Hunter: Complement Flashcards
(63 cards)
Group of > 30 constitutively expressed serum and cell surface proteins
complement
Is complement an innate or adaptive response to pathogens?
innate *works with antibodies in the humoral immune response to pathogens
The complement system plays an important part in eliminating (blank)
immune complexes
Genetic defects in various complement components can increase the risk for infections with pathogens, especially (blank), and can precipitate (blank)
pyogenic bacteria; immune complex diseases
The complement system is similar to which two cascade-like systems?
coagulation and kinin systems
In the complement system response, (blank) are cleaved which causes molecules downstream in the pathway to be cleaved as well. This (blank) the response to microbes.
zymogens; AMPLIFIES
What are the 4 major functions of the complement system?
- complement molecules bind directly to pathogens and coat them for phagocytosis
- complement molecules cause inflammation and promote chemotaxis and activation of immune cells
- some complement molecules help clear immune complexes (antigen-antibody complexes)
- some complement molecules form pores in pathogen membranes and directly cause lysis and death
What are the 3 components of the complement system?
- classical pathway
- lectin pathway
- alternative pathway
What do all 3 pathways ultimately lead to?
activation of C3 convertase and the formation of C3b which binds to complement receptors for destruction of pathogens and removal of immune complexes
What is odd about the order of complement protein activation?
C1, C4, C2, C3, C5-9
Which protein in the complement system is typically the “small” fragment, and which is the “large” fragment?
small fragment is “a,” while the large fragment is “b” *except in the case of C2, in which the small fragment is C3b
This is a pattern recognition receptor involved in the classical complement pathway that can bind to certain repeat molecular motifs on pathogens (ex: bacterial porins and LPS, as well as IgM, IgG)
C1q
Explain the generation of the C3 convertase by the classical pathway.
- C1q binds to the pathogen surface
C1s becomes an active serine protease and cleaves C4 into C4a and C4b - C4b binds to the pathogen surface or is quickly hydrolysed, while the small C4a floats away
- C1q then cleaves C2 into a small and large fragment, the large fragment (C2a) associates with C4b, the small C2b fragment floats away
- C4b2a complex is the C3 convertase and cleaves C3 into C3b which binds to the pathogen and C3a which floats away
- Lots of C3b molecules bind to the pathogen
What happens to C3b and C4b to ensure that they do not become highly reactive?
they are hydrolyzed rapidly if they don’t bind to pathogen surfaces
What happens once a pathogen is opsonized by C3b?
it is endocytosed and killed by phagocytic cells
What is the most important defense against extracellular pathogens?
the C3b mediated opsonization and killing of pathogens
Complement activation promotes clearance of (blank)
immune complexes
Antigen/antibody complexes form during infections and in some autoimmune diseases. (blank) binds and results in the deposition of C4b and C3b on the complexes. Immune complexes bind to complement receptor 1 on (blank) via C4b and C3b. When the RBCs pass through the spleen and liver, they are stripped and degraded.
C1q; RBCs
Antigen/antibody complexes form during infections and in some autoimmune diseases. C1q binds and results in the deposition of (blank) and (blank) on the complexes. Immune complexes bind to (blank) on RBCs via C4b and C3b. When the RBCs pass through the spleen and liver, they are stripped and degraded.
C4b; C3b; complement receptor 1 (CR1)
Deficiencies in which complement proteins result in immune complex disease?
C1, C4, C2
The lectin pathway is similiar in function to the classical pathway. What is the equivalent to C1q in the lectin pathway? What is the equivalent to C1r/s in the lectin pathway?
mannose bindng lectin and ficolins; MASP-1/2
What is the convertase that forms in the mannose binding lectin pathway?
C3 convertase *just like the classical pathway
This pathway can amplify both the classical and lectin pathways
alternative pathway
What engages the alternative pathway?
C3b deposition on the pathogen surface via the classical or lectin pathway
