Unit 4 Question Bank
The five tabs are the five sections of the real paper. Items tagged
Past Paper 2019 or 2020 are the genuine questions, reproduced verbatim.
Items tagged Slide come from the TMU lecture; items tagged Janeway's are built
from the textbook to cover examinable ground. Nothing is invented. Janeway's 10e is a reflowed
edition with no printed page numbers, so it is cited by numbered section (§1-14), not by page.
0 / 29 answered
1Which component can be shared by the three pathways of complement activation?
Answer: D
C3. C1 belongs to the classical pathway alone; C2 and C4 are used by the classical and lectin pathways but not by the alternative. Only C3 appears in all three — every pathway exists in order to cleave it. This is also why C3 deficiency is the most severe complement deficiency.Past Papers 2019 & 2020, Section III Q5 — verbatim, both years
2Complement C1 is composed of:
Answer: A
One C1q plus two molecules each of the serine proteases C1r and C1s. C1q itself is built from 18 polypeptide chains forming six collagen-like triple-helical arms — the shape that lets it reach two antibody Fc regions at once.Past Paper 2019, Section II Q6 · TMU Lecture 4 (Juan Li) Slides 10, 18
3The C3 convertase of the classical pathway is:
Answer: B
C4b2a — surface-bound C4b joined by C2a, the larger active fragment of C2. Adding a C3b converts it into the C5 convertase C4b2a3b. C3bBb and C3bBb3b are the alternative pathway's pair.Past Paper 2019, Section II Q4 · TMU Lecture 4 (Juan Li) Slide 34
4The C5 convertase of the alternative pathway is:
Answer: C
C3bBb3b. The rule for every pathway is the same: the C5 convertase is the C3 convertase with a C3b added. So C3bBb → C3bBb3b for the alternative pathway, and C4b2a → C4b2a3b for the classical and lectin pathways.Past Paper 2020, Section II Q4 · TMU Lecture 4 (Juan Li) Slide 41
5Which pathway of complement activation requires antibody?
Answer: D
Only the classical pathway is antibody-dependent — it is initiated by an antigen–antibody immune complex. The alternative and lectin pathways recognise microbial surfaces directly and belong to innate immunity, which is why they act earlier in an infection.TMU Lecture 4 (Juan Li) Slides 9, 71
6Which immunoglobulin is the most efficient activator of the classical pathway?
Answer: A
IgM. C1 must engage at least two antibody molecules at once, and IgM is a pentamer — a single bound IgM presents several Fc regions together. IgG can do it, but needs two separate molecules to land close enough on the surface, so far more antibody is required. IgA and IgE do not activate the classical pathway.TMU Lecture 4 (Juan Li) Slides 20, 25, 28
7Free (unbound) antibody in the circulation does not activate complement because:
Answer: B
Before antigen binds, the antibody sits in a T shape and the C1q site in CH2 is inaccessible. Antigen binding swings the arms into a Y shape and exposes it. This is the built-in safety catch that stops the grams of circulating IgG in your blood from consuming complement continuously.TMU Lecture 4 (Juan Li) Slides 16, 21, 24
8The alternative pathway distinguishes host cells from microbes because:
Answer: C
The pathway does not recognise the pathogen — spontaneous C3 hydrolysis deposits C3b indiscriminately. What differs is that host membranes carry DAF, MCP and factor H, which strip or inactivate it, while microbial surfaces do not. The alternative pathway recognises the absence of self-protection.TMU Lecture 4 (Juan Li) Slides 40, 52 · Janeway's Immunobiology 10e, §2-10
9Which protein stabilises the alternative pathway C3 convertase?
Answer: D
Properdin binds and stabilises the otherwise short-lived C3bBb complex, allowing it to generate large numbers of C3b molecules. Factor D is the enzyme that cleaves factor B; factor I and C4bp are regulators that inactivate the cascade rather than sustain it.TMU Lecture 4 (Juan Li) Slides 41, 43
10Mannose-binding lectin is structurally similar to which complement component?
Answer: A
C1q. Both are recognition molecules that grip a surface and then activate a pair of serine proteases — C1q activates C1r and C1s, MBL activates MASP-1 and MASP-2. The difference is only in what they grip: C1q binds antibody, MBL binds mannose. Downstream they are identical, which is why they share convertases.TMU Lecture 4 (Juan Li) Slides 55–56
11Which MASP performs the same role as C1s, cleaving C4 and C2?
