Complement system

5 DOH Abu Dhabi (HAAD) lab licensing practice questions on Complement system, part of Immunology and Serology. The first 5 are below; the first 5 with answers and explanations (tap Show answer after you have chosen), the rest in Learn with a free account.

1. Question 1 · Medium

   A patient's CH50 was normal last month. Today's serum, left on the bench at room temperature overnight before testing, gives a very low CH50, while C3 and C4 concentrations are normal. The most likely explanation is:

   1. AConsumption of complement by immune complexes
   2. BLoss of heat-labile complement during storage
   3. CInherited deficiency of an early classical component
   4. DAn acute-phase increase in complement proteins

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   Answer: B · Loss of heat-labile complement during storage

   Functional complement activity falls quickly when serum is kept at room temperature, even though the C3 and C4 proteins are still detected by immunoassay. Serum for CH50 should be separated soon after clotting and tested promptly or frozen at -70 °C, and sent frozen. The normal result last month rules out an inherited deficiency. Consumption by immune complexes usually lowers C3 and C4 as well.

   • A: Immune complex consumption usually lowers C3 and C4 as well.
   • C: An inherited deficiency would also have given a low CH50 last month.
   • D: An acute-phase rise in complement would raise, not lower, the CH50.

2. Question 2 · Medium

   Which complement result pattern points to activation of the alternative pathway rather than the classical pathway?

   1. ALow C3 with low C4
   2. BNormal C3 with low C4
   3. CLow C3 with normal C4
   4. DNormal C3 and C4 with low CH50

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   Answer: C · Low C3 with normal C4

   The classical and lectin pathways use C4 and C2 before C3, so activation through them lowers both C4 and C3, as in active lupus nephritis. The alternative pathway bypasses C4 and acts directly on C3, so C3 falls while C4 stays normal. This pattern is typical of post-streptococcal glomerulonephritis and of C3 glomerulopathy with C3 nephritic factor. A low C4 with normal C3 is typical of hereditary angioedema.

   • A: Low C3 and low C4 together point to classical or lectin pathway activation.
   • B: Low C4 with normal C3 fits C1 inhibitor deficiency or early classical consumption.
   • D: Normal C3 and C4 with a low CH50 suggests another component deficiency or a handling error.

3. Question 3 · Hard

   A 26-year-old woman has a photosensitive rash and joint pain and has had two pneumococcal pneumonias. Results: CH50 undetectable; AH50 normal; C3 and C4 concentrations normal. Which deficiency is most likely?

   1. AC8 deficiency
   2. BFactor B deficiency
   3. CC2 deficiency
   4. DC1 inhibitor deficiency

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   Answer: C · C2 deficiency

   An undetectable CH50 with a normal AH50 places the defect in a component used only by the classical pathway: C1, C4 or C2. Because C4 is normal, C1 or C2 is the gap, and C2 deficiency is the most common inherited deficiency of the classical pathway. Early classical deficiencies impair the clearance of immune complexes and apoptotic cells, giving lupus-like disease, and also raise the risk of infection with encapsulated bacteria. A terminal (C5 to C9) deficiency would make both CH50 and AH50 abnormal.

   • A: C8 is in the shared terminal pathway, so the AH50 would also be undetectable.
   • B: Factor B is used only by the alternative pathway, so the AH50, not the CH50, would be low.
   • D: C1 inhibitor deficiency lowers C4, which is normal here.

4. Question 4 · Easy

   Which complement fragment coats bacteria and acts as the main opsonin for phagocytosis?

   1. AC5a
   2. BC3a
   3. CC5b
   4. DC3b

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   Answer: D · C3b

   A C3 convertase splits C3 into the small C3a and the large C3b, which binds covalently to nearby microbial surfaces. Phagocytes carry complement receptors, such as CR1, for C3b and its breakdown product iC3b, so coated bacteria are ingested far more efficiently. C3 is the point where all three pathways meet, which is why C3 deficiency causes severe recurrent pyogenic infections. C3b also forms part of the C5 convertase.

   • A: C5a is an anaphylatoxin that attracts neutrophils but does not coat bacteria.
   • B: C3a is a small anaphylatoxin released into the fluid phase; it does not coat bacteria.
   • C: C5b starts the membrane attack complex rather than acting as an opsonin.

5. Question 5 · Easy

   Which complement pathway starts on microbial surfaces without antibody and uses factor B, factor D and properdin?

   1. AAlternative pathway
   2. BLectin pathway
   3. CClassical pathway
   4. DTerminal pathway

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   Answer: A · Alternative pathway

   In the alternative pathway, C3 in plasma breaks down slowly on its own, and C3b that lands on a microbial surface binds factor B. Factor D then cleaves the bound factor B to form the C3 convertase C3bBb, which properdin stabilizes. Host cells are protected by regulators such as factor H and CD55 (decay-accelerating factor). The AH50 assay tests this pathway.

   • B: The lectin pathway starts when mannose-binding lectin or ficolins bind microbial sugars and activate MASPs.
   • C: The classical pathway is usually started by antibody bound to antigen, through C1q.
   • D: The terminal pathway (C5 to C9) is the shared end stage, not a starting pathway.