Course: Clinical Immunology

Course Instructor : Qurrat Ul Ain Malik

Semester: 4th (Medical Laboratory Technology)
Topic: Complement System
 COMPLEMENT PROTEINS

• An important component of our host defenses.

• > 20 soluble and cell-bound protein present in normal human.

• Participate in both innate and adaptive immunity.

• Synthesized by the liver hepatocytes (mainly), monocytes and

epithelial cells of the gastrointestinal and genitourinary tracts.
 COMPLEMENT PROTEINS

History

• 1890 Paul Ehrlich

• 1919 Jules Bordet (Nobel Prize one year later, in 1920)

 COMPLEMENT PROTEINS

There are three main effects of complement:

i. Lysis
ii. Generation of mediators
iii. Opsonization
iv. Clear immune complexes
v. ↑ Vascular permeability
vi. ↑ Metabolism
vii. Accumulation of monocytes and neutrophils
 COMPLEMENT PROTEINS

Several complement components are proenzymes (zymogens),

which must be cleaved to form active enzymes.
 COMPLEMENT PROTEINS

Pathways

1. Classical
i. Recognition Unit

ii. Activation Units

iii. Membrane Attack complex

2. Alternative/Properdin Pathway

3. MBL Pathway
 COMPLEMENT PROTEINS

1. Classical Pathway – Begins with the formation of Ag-Ab

complex.
2. Alternative Pathway – is initiated by cell-surface constituesnts
that are foreign to the host (Pathogens/damaged tissues).

3. Lectin Pathway – is activated by the binding of mannose-

binding lectin (MBL) to mannose residues on glycoproteins or
carbohydrates on the surface of microorganisms.
 COMPLEMENT PROTEINS

All three pathways lead to the production of C3b, the central

molecule of the complement cascade.
(1) It combines with other complement components to generate
C5 convertase, the enzyme that leads to the production of the
membrane attack complex.
(2) It opsonizes bacteria because phagocytes have receptors for
C3b on their surface.
 COMPLEMENT PROTEINS

Opsonization:
Microbes, such as bacteria and viruses, are phagocytized much
better in the presence of C3b because there are C3b receptors on
the surface of many phagocytes.
 COMPLEMENT PROTEINS

Chemotaxis:
C5a and the C5, 6, 7 complex attract neutrophils. They migrate
especially well toward C5a. C5a also enhances the adhesiveness
of neutrophils to the endothelium.
 COMPLEMENT PROTEINS

Anaphylatoxin:
C3a, C4a, and C5a cause degranulation of mast cells with release
of mediators (e.g., histamine), leading to increased vascular
permeability and smooth muscle contraction, especially
contraction of the bronchioles leading to bronchospasm.
 COMPLEMENT PROTEINS

Cytolysis:
Insertion of the C5b,6,7,8,9 complex into the cell membrane
forms a “pore” in the membrane. This opening in the membrane
results in the killing (lysis) of many types of cells, including
erythrocytes, bacteria, and tumor cells.
 COMPLEMENT PROTEINS

Enhancement of Antibody Production:

The binding of C3b to its receptors on the surface of activated B
cells greatly enhances antibody production compared with that by
B cells that are activated by antigen alone.
 COMPLEMENT PROTEINS

Reference Book
Chap 65-Microbiology and Immunology by Levinson
Chap 06-Clinical Immunology and Serology by Christine D
Stevens
THANK YOU