As most of the cells and molecules of the immune system spend some or all of their time in the blood, sampling them is usually straightforward, and the standard tests illustrated here account for a substantial part of the routine work of the immunology and haematology laboratories, and often of microbiology and biochemistry too. The assays are mainly automated and a report will usually give the normal values and indicate which results are abnormal. Nevertheless, because of the considerable differences between individuals, and in the same individual with time, interpretation is not always obvious, even to those well versed in other aspects of medicine. The interpretation of tests for autoimmunity is particularly tricky.
Assays of both immunological molecules (e.g. antibody) and cells mainly make use of standard reagents, which are themselves frequently monoclonal antibodies, designed to react with only one molecular feature or cell-surface marker. The use of antibodies, whether monoclonal or not, to detect antigens of any kind is referred to as immunoassay (see Fig. 45). For detection, antibodies may be labelled with a radio-isotope (radioimmunoassay), an enzyme (ELISA) or a fluorescent molecule (immunofluorescence).
Occasionally, something more elaborate may be requested, e.g. a skin test for hypersensitivity, a bone marrow or other organ biopsy, blood or tissue typing before a transfusion or an organ graft, or the analysis of a leukaemia. Immunological tests are also used in epidemiology, e.g. to assess the extent of epidemics or the success of vaccines, and for the diagnosis of infections where the pathogen itself is not easily detected. In general, IgM antibodies denote recent, and IgG past, exposure.
Both the immune system and pathogens are increasingly studied through genes (see Fig. 47). Many diagnostic tests now rely on the PCR (see Fig. 45) to detect specific pathogens. High throughput techniques make it feasible to measure and analyse thousands of different proteins, genes and metabolites in tiny samples of tissue or blood: in the medicine of the future, these technologies will be used increasingly for diagnosis, and the development of ever more individualized medical treatments.
Investigating Immunodeficiency (see also Fig. 33)
Antibody Deficiencies
Total immunoglobulins and individual classes (e.g. IgG, IgA) can be measured by nephelometry or turbidimetry, ELISA, etc. A complete lack of immunoglobulins can be detected by absence of the γ-globulin arc in gel electrophoresis. Levels of antibody against particular antigens (e.g. a candidate virus) are measured by ELISA.