The Innate Immune System III – Complement

A vocabulary set covering the major molecules, pathways, regulatory factors, and effector functions of the complement system in innate immunity.

Complement

A group of >30 soluble and membrane-bound proteins that recognize pathogens and mediate lysis, opsonization, inflammation, and clearance of immune complexes.

Classical Pathway

Complement activation route triggered by antigen-antibody (IgM or IgG1/2/3) complexes that activate C1 and generate C4b2a (C3 convertase).

Lectin Pathway

Antibody-independent complement route initiated when mannose-binding lectin (MBL) binds microbial carbohydrates and, with MASPs, activates C4 and C2.

Alternative Pathway

Antibody-independent route begun by spontaneous hydrolysis of C3; forms C3bBb (C3 convertase) on microbial surfaces and is stabilized by properdin.

C1 Complex

Initiator of the classical pathway composed of pathogen sensor C1q and proteases C1r and C1s.

C1q

Subunit of C1 that binds Fc regions of antibodies in immune complexes, launching the classical pathway.

C1r & C1s

Serine protease subunits of C1 that, once activated, cleave C4 and C2.

Mannose-Binding Lectin (MBL)

An acute-phase lectin that recognizes mannose residues on microbes and starts the lectin pathway.

MASP (MBL-Associated Serine Protease)

Proteases that bind MBL and cleave C4 and C2, mimicking C1 activity.

Properdin

Complement protein that stabilizes the C3bBb convertase in the alternative pathway.

Factor B

Binds C3b on microbial surfaces and, after cleavage by Factor D, forms part of the alternative C3 convertase (C3bBb).

Factor D

Serine protease that cleaves Factor B when it is complexed with C3b, producing the alternative pathway C3 convertase.

C3 Convertase

Enzyme complex that cleaves C3 to C3a and C3b; forms as C4b2a (classical/lectin) or C3bBb (alternative).

C5 Convertase

Enzyme complex that cleaves C5 to C5a and C5b; forms when C3b binds a C3 convertase (e.g., C4b2a3b or C3bBb3b).

C3a

Small split product of C3; functions as an anaphylatoxin that promotes inflammation.

C3b

Large split product of C3; acts as a potent opsonin and component of convertases.

C4a

Anaphylatoxin produced during C4 cleavage in the classical/lectin pathways.

C4b

Opsonin fragment that anchors C3 convertase (C4b2a) to pathogen surfaces.

C5a

Powerful anaphylatoxin and chemotactic factor released from C5; recruits and activates leukocytes.

C5b

Fragment that initiates assembly of the membrane attack complex (MAC).

Membrane Attack Complex (MAC)

Lytic pore formed by C5b, C6, C7, C8, and multiple C9 molecules that disrupts target cell membranes.

Opsonization

Coating of pathogens with molecules such as C3b or antibodies to enhance phagocytosis via complement receptors.

Anaphylatoxin

Complement fragments (C3a, C4a, C5a) that induce inflammation by triggering mast cells and attracting leukocytes.

Complement Receptor 1 (CR1)

Receptor on phagocytes and RBCs that binds C3b/C4b to mediate immune-complex clearance and phagocytosis.

Acute Phase Protein

Serum protein up-regulated during inflammation; MBL is an example involved in complement activation.

PAMP (Pathogen-Associated Molecular Pattern)

Conserved microbial structure recognized by innate molecules like complement and PRRs.

Sialic Acid

Surface sugar on mammalian cells that inactivates bound C3b, preventing complement attack on host tissue.

C1 Inhibitor (C1-INH)

Regulatory protein that dissociates C1r and C1s from C1q, halting classical pathway activation.

Properdin-Regulated Convertase

Stable C3bBb complex of the alternative pathway protected from rapid decay by properdin.

Cell Lysis

Destruction of cell membranes, chiefly executed by the MAC in complement-mediated immunity.

Humoral Immunity

Immune defenses mediated by soluble molecules in body fluids; includes antibodies (adaptive) and complement (innate).

Opsonin

Any molecule, such as C3b, C4b, or antibody Fc, that tags pathogens for enhanced phagocytosis.

Immune Complex

Aggregate of antigen bound to antibody; cleared from circulation by complement activation and CR1-bearing RBCs.

Inflammation (Complement-Induced)

Vascular and cellular responses triggered by anaphylatoxins leading to increased permeability and leukocyte recruitment.