The Complement System Reviewer

50 fill-in-the-blank practice questions covering core components, activation sequences, pathways, convertases, and regulatory mechanisms of the complement system based on the lecture text.

The complement system is composed of a complex series of __________ distinct serum proteins.

14

The 14 distinct serum proteins of the complement system comprise __________ core components.

9

Complement components are numbered strictly in the order of their __________.

discovery

The correct classical activation sequence for core complement components is __________.

C1, C4, C2, C3, C5, C6, C7, C8, C9

Prior to activation, complement proteins normally circulate in blood plasma as inactive precursor __________.

zymogens

Complement activity in serum is heat-labile and destroyed by heating to __________ for 30 minutes.

56°C

The majority of plasma complement proteins are synthesized in the __________.

liver

Unlike most complement proteins synthesized in the liver, C1 components are mainly produced by __________.

intestinal epithelial cells

Factor D, an essential serine protease of the alternative pathway, is produced in __________.

adipose tissue

According to general complement cleavage nomenclature, the __________ fragment is usually the larger portion that binds to the cell membrane.

'b'

The complement component __________ represents a noted exception where the 'a' fragment is the larger, bound enzymatic portion.

C2

The primary biological role of complement activation on a foreign cell surface is __________ via destruction of the cell membrane.

cell lysis (cytolysis)

The complement cleavage fragment __________ coats pathogenic microorganisms to act as a powerful opsonin for phagocytosis.

C3b

The fragment __________ acts as a powerful chemotaxin that directs neutrophils and other immune cells to the site of infection.

C5a

Anaphylatoxins C3a and C4a induce vascular permeability by triggering the release of __________ from mast cells or basophils.

histamine

A key housekeeping function of complement involves recognizing cellular debris, apoptotic cells, and __________ for safe removal.

immune complexes

The classical complement pathway is an antibody-dependent mechanism triggered by __________.

antigen-antibody (Ag-Ab) complexes

The immunoglobulins capable of efficiently activating the classical pathway are IgM and IgG, specifically IgG subclasses __________.

IgG1, IgG2, and IgG3

The specific IgG subclass that is INCAPABLE of activating the classical complement pathway is __________.

IgG4

The intact C1 macromolecular complex has a total molecular weight of __________ Daltons.

740,000

The C1 recognition complex consists of one C1q molecule, two C1r molecules, and __________ C1s molecules.

two

The C1 complex requires __________ to maintain its structural integrity and stability.

calcium

Structurally, the C1q molecule possesses six globular heads and a __________ tail.

collagen-like

To initiate the classical cascade, C1q globular heads must attach to a minimum of two molecules of IgG or __________ molecule(s) of IgM.

1

C1q binding requires at least two molecules of IgG bound within __________ of each other on the target surface.

30 to 40 nm

Conformational change upon C1q binding first induces autoactivation of the serine protease subunit __________.

C1r

Activated C1s mediates the cleavage of __________ during the enzyme activation phase of the classical pathway.

C4 and C2

In the first amplification step of the classical pathway, roughly __________ molecules of C4 are split for every C1 complex.

30

The combination of C4b and C2a forms the C4b2a complex, which serves as the __________ of the classical pathway.

C3 convertase

The component recognized as the most abundant complement protein in human serum is __________.

C3

Addition of C3b to C4b2a forms the trimolecular C4b2a3b complex, known as __________ in the classical and lectin pathways.

C5 convertase

Cleavage of C5 yields C5a and C5b, where __________ binds to the cell membrane as the foundation for Membrane Attack Complex (MAC) assembly.

C5b

In MAC assembly, membrane-bound C5b sequentially binds C6, C7, and C8 to form the __________ complex.

C5b678

The C5b678 complex recruits C9, where __________ molecules of C9 polymerize to form a transmembrane pore.

18

Polymerized C9 forms a transmembrane water channel with an internal diameter of __________.

70 to 100 Angstroms

Target cell swelling and cytolysis directly result when __________ rushes into the cell down its osmotic gradient following MAC pore formation.

water

Triggers for the alternative pathway include bacterial cell walls, bacterial LPS, virally infected cells, rabbit erythrocytes, and fungal cell walls known as __________.

zymosan

The alternative complement pathway operates independently of antibodies and bypasses classical components __________.

C1, C4, and C2

The activation sequence of core components in the alternative pathway is __________.

C3, C5, C6, C7, C8, C9

In the alternative pathway, C3b binds with Factor B (cleaved by Factor D) to form the __________ complex, which serves as the major C3 convertase.

C3bBb

The essential physiological role of Properdin (Factor P) in the alternative pathway is that it stabilizes the __________ complex.

C3bBb

In the alternative pathway, the C5 convertase complex is __________.

C3bBb3bP (or C3b-Bb-P-C3b)

Activation of the lectin pathway begins when Mannose-Binding Lectin (MBL) adheres to __________ on microbial carbohydrates.

mannose groups

MBL associates with serine proteases __________ and __________, which are structurally and functionally equivalent to C1r and C1s.

MASP-1 and MASP-2

The MBL-MASP complex converges into the classical sequence when MASP-2 enzymatically cleaves C4 and C2 to form __________.

C4b2a

C1 Inhibitor (C1-INH) regulates classical pathway activation by blocking assembly of the C1 complex, inhibiting activation of __________.

C2 and C4

The regulatory protein __________ inactivates the C3b molecule, halting the amplification loop and opsonization process.

Factor I

Factor H regulates alternative pathway activation by removing the __________ protein from the C3bBb complex.

Bb

Besides the liver, monocytes and macrophages serve as secondary synthesis sources for early complement components __________.

C1, C2, C3, and C4

All three separate complement activation pathways (Classical, Alternative, Lectin) ultimately converge to form a common final structure called the __________.

Membrane Attack Complex (MAC)