Complement

Complement

soluble and cell-bound proteins

lyse foreign cells, opsonize and tag the invaders for clearance, and direct the adaptive immune system to the site of infection

proinflammatory role & “housekeeping” role

Chronic activation can lead to inflammation and tissue damage to the host

Any deficiencies to the complement system can result in an increased susceptibility to infection or the accumulation of immune complexes resulting in possible autoimmune disorders

C1 components (intestinal epithelial cells)

Factor D (Adipose tissue)

early complement components of C1, C2, C3 and C4 (Monocytes and Macrophages)

Most plasma complement proteins are synthesized in the liver except

the classical pathway

lectin pathway

Alternative pathway

Pathways of the Complement System

Jules Bordet

awarded the nobel prize for his role in elucidating the nature of complement

Paul Ehrlich

coined the term complement because the substance complements the action of antibody in destroying microorganisms

56 C for 30 minutes

complement can be easily inactivated by heating serum to

classical pathway

triggered primarily by antigen–antibody combination

the main antibody-directed mechanism for triggering complement activation

C1q (1)

C1r (2)

C1s (2)

RECOGNITION UNIT C1 complex

Lectin pathway

recognition of surface moieties that are found on pathogens

involves nonspecific recognition of carbohydrates that are common constituents of microbial cell walls and that are distinct from those found on human cell surfaces

most recently described of the three activation pathways of complement, but probably the most ancient

mannose- (or mannan-) binding lectin (MBL) pathway

Lectin pathway can also be called as

lectins, ficolins, and CL-K1

The role C1q serves in the classical pathway is filled by three classes of recognition molecules collectively known as COLLECTINS in the lectin pathway:

mannose-binding, or mannan-binding, lectin (MBL)

acute phase protein

MBL-associated serine proteases (MASPs)

The enzymatic role played by C1r and C1s in the classical pathway is played in the lectin pathway by serine proteases called

Pillemer and his associates in the early 1950s

Alternative pathway was first described by

Alternative pathway

Functions mainly as an amplification loop for activation started from the classical or lectin pathways

properdin system

Alternative pathway was previously called as

stabilize

Although properdin has been confirmed to bind and initiate activation, the primary function of properdin is to ___ the C3 convertase formed from activation of other factors.

C3

a key component of this pathway as well as the two other pathways

Factor H

principal soluble regulator of the alternative pathway

binding to C3b; preventing the binding of Factor B

accelerates the dissociation of the C3bBb complex on cell surfaces

acts as a cofactor that allows Factor I to break down C3b; only those molecules with tightly bound Factor H acquire high-affinity binding sites for Factor I

S protein

interacts with the C5b-7 complex as it forms in the fluid phase and prevents it from binding to cell membranes

Binding of C8 and C9 still proceeds, but polymerization of C9 does not occur; therefore, the complex is unable to insert itself into the cell membrane or to produce lysis

Membrane inhibitor of reactive lysis (MIRL) or CD59 - Block formation of the MAC

widely distributed on the cell membranes of all circulating blood cells, including RBCs, and on endothelial, epithelial, and many other types of cells

vitronectin

S protein can also be called as

C4-binding protein (C4BP)

abundant in the plasma is capable of combining with either fluid phase or bound C4b

CR1 or CD35

found mainly on peripheral blood cells

binds C3b and C4b but has the greatest affinity for C3b

main function is as a receptor on platelets and red blood cells (RBCs), which helps to mediate transport of C3b-coated immune complexes to the liver and spleen

MCP or CD46

found on virtually all epithelial and endothelial cells except erythrocytes

most efficient cofactor for Factor I-mediated cleavage of C3b

DAF or CD55

found on peripheral blood cells, on endothelial cells and fibroblasts, and on numerous types of epithelial cells

capable of dissociating both classical and alternative pathway C3 convertases; binds to both C3b and C4b; does not prevent initial binding of either C2 or Factor B to the cell but can rapidly dissociate both from their binding sites

does not permanently modify C3b or C4b; they are capable of re-forming elsewhere as active convertases

presence of DAF on host cells protects them from bystander lysis

one of the main mechanisms used in discrimination of self from nonself because foreign cells do not possess this substance

Membrane inhibitor of reactive lysis (MIRL) or CD59

Block formation of the MAC

widely distributed on the cell membranes of all circulating blood cells, including RBCs, and on endothelial, epithelial, and many other types of cells