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What is the complement system?
a group of serum proteins that interact to destroy invading microbes
Where are most plasma complement proteins synthesized?
in the liver
What is the most popular complement protein?
C3
Why is C3 the most popular complement protein?
that's where all 3 pathways converge
What do all cleavage steps in the alternate pathway do?
yield activation
What is the most innate pathway?
the lectin pathway
What are the early complement components?
C1, C2, C3, C4
What are the half lives of complements?
short
What are the duties of complements?
acts as opsonins
increase vascular permeability
recruit monocytes and neutrophils to antigens
trigger secretion of cytokines
What are the three complement pathways?
classical
lectin
alternative
What is the end product of the complement system?
lysis of the invading cell
What is the characteristic of the classical pathway?
primarily antigens and antibodies
What is the characteristic of the lectin pathway?
does not require antibodies
What is the characteristic of the alternative pathway?
supports classical and lectin pathway
What is the classical pathway
start with C1qrs
C4 and C2 come in
C4a and C2b leave
C4b2a is left (C3 convertase)
C3 comes in
C3 a leaves
C4b2a3b is left (C5 convertase)
C5 comes in
C5a leaves
C5b is left
C6, C7, C8, C9 comes in
these are polymerized and turns into C5b6789
What is C5 covertase?
C4b2a3b
What is the most efficient antibody in the classical pathway?
IgM
because of its multiply binding sites
What are the substances that activate the classical pathway?
C-reactive protein
certain viruses
mycoplasmas
some protozoa
What is the C1 complex?
C1q, C1r, C1s
calcium is required
What is the recognition unit of the classical pathway?
C1q recognizes the Fc region
two globular heads of C1q needs to be bound
C1r and C1s are converted
C1r is activated
C1r cleaves and C1s is activated
C1 is activates and recognition ends
When does activation begin in the classical pathway?
when C1s cleaves C4 to create C4b and C2 to create C2a
What is the membrane attack complex of the classical pathway?
when C5b attaches to the membrane to create C5b6789
What is the main point of the lection pathway?
a defense mechanism in infancy in between loss of maternal antibody and development of full antibody response
What are the recognition molecules of the lectin pathway?
lectins, ficolins, CL-L1
When does the lection pathway become identical to the classical pathway?
after the cleaving of C4 and C2
How does the lectin pathway activate the coomplements?
by recognizing carbohydrates on microbial cell walls
What is the mannan-binding lectin?
binds to mannose or related sugars in a calcium-dependent manner to initiate pathway
What is the alternative pathway?
C3 is hydrolyzed and produces C3b
C3b binds to B
B is cleaved
Bb combines with C3b
More C3 is cleaved
C3bBbP is left
C5 is cleaved by C3bBbP
Identical to classical pathway after
What is the C5 convertase in the alternative pathway?
C3bBbP
What is the C1-INH serum protein?
dissociates C1r and C1s from C1q
What are the system controls?
C1-INH, Factor I, Factor H, S protein
What is factor I?
Cleaves C3b and C4b
What is Factor H?
Cofactor with I to inactivate C3b; prevents binding of B to C3b
What is the S protein?
Prevents attachment of C5b67 complex to cell membranes
What are the manifestations of complement activation?
amplifies inflammatory response
destruction of antigen
facilitate B cell activation
When can complement be harmful?
it is activated systemically on a large scale
it is activated by tissue necrosis
lysis of RBCs occurs
What is the CH50 functional test?
measures the function of the complete classical pathway
What if the results of a CH50 functional test is outside the normal range?
each complement level must be measured to look for hereditary or acquired deficiencies
What are the immunological assays of individual components?
radial immunodiffusion (RID)
nephlometry
What are the classical pathway assays?
hemolytic titration (CH50)
CH50 for lysis of liposomes
radial hemolysis
What are the alternative pathway assays?
AH50
ELISA