chapter 5 Flashcards
A group of serum and cell membrane proteins that interact with one another and with other molecules of innate and adaptive immunity to carry out key effector functions leading to pathogen recognition and elimination
complement system
What are examples of anatomical and physiological barriers?
skin, ciliary clearance, low stomach pH, and lysozymes in tears and saliva
What are the letters for small and large fragments?
a and b
What symbol distinguishes enzymatic complexes?
a bar
Once the complement system is activated, what are some possible outcomes?
-target cell membrane lysis
-chemotaxis
-opsonization to enhance phagocytosis
-complement pathway
-antigen-antibody immune complexes
classical pathway
-complement pathway
-PAMP recognition by lectins (carbohydrate)
Lectin pathway
-complement pathway
-spontaneous hydrolysis
alternative pathway
What are the 3 steps of the complement activation pathways?
initiation, amplification, termination
describe the classical pathway:
-initiated by antibody binding
-IgM or IgG binds to a multivalent antigen
-this allows the binding of C1q, beginning the process of complement deposition
-C1 binds Fc on adjacent igG molecules or on IgM bound to anitgen
what initiated the lectin pathway?
when soluble proteins recognize microbial antigens
What do lectins bind to?
microbial surfaces
Lectins can serve as docking sites for __________________
MBL-associated serine proteases (MASPs)
MASPs cleave C4 and C2 to form the ______ convertase
C3
-alternative pathway
-Small amounts of C3 are always being cleaved
-Usually quickly inactivated if nothing is around for it to bind to
-Activated C3b binds to membrane of target cell
alternative tickover pathway
-alternative pathway
-Properdin can directly bind to a surface
-this can then recruit C3b and Factor B
alternative properdin-activated pathway
-alternative pathway
-Initiation of clotting cascades has also been shown to stimulate cleavage of complement proteins
-Thrombin cleaves C3 and C5 in vitro
-Platelet activation releases ATP, calcium ions, and serine/threonine kinases that could stabilize C3b in fluid phase
alternative protease-activated pathway
The three complement pathways converge at the formation of the _________________
C5 convertase
C5 initiates the generation of the__________________
Membrane Attack Complex (MAC)
is the result of deposition of C5b, C6, C7, C8, and C9 in target cell membranes
membrane attack complex
what is disrupted by MAC?
the pore structure disrupts osmotic integrity, resulting in cell death
What are the 3 main classes of complement activity in the service of host defense?
-innate defense against infection
-interface between innate and adaptive immunity
-complement in the contraction phase of the immune response
What do complement receptors connect?
complement-tagged pathogens to effector cells
On erythrocytes, CR1 helps to bring immune complexes to the liver for ______________
clearance by phaocytes
On phagocytes, CR1 helps bind to complement-coated bacteria to enhance ingestion and destruction which is called _______________
opsonization
On B cells, CR1 helps bind to complement-coated antigens, enhancing ingestion for ____________________________
processing and presentation to helper T cells
CR2 on B cells binds to C3b on opsonized bacteria/antigens to help_______________
provide secondary signals to B cells through BCR complex for more efficient activation
How does C3aR/C5aR affect granulocytes?
Stimulates release of proinflammatory cytokines and granule components from basophils, eosinophils, neutrophils
how does complement enhance host defense against infection?
-MAC-induced cell death
-promotion of inflammation
-promotion of opsonization
how does complement mediate interface between innate and adaptive immunities?
- Enhances antigen uptake of antigen by APCs
- Enhances B-cell response by an increasing avidity of B-cell binding to complement-bound antigen
- Lyse immature T cells
- Facilitates mature T cells growth, differentiation, and survival
As lymphocytes are no longer required, complement aids in disposal of _________________________
apoptotic cells and bodies
Complement also aids in removal/disposal of ___________________________ formed during responses
immune complexes
the contraction phase of the immune response helps avoid______________
damaging inflammation induction in the absence of antigens following clearance of an infection
Complement activity is passively regulated by _________________________
protein stability and cell-surface composition
C3 convertase has a short half-life unless stabilized by ___________
properdin
self-cells possess different carbohydrate structures that are more effectively bound by____________________________
fluid-phase proteases
The C1 inhibitor, C1INH, promotes _____________________
dissociation of C1 components
Work to accelerate the decay of C4b2a (C3 convertase) on the
surface of host cells
Decay accelerating factors
Cleaves membrane-associated C3b and C4b into inactive fragments
Factor I
-inhibits the MAC attack
-Binds C5b678 complexes deposited on host cells
Protectin (CD59)
soluble complement S protein binds fluid phase
C5b67 to prevent insertion into host cell plasma membranes
vitronectin
Patients with any C1q, C1r, C1s, C4, or C2 deficiency often present with immune complex disorders due to inadequate_______________
clearance
Some with MBL deficiency may exhibit greater frequency of infections by _________________ due to inefficient opsonization and phagocytosis
encapsulated bacteria
What are the different microbial complement evasion strategies
- Some interfere with the first step of Ig-mediated complement
activation - Microbial proteins may bind and inactivate complement proteins
- Microbial proteases destroy complement proteins
- Some microbes mimic or bind complement regulatory proteins
