490 Delayed Hypersensitivity - Type Granuloma ~ ' Ormation

Granulomatous inflammation plays a major role in the pathogenesis of a wide variety of diseases caused by infectious agents, including mycobacteria (tuberculosis, leprosy); fungi (coccidioidomycosis, histoplasmosis); worms (schistosomiasis, fllariasis) ; and possibly viruses and protozoa (1, 2). Although it has long been suspected that the granuloma may be a manifestation of delayed hypersensitivity, significant data supporting this concept have been gathered only in the past 15 yr (2). As recently as 1967 a review of granulomatous hypersensitivity concluded that the evidence was still insufficient to include the granuloma in the spectrum of delayed responses (2). Since then, the Schistosoma mansoni egg granuloma, a quantifiable model of granulomatous inflammation (3), has been established as a form of delayed hypersensitivity. Mice previously exposed to schistosome eggs develop larger granulomas more rapidly than control unsensitized animals (4). The anamnestic reaction is specific in relation to other worm genera (4), to the two other schistosome species infective to man (5), and even to the different life cycle stages of S. mansoni itself (6). Sensitization is transferrable from infected to uninfected inbred mice by lymph node and spleen cells, but not by serum (4). Finally, the granulomatous response is strongly inhibited by a series of immunosuppressive measures known to be particularly effective against delayed hypersensitivity (7-9) and is unaffected by measures directed primarily against antibodymediated reactions (9, 10). The schistosome egg granuloma is a local inflammatory response composed mainly of macrophages and their derivatives, lymphocytes and eosinophils (11). Immunofluorescent studies have shown that the parasite eggs emit specifically stainable antigens through submicroscopic pores in their shells (11, 12). These antigens are taken up by phagocytic cells clustered about the eggs (12).