BIOL 435 Ch. 5 Part Two (The Complement System) Flashcards
3 classes of C’ activity
- Innate defense against infection
- Interface between innate and adaptive immunity
- C’ in the contraction phase of the immune response
C’ receptors
-connect complement-tagged pathogens to effector cells
>receptors on host cells allow for discrete and differentiated responses
C’ receptors examples
- CR1
- CR2 (CD21)
- C3aR
- C5aR
CR1
- on leukocytes and erythrocytes
- recognize C3b
CR1 on leukocytes
-helps bring immune complexes (Ag/Ab) to the liver for clearance by pathogens
CR1 on phagocytes
-helps bind complement-coated bacteria to enhance ingestion and destruction
CR1 on B-cells
-helps bind to complement coated Ag
>enhances ingestion for processing and presentation to helper T-cells
CR1 on B-cell binds C3b on pathogen
-C3b cleaved by factor 1= iC3b and C3d
-C3d helps activate B-cell
>allows less exposure needed to be activated
C3aR/C5aR
- on granulocytes
- GPCR
- stimulate release of proinflammatory cytokines and granule components from basophils, eosinophils and neutrophils
C’ enhances host defense against infection
- MAC-induced cell death
- Connect C’ tagged pathogens to effector cells
- Promote inflammation
- Promote opsonization
promotion of opsonization
- opsonized microbes easier to ingest/destroy
- opsonized immune complexes easier to clear
C’ mediates interface between innate and adaptive
- Enhance antigen uptake
- Enhance B-cell response
- Lyse immature T-cells with low sialic acid
- Bind C3a, C5a and C3b
enhane Ag uptake
-of Ag bound to MBL, C1q, C3b, and C4b that binds receptors on APCs
enhance B-cell response
-by increasing avidity of B-cell binding to C’-bound Ag
>triggers adaptive at a lower rate
sialic acid
-a CHO that increases in concentration as a protective coating on maturing T-cells
>keeps immature T-cells from being released to early
binding of C3a, C5a and C3b
- to their receptors on mature T-cells
- facilitates their growth, differentiation, and survival
C’ aids in contraction phase of immune response
- disposal of apoptotic cells and bodies as lympocytes are no longer required
- removal of immune complexes formed during response
- these avoid damaging inflammation induction in the absence of Ag following clearance of an infection
C’ activity passively regulated by
- Protein stability
- Cell-surface composition
>self-cells
protein stability
-short half-life of C3 convertase unless stabilized by properdin
self-cells
-possess different CHO structures that are more effectively bound by inhibitory enzymes (fluid-phase proteases)
>these more readily inactivate C3b through hydrolysis, protecting self cells
C1INH
-C1 inhibitor
-promotes dissociation of serine proteases
-causes C1r2s2 to dissociate from C1q
>no further clevage of C4 or C2 is possible
-inhibits initiation of classical and lectin C’ pathway
decay accelerating factors (DAF)
-promote decay of C3 convertases (C4b2a on surface of host cells)
-several different proteins wiht similar activities
>DAF (CD55)
>Factor H
Factor H
-binds negatively charged cell surface sialic acid and heparin (molecules unique to eukaryotic cell surfaces)
Factor 1
- degrades C3b and C4b
- soluble, constitutively active serine protease
- cleaves membrane-associated C3b and C4b into inactive fragments
protectin
-CD59
-inhibits the MAC attack
-binds C3b678 complexes deposited by host cells
>prevents insertion into PM
>blocks C9 recruitment
vitronectin
- soluble C’ S protein
- binds fluid phase C5b67 to prevent insertion into hostcell PM
carboxypeptidases
-can inactivate the anaphylatoxins (C3a, C5a)
-remove arginine resides
>creates des-Arg inactive forms
>helps shut down unnecessary or dangerous chemotactic and inflammatoion induction
genetic deficiences
- described for each C’ components
- outcomes vary
C1q, C1r, C1s, C4 or C2 deficiency
- immune complex disorders due to inadequate immune complex clearance
- anything before/above C3b=problem!
MBL deficiency
-may exhibit greater frequency of infections by encapsulated bacteria due to inefficient opsonization and phagocytosis
microbial C’ evasion strategies
- Interfere with first step of Ig-mediated C’ activation
- Microbial proteins may bind and inactivate C’ proteins
- Microbial proteases destroy C’ proteins
- Mimic or bind C’ regulatory proteins
