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Complement System - Coggle Diagram
Complement System
Key mechanism of activation
Destroying pathogen cell membranes
Increasing recognition of pathogens and facilitating phagocytosis (opsonization)
Increasing vascular permeability and chemotaxis
Inactive pro-proteases Activation
Alternative pathway
C3 undergoes spontaneous hydrolysis
Occur once C3b has been produced by lectin or classical pathway activation
Occur spontaneously in plasma by specific convertase
Alternative convertases
short-lived
can be stabilized by factor secreted by neutrophils (properdin)
Lectin pathway
Triggered by PRRs that circulate in blood
Mannose-binding lectin
Ficolins
Expression of the PRRs increase during infection
PRRs can recognize and bind carbohydrates on the surface of pathogens
Triggers signaling cascade on pathogen
C3 convertase is generated
C3 cleaved into C3a (small, specific function) and C3b (large, proteolytic activity on a new substrate)
Classical pathway
C1q binds pathogen surface.
Indirect binding to antibodies on the pathogen surface (implies that an immune response has happened in the past)
Connects adaptive to innate immunity
Direct binding
Once C1q binds
triggers signaling cascade on pathogen surface
C3 convertase is generated
C3 cleaved into C3a (small, specific function) and C3b (large, proteolytic activity on a new substrate)
All pathways converge on C3
C3 convertase cleaves C3 into C3a and C3b
Many downstream effects
Inflammation
Large amounts of C3a and C5a = anaphylactic shock
Additional signaling results in cleavage of other complement molecules
C3a and C5a recruit phagocytes and promotes inflammation
Increased phagocytosis
phagocytes have receptors for C3b
opsonization of pathogen = easier phagocytosis
opsonization can occur via complement deposition and/or antibodies
Pathogen lysis
Additional complement factors (e.g. C6, C7) create membrane-attack complex (MAC
cell lysis
3 pathways result in activation of C3 convertases
(category of proteins)
Negative regulation of Complement system
In plasma or cell surfaces
Prevent complement activation from proceeding using normal/basal conditions
prevent appearance of C3 convertase
promote disappearance of C3 convertase
complement-regulatory proteins
A group of soluble proteins
Types: proteases (enzyme that performs proteolysis) > 30
other proteins
Nomenclature: mostly called C followed by a number
Found in blood and other fluids
Mostly produced by liver