The Complement System

Flashcards covering key components, pathways, functions, and regulation of the complement system based on the provided lecture notes.

Complement system

The major effector of the humoral branch of the immune system, consisting of nearly 30 serum and membrane proteins that act in an enzymatic cascade to facilitate antigen clearance and inflammatory response.

Membrane-attack complex (MAC)

The terminal reaction shared by all three complement activation pathways, resulting in the lysis of various cells, bacteria, and viruses.

Complement activation effects

Includes direct lysis of foreign cells, vasodilation, chemotactic attraction of phagocytic cells, increased inflammatory reaction (anaphylatoxin), opsonization, and activation of B lymphocytes.

Classical pathway (initiation)

Commonly initiated by the formation of soluble antigen-antibody complexes or by the binding of antibody (IgM and certain IgG subclasses like IgG1, IgG2, IgG3) to antigen on a target.

C1 complex

In the classical pathway, C1q binds to the Fc region of an antibody, activating C1r, which then cleaves C1s.

C1q

The recognition unit in the classical pathway; binds to the Fc region of IgM and IgG antibodies.

C4bC2a

The C3 convertase of the classical and lectin pathways; formed when C1s cleaves C4 and C2.

C4bC2aC3b

The C5 convertase of the classical pathway; formed when C4bC2a cleaves C3, and C3b binds.

C9

A complement component that binds to the C5b678 complex and polymerizes to form trans-membrane channels, leading to cell lysis (the 'smoking gun' of the MAC).

Alternative pathway (initiation)

Initiated by various cell surface constituents foreign to the host, such as Gram-negative/positive bacteria, fungal/yeast cell walls (Zymosan), some viruses, tumor cells, and parasites.

C3 (Complement component)

Plays a key role in all complement pathways, is the most abundant complement protein, and its major function is opsonization. Subject to spontaneous hydrolysis into C3a and C3b.

Factor B

A serum protein in the alternative pathway that binds C3b and is cleaved by Factor D.

Factor D

A serine protease in the alternative pathway that cleaves Factor B when it is bound to C3b, forming C3 convertase.

Properdin

A serum protein in the alternative pathway that binds to and stabilizes the C3bBb complex, extending its half-life.

C3bBb

The C3 convertase of the alternative pathway; formed from C3b, Factor B, and Factor D. Stabilized by Properdin.

Sialic acid

High levels on mammalian cell membranes rapidly inactivate bound C3b, protecting host cells; low levels on foreign surfaces allow C3b to remain active.

Lectin Pathway

An antibody-independent complement pathway initiated by Mannose-Binding Lectin (MBL) that binds carbohydrates on foreign surfaces, involving activation of C4 and C2.

Mannose-Binding Lectin (MBL)

A serum protein that recognizes mannose carbohydrates on the cell walls of bacteria, fungi, and some viruses, initiating the lectin complement pathway.

MASP1/MASP2

Mannose-binding lectin associated serine proteases that activate downstream complement components in the lectin pathway.

C1INH

A complement regulator that dissociates C1r and C1s from C1q.

Factor I

A complement regulator that cleaves C3b and C4b.

Factor H

A complement regulator that acts as a cofactor with Factor I to inactivate C3b and prevents the binding of Factor B to C3b.

DAF (Decay Accelerating Factor / CD55)

A cell-bound complement receptor that dissociates C2b or Bb from binding sites, preventing the formation of C3 convertases on host cells.

MCP (Membrane Cofactor Protein / CD46)

A cell-bound complement receptor that acts as a cofactor for Factor I in the cleavage of C3b and C4b.

CR1 (Complement Receptor type 1 / CD35)

A cell-bound complement receptor that acts as a cofactor for Factor I and mediates the transport of immune complexes.

MIRL (Membrane Inhibitor of Reactive Lysis / CD59)

A cell-bound complement receptor that prevents the insertion of C9 into the cell membrane, thereby inhibiting MAC formation.

Opsonization (beneficial effect)

The binding of complement proteins (opsonins, e.g., C3b) to surfaces of foreign organisms or particles, promoting their phagocytosis by cells with specific receptors.

Anaphylatoxins (beneficial effect)

Small complement fragments (C3a, C4a, C5a) that cause degranulation of mast cells and release of histamine and other inflammatory mediators, increasing the inflammatory response.

Immune complex clearance (beneficial effect)

C3b facilitates the binding of immune complexes to surfaces (e.g., erythrocytes) and enhances their removal by the liver and spleen.