PHSC1312 Microbiology/Immunology Lecture 6 Complement

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What form will substrates in the complement cascade be in?

classical, MB lectin, alternative

three pathways of the complement system

inflammation, opsonization promoting phagocytosis, membrane attack complex and lysis

three main outcomes of complement

antibodies bound to target cell membrane

What is the classical pathway dependent on to start?

IgG and IgM

first two antibody types made in an immune reaction, help activate the classical pathway

C1

a complement protein that recognizes the stem of the antibodies bound to the target; cleaves C2 and C4 in the classical pathway

bind and cleave C2 and C4 in classical pathway

What does C1 do?

C3 convertase

enzymatic complex made by multiple proteins in the complement pathway that splits molecule of C3 and splits it into a and b subunits

lectin and alternative

What complement pathways are antibody independent?

MBL/MASPs

bind and cleave C2 and C4 in the lectin pathway

bind and cleave C2 and C4 in lectin pathway

What do MBL/MASPs do?

alternative

fastest complement pathway

attach directly to surfaces of bacteria, viruses, or fungi

What does C3 do at the beginning of the alternative pathway?

properdin

protein that kicks off the alternative pathway through spontaneous hydrolysis

pathogen cell surface molecules like endotoxin

can trigger the alternative pathway to begin (not the protein)

spontaneous hydrolysis of C3 and Factor B joins C3b before cleavage by factor D

What happens to form the C3 convertase in the alternative pathway?

amplification loop

feature of the alternative pathway formed because on some level C3 continues splitting

split C3 into a and b subunits

What does C3 convertase do?

diffuses away and promotes inflammation

What happens to the C3a subunit?

becomes an opsonin and helps form C5 convertase

What does the C3b subunit do?

split C5 into a and b subunits

What does C5 convertase do?

recruit neutrophils, activate mast cells, serve as ligands for immune receptors

What do the C5a and C3a subunits do?

helps form membrane attack complex

What does the C5b subunit do?

lysis

What does the membrane attack complex do?

C1, C4, C2

form the C3 convertase

anaphalatoxins

induce systemic inflammatory reactions (examples: C3a, C4a, C5a)

mast cell degranulation, increased vascular permeability, smooth muscle contractions, recruit and activate innate immune cells

What do anaphylatoxins cause?

histamine and TNF alpha

What do anaphylatoxins cause mast cells to degranulate?

swelling and expression of adhesion molecules on endothelium

What does increased vascular permeability by anaphylatoxins involve?

increase motility, stimulate respiratory burst, production of reactive oxygen species

What do neutrophils do when anaphylatoxins induce acute inflammation?

complement proteins, order of antibody production, complement binding site on antibodies, C1 inhibitor, decay accelerating factor

five ways complement is regulated in the host

short half life, inducible, and inactive in pro enzymatic state

How do complement proteins help regulate complement in the host?

remains inaccessible until binds to antigen

How does the complement binding site on antibodies help regulate complement in the host?

bind C1 and acute phase lectin pathway initiators

What does C1 do to regulate complement?

decay accelerating factor

glycoprotein on human cells that binds to C3b and C4b and restricts C3b and C5 convertase formation

membrane attack complex on human cells

What does decay accelerating factor prevent?

glycoprotein

What type of molecule is decay accelerating factor?