Complement System Flashcards
Who discovered the complement system?
Jules Bordet
True or false - the complement system is conserved across invertebrates and vertebrates
True
How many different humoral proteins are there?
30
What are the three ways the complement system is activated?
carbohydrate PAMPS
antibodies bound to microbial antigens
coagulation and fibrinolytic systems
What does the Membrane Attack Complex (MAC) do?
punch holes in the microbial membrane to initiate osmotic lysis
What are the 3 pathways of the complement system that lead to the MAC?
alternative, lectin binding, classical
Which pathway is the oldest?
Alternative
What are the 2 oldest complement genes?
Factor B and C3
Gene duplications of C3 lead to?
C4 and C5
Gene duplication of Factor B led to?
C2
What pathway is 600 MYO?
Classical
Gene duplication in the Classical pathways led to?
C6-9
What pathway is 900 MYO?
Lectin Binding
The lectin binding pathway involves what key gene?
MASP
Gene duplication of MASP led to?
C1r and C1s
What are the two reasons all these pathway lead to formation of the MAC?
redundancy
each targets different molecules so a wide range of pathogen types can be recognized
What complement genes do chickens LACK?
C2, C9, MASP1 and properdin
What complement genes do teleost fish LACK?
MASP1 & MASP2
Why do we need to look at functional characteristics of complement genes in zebra fish?
because they have multiple copies of the same gene and other appear to be homologous to more than one gene
What are the 4 complement proteins produced by the liver?
C3, C6, C8 and Factor B
What are the 8 complement proteins produced by macrophages?
C2, C3, C4, C5, Factor B, Factor D, Factor P (properdin), Factor I
What are the 2 complement proteins produced by neutrophils?
C6, C7
Complement proteins act as?
opsonins and chemoattractants
What are C3a and C5a and what do they do?
they are anaphylatoxins which trigger mast cell degranulation and platelet activation which causes the release of vasoactive compounds
What are the components of the Host complement pathway? Draw it
C3, C3b & a, Factor H, Factor I, C3d and iC3b
What does iC3b do?
acts as an opsonin and activate immune cells by binding complement receptors
What are the 3 complement receptors iC3b binds to?
CR1, CR3, CRIg
What are the components of the Microbe complement pathway? Draw it
C3, C3b&a, Factor B, Factor D, Ba, C3bBb, properdin
Why is C3 broken down in host cells?
Because it’s an anaphylatoxin so you don’t want it there for longer than it needs to be
What factor is lacking in the microbial cell?
Factor I
What complement components are involved in construction of the anchor molecule? Draw it
C5, C5C3b, C5 convertase (C3bBb or C4bC2b), C6, C7
What complement components are involved in the assembly of the MAC? Draw it
C9, C8, ANCHOR
Draw the lectin-binding pathway
draw it
What is the secondary usage of MASP2?
thrombin activation causing fibrin deposition during coagulation
Draw the classical pathway
draw it
For the classical pathway, how many IgM vs IgG are needed to bind C1Q?
1 IgM molecule and 2 IgG molecules because IgM is more efficient
What component inhibits the Classical pathway?
C1-INH
What components inhibit convertases by binding them thus increasing their rate of decay?
CD55, Factor H, Factor I, C4 binding protein, CD35 (CR1)
Where is CD55 found?
on RBCs, N, M0, lymphocytes, platelets, endothelial cells
What components inhibit the construction of MAC from C3b? How do these components do this?
CD59 (protectin), vitronectin, clusterin
block insertion of C56678 and polymerization of C9
What are the ligands for complement receptors 1 (CR1)?
C3b, C4b, iC3b
90% of CR1 are found on what? and why?
RBCs to attache to pathogens in circulation
What is the ligand for CR2? How does it work?
C3d
Forms complex with CD19 providing co-stimulatory signal for B cell activation
What is the ligand for CR3?
iC3b
What is CR3 expressed?
M0, N, T cells, NK cells, platelets
What are 3 things CR3 mediates?
phagocytosis, cytotoxicity, possibly clotting
Where are C3aR and C5aR found?
Ma, eosinophils, basophils
C3aR and C5aR are part of the pathogenesis of what? Why?
allergic reactions because they trigger release of vasoactive compounds (ex. histamine)
What is the ligand for C1QRs?
C1Q
What does C1QRs do?
influences Mo-M0 differentiation and DC migration
What are the ligands for CRIg?
C3b, iC3b
Where are CRIg found?
on tissue M0
What is CRIg involved in?
phagocytic removal of blood-borne pathogens
What is the function of C2a?
increase vascular permeability
What are the 4 functions of C3a?
anaphylatoxin/mast cell degranulation (therefore a potent inflammagen)
eosinophil chemoattractant
increase vascular permeability
bacterolytic
What is the function of C3d?
immunoregulatory
What is the function of C1Q, C4b, iC3b, and C3b?
they are opsonins therefore they enhance phagocytic clearance
What are the 3 functions of C5a?
anaphylatoxin/mast cell degranulation (therefore a potent inflammagen)
N, eosinophil, M0 chemoattractant/activation
increase vascular permeability
What causes leukocyte adherence deficiency (BLAD) in cattle?
SNPs in CD18 therefore decreasing B2-integrin expression
What causes excessive C3b production?
SNP on Factor H
What predisposes an individual to asthama?
SNPS in C3, C5, C5aR and C3aR
What is the complement system activated by during coagulation-fibrinolysis?
kallikrein acting as a C3 convertase but can also be activated by coagulation factors, thrombin and plasmin
How does strepotococci overcome the complement system?
Its M proteins block opsinization by masking C3b binding sites
How does staphylococcus aureus overcome the complement system?
produced fibrinogen-binding proteins altering the shape of C3b so it cannot interact with Factor B
How does salmonella overcome the complement system?
has a gene call Rck which prevents insertion of MAC into the bacterial outer membrane
