH C. | DEN222

MICROBIOLOGY
 upon C5 convertase  C5b will join pentameric. Your body needs to sense
C6,C7,C8,C9 forming the membrane that microbial body. How is it possible?
attack complex It is possible when the immunoglobulin
was able to attach C1 to the FC portion.
When they bind, it will now activate the
classical pathway.

- C1 is the one that is related to humoral

immunity.
- Linked to antibodies antigen complexes

- The IgM antiflagellum antibody there is

activation of the complement system.

- In an immunoglobulin, there is a portion

that the C1 will bind. That is the FC
portion. Do take note, your IG M is

BAINO, GWYNETH C. | DEN222

MICROBIOLOGY
 THE MANNOSE-BINDING LECTIN PATHWAY

- Does not depend on antibody for its

activation
- Originates with host proteins (MBL)
binding microbial surfaces.

- C3 contains an unstable thioester bond.

= that’s is why it is usually the one that
is readily available for amplification

THE ALTERNATIVE PATHWAY

- Does not depend on antibody for its

activation
- Being initiated in most cases by cell-
surface constituents that are foreign to
the host.

BAINO, GWYNETH C. | DEN222

MICROBIOLOGY
 - THE THREE COMPLEMENT PATHWAYS
CONVERGE AT THE MEMBRANE-
ATTACK COMPLEX

ANTIBODY-MEDIATED MECHANISMS FOR

COMBATING INFECTION BY EXTRACELLULAR
BACTERIA

- The critical function of the complement

system in converting a humoral antibody
response into an effective defense
mechanism.

BIOLOGICAL CONSEQUENCES OF
COMPLEMENT ACTIVATION

Cell lysis – from the membrane attack complex

Inflammatory response – C3a, C4a, and C5a

(anaphylatoxins)

Opsonization – C3b

Degranulation of eosinophils and Chemotaxis –

C5a

BAINO, GWYNETH C. | DEN222

MICROBIOLOGY
 - A series of regulatory proteins
(regulators of complement activation
[RCA] gene cluster – chromosome 1 in
humans)

The complement system neutralizes viral

infectivity

 Formation of larger viral aggregates

- Reduce the net number of infectious
viral particles
 A coating of Ab and/or complement to
the surface of a viral particle
- Blocking attachment to susceptible host
cells
- Facilitate binding of the viral particle to
cells possessing Fc or CR 1
- Lysing most enveloped viruses.

REGULATION OF THE COMPLEMENT SYSTEM

- Inclusion of highly labile components

that undergo spontaneous inactivation if
they are not stabilized by reaction with
other components.

BAINO, GWYNETH C. | DEN222

MICROBIOLOGY
COMPLEMENT-BINDING RECEPTORS THE COMPLEMENT SYSTEM IN DISEASE

- Many of the biological activities of the - Immune-complex diseases (genetic

complement system depend on the deficiencies)
binding of complement fragments to - Recurrent infection
complement receptors, which are - C3 deficiencies: with the most severe
expressed by various cells. clinical manifestations
- Hereditary angioedema:
 Deficiency of C1Inh
 Localized edema of the tissue
- Paroxysmal nocturnal hemoglobinuria
(PNH): defect in cell-surface DAF and
MRL
- Studies using knock-out mice

A. COMPLEMENT DEFICIENCIES
1. Genetic deficiencies in classical
pathway components (C1q, C1r, C4,
Role of complement in B cell activation C2 and C3)
2. Deficiencies in components of the
- The immunoglobulin will bind together alternative pathway (properdin,
with the B-cell coreceptor and B-cell factor D, C3)
activation. Indirectly, the complement 3. Deficiencies in the terminal
system can have a role inn b-cell complement components (C5, C6,
activation. C7, C8, C9, Neisseria bacteria)
4. Deficiencies in complement
regulatory proteins (abnormal
complement activation)

BAINO, GWYNETH C. | DEN222

MICROBIOLOGY
 5. Deficiencies in complement inflammation, and clearance of immune
receptors (CR3 & CR4 – inadequate complexes.
adherence of neutrophils to 7. Interactions of complement proteins
endothelium at tissue sites of and protein fragments with receptors on
infection) cells of the immune system control both
innate and acquired immune responses.
8. Because of its ability to damage the host
organism, the complement system
requires complex passive and active
regulatory mechanisms.
9. Clinical consequences of inherited
complement deficiencies range from
increases in susceptibility to infection to
tissue damage caused by immune
complexes.

SUMMARY

1. The complement system comprises a

group of serum proteins, many of which
exist in inactive forms.
2. Complement activation occurs by the
classical, alternative, or lectin pathways,
each of which is initiated differently
3. The three pathways converge in a
common sequence of events that leads
to generation of a molecular complex
that causes cell lysis
4. The classical pathway is initiated by
antibody binding to a cell target;
reactions of IgM and certain IgG
subclasses activate this pathway.
5. Activation of the alternative and lectin
pathways is antibody-independent.
These pathways are initiated by reaction
of complement proteins with surface
molecules of microorganisms.
6. In addition to its key role in cell lysis, the
complement system mediates
opsonization of bacteria, activation of

BAINO, GWYNETH C. | DEN222

MICROBIOLOGY
BAINO, GWYNETH C. | DEN222
MICROBIOLOGY