Innate Immunity

Complement System

The complement system is an important part of the immune system that enhances the activity of white blood cells and antibodies to target invading microbes and damaged host cells.

One important mechanism by which the innate immune response is able to prevent infection is called the complement system. The complement system is a collection of immune system pathways and complement proteins that protect the body from microbes by enhancing the function of leukocytes and antibodies. A complement reaction is referred to as a signal cascade, where one detection protein triggers a response in other signal proteins, which in turn trigger others, and so on. This enables individual molecules far from lymph nodes and immune organs to command significant responses to injury and infection very rapidly. The complement system is activated through three major pathways, depending on which molecules are present to activate the system: the classical pathway, the alternative pathway, and the lectin pathway.

The classical pathway is the complement pathway activated when complement signal proteins encounter an antibody bound to an antigen, which could be a potential pathogen or allergen. The lectin pathway, also known as the mannose pathway, is the complement pathway activated when the signal protein mannan-binding lectin binds to mannose or other sugars found on the surface of most organisms cells but that are prominently displayed on pathogens. This allows for the complement to be activated through a more generalized mechanism than the classical pathway, which relies on antibodies. In the alternative pathway, signal molecules bind to the surface of all cells, including host cells and pathogens. When the signal proteins bind to a pathogen, the complement signals are fully activated. However, host cells possess the cell surface proteins that prevent the signal cascade being activated.

Even though the initial events of activation of the complement cascade are different for the three pathways, the pathways eventually converge and provide the same protection against pathogens. The first protective mechanism is activation of the inflammatory response by complement proteins C3a and C5a, which makes the surrounding tissue inhospitable for pathogens and attracts leukocytes. The second mechanism is opsonization, which involves coating the surface of an antigen with opsonins to enhance the interaction between phagocytic cells and the antigen. During opsonization, complement proteins, such as C3b, coat the entire surface of a pathogen, directing leukocytes toward pathogens and promoting phagocytosis. The third mechanism is called the membrane attack complex (MAC), in which complement proteins (C5b, C6, C7, C8, and multiple units of C9) aggregate and form a complex on the surface of pathogens. Insertion of MAC in the cell membrane of a pathogen forms pores in the cell surface, causing the cell contents to leak out and killing the pathogen.

Complement System

The complement system is a complex cascade of chemical signals that regulate inflammation, attract leukocytes, and directly attack pathogens.