VMC 221: Veterinary Immunology and Serology (1+1)

COMPLEMENT SYSTEM

• The complement system is one of the major effector mechanisms of humoral immunity and as well as of innate immunity.
• The complement system is composed of several (at least 19) heat labile (56^oC in 30 minutes) serum (plasma) proteins and constitutes about 10% of the globular fraction of serum.
• Molecular weight of the complement components varies from 24 KDa (factor D) to 460 KDa (C1q).
• The complement proteins are labeled numerically with the prefix C (C1, C2, C3 --- C9) or designated by letters of the alphabet (B, D, P etc).
• Peptide fragments formed by activation of a component are denoted by small letter (C3a, C3b etc).
• The complement fragments interact with one another to form functional complexes.
• Those complexes with enzymatic activity are denoted by a bar over the number or symbol.
• Complement proteins constitute nearly 10% serum proteins. Complement components are synthesized at various sites like liver macrophages.
• Complement system is normally inactive but activated under certain condition like microbial infection and generates effector mechanism to destroy the activator (i.e the microbes).
• Activation of complements involve the sequential proteolysis of proteins to generate enzymes with proteolytic activity.
• Proteins that acquire proteolytic enzymatic activity by the action of other proteases are called zymogens (proenzymes).
• Zymogens are activated sequentially i.e. the product of first reaction catalyzes a second reaction and the product of second reaction catalyzes third reaction and so on. This types of chain of enzymatic reaction are known as cascade reaction.
• The products of activated complement attach covalently to microbial cell surfaces or antibody coated microbes or other antigens and cause lysis of the target cells (e.g.microbe).
• Complement activation is inhibited by regulatory proteins that are present in normal host cells in absence of microbes. Thus normal host is not affected.
• Guinea pig serum contains all the factors of the lytic complement in correct proportion. Hence, fresh guinea pig serum, preferably pooled is the best source of complement.
• While collecting blood for separation of serum for CFT, there should not be any hemolysis or tissue damage. In both these conditions anticomplement factors are released. Mouse and horse complements are incomplete and poorly lytic.
• Pathways of Complement Activation - There are three major pathways for complement activation
  • The Classical Pathway – which is activated by certain antibodies bound to antigens.
  • The Alternative Pathway – which is activated by microbial cell in the absence of antibody.
  • The Lectin Pathway - which is activated by plasma lectin bound to mannose residues on microbes.