Answer: B
MASP-2 cleaves C4 and C2, generating the same C4b2a convertase as the classical pathway. MASP-1 additionally cleaves C3 directly, feeding the alternative pathway's amplification loop.TMU Lecture 4 (Juan Li) Slides 56, 58
12The membrane attack complex consists of:
Answer: C
C5b–C9. Assembly is enzyme-free: C5b binds the surface, then C6, then C7 (which inserts into the bilayer), then C8, and finally several C9 molecules polymerise to form the pore. C3a, C4a and C5a are the anaphylatoxins, not part of the MAC.TMU Lecture 4 (Juan Li) Slides 59–66
13Which complement component polymerises to form the pore in the target membrane?
Answer: D
C9 is the only component present in multiple copies; it polymerises onto the C5b678 complex to create the channel. C7 and C8 insert into the bilayer but do not form the pore themselves.TMU Lecture 4 (Juan Li) Slide 64
14Which complement fragment is the principal opsonin, and which receptor binds it?
Answer: A
C3b coats the microbe and is bound by CR1 (CD35) on phagocytes. Note Janeway's detail: CR1 binding alone is not enough to trigger ingestion — the phagocyte also needs C5a acting on its C5a receptor. C3b says where; C5a says go.Janeway's Immunobiology 10e, §2-13 · Fig. 2.31
15The anaphylatoxins of the complement system are:
Answer: B
The small fragments released into the fluid phase — C3a, C4a and C5a — trigger mast-cell degranulation and increase vascular permeability. C5a is the most potent, and is also the strongest chemoattractant for neutrophils and monocytes. The corresponding 'b' fragments stay bound to the surface and opsonise instead.Janeway's Immunobiology 10e, §2-14
16Deficiency of C1 inhibitor causes:
Answer: C
Without C1INH, C1 activates spontaneously and consumes C4 and C2, producing episodic non-itchy swelling of face, airway and gut. Crucially it is not histamine-mediated, so antihistamines and adrenaline do not work — a clinical fact that identifies the mechanism. PNH follows loss of the GPI-anchored DAF and CD59; recurrent Neisseria infection follows terminal-component (MAC) deficiency.Janeway's Immunobiology 10e, §2-16, §2-17
1 Complement (C) — 3 marks+
A collective name for a group of plasma proteins that become proteolytic enzymes after activation, and which opsonise and destroy pathogens. They exist in blood serum, tissue fluid and on cell membranes, circulate as inactive zymogens, and are activated by proteolytic cleavage in a cascade. Complement is a major effector mechanism of both humoral and innate immunity.TMU Lecture 4 (Juan Li) Slides 7–8
2 Classical pathway — 3 marks+
The antibody-dependent route of complement activation. Initiated by an immune complex (antigen bound to IgM or IgG1–IgG3); C1q binds the Fc (CH2 of IgG, CH3 of IgM), activating C1r then C1s, which cleave C4 and C2 to form the C3 convertase C4b2a and then the C5 convertase C4b2a3b. Requires Ca²⁺ and Mg²⁺.TMU Lecture 4 (Juan Li) Slides 16–38
3 Alternative pathway — 3 marks+
The antibody-independent route, initiated by spontaneous hydrolysis of C3 whose product C3b is sustained on microbial surfaces (LPS, peptidoglycan, zymosan). C3b binds factor B, factor D cleaves it, and the resulting C3bBb C3 convertase — stabilised by properdin — generates more C3b in an amplification loop, then forms the C5 convertase C3bBb3b. Requires Mg²⁺ only.TMU Lecture 4 (Juan Li) Slides 39–52
4 Lectin (MBL) pathway — 3 marks+
An antibody-independent route initiated when mannose-binding lectin (MBL) — structurally similar to C1q — binds mannose or other carbohydrate residues on a microbial surface. MASP-2 then acts like C1s, cleaving C4 and C2 to give the same convertases as the classical pathway, C4b2a and C4b2a3b. MASP-1 can cleave C3 directly. Requires Ca²⁺.TMU Lecture 4 (Juan Li) Slides 55–58
5 Membrane attack complex (MAC) — 3 marks+
The complex of complement components C5b, C6, C7, C8 and C9 (C5b–C9), formed in the terminal steps of all three pathways, which mediates cell lysis by creating a pore in the target cell membrane. Assembly requires no further enzymes; several C9 molecules polymerise to form the channel.TMU Lecture 4 (Juan Li) Slide 59
6 Anaphylatoxin — 3 marks+
The small fragments C3a, C4a and C5a, released into the fluid phase during complement activation, which act as peptide mediators of inflammation — triggering mast-cell degranulation and increasing vascular permeability. C5a is the most potent and is also a powerful chemoattractant and activator of neutrophils and monocytes.Janeway's Immunobiology 10e, §2-14
7 Opsonisation by complement — 3 marks+
Coating of a microbe with C3b (and its cleavage product iC3b), which is then bound by CR1 (CD35) on phagocytes, greatly increasing ingestion. It is quantitatively the most important function of the complement system. CR1 binding alone is insufficient — the phagocyte must also be activated by C5a.Janeway's Immunobiology 10e, §2-12, §2-13
1In the classical pathway of complement activation, C3 convertase is ? ; C5 convertase is ? ; MAC is ? .3 mark(s)
⚠️ Write C4b2a, not C4b2b. The circulated student review sheets give C4b2b, but TMU's own Lecture 4 deck writes C4b2a seventeen times and C4b2b never; Janeway's confirms that C2a is the larger, active fragment of C2.
