Complement System Flashcards
Complement system
- Discovered in 1980s by Jules Bordet as a heat-labile substance in blood plasma
- Evolutionary very old system
- Contains more than 30 inactive proteins
- Protein cascade: one protein activates the next and so on
- Purpose is to destroy pathogens
Advantage to a protein cascade
One protein can activate many others= Amplification
Three main functions of complement system
- Lysis
- Opsonization
- Recruitment
Recruitment
- Increases vascular permeability (C2a)
- Anaphylatoxin (C3a) and neutrophil activation (C3a, C5a)
- Leukocyte chemotaxis (C5b67)
Opsonization
Facilitate uptake and destruction of pathogens by phagocytes (C3b)
- Complement receptors recognize pathogens that are opsonized by complement proteins
Often require activation of more than one receptor
Lysis
Membrane attack complex (C7, C8, C9)
Three pathways for the complement system
- Alternative
- Classical
- Lectin
**2 bind right to pathogen, and 1 binds to antibody
Classical pathway steps
- C1 complex binds to antibody (IgM or IgG) bound to microbe (antigen).
- Activates complement
- C3b covalently binds to surface components of pathogen
- Results in recruitment of inflammatory cells, opsonization of pathogens (facilitating uptake and killing by phagocytosis), perforation of pathogen cell membrane by membrane attack complex (MAC)
- Death of pathogen
Lectin pathway steps
- Mannose-binding lectin binds to carbohydrates on pathogen cell membranes
- Activates complement
- C3b covalently binds to surface components of pathogen
- Results in recruitment of inflammatory cells, opsonization of pathogens (facilitating uptake and killing by phagocytosis), perforation of pathogen cell membrane
- Death of pathogen
Sugar binding lectin
- Binds to mannose, fucose, N-acetylglusoamine, and then can bind to the carbohydrates in cell membranes of pathogens
- Recognized as PAMPS of bacteria, fungi, and some parasites and viruses
Alternative pathway
- Pathogen cell wall creates local environment conducive to complement activation (in blood). Mediated by C3 protein
- Activates complement
- C3b covalently binds to surface components of pathogen
- Results in recruitment of inflammatory cells, opsonization of pathogens (facilitating uptake and killing by phagocytosis), perforation of pathogen cell membrane
- Death of pathogen
Protein cascade
Proteins are cleaved and bind together and eventually will form membrane attack complex
How do we prevent our complement system from attacking self?
Differences on our cell surface called factors (H or I factors) signal to our complement system that they are safe
Regulation of complement pathways
- Controlled by acute phase proteins
- Often inhibit the protease function of proteins
- Specific factors (such as factor H)
- Cell surface molecules that shield cells surfaces from C3 attaching to it
Disregulation of complement pathways
Genetic defects in complement are associated with higher susceptibility to bacterial infections
- Defects to C3 prevents other parts of cascade from continuing. Can be associated with the glomerula and glomerulonephritis
