This PPT includes overview of all the three pathways of complement system and their clinical significance

1. CLASSICAL PATHWAY OF COMPLEMENT
SYSTEM
BY
KULDEEPKUMAR
MSC PART1
ROLL NO.27

2.  The Complement (C) system refers to a system
consisting of a group of Specific & non-specific
proteins (approximately 20) present in normal human
and animal serum
 Term “complement” refers to the ability of these
proteins to complement.
 Complement is an important component of our innate
host defenses

3.  Term complement was coined by Paul Ehrlich
 Present in inactivate form, but when activated they augment
immune response
 Their level does not increase by infection or vaccination
 They are heat-labile, inactivated at 560C for 30 minutes
 Synthesized mainly by liver, also produced by blood
monocytes, tissue macrophages, epithelial cells of GIT and
genitourinary tracts

4.  Bind to Fc portion of antibody
 Does not combine with free antigen or antibody, but
only with antigen-antibody complex
 Among Igs, only IgM, IgG3, IgG1 and IgG2 in that
order fix complement
 This property is due to the presence of C binding site
on the Fc portion of these immunoglobulins

5. COMPLEMENT COMPONENTS
 Complement system consists of about 20 proteins which
include the complement components, the properdin system
and the regulatory protein
 There are 9 complement components. i.e, C1-C9. C1 has 3
subunits i.e, C1q, C1r and C1s
 Factors B, D, H and I, properdin (P)
 Mannose binding lectin (MBL), MBL associated serine
proteases (MASP-1 MASP-2)
 C1 inhibitor (C1-INH, serpin), C4-binding protein (C4-BP),
decay accelerating factor (DAF), Complement receptor 1
(CR1), protein-S (vitronectin)

6. Complement pathways
 Sequential activation of complement
components occurs via one of the 3
pathways
1) Classical pathway
2) Alternate pathway
3) Lectin pathway

7.  In the classical pathway, antigen-antibody
complexes activate the pathway
 In the alternative pathway (antibody independent
pathway), many cell surface substances initiate the
process - bacterial lipopolysaccharidess (endotoxin),
fungal cell wall, viral envelopes etc
 In the lectin pathway (antibody independent
pathway), mannan-binding lectin (MBL) binds to the
surface of microbes bearing mannan ( a polymer of
mannose) and this activates the process

8. Stages of complement
activation
1. Initiation of pathway
2. Formation of C3 convertase.
3. Formation of C5 convertase.
4. Formation of membrane attack complex (MAC)
all the three pathways differ each other in their initial
process till formation of C3 convertase.

9. Structure of C1

11. function of complement system
 Opsonisation
 Chemotaxis
 Cell Lysis
 Immune Clearance
 Activation of inflammatory Response

13. Clinical Significance.
 Complement is responsible for immune inflammatory response in
adipose tissues which has been implicated in the development
of obesity.
 Immunotherapies have been developed to detect and destroy cells
infected by the HIV virus via classical complement activation.
 Lack of regulation of the classical complement pathway through the
deficiency in C1-inhibitor results in episodic angioedema.
 Deficiency in the C1q protein of the classical complement pathway can
lead to development of systemic lupus erythematosus.