Past Paper 2019, Section II Q4 — set for the classical pathway in 20192In the alternative pathway of complement activation, C3 convertase is ? ; C5 convertase is ? ; MAC is ? .3 mark(s)
The 2020 paper asked the same question about the alternative pathway instead of the classical — so learn both rows. In every pathway the C5 convertase is simply the C3 convertase with a C3b added.
Past Paper 2020, Section II Q4 — set for the alternative pathway in 20203Complement C1 is a large protein complex composed of ? , ? and ? .3 mark(s)
One C1q with two molecules each of C1r and C1s. C1q has 18 polypeptide chains forming six collagen-like arms, which is how it engages two antibody Fc regions at once — the minimum needed for activation.
Past Paper 2019, Section II Q64The three pathways of complement activation are ? , ? and ? .3 mark(s)
Classical is antibody-dependent; alternative and lectin are antibody-independent and belong to innate immunity, acting earlier in infection.
TMU Lecture 4 (Juan Li) Slide 9 · phrasing confirmed by the student review sheet5The initiating substance of the classical pathway is the ? complex; of the alternative pathway, components on the ? surface; of the lectin pathway, ? residues.3 mark(s)
Three different recognition events converging on the same amplifier. Only the classical route needs a prior adaptive immune response.
TMU Lecture 4 (Juan Li) Slide 716The alternative pathway C3 convertase is stabilised by ? , also known as factor ? .2 mark(s)
Without properdin the C3bBb complex is short-lived. Stabilised, it drives the amplification loop that generates up to 90% of all deposited C3b regardless of which pathway started the reaction.
TMU Lecture 4 (Juan Li) Slides 41, 437The membrane attack complex is composed of complement components ? through ? , and the component that polymerises to form the pore is ? .3 mark(s)
C5b binds the surface, C6 joins, C7 inserts into the bilayer, C8 follows, and several C9 molecules polymerise into the channel.
TMU Lecture 4 (Juan Li) Slides 59–641Free antibody circulating in plasma can bind and activate complement.
FALSE
False. The lecture states it explicitly: free antibody cannot bind or activate complement. The C1q site in CH2 is exposed only after antigen binding shifts the molecule from a T shape to a Y shape — the geometric safety catch that keeps your circulating IgG inert.TMU Lecture 4 (Juan Li) Slides 16, 21
2IgM is a more efficient activator of the classical pathway than IgG.
TRUE
True. C1 must engage at least two antibody molecules at once. A single pentameric IgM presents several Fc regions together and can do it alone; IgG requires two separate molecules to land close enough on the surface.TMU Lecture 4 (Juan Li) Slides 20, 25, 28
3The alternative and lectin pathways both require antibody to be initiated.
FALSE
False. Both are antibody-independent and belong to innate immunity — which is why they operate in the early stage of an infection, before an adaptive response exists. Only the classical pathway needs antibody.TMU Lecture 4 (Juan Li) Slide 71
4The lectin pathway uses the same C3 and C5 convertases as the classical pathway.
