Complement System :

Def : Complement represents a

group of proteins normally found
in serum in Inactive form but when activated enhances Immune
, response
·
constitute 5% of normal serum proteins.

complement Pathway :

C cascade
The is
triggered by three
parallel but independent
pathway which differ in initial step of Activation

if Classical pathway
ii) Alternative pathway &

asked
(
as
will be
iD Lectin pathway
a
only pathway
(essay effector function
1
with
along regulation

i) CLASSICAL PATHWAY :
(Antibody dependent)

·
Not all antibodies can bind to complements

IqM <
IgG3 >
IgG ,
>
IgG2

It
begins with initiation followed by C , Cs Comvertase &

finally forms Membrane Attack Complex

Note. that only initiation step varies in all three pathways

Initiation :
·
Binding of C to Ag-Ab complex
·
Gig attaches to FC portion of Ab by atleast two of it's globular site

IgM
-

pentameric (has 5 Ec regions) , therefore one

IgM can initiate .

IgG-Monomeric (has regions) therefore two IgG molecules needed

-

F are
,

Formation of C convertase

circulation <
C Combines
>
-
· Activated 4s [Cs) Cleaves C4 to produce Cya +
Cyb
· Forms (14b M> Combines)
[22 +
(2D -> circulation

C14b2a-Cy convertase

Formation of Cs convertase :

circulation Combines
E -
· Cs convertase hydrolyses ( >
-

(32 + Cyb

C14b2236 Complex -

Cs convertase
Formation of Membrane Attack Complex

·
Cs convertase cleaves Cs >
-

Ca + Csb
·
Csb gets stabilized by forming (sb67 + (8 >
-
(Sb678
·
CSb678 has Catalytic property hence when it binds to C9 it results
,

in formation of channels or
pores on
target cell membrane

leads to free water

This passage of ions a > Cell
swellinga Lysis
· -

Complem nt-mediated
·
This type of Cytolysis is known as
cytotoxicity
ii] ALTERNATIVE PATHINAY (Antibody Independent) :

· CI , 24 & C2 are not involved ,

instead it requires factor B D
,

& Properdin .

initiation
combines
circulation >
-
·
Free Cs in Serum (3 > (32 + (3) (bb Coated foreign cell)
-

Formation of Cy convertase

factor B
circulation >
-
Combines

· Factor D >
-
Ba + Bb
·
CzBD-C3 convertase (12 life-smins) ,
stabilized by
properdin (12 life -

30
mins) .

iii) LECTIN PATHWAY :

(Antibody independents
· Interacts with Mannose residues on MicrobialSurface
·
Has special proteins MBL (Mannose Binding Lectins)
·
Does not involve G
 initiation
·
MBL binds to mannose residues ,
MASP forms Complex with MBL
·
MBL-MASP Complex cleaves (4 > Splits (2 > MBLMASP Cyb28
- -
-

acts as C3 convertase

Effector functions of complement

1 .

Target lysis by MAC : [complement mediated cell Lysis]

-

pore channels
-
Cell lysis eg-Bacteria, enveloped virus
.
2
Inflammatory response :

Ca , Cya & Csa Anaphylatoxins (release inflam

Mediators)
-
-

:
3 Opsonization :

Cyb & Cyb-opsotins particulate antigens enhance phagocytosis

4 .

Removing Complex
Immune from blood :

Cob recognized by CRI RBC are

phagocytosed in Liver & Spleen
-

on

.
5 Viral Neutralization

REGULATION : Since Complement system are non specific they are capable of attacking host cells as well

1 :
C , esterase inhibitor >
-

Cigs >
-

Cq + Gos

2 .

Decay accelerating factor- CD35 molecule accelerates dissociation of C3