# The Complement System The complement system is a series of [[proteins]] that act to: 1. [[Cellular Interactions#Opsonization|Mark]] an invading pathogen to be [[Cellular Interactions#Phagocytosis|destroyed]] by other [[Cells of the Immune System|immune cells]]. 2. Destroy pathogens by poking In a nutshell, the complement system does three things: - It maims the enemies and makes their - It activates [[Cells of the Immune System|immune cells]] and guides them to invaders so they can kill them ### Complement Proteins There are a little over 30 different [[proteins]] which make up the complement system. These are referred to as **complement proteins** (or fragments) and act as puzzle pieces that bump around > *Recall that the structure of a protein is what determines its function* Complement Component 3 (C3) is by far the most important protein within the complement system - **Proteolytic Enzymes (Proteases)**: Enzymes that break down protein molecules - Zymogens: The functionally inactive form of a protease, which requires cleavage by another protease to become active ##### Events - Complement Fixation: --- ### Pathways of the Complement System ![[The Complement System Pathways.png|400]] [[Cellular Interactions#Biological Pathways|biological pathways]] 1. [[The Alternative Pathway]] 2. The Lectin Pathway 3. TheClassical Pathway A **convertase** is called *soluble* if it has yet to bind to a bacteria cell. ![[Complement Proteins.png|400]] [[Immunology Classical Pathway.excalidraw]] ![[Pathways of The Complement System.png|400]] --- ### Characteristics of C3b When attacked by water molecules, hydrolyzed C3b remains soluble and unable to participate in any subsequent cascade reaction. --- C3b and C3a contribute to downstream immunological functions. C3b interacts with host and microbial cells by opsonizing to microbe cell surfaces and increasing phagocytosis. C3b also is a critical component of the C5 convertase, which initiates the terminal complement functions of forming the membrane-attack complex (MAC). C3a recruits phagocytes and induces inflammatory responses from endothelial cells. --- The lectin pathway is the only pathway where the earliest component binds directly to the pathogen surface. For the lectin pathway, the mannose-binding lectin protein binds to mannose on the pathogen surface. The alternative pathway starts in the plasma near, but not on, the pathogen surface. The classical pathway first binds to an antibody or C-reactive protein attached to the pathogen. --- All three pathways of complement activation lead to the formation of a C3 convertase. Though the alternative C3 convertase is made of different proteins than the classical and lectin pathways, the function of cleaving C3 into C3a and C3b is the same. Further, the end results of the C3 convertase functions are shared across the pathways: inducing inflammation, recruiting immune effector cells, and providing the foundation necessary to activate the terminal complement components and the membrane-attack complex (MAC). Of the three pathways, the alternative pathway is activated first and protects against microorganisms that the body has not seen before. --- The liver synthesizes soluble proteins collectively known as complement. Many of these proteins become activated by a series, or cascade, of enzymatic reactions in which each protease cleaves and activates the next protease in the pathway. The alternative pathway is the first to be activated in the course of an infection, followed by the lectin pathway during the innate immune responses. After the adaptive immune response has begun, the classical pathway can be activated by binding to antibodies or C-reactive protein on the microbe’s surface. All three initiation pathways converge to generate C3b through a C3 convertase and then continue through the cleavage cascade to the terminal complement components. ### C5 Convertase "just add a C3b to the C3 convertase of the respective pathway" - alternative: C3bBb -> C3b_2Bb - lectin/classical: C4b2a -> C4b2a3b