Studies on the Mechanism of Immunity in Typhus Fever

This study of the lesions produced in the skin of guinea pigs inoculated intracutaneously with Mexican typhus virus, shows that there is an early polymorphonuclear response at the point of inoculation. As early as 24 hours after the virus is given, a mononuclear phagocytic infiltration, which is more pronounced around the larger vessels of the corium, vascularis, and muscularis, replaces the polymorphonuclear infiltration. The endothelial cells of capillaries and small vessels swell up, thus partially occluding the lumina. Rickettsia bodies are found in the swollen cells, in numbers which remind one of the intracellular Rickettsiae of the tunica in typhus infected guinea pigs. The mature Mooser's cells are found in abundance on the 3rd to the 4th day after inoculation. They are found in various positions as follows: (a) in the endothelial cells of capillaries, particularly in places of little or no infiltration; (b) within the mononuclear nodules formed around the larger vessels and within the dense infiltration of the vascularis (the parasitized cells are usually traced to a capillary wall); and (c) less frequently the organisms are found within the swollen cells of arterioles and small veins. The organisms disappear gradually from the zones of increasing polymorphonuclear infiltrations, suggesting that the presence of such polymorphonuclears is due to the bursting of the infected cells. In the artificial lesions produced in the skin by the inoculation of considerable numbers of Rickettsiae, the tissue reactions are abnormally enhanced. One can see in the same slide different stages of the development of the lesions and their relationship to the infecting agent. The early perivascular infiltration by mononuclear phagocytes does not seem to be related to an actual infection of the endothelial lining by the inoculated virus, but seems rather, when properly controlled, to be primarily due to a nonspecific type of response. The capillaries or small vessels within these infiltrated zones may become parasitized and call forth a polymorphonuclear reaction which may thus transform the cytological picture of the nodule. The subsequent migration of macrophages terminates the histological sequence. In capillaries apart from areas of cellular infiltrations, the polymorphonuclear reaction is first to appear, when the Rickettsiae are liberated from the cells. One cannot safely generalize from the results observed in an artificial typhus lesion, but in the light of these observations, it is probable that the Rickettsia bodies are difficult to find in typhus patients or infected animals because they disappear rapidly from the nodules, or perhaps because some nodules are not necessarily related to an infected endothelium. At any rate, a late typhus lesion is not likely to reveal Rickettsiae which most probably have been removed by the early polymorphonuclear invasion.