Complement Flashcards
under which circumstances is classical pathway activated
when antibody is bound to antigen
how is the classical pathway activated
- antigen binding to antibody causes a conformational change in the Fc receptor of the antibody allowing it to bind C1q.
- C1q undergoes conformational change which acitivates C1s
- C1s cleaves C4 which creates active C4a and C4b.
- C4b binds microbe and is accompanied by C2b.
- C2b is a C3 convertase which activates C3b
- C3b binds the microbe allowing opsonic recognistion by macrophages
- C2b also has c5 convertase activity. C5b, C6, C7, C8 and C9 form the membrane attack complex
which complement pathway is innate
lectin pathway
how is the lectin pathway activated
manose binding lectins, ficolins or CRP which recognise non-self carbohydrates
how does the immune system avoid lectin pathway activation as a result of the odd manose molecule
MBL, ficolins and CRP all have multiple binding sites so will only be activated upon binding of multiple manose molecules. multiple manose are only present on microbial cell wall
how does the lectin pathway mechanism of action differ to classical
MASP1 and MASP2 are analogous to C!q and activate the C2b converts. other than that opsonisation and membrane attack complex occurs in the same way
what sort of molecules activate the alternative pathway
can bind almost anything including water
describe the mechanism of the alternative pathway
C3b has a thirster bond which is able to bind and be activated by OH groups. this forms C3b* which is highly reactive. C3b* binds to B complex which forms a C5 convertase. This results in the formation of C3 in a positive feedback loop mechanism
how is the alternative pathway regulated
host cells have complement inhibitory proteins which prevent positive feedback loop occurring
for which sort of pathogen does complement mostly defend against
gram-negative as gram-positive pathogens have large carbohydrate coating preventing recognition of the bacterial cell wall
what is one of the main advantages of activating complement
one antibody binding to antigen can activate an enzyme which activates multiple copies of C1s activating lost of C3b etc forming multiple membrane attack complexes. signal amplification.
what are the roles of C3a and C5a in the complement cascade
they act as chemoattractants for neutrophils, activate endothelial cells
what is the possible negative effect of C3a and c5a
they are anaphlatoxins so can cause anaphylactic shock
how does C3b act as an opsonin
it binds the C3b receptor on phagocytes resulting in either a Th1 or Th17 response
what is the role of C1q
it can bind to macrophages via the C1q receptor resulting in phagocytosis and antigen presentation leading to a Th2 response
