Week 8 S - Complement System Flashcards

Flashcards on the Complement System

The Complement System Components

More than 20 individual components that are inactive precursor molecules (C1, C2, C3 etc.), produced in the liver, present in low levels in normal serum, and can be converted into active enzymes when triggered.

Enzyme-Amplifying Cascade

Pro-enzyme 1 becomes activated enzyme 1 + cleavage fragment, and many of the complement molecules generated have powerful biological effector roles .

Three Activation Pathways of the Complement System

Classical Pathway, Alternative Pathway, Lectin Pathway. Pathways converge at the point where complement component C3 is cleaved.

Classical Pathway

Involves antibody binding to antigen and is dependent on adaptive immune response.

Alternative Pathway

Does not involve antibody and is triggered on contact with certain microbes, considered part of innate immune response.

Lectin Pathway

Does not involve antibody and is triggered by mannose-binding lectin sticking to mannose on the surface of certain microbes, considered part of innate immune response.

Activation of C1

Requires at least 2 Fc regions to bind simultaneously to 2 globular heads of C1q molecule.

C3 Convertase

Cleaves C3 into C3a and C3b, central event in complement cascade!

Membrane Attack Complex (MAC) assembly

Deposition of C5b on target surface leads to sequential assembly of "MAC" from C5b, C6, C7, C8, and multiple C9 molecules.

MB-Lectin Pathway Activation

MBL recognizes a pathogen, its lectin domain binds to mannose or other carbohyrate sugar residues on the pathogen surface, and activates complement via the MB-lectin pathway

Initiators of the Alternative Pathway

Include many strains of gram-negative and gram-positive bacteria, lipopolysaccharides, teichoic acid, fungal and yeast cell walls, some viruses, some tumor cells, and parasites.

Biological roles of complement

Opsonization (C3b), activation and attraction of phagocytes (C3a, C5a), degranulation of mast cells (C3a, C5a), lysis of target cells (C5b-C9 “MAC”)

Opsonization

Enhances phagocytosis; both antibodies and complement C3b act as opsonins, so synergistic effect.

Anaphylatoxins

C3a, C4a, C5a, promote mast cell degranulation.

Membrane-attack complex (MAC)

C5b-C9 complex: Comprises C5b,C6,C7,C8,(C9)n pores inserted in membrane, through which electrolytes and water can flow resulting in osmotic lysis

Functions of Complement

Cell-bound C3b is an opsonin, C5A, C3A, and C4A stimulate leukocyte recruitment and inflammation, and the MAC lyses cells.

Effective collaboration

Innate and adaptive immune response to facilitate microbe destruction and/or elimination; key role played by complement.

Deficiencies in early complement components (C1, C2, C4)

Recurrent disseminated infections with pyogenic bacteria (e.g. streptococci, staphylococci – gram +ve).

Deficiencies in lytic “MAC” components (C5-C8)

Disseminated infections with neisseria bacteria (e.g. N. gonorrhoeae, N. meningitides).

Lacking complement receptors (on phagocytic cells)

Recurrent infections with pyogenic bacteria due to impaired chemotaxis, opsonization, phagocytosis.