Complement Cascade
in the activation phase, what component becomes bound to the antigen-antibody complex
(inactivated) C1q
what does the configural change shape activate?
(inactivated) C1r and C1s
how many proteins is complement composed of?
30
HEMOLYSINS
ANTIBODIES WHICH BIND TO COMPLEMENT AND CAUSE HEMOLYSIS OF RED CELLS IN VITRO
ANAPHYLATOXINS
Are fragments produced due to complement activation (C3a and C5a): trigger release of histamine
which component of the compliment is a viral neutralizer?
C1
in the activation phase, what binds to the Fc portion of the antibody molecule?
C1q (activated)
what activated molecule DOES NOT play a significant role in furthering the cascade
C1r (activated)
which molecule ENZYMATICALLY cleaves the C4?
C1s
In the presence of ionized calcium (Ca++), C1 then acts upon C4 through which activated enzyme?
C1s (activated)
what activated molecule DOES play a significant role in furthering the cascade
C1s (activated)
C4b now acts on the next component of complement which is?
C2
what happens to C2 in the presence of ionized magnesium?
C2 is then adsorbed to cell bound C4b and splits into 2 fragments - C2a and C2b
C4b2a acts on the which complement component next?
C3
the complement component found in the highest concentration is what?
C3
what component coats the cell?
C3
what is the most critical component of the cascade?
C3
what is the complex C4b2A also known as?
C3 convertase
what is the major split portion found on B lymphocytes and monocytes?
C3b
C1s then acts on what following complement component ?
C4 (inactivated)
what happens to C4 due to activation of classical complement pathway?
C4 is cleaved
What is C4 cleaved into?
C4a and C4b
what is an activated complex held together by ionized magnesium?
C4b2a
when C5b binds, what does it form?
C5b6789
what binds to ionized calcium?
EDTA
What does the activation of C2 cause?
Edema
what other part of immune response can C3 be?
HIM
where do compliment proteins circulate
I the plasma, inactivated form
the naturally-occurring expected antibodies -anti-A and anti-B and anti-AB are what type of immunoglobuline>
IgM
the activation/recognition phase is made in response to what antibody?
IgM or IgG
what is C5b6789?
Membrane Attack Complex (MAC)
the complement proteins circulate in an INACTIVE form known as what?
Precursor form
what do some of the C4b fragments attach to
RBC's
what does the number of antigen sites on RBS mean in relationship to the ABO System?
The A and B antigens are in very high concentration on the red blood cells
when is the compliment activated in transfusion medicine?
When AB binds to AG
what is the compliment system
a collection of blood and cell surface proteins that is a major primary defense
what type of complex is C1?
a macromolecular complex, consisting of 3 subunits - C1q, C1r and C1s
OPSONINS
an antibody or complement split product that, on attaching to foreign material enhances phagocytosis by leukocytes and other macrophages (C3b and C4b)
how is C3b activated?
attaches to the surface of the red cell
what does C5b bind?
binds to the surface of the target cell and subsequently binds C6, C7, C8, and a number of monomers of C9
what can C3b do?
can alter bacteria rendering them more susceptible to phagocytes (opsonize)
what can C3 convertase do?
cleave hundreds of molecules of C3 into C3a and C3b
compliment products are the result of what?
cleaving of proteins during activation
IgG4
does not activate complement
complement component C3 plays a role in what pathways?
in both the classical and alternative complement pathways
where are compliment proteins synthesized?
in the liver
Where does C2b get lost after it is cleaved?
in the plasma
what is the compliment activation status in serum?
inactivated
what molecule does calcium stabilize?
inactivated C1
What type of immunity is the compliment system?
innate and adaptive
what happens when complement cascade goes to completion?
intravascular hemolysis
What are the results of ABO incompatibilities?
intravascular transfusion reactions from the activation of the classical pathway
in the activation phase, what keeps the assembly in place?
ionized calcium
what does C4 do?
is a viral neutralizer and coats cells
how is C3: not antigen specific: activated?
is activated immediately in the presence of pathogen = part of innate immunity
what happens to C3a?
is released into the plasma and takes no further parting the reaction
in the activation phase, what happens when inactivated C1q binds?
it undergoes a configural change
what happens to Damaged cells
lead to decreased cell survival and possible activation of Hageman factor that in turn leads to coagulation activation
what does the binding of the C4 molecules allow for?
modifies the enzymatic activity of the (activated)C1s and allows for C2 activation.
IgG1
most efficient at crossing placenta
What Determines Whether or Not Complement Will Be ?
nature of antibody coating cells NUMBER OF ANTIGEN SITES ON RBC
activation as part of the innate immune response
no antibodies or T cell receptors involved
where does C4b2a remain?
on the cell surface
When does the compliment become activated?
once the first component of complement is stimulated
How many C1q molecules are there?
one
what happens to C4a when it is cleaved?
plays no further role in the cascade reaction
what happens to C2b when it is cleaved?
plays no further role in the reaction
C5a is considered as what?
powerful chemotactic and an anaphylatoxin
what is the process called when the pattern of events in death by suicide is so orderly ?
programmed cell death or PCD
what is C3a responsible for?
release of histamine and mediators from basophils
what is the most common complication of an untreated hemolytic transfusion reaction
renal failure
define compliments
the cells of the immune system
Anaphylatoxin and chemoattractants
the smaller components that break off into the plasma go on to be involved in inflammation
INTRAVASCULAR HEMOLYSIS
there is a change in the permeability of the cell membrane - causing lysis
CHEMOATTRACTANTS
these begin the healing process (C5a); neutrophils clean up the damages cells and attract cells responsible for tissue repair.
what happens to cells coated with with C3b
they are removed from circulation via macrophages and neutrophils
why are IgM mores efficient in binding?
they have more antigen binding sites
IgG3
this is the best for complement activation (plays a role in both classical and alternative)
how is C5 activated?
through cleavage by the C4b2a3b enzyme and splits into C5a and C5b
how many C1r molecules are there?
two
how many C1s molecules are there?
two
when does C4b become activated?
when it attaches to the red cell surface
Extravascular hemolysis
where the complement cascade stops at C3b step