TRUE
True. MASP-2 does the job of C1s, cleaving C4 and C2, so the lectin pathway generates C4b2a and C4b2a3b — identical to the classical pathway. Only the recognition step differs: MBL binds sugar where C1q binds antibody.TMU Lecture 4 (Juan Li) Slides 58, 71
5C3a, C4a and C5a form the membrane attack complex.
FALSE
False. Those are the anaphylatoxins — small fragments released into the fluid phase to drive inflammation. The MAC is built from the 'b' and terminal components: C5b, C6, C7, C8, C9.TMU Lecture 4 (Juan Li) Slide 59 · Janeway's Immunobiology 10e, §2-14
6In paroxysmal nocturnal haemoglobinuria, red cells are lysed by the patient's own complement because they lack GPI-anchored regulatory proteins.
TRUE
True. A somatic mutation in the GPI-anchor pathway strips both DAF (CD55) and CD59 from the red-cell surface at once, leaving the cells defenceless against the constantly ticking alternative pathway. It is the clearest demonstration that the alternative pathway spares host cells only because host cells are protected.Janeway's Immunobiology 10e, §2-16, §2-17
1
Compare the three pathways of complement activation.
6 marks
| Classical | Alternative | Lectin (MBL) | |
|---|---|---|---|
| Initiator | Ag–Ab immune complex (IgM, IgG1–IgG3) | Microbial surfaces — LPS, peptidoglycan, zymosan | Mannose residues on microbial surfaces |
| First component | C1q | C3 | MBL |
| Components | C1, C4, C2, C3 | C3, factors B, D, P | MBL, MASP, C4, C2, C3 |
| Antibody needed | Yes | No | No |
| Ions | Ca²⁺, Mg²⁺ | Mg²⁺ | Ca²⁺ |
| C3 convertase | C4b2a | C3bBb | C4b2a |
| C5 convertase | C4b2a3b | C3bBb3b | C4b2a3b |
| Immunity / timing | Adaptive; later stage | Innate; initial stage, amplification loop | Innate; early stage, promotes the other two |
Marking guide: Roughly 0.75 per row. The rows that must be right are antibody needed and the two convertase rows — an answer that gets the convertases wrong cannot pass, and writing C4b2b instead of C4b2a is the commonest way to lose them.
2
Describe the biological functions of complement.
6 marks
① Opsonisation — C3b (and iC3b) coats the microbe and is bound by CR1 (CD35) on phagocytes, greatly increasing ingestion. Quantitatively the most important function.
② Inflammation — the anaphylatoxins C3a, C4a and C5a trigger mast-cell degranulation and increase vascular permeability.
③ Chemotaxis — C5a is the most potent chemoattractant for neutrophils and monocytes, and activates them so that CR1-bound microbes are actually ingested.
④ Cell lysis — the MAC (C5b–C9) forms a membrane pore; particularly important against Neisseria.
⑤ Clearance of immune complexes — C3b-tagged complexes bind CR1 on erythrocytes and are carried to liver and spleen.
⑥ Linking innate to adaptive immunity — C3d bound to antigen engages CR2 (CD21) on the B-cell co-receptor, lowering the activation threshold.
Marking guide: 1 mark each for six functions, or 1.5 each for four well-explained ones. Naming the mediator (C3b, C5a, MAC) alongside the function is what separates a full answer from a list.
3
How is complement activation regulated, and what happens when regulation fails?
6 marks
| Regulator | Action | Disease if deficient |
|---|---|---|
| C1 inhibitor (C1INH) | Serpin — inactivates C1r and C1s, limiting C4 and C2 cleavage | Hereditary angioedema |
| DAF (CD55) | Displaces Bb and C2a from C3b and C4b, decaying the C3 convertase | PNH |
| MCP (CD46) | Cofactor for factor I | Atypical haemolytic uraemic syndrome |
| Factor I (+ factor H) | Cleaves C3b to inactive iC3b | — |
| CD59 (protectin) | Inhibits MAC formation at C8 | PNH |
Two clinical points earn the final marks. In hereditary angioedema the swelling is complement-mediated, not histamine-mediated, so antihistamines and adrenaline are ineffective. In PNH, DAF and CD59 are both GPI-anchored, so a single anchor defect removes both at once and the patient's own alternative pathway lyses their red cells.
Marking guide: 1 mark per regulator with its action; up to 2 for the disease correlations. Explaining why PNH loses two regulators together (shared GPI anchor) is the discriminating detail.