Question

Describe the classical pathway of complement activation in the absence of antibodies and how it is used during an innate immune response to clear the pathogen.

Answer 1

Classic complement pathway

The complement system is a part of the immune system, which aid in the destruction of pathogens by a number of proteins called complement proteins that interact with one another.

The classical pathway is usually activated by antigen antibody complexes or directly by pathogens binding to the first protein of the complement cascade - C1q. This binding activates C1s, which then cleaves the C4 complement protein into C4a and C4b. C2 is also cleaved by C1s forming C2a and C2b. This leads to formation of C4b2b.

C4b2b is known as the classical C3 convertase, which cleaves C3 into C3a and C3b. C3a acts as a recruiter of inflammatory cells (known as anaphylatoxin), while C3b binds to C4b2b forming C4b2b3b. C3b is a potent opsonin i.e, it causes coating of an antigen that facilitate phagocytosis.

C4b2b3b is known as the classical C5 convertase, which cleaves C5 into C5a (anaphylatoxin) and C5b.

C5b then attaches to C6, and subsequently binds to C7, C8, C9 forming the membrane attack complex. The membrane attack complex ( C5b - C9) acts by creating pores in the bacterial membranes leading to their lysis.

Complement in Innate immune response

In innate immune response against a pathogen, the antigen trigerred activation of the classical complement pathway leads to formation of membrane attack complex, which kills the invading microbe by complement mediated lysis. Also, other component of the complement like C3a and C5a are potent anaphylotoxins that mediate chemotaxis and inflammation. Also, the C3b component of the complement is a potent opsonin and helps in opsonisation of the invading pathogen to facilitate its phagocytosis.