Untitled - D Ank Unlimited

C2 deficiency 124 C3 deficiency
assembly. Available evidence indicates that C2b possesses
a C4b-binding site and that Ba contains a corresponding
C3b-binding site. In considering assembly and decay of C3
convertases, initial binding of the three-domain structures
C2 or B to activator-bound C4b or C3b, respectively,
requires one affinity site on the C2b/Ba domain and another
on one of the remaining two domains. A transient change
in C2a and Bb conformation results from C2 or B cleavage
by C1s or D. This leads to greater binding affinity, Mg 2+
sequestration, and acquisition of proteolytic activity for
C3. C2a or Bb dissociation leads to C3 convertase decay.
Numerous serum-soluble and membrane-associated regulatory
proteins control the rate of formation and association
of C3 convertases.
C2 deficiency
Rare individuals may demonstrate a failure to express
C2. Although no symptoms are normally associated with
this trait, which has an autosomal-recessive mode of
inheritance, autoimmune-like manifestations that resemble
features of certain collagen-vascular diseases, such as systemic
lupus erythematosus (SLE), may appear. Thus, many
genetically determined complement deficiencies are not
associated with signs and symptoms of disease. When they
do occur, it is usually manifested as an increased incidence
of infectious diseases that affect the kidneys, respiratory
tract, skin, and joints.
C3 (complement component 3)
A 195-kDa glycoprotein heterodimer that is linked by
disulfide bonds. It is the fourth complement component
to react in the classical pathway, and it is also a reactant
in the alternative complement pathway. C3 contains α
and β polypeptide chains and has an internal thioester
bond that permits it to link covalently with surfaces of
cells and proteins. Much of the C3 gene structure has
now been elucidated. It is believed to contain approximately
41 exons. Eighteen of 36 introns have now been
sequenced. The human C3 gene is located on chromosome
19. Hepatocytes, monocytes, fibroblasts, and endothelial
cells can synthesize C3. More than 90% of serum C3
is synthesized in the liver. The concentration of C3 in
serum exceeds that of any other complement component.
Human C3 is generated as a single chain precursor which
is cleaved into the two-chain mature state. C3 molecules
are identical antigenically, structurally, and functionally,
regardless of cell source. Hepatocytes and monocytes
synthesize greater quantities of C3 than do epithelial
and endothelial cells. C3 convertases split a 9-kDa C3a
C4
Activated C1s cleaves
C4 to C4a and C4b
C1s C4
C4a
C1s C4a
C4b
C3b
C4b,2b
C4b binds to C2,
forming the C4b, 2b
complex
fragment from the α chain of C3. The other product of
the reaction is C3b, which is referred to as metastable C3b
and has an exposed thioester bond. Approximately 90%
of the metastable C3b thioester bonds interact with H 2O
to form inactive C3b byproducts that have no role in the
complement sequence. Ten percent of C3b molecules may
bind to cell substances through covalent bonds or with the
immunoglobulin bound to C4b2a. This interaction leads
to the formation of C4b2a3b, which is classical pathway
C5 convertase, and serves as a catalyst in the enzymatic
splitting of C5, which initiates membrane attack complex
(MAC) formation. When C3b, in the classical complement
pathway, interacts with E (erythocyte), A (antibody), C1
(complement 1), and 4b2a, EAC14b2a3b is produced. As
many as 500 C3b molecules may be deposited at a single
EAC14b2a complex on an erythrocyte surface. C3S (slow
electrophoretic mobility) and C3F (fast electrophoretic
mobility) alleles on chromosome 19 in humans encode
99% of C3, with rare alleles accounting for the remainder.
C3 has the highest concentration in serum of any complement
system protein with a range of 0.552 to 1.2 mg/
mL. Following splitting of the internal thioester bond, it
can form a covalent link to amino or hydroxyl groups on
erythrocytes, microorganisms, or other substances. C3
is an excellent opsonin. It was known in the past as β 1C
globulin.
C3 convertase
An enzyme that splits C3 into C3b and C3a. There are two
types: one in the classical pathway designated C4b2a and
one in the alternative pathway of complement activation
termed C3bBb. An amplification loop with a positive feedback
is stimulated by alternative pathway C3 convertase.
Each of the two types of C3 convertase lacks stability,
leading to the ready disassociation of their constituents.
However, C3 nephritic factor can stabilize both classical
and alternative pathway C3 convertases. Properdin may
stabilize alternative pathway C3 convertase. C2a and Bb
contain the catalytic sites.
C3 deficiency
An extremely uncommon genetic disorder that may be
associated with repeated serious pyogenic bacterial infections
and may lead to death. C3-deficient individuals are
deprived of appropriate opsonization, prompt phagocytosis,
and the ability to kill infecting microorganisms. Classical
and alternative pathway activation is defective. Besides
infections, these individuals may also develop an immune
complex disease such as glomerulonephritis. C3 levels that
C3
C4b,2b
C3b
C4b, 2b is an active
C3 convertase
cleaving C3 to C3a
and C3b
C3a C3
C4b,2b
Classical pathway of complement activation generates a C3 convertase.
C3a
C3b
Many C3b bind to the
microbial surface