Complement (class 2) Flashcards
Alternative pathway steps
C3 binds to cell surface
Binding causes conformation change and allows factor B to bind
Binding exposes cleavage site on factor B to factor D
Plasma serine protease
Releases Ba and Bb binds to C3B
C3bBb complex called alternative pathway C3 convertase
C3bBb cleaves more C3 into C3b and C3a
Some C3b binds to C3bBb to form C3bBb3b to form C5 convertase
Alternative pathway triggers and background
Pathogens can be destroyed in the absence of antibody by means of the alternative pathway, which acts as part of innate or natural immunity.
This pathway was originally named for the protein properdin.
Properdin does not initiate this pathway but rather stabilizes the C3 convertase formed from activation of other factors.
In addition to properdin, the serum proteins that are unique to this pathway include factor B and factor D.
Triggering substances for the alternative pathway include bacterial cell walls, especially those containing lipopolysaccharide, fungal cell walls, yeast, viruses, virally infected cells, tumor cell lines, and some parasites, especially trypanosomes.
Lectin pathway steps
Some C3b binds to cell surface to initiate new pathway
Grows exponentially- amplification loop
C3a is released to initiate biological activity
Chemoattraction
Inflammation
Promote adaptive processes
Complex is somewhat unstable and held together with properidin
Once MBL binds to a cellular surface, MASP-2, which is homologous to C1s, autoactivates.
MASP-2 thus takes the active role in cleaving C4 and C2, while the functions of MASP-1 and MASP-3 are unclear at this time.
Once C4 and C2 are cleaved, the rest of the pathway is identical to the classical pathway.”
How is the lectin pathway different from the classical pathway?
C1q is substituted by mannose binding lectin (MBL)
MBL binds mannose residues found on bacterial, but not mammalian, cells
C1r and C1s are substituted by MBL-associated serine proteases (MASP) (Evolutionary homologues to C1r and C1s) “
What is the function of complement pathway inhibitors?
To ensure that infectious agents and not self-antigens are destroyed and that the reaction remains localized, several plasma proteins act as system regulators.
In addition, there are specific receptors on certain cells that also exert a controlling influence on the activation process.
Hereditary deficiency of any complement protein
usually manifests itself in increased susceptibility to infection and delayed clearance of immune complexes.
Most of these conditions are inherited on an autosomal recessive gene, and they are quite rare, occurring in 0.03 percent of the general population.
Mannose-binding lectin deficiency
found in 3–5 percent of the population.
Lack of MBL has been associated with pneumonia, sepsis, and meningococcal disease in infants.
How can complement be harmful?
(1) activated systemically on a large scale, as in gram-negative septicemia,
(2) it is activated by tissue necrosis such as myocardial infarction, or
(3) lysis of red cells occurs.
Lysis may be another end result of complement activation, such as in cold autoimmune hemolytic anemia.
Hemolytic titration (CH50) assay
most commonly used to measure lysis, the end point of complement activation, as a functional test of complement activity.
This measures the amount of patient serum required to lyse 50 percent of a standardized concentration of antibody-sensitized sheep erythrocytes. (Which pathway?)
The CH50 titer is expressed in CH50 units, which is the reciprocal of the dilution that is able to lyse 50 percent of the sensitized cells.
The 50 percent point is used because this is when the change in lytic activity per unit change in complement is at a maximum.
AH50 assay
Alternative pathway activation by means of the AH50 assay can be performed in a manner similar to the CH50.
This test’s buffer system chelates calcium, thus blocking classical pathway activation.
ELISA assay importance to complement
ELISA assays have been designed as another means of measuring activation of the classical pathway.
ELISA assays can detect C3bBbP or C3bP complexes.
why might complement components or activity be decreased?
(1) decreased production, (2) increased in vivo consumption, or (3) in vitro consumption.
What might a typical screening test for complement abnormalities include?
C3, C4, and factor B levels.
What is the importance of complement fixation to the clinic/lab?
has been used in the detection of viral, fungal, and rickettsial antibodies
Process of complement fixation
1) a test system with antigen and antibody, one of which is unknown, and
(2) an indicator system consisting of sheep red blood cells coated with hemolysin, which will cause lysis of the indicator cells in the presence of complement.
