complement

The Complement System

The Complement System

A complex plasma protein network that enhances innate immunity

• Induces innate immunity

• Has over 30 proteins

• Synthesized in the Liver

• Present in blood, lymph, and extracellular fluid

Many roles:

• Marks pathogens for phagocytosis

• If pathogens are coded with complement, it Enhances phagocytosis o

• Induces inflammation

• Pokes holes in microorganism membranes

Complement is a ZYMOGENS

Proteolytic enzyme that are currently inactive.

Pathway

On cleavage, one complement protein cleaves its target in a highly specific manner o Creates the complement cascade

Alternative Pathway

• Immediate

• The first pathway activated after infection

• Activated when complement sees some sort of bacterial feature like and then complement deposits itself into bacteria without the innate immune system by recognition of features on a microbial surface

• Baseline level of C3 conversion that is slow

• Speeds ups when C3 can be deposited onto a microbial surface

Lectin Pathway

• Slower

• Activated by mannose-binding lectin (MBL)

• MBL binds to sugars on microbial surface

• MBL conformation changes allow it to cleave C3

What is the classical complement pathway?

Activated by CRP or antibodies (especially IgG) binding to a pathogen. This causes conformational changes that lead to C3 cleavage and formation of C3 convertase. It connects adaptive immunity (antibodies) with innate immunity (complement).

What are the 3 complement pathways?

Classical, Lectin, and Alternative.

Where do the 3 pathways eventually come together?

At C3 convertase

What activates the classical pathway?

CRP or antibodies binding to a pathogen.

How do antibodies activate the classical pathway?

IgG antibodies bind to the pathogen surface.

What activates the lectin pathway?

MBL binds to carbohydrates on the pathogen.

What activates the alternative pathway?

C3 is cleaved on the pathogen surface.

Membrane Attack Complex

Large pore formed in pathogen membranes that disrupts structural integrity and causes cell lysis

C3: Central Complement Protein

Director of the complement cascade