MIDTERM - complement system Flashcards
_ is a complex series of more than 30 soluble
and cell-bound proteins that interact in a very specific way
to enhance host defense mechanisms against foreign cells.
complement
complement is a complex series of more than how many soluble and cell bound proteins?
30
Complement systems is also called __.
complement pathway.
are complement proteins heat-labile or not?
heat labile
A termed “Complement” was given by ___ in the year (1980’s
Paul Erlich
In year, she was awarded a Noble Prize for
elucidating the nature of complement.
1919, Jules Bordet
In elucidating the nature of complement it was
___
jules bordet
what are the 3 effects of complement activation
Activation of immune system
Opsonization (C3b, C4b, C5b)
LYSIS of Foreign cells and Immune complexes
what are the 3 example of opsonins
(C3b, C4b, C5b)
What are the complement proteins that are mainly incorporated with the process of opsonization?
(C3b, C4b, C5b)
an effect of complement activation that is to
ENHANCE the host mechanism against the
foreign cells
Activation of immune system
an effect of complement activation that is for
facilitating and preparing the cell eating.
Opsonization (C3b, C4b, C5b)
Chronic activation of complement pathway will lead to
inflammation and tissue damage
Complement pathway play an essential role as a ____.
That’s why the complement pathway is connected also with the acute phase reactants,
pro-inflammatory agent
acute phase reactants or APR or toll like receptors are produced by
hepatocytes
acute phase reactants are produced within how many hours in response to an increase in certain intracellular signaling polypeptides
12-24 hrs
hepatocytess are also called as
liver cell or liver parenchymal cells
it is the one that regulates the amount or the production of apr. It will give signal or serve as a chemical messenger
cytokines
what are the 2 major apr?
Serum Amyloid A and C reactive protein
what is the function of C reactive protein
opsonization and for complement activation,
what is the function of Serum amyloid A
removal of cholesterol.
what is the most important component or protein complement under the activation unit?
Complement C3
is associated with a
specific pathway which is the lectin pathway
mannose binding protein
where can we be able to find mannose?
within the outer coating
of bacteria, yeast, viruses and even protozoa.
Most plasma complement proteins are synthesized in the __-.
liver
Most plasma complement proteins are synthesized in the liver except __
C1 components
C1 is synthesized by epithelial cells and factor D. Whereas Factor D is made up of ___
adipose tissue
C1 is synthesized and produced by the ____
epithelial cells and factor D
Example of additional source of early
complement components ___
C1, C2, C3 and C4.
the common objective associated with complement activation, it is the end product of activation of complement activation
lysis of the foreign cells and immune complexes
2 factors contributing the end product of the complement pathway
lysis of the foreign cells and immune complexes
the one responsible for controlling or inhibiting a particular complement protein preventing chronic activation
complement component protein regulators
response time of c reactive protein for opsonization and complement activation
6-10 hrs
a generalized marker of acute inflammation
C reactive protein
complement component proteins are like enzymes as they are produced in what form?
inactive form or zymogen
They are release in inactive precursors of complement
proteins are called __.
zymogen
once the zymogen are released and activated it will be called as
holoenzyme
The complement system can be activated in three different ways. What are those?
Classical pathway
alternative or properdin pathway
Mannose-binding lectin pathway
a complement pathway that is antibody dependent
classical pathway
How many proteins are involved in classical pathway?
9 proteins
The 9 proteins in classical pathway is triggered by what combination
antigen and antibody combination/formation
In the year 1950s, ___ discovered an antibody-independent pathway and this plays a major role as a natural defense system.
Pillemer and colleagues
alternative pathway is also called as
properdin system
function of properdin in alternative pathway
stabilize the key enzyme complex called C3bBb (or C3 convertase)
lectin pathway’s major constituent
mannose
If lectin’s major constituent is MBL, where can we seen the constituent of alternative pathway?
serum constituent
lectin pathway is also called as
mannose-binding lectin pathway
In lectin pathway, it is the ___ that will adhere to mannose which found in the outer coating of the bacteria, yeast, viruses and protozoa
MBL mannose binding lectin or the mannose binding protein
Under the classical pathway it is always involved with what complement component
Complement component C1
C1 is composed of ___ how many strands
6 strands
6 strands of C1 complement will form _
6 globular head with a collagen-like tail portion
what are the 3 sub units of C1
C1q, C1r and C1s.
A subunit of C1 that will recognized/binds the fragment crystallizable or FC region or FC fragments of two adjacent antibody molecules.
