BIOL 435 Ch. 5 Part One (The Complement System) Flashcards
complement (C’) system
- group of serum proteins circulating in inactive form
- once activated, multiple possible outcomes
multiple possilbe outcomes (C’ system activated)
- target cell membrance lysis (MAC)
- chemotaxis
- opsonization to enhance phagocytosis
- inflammation
functional categories of C’ proteins
- initiators
- convertase activators
- enzymatic mediators
- opsonins
- anaphylatoxins
- membrance attack complex
- complement receptors
- regulators
3 pathways in C’ system
-classical
-lectin
-alternative
*all generate C3b
>an important, multifunctional C’ protein
classical pathway
-IgM or IgG binds to a multivalent Ag
>allows binding of C1q
-C1 finds Fc on adjacent IgG molecules or IgM bound to Ag
*need at least 2 Ab
binding of C1q
-begins the process of C’ deposition
C1qr2s2
-inititates a cascade of reactions enabling the next reaction in the sequence
C1 binding followed by
- cleavage of C4: C4b bound to pathogen membrane
- then cleaveage of C2
- C4b2a
C4b2a
-bound to cell surface
=C3 convertase
-cleaves many C3 proteins
C5 convertase
=C4b2a3b
- C3 converts and C3 proteins
- cleaves C5 protein
- embedded in membrane
C3a and C5a
-anaphylotoxin: promotes inflammation
when C4 is cleaved
-a thioester bond is exposed on C4b (or C3b)
>reactive
>binds amino groups on target surface
>bonding must happen quickly
-if no target is present, bond is hydrolyzed and rendered inert
*90% don’t get bound
C3b (+C4b)
- bind microbial surfaces: opsonization
- attach to Fc of Ab
- bind Fc receptors on macrophages and RBC and are cleared
Ag
-large
-substance that generates an immune response
-a single Ag, may have many BCR specific for it
>only a small part binds to BCR/Ab
epitopes
-antegenic determinant
-1 to 6 monosaccharides
-5 to 8 AAs
-small pieces of Ag
-any Ag can have multiple of them
-based on shape or linear sequence
>may ‘change’ when Ag changes shape
C1r
-cleaves the other C1r, then cleaves C1s2
>C4 clevage
C5b
- embedded in membrane
- begins membrance attack complex (MAC)
common components in all 3 pathways
- *C3b: opsonin
- MAC
- C3a and C5a: anaphylotoxin
Ag/Ab complexes/clusters
-bring together all Ag and make them more visible
>more likely to be cleared
lectin pathway initated
-when soluble proteins recognize microbial CHO antigens
lectins
- bind to microbial surfaces
- serve as docking sites for MBL-associated serine proteases (MASPs)
ex. MBL
MASPs
-MBL-associated serine proteases
-cleave C4 and C2 to form the C3 convertase
>subsequent steps are same as the classical pathway (forms C5 convertase)
3 ways alternative C’ pathway is initiated
- Tickover pathway
- Properdin-activated pathway
- Protease-activated pathway
alternative C’ pathway no matter how it starts
- actived C3b binds to membrane of target cell
- factor B (fB) binds and is cleaved by factor D (fD) =Bb
- C3bBb=C3 convertase
- Properdin (fP) stabilizes the C3 convetase
tickover pathway-always on
-C3 is constantly made and inactivated
1. Spontaneous hydrolysis of C3=C3(H2O)
2. C3(H2O) bind fB
3. fB is cleaved by fD
4. C3(H2O)Bb is a ‘fluid-phase convertase’
>cleaves C3
tickover pathway if membrane around
- Some C3b bind to microbial surface
- C3b binds fB
>cleaved by fD=C3bBb - C3bBb=membrane bound C3 convertase
>stabilized by Properdin - Another C3b binds
>C3bBbC3b formed=C5 convertase
Properdin pathway
- Properdin can directly bind to a surface
- Can recruit C3b and fB
>fD recruited, cleaving fB into Bb - C3bPBb=active C3 convertase
- Identical to tickover pathway
protease-activated pathway
-initiation of clotting cascades can stimulate cleave of C’ proteins
>thrombin cleaves C3 and C5
>platelet activation
*strong inflammatory reactions could activate C’ systems
platelet activation
-releases ATP, calcium ions and serine/theronine kinases
>can stabilize C3b in fluid phase
C5 initiates
-generation of MAC
MAC
- membrane attack complex
- result of deposition of C5b, C6, C7, C8 and C9 in target cell membrane =pore structure
- disrupts osmotic integrity, resulting in cell death
MAC formation
- C6 embeds
- C7 embeds
- C8 all the way through
- C9 produce massive hole: many of them come together
cell ‘fights’ MAC
- endocytosis if only a few
- exocytosis and release them
