Immunology
Immunology questions ask you to connect immune mechanism to laboratory result: which immunoglobulin dominates a response, which hypersensitivity type fits a clinical story, which serologic method suits an analyte, and what a positive result actually predicts in a given population.
Immune fundamentals
- IgM is the first antibody in a primary response, is pentameric, fixes complement well, and cannot cross the placenta; IgG is monomeric, dominates secondary responses, crosses the placenta, and is the main antibody in IAT-reactive red cell alloantibodies.
- IgA guards mucosa and is the main immunoglobulin in secretions; IgE mediates type I hypersensitivity; IgD is a B-cell surface marker.
- Adaptive immunity: B cells make antibody; CD4 T cells coordinate; CD8 T cells kill. MHC class I presents to CD8 cells on nearly all nucleated cells; MHC class II presents to CD4 cells on antigen-presenting cells.
Hypersensitivity types
- Type I: IgE and mast cells (anaphylaxis, allergic rhinitis).
- Type II: antibody against cell-bound antigen (autoimmune hemolysis, Goodpasture).
- Type III: immune complex deposition (serum sickness, post-streptococcal glomerulonephritis, SLE).
- Type IV: T-cell mediated, delayed (tuberculin reaction, contact dermatitis).
Methods and interpretation
- ELISA, indirect immunofluorescence, nephelometry, particle agglutination, flow cytometry and molecular amplification each have different sensitivity and turnaround trade-offs.
- Prozone is antibody excess giving a falsely negative agglutination or turbidimetric result; postzone is antigen excess. Dilute and repeat.
- Antinuclear antibody is a screening test; anti-dsDNA and anti-Smith are specific for SLE, and anti-CCP is specific for rheumatoid arthritis.
- Protein electrophoresis with immunofixation detects monoclonal gammopathy; a monoclonal band plus anemia, renal failure and hypercalcemia suggests myeloma.
Worked example
A screening test has 95% sensitivity and 90% specificity. Prevalence is 1% in 10,000 people. Diseased: 100, so 95 true positives and 5 false negatives. Healthy: 9,900, so 990 false positives and 8,910 true negatives. Positive predictive value = 95 / (95 + 990) = 8.8%; negative predictive value = 8,910 / 8,915 = 99.9%. Reasoning: at low prevalence, most positives are false, so a screening positive needs a specific confirmatory test, and a negative result is far more informative than a positive one.
Traps that cost marks
- Reporting an agglutination result as negative without checking for prozone.
- Treating ANA as diagnostic of SLE rather than as a sensitive screen.
- Confusing type III with type II hypersensitivity in glomerular disease questions.
- Ignoring rheumatoid factor interference in nephelometric and immunoassay measurements.