Notes

COMPLEMENT

  • Definition: series of heat-labile (56°C for 30 min), non specific serum proteins.
  • Binds to Fc region of antibody-IgM (binds strongly) followed by IgG3à1à2
  • Site: serum and all tissue fluids except urine and CSF
  • Synthesis: In liver – C3, C6, C9 appear in fetal circulation during 1st 13 Week.

GIT- C1
Macrophage- C2, C4
Spleen- C5, C8

  • Function: Responsible for certain aspects of immune response and inflammatory response
  • Activation: antigen-antibody complex or endotoxin, capsule series of proteins activated sequentially
  • Inactivation: inhibitors in plasma (short lived)
  • Biological effects: either beneficial or harmful to host

Components:

  • The complement system consists of at least 30 chemically & immunologically distinct serum proteins which make up the complement components, the properdin system & the control proteins.
  • The biological activities of this system affect both innate & acquired immunity.

Fractions: Complement is a complex of 9 different fractions, C1-C9.

  • Fraction C1 occurs in serum as a calcium dependent complex, which on chelation with EDTA yields 3 protein subunits called C1q, r and S.
  • Thus complement is made up of 11 different proteins.

COMPLEMENT PATHWAY

  1. A) Classical pathway:
  • - Complement is activated by antigen –antibody complex (IgM or IgG)
  • - Fc portion of the antibody form a binding site for C1q
  • - The numerical sequence of the complement factors in the classic pathway is:
  • C1q, r, s , C4, C2, C3, C5, C6, C7, C8, C9

The reaction sequence divided into three stages:

1) Recognition stage:

  • - C1q act as the recognition element
  • - It binds to Fc portion of IgM or IgG
  • - The activated C1 molecule can cleave many C4 molec.

2) Activation stage:

  • The complement components C4, C2, C3, C5, C6, C7, C8, C9 participate in that order.

3) Membrane attack stage:

  • Complement components C5, C6, C7, C8, C9 participate where cell membrane damage and cell lysis occur.

  1. B) Alternative pathway

This pathway is initiated by:

  • Bacterial endotoxin, polysaccharide capsule, aggregates of IgE and properdin.
  • It starts at C3 then C5, C6, C7, C8, C9.
  • The complement compon. C1, C4, C2 are by-passed.
  • Antibodies are not required to initiate activation of this pathway.
  • This pathway provides a means of non-specific resistance.

  1. C) Lectin pathway
  • Lectin pathway is also bacterial &fungal defense mechanism. Mannose binding protein (earlier RaRF), is a large serum protein that binds to non-reduced mannose, fructose & glucosamine on surface of bacteria & other cells.
  • Microbial surfaces(mannose) & others ( e.g IgA) are needed. In this pathway, MBP resembles & replaces the complement C1q & binds to bacterial cells.
  • On binding to bacterial surface, it activates the cleavage of MBP associated serine MBP associated serine protease cleaves the C4 & C2 components producing the C3 convertase which is the junction point of complement cascade.

Classic and Alternative pathways main differences.

Biological Effects of Complement

Beneficial effects:

1) Cytolysis:

  • Activated complement proteins polymerize on cell surfaces of bacteria or erythrocyte to form pores in its membrane (killing by osmotic lysis).

2) Opsonization:

  • Binding of complement proteins opsonin (C3b) to surfaces of foreign organisms or particles
  • Phagocytic cells express specific receptors for opsonins, so promote phagocytosis

3) Inflammatory response:

  • Small fragments released during complement activation have several inflammatory actions:
  • C5a is chemotactic and attract neutrophils and macrophages.
  • C5a activate phagocytes and neutrophils.
  • C3, C4 and C5 are anaphylatoxins cause degranulation of mast cells and release of histamine and other inflammatory mediators.

4) Immune complex clearance:

  • C3b facilitate binding of immune complex to several surfaces (erythrocytes) and enhance removal by liver and spleen.
  • binds erythrocytes to blood vessels, make them as easy prey for phagocytosis.
  • C3 deficiency associated with Immunocomplex disease and susceptibility to recurrent infections.

5) Enhancement of antibody production:

  • Binding of C3b to its receptors on activated B cells (CR2) greatly enhances antibody production.
  • Patient who are deficient in C3b produce much less antibody than normal individuals and more susceptible to pyogenic infection.

Harmful effects:

  • If complement activate systematically on a large scale (Gm –ve bacilli).
  • If activated by an autoimmune response to host cells.

Complement deficient states

Deficiency of complement

Syndrome associated

C1 Esterase inhibitor

Hereditary angioneurotic oedema

Early components of classical pathway (C1, C2, C4)

SLE & other collagen vascular disease

Pyogenic infection

C3 and its regulatory protein

Severe recurrent pyogenic infection

Complement C5-9 (membrane attack complex)

Gram –ve diplococci (Neisseria), Toxoplasma

D, I

Pyogenic infections

Properdin

Neisseria infections

H

Hemolytic uremic syndrome
www.000webhost.com