Immunology MCQs: The Complement System (With Answers and Explanations)

Ten multiple choice questions with answers and explanations on the complement system: the classical and alternative pathways, C3 and C5 convertases, C3b, C5a, the membrane attack complex, and complement fixation. Write down your answers first, then check them against the key at the end.

1. Complement component C3 is cleaved by:
   a. C3b
   b. C3bBb
   c. Factor B
   d. Factor D
   e. Factor H
2. The membrane attack complex (MAC) in the complement pathway consists of:
   a. C3b3b,Bb
   b. C5b,6,7,8,9
   c. Colicins
   d. OH
   e. Properdin
3. Complement component C3b:
   a. Directly injures bacteria
   b. Is an anaphylatoxin
   c. Is chemotactic
   d. Is the inactive form of C3
   e. Opsonizes bacteria
4. A complement component that is strongly chemotactic for neutrophils is:
   a. C3
   b. C3b
   c. C5a
   d. C5b
   e. C9
5. The initial complement component that is bound by complement-fixing antibodies is:
   a. C1q
   b. C1s
   c. C3b
   d. C5a
   e. C9
6. Several of the complement components are:
   a. Antibodies
   b. Cytokines
   c. Enzymes
   d. Glycolipids
   e. Hormones
7. The classical and alternative pathways meet at complement component:
   a. C3
   b. C4
   c. C4b
   d. C5
   e. Factor D
8. One principal function of complement is to:
   a. Bind antibodies attached to cell surfaces and lyse these cells
   b. Cross-link allergens
   c. Inactivate perforins
   d. Mediate the release of histamine
   e. Phagocytize antigens
9. Which of the following correctly pairs a complement activation pathway with its trigger?
   a. The classical pathway is triggered directly by microbial surface polysaccharides
   b. The classical pathway is triggered by antigen-bound IgG or IgM
   c. The alternative pathway requires an antigen-antibody complex to begin
   d. The lectin pathway is triggered by C5a binding to mast cells
10. Complement fixation:
    a. Can be modified by cholera toxin
    b. Has intrinsic guanylate cyclase activity
    c. Can be desensitized by phosphorylation
    d. Is an effector function of IgG and IgM following antigen binding

Answer key

1. b. C3bBb
2. b. C5b,6,7,8,9
3. e. Opsonizes bacteria
4. c. C5a
5. a. C1q
6. c. Enzymes
7. a. C3
8. a. Bind antibodies attached to cell surfaces and lyse these cells
9. b. The classical pathway is triggered by antigen-bound IgG or IgM
10. d. Is an effector function of IgG and IgM following antigen binding

Why these are the answers

1. C3bBb. C3bBb is the C3 convertase of the alternative pathway, an active enzyme complex formed from the C3b fragment and the cleaved fragment of factor B (Bb). This convertase cleaves intact C3 into C3a (an anaphylatoxin) and C3b (an opsonin), and because each new C3b can form more convertase, it drives the amplification loop of the cascade. Factors B, D, and H are involved in the pathway but are not themselves the enzyme that cleaves C3. See this article to revise complement system.
2. C5b,6,7,8,9. The membrane attack complex is the terminal, lytic unit of complement. It begins when C5 is split into C5a and C5b; C5b then binds C6, C7, and C8 and anchors into the target membrane, and multiple C9 molecules polymerize into a ring that forms a pore. The pore destroys the cell's osmotic balance and lyses it. The other options are not the MAC.
3. Opsonizes bacteria. C3b is the major opsonin of the complement system: it coats a pathogen surface, and phagocytes (via complement receptor CR1) grip the C3b-coated microbe and engulf it far more efficiently. C3b does not directly injure bacteria, and it is not an anaphylatoxin or a chemotaxin, those roles belong to the small fragments C3a and C5a.
4. C5a. C5a is the most potent chemotactic factor of the complement system. It sets up a chemical gradient that draws neutrophils and macrophages to the site of infection, and it is also an anaphylatoxin, triggering mast cell degranulation and increasing vascular permeability. The large membrane-binding fragments (C3b, C5b) and the pore component C9 are not chemotactic.
5. C1q. The classical pathway starts when IgM or IgG binds antigen on a surface, which exposes a site on the antibody's Fc region. C1q, the recognition subunit of the C1 complex, binds that site and sets the cascade in motion. So the first component engaged by complement-fixing antibody is C1q, not the later components.
6. Enzymes. Complement works as a proteolytic cascade: many components circulate as inactive proenzymes (zymogens) and, once cleaved, become active serine proteases (for example C1r, C1s, factor D, and the C3 and C5 convertases) that carry out the next step. So several complement components are enzymes, not antibodies, cytokines, glycolipids, or hormones.
7. C3. The classical pathway (triggered by antigen-antibody complexes) and the alternative pathway (triggered directly by microbial surfaces) use different early components, but both generate a C3 convertase and converge at the cleavage of C3. From C3 onward the terminal sequence leading to the membrane attack complex is shared. C3 is therefore the meeting point of the pathways.
8. Bind antibodies attached to cell surfaces and lyse these cells. A principal effector function of complement is to recognize antibody bound to a target cell and then drive the terminal cascade that lyses that cell through the membrane attack complex. Complement itself does not phagocytose (it marks targets for phagocytes rather than engulfing them), does not cross-link allergens, does not inactivate perforins, and while its fragments help trigger histamine release, that is not the "principal function" described here.
9. The classical pathway is triggered by antigen-bound IgG or IgM. Each pathway has its own trigger. The classical pathway is antibody-dependent: it starts when IgG or IgM already bound to antigen recruits C1q. The alternative pathway is antibody-independent, triggered directly by microbial surface molecules (so option a describes the alternative pathway, and option c has it backwards). The lectin pathway is triggered by mannose-binding lectin recognizing microbial sugars, not by C5a. Matching each pathway to its correct trigger is the point.
10. Is an effector function of IgG and IgM following antigen binding. Complement fixation is a downstream (effector) action of antibody. It does not happen with free antibody floating in serum; it requires IgG or IgM to first bind antigen, which changes the antibody's shape and exposes the C1q binding site that starts the classical pathway. The other options describe unrelated biochemical mechanisms.