Anatomy And Physiology

Complement System of the Nonspecific Immune Response

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Complement cascade is one of the first defences we have against invading pathogens, part of our innate immunity. Complement are serine proteins which work with antibodies to destroy pathogens. Complement controls inflammation, phagocytosis, and lyses some cells (breaks apart, cell death). Macrophages produce complement proteins. Many of these complement proteins are pro-enzymes, which can cleave the next stage in the complement cascade upon their activation (usually through their own cleavage), where they become proteases. There are three complement cascades, which lead to different immune defence responses, the classical pathway, the alternative pathway, and the lectin pathway.

The classical pathway starts with C1 component, a protein complex of Clr, Cls, and Clq, which is calcium dependent, and activated when Clq binds to an antibody, changing its structure so it can now become a autocatalytic Clr enzyme. Clr transforms Cls into a protease form, where it can cleave C4 and C2, so that they can bind to each other and form C3 convertase. C3 convertase cleaves C3 into C3a (chemotactant) and C3b (opsonin). Some C3b binds to an activating surface to create C4b2a3b, this enzymatic complex is called C5 convertase. C5 convertase binds to C5, and is cleaved by C2 in the complex, which creates C5b. C5b binds to C6 and C7, causing a conformational change in C7, and this C5b67 complex binds to the lipid bilayer of the cell membrane (of the pathogen), C8 joins the complex, along with C9 that forms a ring shape, this complex C5b678 and poly-9 makes pores in the pathogen cell membrane, which causes it to lyse (die).

The alternative pathway s involves C3, and C5 convertase, C3b interacts with factor B to form C3bB, factor D splits B into Bb and Ba, which creates C3bBb. Properdin from the serum binds to Bb forming C3bBbP, which is a C3 convertase, and converts C3 into C3a and C3b. Some C3b binds to C3bBb to form C3bBb3b, which is a C5 convertase, cleaving C5 into C5a and C5b. Some C3b however binds to receptors on phagocytes, causing opsonization, and phagocytosis of the pathogen.

The lectin pathway involves mannan-binding protein MBP, this enzyme is similar to C1q, which binds to mannose on antigens. MASP1 and MASP2 bind to MBP, and creates an enzyme like C1, which cleaves C2 and C4 to make C3 convertase C4bC2a, which splits C3 into C3a and C3b. C4a and C2b act as chemo-attractants.

These pathways all interlink, and cause phagocytosis through C3b interactions with phagocytes, C5b causes the membrane complex which punches holes into pathogens, and C3a and C5a interact with mast cells to cause vascular permeability, which increases inflammatory responses.

More about this author: Triana Rathads

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