The complement Flashcards
how was the complement system originally described as in the serum
a heat-labile component of normal serum that augmented the opsonization of bacteria by a heat-stable component of serum (antibodies)
where did the name “the complement” come from
this activity exhibited by the complement helped the antibacterial activity of antibodies
T/F the complement can be activated earlier infection without antibodies
True
what is the complement
complement is a system of proteins that is activated by the presence of pathogens
how many plasma proteins makes up the complement
over 30
most of the protein components are __________ that become active only after cleavage
most of the protein components are inert enzymes that become active only after cleavage
how must the proteins interact when activated
they interact sequentially forming a self-assembling enzymatic cascade and generating biologically active molecules, important for full inflammatory response
where is one of the most important key sites for the activation of the complement
is the surface of pathogens
what must happen for the complement to be useful immunologically
it has to be activated first
what are the 3 distinct pathways through which complement can be activated
- Classical pathway
- Lectin pathway
- Alternative pathway
what is the differences between the 3 different pathways of activation for the complement
depend on different types molecules for their initiation
what are the 3 ways in which the complement system protects against pathogens
- Recruitment of inflammatory and immunocompetent cells
- opsonization of pathogens
- killing of pathogens
First way of protection: recruitment
some components of the complement act as chemoattractants to recruit phagocytic cells to sites of complement activation
Second way of protection: opsonization
generation of large amounts of activated complement proteins that bind covalently to the pathogens opsonizing them for phagocytosis
Third way of protection: Killing of pathogens
the final components of the complement activation kill (damage) microbes by creating pores in their membranes
how does the complement also activate the adaptive immunity
- opsonization by complement components allows uptake of microbes by antigen-presenting cells (APC) such as dendritic cells
- B cells have complement receptors for certain complement receptors for certain complement proteins which enhance B cell response to complement coated microbes
what letter is designated by the letter C
the native components
how were the components numbered
not in numerical order but according to the order of discovery
what was the order of discovery of the complement components
- C1
- C4
- C2
- C3
- C5
- C6
- C7
- C8
- C9
how are the products of complement cleavage designated
the products of complement cleavage are designated by added lower case letter
what is the smaller cleaved fragment designated
the smaller cleavage fragment is designated “a”
What is the larger cleavage fragment of the complement components designated
- the larger cleavage fragment is designated “b”
- i.e. C4 is cleaved to C4a and C4b
- and C4b is larger fragment
- i.e. C4 is cleaved to C4a and C4b
what is the exception to the nomenclature of the products of complement cleavage
- C2
- the larger fragment is C2a
- the one with enzymatic activity
what are the complement component of the alternative pathway
- they are designated by different capital letters
- the cleavage products are designated lower case letters “a or b”
- larger fragment of factor cleavage is Bb and smaller is Ba
how it the classical pathway initiated
the classical pathway is initiated by binding of C1q (first protein of the cascade) to the surface of a pathogen
How does C1q bind to the surface of pathogens in
- binds directly to the surface of bacterial components
- proteins, lipoteichoic acid
- Binds to C-reactive protein that initially binds to phosphocholine residues on bacterial polysaccharides
- binds to antigen-antibody complex on the pathogen surface
which pathway of C1q binding to the surface of a pathogen is the most effective
when it binds to the antibody-antigen complex
how is the lectin pathway initiated
by binding of carbohydrate-binding proteins to carbohydrates on the surface of pathogens
the carbohydrate-binding proteins in the lectin pathway include
- Mannose binding lectin (MBL)
- Ficolins
(MBL) mannose binding lectin:
a lectin that binds mannose-containing carbs on microbial surface
Ficolins
bind N-acetylglucosamine on the surface of some microbes
how is the alternative pathway of the complement be initiated
by binding of spontaneously derived plasma C3b to pathogen surfaces
In each pathway, sequential reactions lead to the generation of a protein complex called________
C3 convertase
The C3 convertase remains bound to the surface of the _______
pathogen
C3 convertase cleaves C3 to yield large amounts of ______
- C3b and C3a
- C3b: the main effector molecule of the complement system
- C3a: a mediator of inflammation
The C3b molecule acts as an
opsonin - binnds covalently to the pathogen surface
A pathogen opsonized with C3b becomes a
target for destruction through phagocytosis
when C3b acts as an opsonin how does it bind to the pathogen
it binds covalently to the pathogen surface
after opsonizing a pathogen with C3b what happens to the pathogen
it becomes a target for destruction through phagocytosis
C3b binds ______ convertase to produce C5 convertase
C3
what happens to C5 convertase after it is formed from C3b binding to C3 convertase
C5 convertase is converts C5 into C5a and C5b
what is important about C5a
it is an inflammatory peptide
what action does C5b have
C5b initiates the last event in the complement system activation
After C5b initiates the last events of activation of the complement system activation the activation culminates in the formation of
MAC: membrane attack complex
what is the most potent activators of the classical complement pathway in most domestic species
IgM and to a lesser extent IgG
when one IgM or several IgG molecules bind to an antigen, the _______ of the antibody can bind to the complement component ___________
Fc portionn
C1 (C1qr2s2)
what is the back bone of C1 made of
C1q
how many globular head domains does C1q have that are connected by linear tails
six
what are the two proteins that are associated with the tail domains of C1q
- two copies of
- C1r
- C1s (serine proteases)
when is C1 activated
C1 is activated when two globular heads of C1q bind two adjacent Fc regions of antibodies bound to an antigen
what does the binding of C1q binding to antibodies activate
- C1q binding to antibodies activates the protease activity of C1r
- C1r then cleaves itself
The active C1r then cleaves the adjacent_____ molecules, which activates the serine protease activity of _____
The active C1r then cleaves the adjacent C1s molecules, which activates the serine protease activity of C1s