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Complement System: (Complements I.E. Assists Functions of Antibody)

The document summarizes key information about the complement system: 1. Jules Bordet discovered complement in the 1890s while observing that heated antiserum could lyse bacteria when combined with normal serum. 2. The complement system consists of over 30 serum and cell surface proteins that play a role in innate and adaptive humoral immunity through activation pathways, effector functions including opsonization and inflammation, and regulatory proteins. 3. Deficiencies or dysregulation of complement components can lead to increased susceptibility to infection, angioedema, hemolytic anemia, or tissue damage in diseases like immune complex diseases and liver disease.

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59 views

Complement System: (Complements I.E. Assists Functions of Antibody)

The document summarizes key information about the complement system: 1. Jules Bordet discovered complement in the 1890s while observing that heated antiserum could lyse bacteria when combined with normal serum. 2. The complement system consists of over 30 serum and cell surface proteins that play a role in innate and adaptive humoral immunity through activation pathways, effector functions including opsonization and inflammation, and regulatory proteins. 3. Deficiencies or dysregulation of complement components can lead to increased susceptibility to infection, angioedema, hemolytic anemia, or tissue damage in diseases like immune complex diseases and liver disease.

Uploaded by

Mona Adam
Copyright
© © All Rights Reserved
We take content rights seriously. If you suspect this is your content, claim it here.
Available Formats
Download as PPT, PDF, TXT or read online on Scribd
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Complement system

(complements i.e. assists functions of antibody)

Jules Bordet
(1870-1961)

1919.
Nobel prize
For complement-mediated
bacteriolysis
Discovery of Complement

1890s Jules Bordet (Institut Pasteur in Paris)


observed:
1. Sheep antiserum to the bacterium Vibrio cholerae
caused lysis of the bacteria.
2. Heating the antiserum destroyed its bacteriolytic
activity.
3. Addition of fresh normal serum, that contained no
Abs against the bacterium and was unable to kill
the bacterium by itself, restored the ability to lyse
the bacteria by the heated antiserum.
Q1: If you were Bordet, what
would
you hypothesize?
A1: Bacteriolytic activity requires 2 different
substances.
a. the specific antibacterial Abs, which
are resistant to the heating process
b. heat-sensitive component responsible
for the lytic activity
c. 56˚C, 30 min will inactivate
complement
Complement system

Consists of serum and cell surface proteins


involved in defense against pathogens and
tissue damage mediated by antibodies

Effector mechanism of both innate and


adaptive humoral immunity
Complement system
Over 30 serum and cell surface proteins:

- Complement components
(in serum inactive, activated sequentially as a cascade)

- Complement receptors
(cell surface, recognize activated components)

- Regulatory proteins of complement


(both in serum and cell surface, inhibit activated components)
Complement system

Pathways of activation

- Classical

- Alternative

- Lectin
Activation and
functions of
complement
(overview)
Activation
pathway Early steps Late steps

Classical C1, C4, C2 C3, C5, C6, C7, C8, C9

Lectin MBL, C4, C2 C3, C5, C6, C7, C8, C9

Alternatve C3, B, D (P) C3, C5, C6, C7, C8, C9


MEMBRANE
ATTACK
COMPLEX
C6 C7 C8 C9
IgG
C5-C9 Lysis
C5a C5b Bacterium
MAC IgM
C5

Activated
C1 C1

C3 CONVERTASE C4 C2
C4b2b3b C4b2b C4a C4b C2b C2a

C5 CONVERTASE

C3
C3b C3a
MEMBRANE
ATTACK
COMPLEX
C6 C7 C8 C9
C5-C9 Lysis
Bacterium
C5a C5b
MAC
C5
MBL

MASP

C3 CONVERTASE C4 C2
C4b2b3b C4b2b C4a C4b C2b C2a

C5 CONVERTASE

C3
C3b C3a
C3a C3b

C3

Alternative C5
Ba Bb convertase

C3 C3b C3bB C3bBb C3bBb3b


Alternative C3
convertase

Bacterium Factor B Factor D Properdin

Lysis

C5-C9 C5b
MAC C5
C5a
MEMBRANE
ATTACK
C9 C8 C7 C6
COMPLEX
C3a
C3
C3b

Anaphylatoxin C3
C5

Alternative
Pathway
C3-Convertase
C5-Convertase C3a C3b
C5b C5aD
C7
C8 BBa
Bb
C9 C6
Effector functions of activated complement

- Cytolysis (MAC)

- Opsonization (C3b, C4b)

- Stimulation of inflammation (C5a, C3a, C4a)

- Stimulation of humoral response (C3d)

- Immune complex clearance (C3b)


Regulatory proteins of complement
CLINICAL ASPECTS OF
COMPLEMENT
(1) Inherited (or acquired) deficiency of C5–C8, greatly
enhancessusceptibility to Neisseria bacteremia and
other infections
A deficiency of MBL also predisposes to severe
Neisseria infections.
A deficiency of C3 leads to severe, recurrent pyogenic
sinus and respiratory tract infections.
(2) Inherited deficiency of C1 esterase inhibitor
resultsin angioedema.
(3) Acquired deficiency of decay-accelerating factor on
the surface of cells results in an increase
incomplement mediated hemolysis (paroxysmal
nocturnal hemoglobinuria).
(4) In transfusion mismatches a large
amounts of anaphylatoxins and membrane attack
complexes are generated.
(5) Immune complexes bind complement, and thus
complement levels are low in immune complex
diseases (e.g., acute glomerulonephritis and systemic
lupus erythematosus).
Binding (activating) complement attracts
polymorphonuclear leukocytes, which release
enzymes that damage tissue.
(6) Patients with severe liver disease cannot synthesize
sufficient complement proteins, are predisposed to
infections caused by pyogenic bacteria.
Complement system
(animation)

http://highered.mcgraw-hill.com/sites/0072556781/student_view0/chapter31/animation_quiz_1.html

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