C1q
how many globular heads are needed for C1q to initiate classical pathway
2 globular heads
the first one that act upon the activation of classical pathway
C1q
complement components found in alternative pathway
factor B
factor D
properdin
c3 convertase is also called as
C3bBb
aside from the mannose that is the major constituent of mannose binding lectin pathway. It is as well associated with different serine proteases?
MASP 1, MASP 2 and MASP 3
what are the 2 antibody INDEPENDENT pathway?
alternative and mannose-binding lectin pathway
the 2 pathway that is part of natural defense system
alternative and mbl pathway
the antibody that is best for complement fixation
antibody IgM
can IgG can help in complement fixation as well?
yesw
which IgG is the one that has no capability for complement fixation?
IgG4
which IgG is the best for complement fixation
IgG3 followed by IgG1 and IgG2
if IgG is the one that will help in complement fixation, how many IgG is needed to attach to an antigen to activate the complement?
2 IgG molecule
IgG needs 2 IgG molecules in order to activate the complement pathway, the attachment of antigen as well must be within how many nanometers between each other to activate it fully?
30-40 nanometers
what are the stages of complement activation for classical pathway?
Recognition stage or recognition unit
Activation stage or activation unit
Formation of MAC - membrane attack complex
what is the only complement component associated with the recognition unit of classical pathway?
complement component C1
C4, C2 and C3 is collectively known as
activation stage or the activation unit
the last stage of classical pathway wherein the lysis of the foreign cell take place
formation of MAC
“MAC” in stages of classical pathway activation stands for __
membrane attack complex
what is the end product of the 3 stages of classical pathway activation?
lysis of the foreign cell and immune complexes
the stage or unit where we can see the C1 components
Recognition unt/stage
what are the 3 components of C1/what are the 3 subunits of C1
C1q, C1r, C1s
is composed of six strands that form six globular
heads with a collagen like tail portion.
C1q
a sub unit of C1 that will “recognizes” the fragment crystallizable (FC)
region of two adjacent antibody molecules.
C1q
what are the 2 adjacent antibodies that the C1q will recognize?
CH2 of IgG and CH3 of IgM
Once the C1q bonds with the fc region of the adjacent antibodies, it will activate ___
C1r
C1r will start to cleave ___
thioester bond of C1s
once the C1r cleave the thioester bond of C1s, it will then activate ___
C1s
Please summarized the steps for recognition stage/unit
It will start with the C1q. It will bind with the FC region of the adjacent antibodies (IgG and IgM)
The bonding will activate C1r
C1r will cleave the thioester bond of C1s
It will activate the C1s
what is the end stage of the last step of recognition unit?
the activation of C1s
what is the last stage of the end product of the activation unit?
c5 convertase or the C5b2a3b
after the activation of the C1s, it will form __ and __ that must be near the proximity of C1s in order to form.
C4 and C2
C4 must be near enough to C1s of about how many nanometers?
atleast 40 nm
C2 must be near enough to C1s of about how many nanometers?
at least 60 nm
what is the most abundant complement protein under the activation unit?
C4
C1s will cleave C4 to form ___
C4a and C4b
C4b must bind to __ or __ immediately or it will react with water molecules or it will be inactivated permanently
protein or carbohydrates
C4b must bind to protein or carbohydrate
within a few seconds, or it will react with
water molecules to form ____ , which is rapidly degraded.
iC4b (inactivated C4b)
C2 gene is closely related to ___ in alternative pathway
factor B
C4b and C2a will combine through what ions
magnesium ions
the combination of C4b and C2a is also called as
C3 convertase (C4b2a)
is the c3 convertase a stable complex?
No
what is the half life of c3 convertase
15 seconds to 3 minutes
the c4b2a will cleave the most important complex in the activation unit
C3
most significant step in the entire process of
complement activation
cleavage of C3
Major function is for the formation of the MAC.
C3b
aside from the formation of MAC, the other function of C3b is it act as ___
opsonin
In C3b, ___ have specific receptors for this
complement. Thus, enhance phagocytosis.
Macrophages
C3b will bound to C4b2a for how many nanometers?
40 nm
If C3b is bound within 40 nm of the C4b2a, then this
creates a new enzyme known as____
C5 convertase.
the beginning of the formation of the membrane attack complex and the last stage of activation unit
c5 convertase
is C5b extremely labile?
yes
C6 will bind to C5b to form
C5b6
C7 will bind to C5b6 to form
C5b67
It is a forming a trimolecular complex that has a high affinity for lipid constituents of the cell membrane.
The forming of C7 and c5b6 to create C5b67
c8 will combined with C5b67 to form
C5b678
__ and ___ Interacts with the cell membrane to
form a small hole in the membrane.
