Complement
The innate immune system serves as a first responder to pathogenic threats that bypass natural physical and chemical barriers of the body. Using a combination of cellular and molecular attacks, the innate immune system identifies the nature of a pathogen and responds with inflammation, phagocytosis (where a cell engulfs a foreign particle), cytokine release, destruction by NK cells, and/or a complement system. In this concept, we will discuss the complement system.
An array of approximately 20 types of soluble proteins, called a complement system, functions to destroy extracellular pathogens. Cells of the liver and macrophages synthesize complement proteins continuously. These proteins are abundant in the blood serum and are capable of responding immediately to infecting microorganisms. The complement system is so named because it is complementary to the antibody response of the adaptive immune system. Complement proteins bind to the surfaces of microorganisms and are particularly attracted to pathogens that are already bound by antibodies. Binding of complement proteins occurs in a specific and highly-regulated sequence, with each successive protein being activated by cleavage and/or structural changes induced upon binding of the preceding protein(s). After the first few complement proteins bind, a cascade of sequential binding events follows in which the pathogen rapidly becomes coated in complement proteins.
Complement proteins perform several functions. They serve as a marker to indicate the presence of a pathogen to phagocytic cells, such as macrophages and B cells, to enhance engulfment. This process is called opsonization. Certain complement proteins can combine to form attack complexes that open pores in microbial cell membranes. These structures destroy pathogens by causing their contents to leak . When innate mechanisms are insufficient to clear an infection, the adaptive immune response is informed and mobilized.
Complement cascade in the innate immune response
The classic pathway for the complement cascade involves the attachment of several initial complement proteins to an antibody-bound pathogen, followed by rapid activation and binding of many more complement proteins and the creation of destructive pores in the microbial cell envelope and cell wall. The alternate pathway does not involve antibody activation. Rather, C3 convertase spontaneously breaks down C3. Endogenous regulatory proteins prevent the complement complex from binding to host cells. Pathogens lacking these regulatory proteins are lysed.