Clinical Immunology and Serology
What this domain tests
This domain covers immunoglobulin structure and function, complement, autoimmune serology, and the design and interpretation of infectious disease serologic tests - especially predictive value and interference.
Immune fundamentals
- IgG is a monomer that crosses the placenta and dominates the secondary response; IgM is a pentamer that dominates the primary response and cannot cross the placenta; IgA is secretory; IgE binds mast cells; IgD is a B-cell receptor.
- Complement: CH50 measures classical pathway function; C3 and C4 are consumed in active immune complex disease such as SLE. Low C4 with a normal C3 and low C1 inhibitor suggests hereditary angioedema.
- ANA by indirect immunofluorescence on HEp-2 cells: report titer and pattern. Homogeneous suggests dsDNA or histone antibodies; speckled suggests Sm, RNP, SSA/SSB; nucleolar suggests Scl-70; centromere suggests limited scleroderma. Low-titer ANA is common in healthy people, so titer and clinical context matter.
Serologic methods
- ELISA performance is described by sensitivity and specificity; positive and negative predictive values depend on prevalence, so a good test in a low-prevalence population yields many false positives.
- Confirm reactive screening tests with a second method (Western blot, immunoblot, NAAT) before diagnosing.
- The window period is the interval before antibody becomes detectable; antigen/antibody combination assays and NAAT shorten it.
- Syphilis: nontreponemal tests (RPR, VDRL) are quantitative and used to monitor treatment; treponemal tests (EIA, FTA-ABS, TP-PA) confirm. In the reverse algorithm, a reactive treponemal EIA is followed by RPR, and discordant results by a second treponemal test.
Worked example
A sample is nonreactive for HIV antibody when tested undiluted but reactive at 1:10. Reasoning: this is a prozone phenomenon - antibody excess saturates the assay reagents. Dilution resolves it and reveals the true positive. The same effect can occur in syphilis serology and in sandwich immunoassays for other analytes.
Traps that cost marks
- Treating a reactive screening test as a diagnosis.
- Missing prozone; always dilute a suspiciously negative sample.
- Rheumatoid factor and heterophile antibodies causing false positives in sandwich assays.
- Biotin interference in streptavidin–biotin platforms.
- Reading IgM positivity as acute infection despite recent vaccination or cross-reactivity.