5 – Innate Immunity II Flashcards
what is th Complement system
Group of soluble proteins that cooperate with both innate & adaptive immune systems
To eliminate: Pathogens, Dying cells, Immune complexes from the body
Complement systems are mostly:
-Mostly Proteases in blood/other fluids
Protease: enzyme that performs proteolysis – break down proteins
most complement are called:
C follow by number
other compliement are called
factor follow by capital letter
Complement proteins are mostly produced by
Liver
complement proteins creates a cascade, what is this?
Set off a chain reaction – help to clear pathogen
key mechanisms of action (3)
-Increase vascular permeability (vasodilate) & chemotaxis (inflammation)
-Destroy pathogen cell membranes (poke holes)
-Increase recognition of pathogen & facilitate phagocytosis – opsonization
what is Opsonization
-coating of surface of a pathogen by antibody and/or complement that makes it more easily ingested by phagocytes
-To make pathogen tastier for phagocytes
what is phagocytosis
internalization of matter by cells by engulfment, in which cell membrane surrounds the material – form an intracellular vesicle (phagosome) containing ingested material
what are inactive complements called and what do they do
inactive pro-proteases
-they circulate and have nothing to do
activated in which 3 pathways
-classical
-lectin
-alternative
pathway lead to a cascade of effect: what happens in this cascade?
all 3 pathways generate C3 convertase (cleave C3 -> C3a +C3b)
Proteolytic cleavage generates 2 fragments
proteolytic cleavage generates 2 active fragments they are:
-1 small
Letter “a” after name
C5a
With specific function
-1 large
Letter “b” after name
C5b
With proteolytic activity on new substrate
Complement nomenclature: C4b binds with C2a
C4b2a
Complement nomenclature: C3b binds with Bb (factor)
C3bBb
C4b2a and C3bBb are known as:
C3 converts
what does C3 convertase do?
(cleave C3 -> C3a +C3b)
complement proteins are only active when
when they are cleaved with protease
All 3 pathways generate
C3 converts
what are he 3 main outcomes from activation of pathways
-Inflammation
-opsonization
-MAC formation
Lectin pathway is Triggered by: give 2 examples
-soluble proteins – lectins (PRR that circulate in blood)
-Not membrane-bound PRRs
Mannose-binding lectin (MBL)
Ficolin
during infection, lectin:
Expression of lectin = increas
Lectin PRRs can:
-PRRs can bind the surface of pathogens
-Trigger signaling cascade on pathogen surface
-C3 convertase generated (C4b2a)
-C3 cleaved -> C3a + C3b
initiator of classical pathway
C1q
what can C1q do:
-C1q binds pathogen surface
-Can bind pathogen directly
-Can bind antibodies bound to pathogen surface
which path way connect adaptive and innate immunity
Classical pathway:
-C1q can bind to antibodies bounf to pathogen surface (geenrated by activated B cells -adaptive immunity)
what happens once C1q is bound:
-Triggers signaling cascade on pathogen surface
C3 convertase generated (C4b2a)
C3 cleaved -> C3a +C3b
Classical & lectin pathway result in generation of which C3 converts
C4b2a
C3a involved in
enhancing inflammation
C3b involed in:
opsonization & C5 convertase -> C5a + C5b
1st alternative pathway
-Once C3b produces by lectin/classical pathway activation
-Amplification loop for C3b formation (depose more C3b on pathogen)
-Require factor B & protease factor D
-Factor D cleave factor B -> Ba +Bb
-makes C3bBb - C3 convertase
what does alternative pathway make:
C3bBb - C3 convertase
2nd alternative pathway
-When high concentration of C3 (liver produced - inactive) –> undergo spontaneous hydrolysis
-Involves factors B & D
-makes C3bBb
whats different from alternaitve pathway C3 convertase (C3bBb) and classical/lectin pathway C3 convertase (C4b2a)
C3bBb is very unstable
how to stabilize C3bBb
-Stabilized by factor P (properdin) secreted by neutrophils
-Properdin stabilize C3 convertase as it can bind to some microbial surfaces
pathogens are mainly … for the complement system. why?
extracellular
-everything is deposited on the pathigen surface –> phagocytosis
-phagocytosis are for extracellular bacteria
-MAC formation-pores forming on cell’s surface
complement system act mainly on:
exracellular pathogens:
-phagocytosis
-MAC formation
Downstream effect of C3 convertase cleaving:
Inflammation
Increase phagocytosis
Pathogen lysis
downstream effect: inflmmation
-Additional signaling = cleavage of other complement molecules
-C3a & C5a recruit phagocytes & promote inflammation
what happens too much inflammation:
-If present in large amount – C3a & C5a –> anaphylactic shock
what happens when promoting inflammation?
-Complement receptors connect complement tagged pathogens to effector cells
-C3aR/C5aR on granulocytes
-Stimulate release of proinflammatory cytokines & granule components from basophils/eosinophils/neutrophils/mast cells
Downstream effect: Increase phagocytosis
-Phagocytes have receptor on C3b
-Opsonization of pathogen
-Opsonization can happen via complement deposition and/or antibodies (phagocytes also have receptors for antibodies)
downstream effect: Pathogen lysis
-Additional complement factors create MAC (membrane-attack complex) -> cell lysis
-C5b (directly) & C3b (indirectly) involved
-Cascade leading to formation of MAC –
Negative regulation of Complement activation: who is responsible
-Complement-regulatory proteins in plasma or cell surfaces
Negative regulation of Complement activation: what happens
-prevent complement activation from proceeding normal/basal conditions
-Prevent appearance of C3 convertase
-Promote disappearance of C3 convertase
2 C3 convertase and what do they do
C4b2a & C3bBb
cleaves C3 to C3a & C3b
C3b role
involved in opsonization & C5 convertase
what is C5 convertase involved in
indirectly involved in MAC
C3a role
inflammation
C5b role
MAC
C5a
inflammation
