Concerted use of immunologic and ultrastructural analyses in diagnostic medicine: immunoelectron microscopy and correlative microscopy.

Electron microscopy (EM) is a valuable tool in diagnostic medicine, and in some cases, can be enhanced by immunological methods. A major medical application of EM, diagnostic virology, can frequently be augmented by employment of immunological reagents. Three immunoelectron microscopy (IEM) methods, aggregation, coating, and gold labeling, provide means for serotyping viruses; aggregation by antibody can also be used to concentrate viruses in dilute suspension or to serotype them. As a research tool, IEM can be useful in studying the relationship of various pathogen proteins to the infected cells or tissues. Delineating the subcellular location of viral components can yield information about how virions are constructed, and hence, suggest methods and compounds for inhibiting that process. Conversely, labeling virus-infected cells with antibodies against various cell receptors and proteins can yield information about the association of the proteins with budding virions. Another research example is the identification by immunological staining of virus-infected cells for subsequent ultrastructural identification of the specific cell type involved. Electron microscopy and immunolabeling methods are also useful in the diagnosis of immune complex disorders, including various forms of postinfectious immune complex glomerulonephritis. Precise analysis of immune complex deposits can be accomplished by using EM to pinpoint their location and immunohistology to probe their composition. Finally, a variety of optical microscopic techniques, including some involving immunofluorescent labeling, can be used to identify areas of interest in inhomogeneous tissues for further study by EM.