Complement Flashcards
what is complement
very complex system of 50 diff proteins in serum or receptors on white cells
wide rage functions
involves enzyme cascade
what do all components of enzyme cascade do
circulate as inactive precursors
makes proteolytic enzymes activating other enzymes
what is the central protein of complement
C3
what does a deficiency of C3 lead to
recurrent bacterial infections
what do all three complement pathways result in
proteolytic cleavage of C3 to C3b and C3a
what is C3b and C3a
C3b - large fragment
C3a - small fragment
what does C3b then do after having been cleaved
deposited onto surface of micro organism and marks it out for destruction via lysis or opsonisation
what enzyme is used during cleavage
C3 convertase
where is a thioester bond
between Cys and Glu on alpha chain
after cleavage what happens to the thioester bond
becomes exposed and unstable
nucleophilic attack by electrons on -OH and -NH2 group
what happens after the thioester bon is nnucelophillic attacked
covalent bond formed to membrane of pathogens
what is the first component of the classical pathway
C1q
what is C1q
hexavalent
base - collagen like triple helices
stalk - triple helices
globular heads
what do the globular heads of C1q do
bind Fc of IgG or IgM
what is the classical pathway activated by
IgG r IgM
what binds C1q
C1r or C1s
what do C1r and C1s become
proteolytic enzymes
lead to C4 and C2 cleaved and C3 cnvretase formed
proteolytically active C1 cleaves what
C4 into C4a and C4b - bind to mem of pathogen and recruit C2
what forms C3 converts
C4b2a
what is MBL
mannose binding lectin
what is the caacteristics of MBL
bouquet like C1q
bind sugar mols found in repeating arrays on microbial surfaces
are there antibodies involved in lectin pathway
no only in classical
what is the lectin pathway
MBL-MASP-2 complex bind C4
C2 comes along and for C3 convertase
C3 cleaved and C3b fragments bind to surface
whats the alternative pathway
also prod C3 convertase but uses diff proteins
what is the alternative pathway actitved by
many types of microorganisms - bacteria, yeast, trypanosomes
when can the alternative pathway function
immediately
before Ab response
hence first line defenceagaisnt systemic infection
what initiates alternative pathway
form and action of soluble C3 convertase iC3b
how does C3 become iC3b
spontaneous hydrolysis of thioester bond and factor B binding
how is C3b which covalently bonds to pathogen surface made from iC3b
cleavage of factor B by factor D
a c3 convertase some of C3b fromed
what si the makeup of C3 conertase fro alternative pathway
C3bBb
what does C3b cleave
C5 to C5b and C5a
what does C5b do
bids to surface micro organisms
four other proteins C6, C7, C8 and C9 form
membrane attack complex which forms funnel shaped hole in cell mem
what is opsonisation
coating of micro organisms by antibody or complement components
what receptors d phagocytes have
C3b receptors
what are the anaphylatoxins
C3a and C5a
what does C3a do as an anaphylatoxin
binds to receptors on mast cells
histamine release
increase vasc perm
recruit other components of inflam response to infection site
what do anaphlatoxins act directly on
blood vessels increasing blood flow and vasc perm
what does C5a trigger
phagocyte chemotaxis
what does C5a bind to
C5a receptors on phagocytes
phagocyte migrates up concentration gradient of C5a to infection site
phagocyte becomes stickier
phagocyte stop moving
what controls the classical pathway
C1 inhibitor
Decay accreting factor
complement receptor 1
what controls the alternative pathway
Factor I
Factor H
CR1
what can some micro organisms do
avoid effects of complement
what else does complement do
removing immune complexes
deficiencies in classical pathway components assc with
immune complex autoimmune diseases
how does complement rid of Ic
IC bind to RBC and phagocytes via complement receptor and eliminate
