Immunology and Serology
Core concepts
Build the framework in layers: innate versus adaptive immunity, antibody structure and class function, complement pathways, MHC presentation, and T and B cell cooperation. Then move to clinical correlations. Type I hypersensitivity is IgE mediated, type II is antibody against cell-bound antigen, type III is immune complex deposition, and type IV is T cell mediated and delayed. Autoimmune serology includes ANA patterns with reflex to anti-dsDNA and anti-Smith for lupus, rheumatoid factor and anti-CCP for rheumatoid arthritis, and anti-neutrophil cytoplasmic antibodies for vasculitis. Transplant testing involves HLA typing, panel-reactive antibody screening, and crossmatch.
Method principles matter as much as results. Enzyme immunoassay, chemiluminescence, nephelometry, agglutination, immunofluorescence, and immunoblot differ in sensitivity and throughput. Sensitivity and specificity are test properties; predictive values depend on prevalence. Be able to explain why a positive test in a low-prevalence population may still be a false positive.
Traps
- Ignoring prozone, where antibody excess produces a false-negative agglutination or turbidity result; dilute and repeat.
- Ignoring postzone, where antigen excess does the same.
- Treating a biological false-positive RPR as syphilis without a treponemal confirmatory test.
- Interpreting IgM without considering rheumatoid factor interference or persistent antibody.
- Confusing cold agglutinins with cryoglobulins; both require careful temperature control of the specimen.
Rule of thumb
When an agglutination or nephelometric assay gives an unexpectedly negative or discordant result and the patient has a very high antibody concentration, suspect prozone and retest a diluted sample. For syphilis, a reactive nontreponemal test is confirmed by a treponemal assay.