Lecture 9 - Complement Flashcards
What is the complement system and where its produced
Collective term for a group of proteins that play key role in host immune responses
Activated by both innate and acquired immune responses
Produced in liver, macrophages and fibroplasts
How are the complement proteins named
Generally designated with a C and number (C1, C2)
Some proteins in alternate pathway designated B, P and D
Peptide fragments formed during cascade indicated with a and b (C3a, C3b)
Role of a and b fragments of proteins in complement
a released to inflammatory responses
b bigger and continue to participate in cascade reaction
What are the functions of complement proteins
In serum in inactivated form Once activated: Cell membrane lysis Chemotaxis Opsonization Inflammation
What are the three complement pathways
Classical - triggered by antibody binding (adaptive response)
Lectin - innate pathway triggered by mannose on microbial surfaces
Alternative - Innate pathway accounts for most complement
Describe the classical pathway
Acquired immune system
Initiated by binding of Ab to Ag
Ab - Ag binds to C1 and activates it
Activated C1 cleaves and activate C4 and C2
Product of this reaction forms C3 convertase and splits C3
C3a is anaphylatoxin C3b activates terminal sequence pathway
some C3b combine with C3 convertase to form C5 convertase which cleaves protein C5 into C5a and C5b
Describe Lectin pathway
Innate immune system
Mannose binding lectin (MBL) binds to mannose on microbial surfaces
MBL forms complex with another serum protein MASP2
Formation of MBL/MASP2 complex results in activation of MASP2
MASP2 acts on C4 and C2 to form C4b2b which acts as a C3 convertase to make C3b
Describe alternative pathway
Innate immune system
Initiated by cell walls that lack sialic acid
These products come in contact with C3b
This allows factor B to bind to C3b in prescence of Factors D and P to produce an alternate pathway C3 convertase (C3bBb)
Describe the terminal complement pathway
Terminal components (C5 - C9) activated when C3b forms a complex with C3 splitting enzymes (convertases)
This complex cleaves C5 and C5b will bind to C6 and C7 to form C5b67
C5b67 binds to C8 and C9 to form C5b6789 called membrane attack complex (MAC)
MAC kills organism by osmotic lysis
C5a is anaphylatoxin which attracts neutrophils and macrophages
What are some of the biological consequences of complement activation
C1 - membrane lysis C2a - increased vascular permeability C3a - Anaphylatoxin and killing C3b - Immune regulation and opsonization C5a - Anaphylatoxin and neutrophil activation C5b67 - leukocyte chemotaxis All can result in cell lysis
What is the complement fixation test
A serological assay for the detection of serum Ab levels to a particular antigen. Test uses the presence of Ab in serum to determine if an individual has been infected by a particular bacteria or virus