C7 and C8
is inserted into the lipid bilayer of the cell
membrane.
c8
a beginning of the formation of form to cause cell to lyse and result the cell to leaks
forming of C5b678
C5b678 will form pores to rbc causing cell leaks, what are the contents of the cell that can possible leak?
(potassium, amino acids, ribonucleotides)
Pore formed are small→ able to lyse RBC but not nucleated
cells
C5b678
in order to complete the lysis of the cell, C5b678 must combine with
c9 forming C5b6789
What would be the end stage of this classical pathway?
lysis of the foreign cells and immune complexes
the most abundant complement component protein in recogition unit is the
C1q
Under the classical pathway kapag tayo ay nagkaroon ng
increase vascular permeability this is cause by
.
anaphylatoxins
We have different proteins involved in case of increase
vascular permeability.
what are those?
C3a, C4a, and C5a
AL<TERNATIVE PATHWAY
The pathway was originally named for the protein
properdin, a constituent of normal serum with a concentration of approximately ___μg/mL
5 to 15
alternative pathwAy
In addition to properdin, the serum proteins that are unique
to this pathway include ____ and ___
factor B and factor D.
Triggering substances for the alternative pathway include:
Bacteria, fungi, viruses, tumor cell lines and some parasites
major factor in complement system (alternative and
classical pathway).
C3
In alternative pathwaY, which is analogous to c2
FACTOR B
in alternative pathway, it Bind to activated C3 to become (C3b)
Factor B
In alterative pathway
Cleaves factor B that are bounded to C3b
Factor D
In alterative pathway
Cleaves factor B to Bb and Ba
Factor D
Cleaves additional C3 into C3a and C3b
C3bBb
___ is considered an acute phase protein because it is
produced in the liver and is normally present in the serum
but increases during an initial inflammatory response
Mannose binding lectin
Lectins are proteins that bind to ___.
carbohydrates
This pathway provides an additional link between the innate
and acquired immune response
lectin pathway
among the serine proteases, which one is homologous to C1s? as it plays an active role in cleaving the C4 and C2
Masp 2
the only pathway that has the acute phase reactants involve?
lectin pathway
C1 inhibitor will inhibits which complement components?
inactivates C1 and Masp 2
___ is a glycoprotein with a molecular
weight of 105,000 that inhibits activation at the FIRST STAGES of both the classical and lectin pathways
C1 inhibitor
c3 convertase are inhibits by 4 regulators, what are they?
C4b binding protein
CR1 “cd 35”
MCP “membrane cofactor protein”
DAF “decay-accelerating factor”
c3 convertase has 4 regulators, all of this works with _____
factor I
Binds to Factor I
then inactivates the C4b resulting into the
dissociation of C4b from the C4b2a complex.
Causing the classical pathway to stop and not able
to continue the pathway.
C4b-binding protein (C4BP)
Also known as
CD35, once CR1 binds to C3b or C4b it is then
degraded by factor I.
Complement receptor 1 (CR1) Also known as
CD35,
Most efficient
cofactor for Factor I-mediated cleavage of C3b.
Membrane cofactor protein (MCP)
Membrane cofactor protein (MCP) - Most efficient
cofactor for Factor I-mediated cleavage of C3b. It
also serves as cofactor for Factor I in cleaving
the C4b not as efficient as the ____ (most efficient
in inhibiting the activity of the classical pathway)
C4bB
Dissociates the
C3 convertase by cleaving the C3b or C4b or both.
Decay accelerating factor (DAF)
Which one is the most common complement deficiency?
C2 lupuslike syndrome ; recurrent infections atherosclerosis
C2 deficient individuals are prone
to recurrence staphylococcal and streptococcal infection. They also
has low levels of Factor B kasi yung gene location or alleles nila ay
close to each other.
Which one is the most serious form of the complement
deficiency?
C3
because they are prone to severe recurrent of life-threatening
infections with encapsulated bacteria such as streptococcus
pneumoniae.
MBL Deficiency
Lack of MBL are associated to ___
pneumonia, sepsis
and meningococcal diseases.
Causes increase susceptibility to systemic Neisseria
infections.
C5-C8
deficiency in MASP 2
pneumococcal diseases
lack of C1INH
hereditary angioedema
lack of c9
no known disease associarion
lack of these complement components will lead to lupus like sydrome
c1, c2, c4,
lack of these complement components will lead to paroxysmal nocturnal hemoglobinuria
DAF and MIRL
lack of c3 will lead to
glomerlonephritis
