48 complement systems

Exam 2

how many plasma proteinsa are in the complement family

30

how are plasma proteins labelled

numerically with prefix C

how are plasma proteins designated as factors

by letters of the alphabet

what does a lower case letter at the end mean

subunit

what do complements proteins do when activated

interact sequentially forming a self assembling enzymatuc cascade

where can complement proteins be found

in the serum, they make up 10% of total proteins

or cell surface to act as markers

where are complement proteins synthesized

liver- heaptocytes and kupffer cells, C3,6,8, FB

macrophages- C2,3,4,5,FB, FD< FP, FI

mast cells- C1q

neutrophils-C6 and 7

what are the 3 complement pathwasy

classical

alternative

mannose-binding or mannan-binding lectin

what do the 3 complement pathways converge to produce

C3 convertase

C5 convertase

form the membrane attack compound (MAC)/terminal complement complex (TCC)

what is the alternative pathway activation

80-90% of all complement activation

what is the most important complement protein for activation

C3

what is C3

synthesized by hepatocytes and macrophages

most abundant component in serum

what is FH binding dependent on in the alternate pathways

the nature of the target surface

What happens in the spontaneous breakdown step of the alternative pathway

C3 is cleaved into C3a and C3b

in healthy cells what binds to C3b alternative pathway

Factor H

What does Factor H binding allow in healthy alternate pathway

Permits Factor I to cleave and inactivate C3b into iC3b and C3c

What happens to surface bound C3b in the bacterial alternate pathways

is bound by Factor B, creating C3bB

what happens after Factor B is added to create C3bB in alternate bacterial pathway

Factor B is cleaved by Factor D, turned into C3bBb, and soluble Ba is released

what is the role of properdin in the alternate bacterual pathway

stabilizes C3bBb into C3bBbP to increase its half life to go cleave more C3

what kind of pathway is the bacterial alternate

Positive feedback loop

how does FH interact with normal body cells

glycoproteins rich in sialic acid (N-acetyl neuraminic acid) and other neutral and anionic polysaccharides

what is different about the alternate pathway on bacterial surfaces

Cell walls lack sialic acid

C3bBb is the C3 converts of the alternate pathway

what is the formation of C5 convertase in the alternative pathway

C5 convertase is C3bBbC3b

converts C5 to C5a and C5b

what is the activation of the classical pathway

single antigen bound molecules of IgM or paired IgG are required to activate C1

what does C1 consist of

3 subunits: C1q, C1r, and C1s

resembles a whip

when is the classical pathway activated

not until antibodies are made and the immune complex is formed

7-10 days after onset of infection

what does activated C1 do in the classical pathway

cleaves C4 into C4a and C4b

what binds to C4b after it is cleaved in the classical pathway

newly cleaved C2b to create C4b2b

What is the job of C4b2b in the classical pathway

cleave C3 into C3a and C3b

what is the C3 convertase of the classical pathways

C4b2b

what is the C5 convertase of the classical pathway

C4b2b3b

what is the Mannose bincing lectin associated with

MBL associated serine proteases 1 and 2

what does MBL bind to

microbial carbohydrate chains such as mannose

what does the MBL binding to mannose do

activated MASP-2

what does the activated MASP2 do in the mannose pathway

cleaves C4 into C4a and C4b

what do masp1 and masp2 do together in the mannose pathway

cleave C2 into C2a and C2b

after being cleaved, what does C4b do in the mannose pathway

attaches to the surface of the microbe and has C2b added to it

what do all the pathways lead to

the formation of a C5 convertase, where it can be cleaved and C5b can attach to cell wall

what is the function of the membrane attck complex

each complement added on goes deeper into the bacterial cell wall, eventually creating a pore

what bacterial cells is the Mac most effective against

gram negative

nucleated cells

enveloped viruses

how do complements cause opsonization

enhanced phagocytosis by C3b and C4b

how do complements cause cytolysis

through the membrane attack complex C5b,6,7,8,9

how do complements cause inflammation

attracts phagocytes to sit of infection (C5a powerful attractant for neutrophils and macrophages)

C3a and C5a can degranulate mast cells can stimulate platelets to release histamine and serotonin

what does C2a do in the body

increased vascualr permeability

what does C3a do in the body

anaphylatoxin

microbial killing

what does C3b do to the body

immune regulation and opsonization

what does C5a do to the body

neutrophil chemotaxis

anaphylatoxin

neutrophil activation

increased vascular permeability

smooth mucle contraction

t cell development

what are the 2 clusters of complement genes

major histocompatibility complex (MHC)

Regulation of Complement Activation (RCA) cluster

What breed of dogs has C3 deficiency

brittany spaniels

what is a canine C3 deficiency

homozygous recessive have no C3

reduced ability to make antibodies (may have more Igm that IgG)

what are the clinical signs of a c3 deficiency in dogs

recurrent sepsis, pneumonia, pyometra, and wound infections

what type of pigs have a Factor H deficiency

yorkshire pigs

what are the clinical signs of a pig Factor H deficiency

born normal but fail to thrive, stop growing, and become anemic

what is found on necropsy of Factor H deficient pigs

multiple petechial hemorrhages on the surface of the kidney