Mechanisms of immunity in typhus infection: some characteristics of Rickettsia mooseri infection of guinea pigs

Abstract

Rickettsia mooseri infection has been studied in syngeneic guinea pigs inoculated intradermally with the objective of developing a model for the study of immune mechanisms. Characterization of infection included the following: a study of replication, dissemination, and clearance of rickettsiae; measurement of the antibody response with different rickettsial antigens and tests; and attempts to measure the cell-mediated immune response using the correlate of delayed-type hypersensitivity skin reactions. Following intradermal inoculation, rickettsiae replicate locally and then spread to the draining lymph nodes and subsequently cause systemic infection. Spread to draining lymph nodes occurred before the appearance of circulating antibody, whereas systemic infection occurred afterwards. Two distinct patterns of acquired resistance developed. The first was marked by a cessation of rickettsial growth within a given organ and the second by a clearance of rickettsiae. The duration of each of these phases differed markedly from one organ to another. Delayed-type hypersensitivity was not demonstrated by skin testing.

Mechanisms of immunity in typhus infection: adoptive transfer of immunity to Rickettsia mooseri

“…infection, measured as clearance of rickettsiae from the primary site of i.d. infection and as a capacity to resist second homologous challenge delivered at skin sites distant from that of primary infection, develops well before the onset of systemic infection (8). It appears, therefore, that systemic infection develops in the presence of the immunological control of the local skin infection.…”

“…inoculation of 3.5 x 104 plaque-forming units (PFU) of R. mooseri (kidney cell seed) into the outer aspect of the thigh was used to initiate immunizing infections. This inoculum and route of infection were selected because the resulting infection and aspects of the host immune response to infection occur in a reproducible sequence (8,9). (iii) Assays for protection.…”

“…When nonimmune guinea pigs are inoculated intradermally (id.) with Rickettsia mooseri (R. typhi), the organisms replicate at the site of inoculation for 3 to 5 days, depending on the size of the inoculum, after which they are rapidly eliminated (8,9). Despite the fact that rickettsiae disappear from the site of inoculation at about the same time as antibodies become detectable in the serum, the local cellular reaction, rather than antibodies, seems to be correlated more closely with their clearance (9).…”

“…Although the local reaction strongly suggests a cell-mediated immune mechanism, the infected animals fail to demonstrate delayed-type hypersensitivity when skin tested with R. mooseri antigen. Furthermore, systemic dissemination ofthe rickettsiae occurs only after they have been eliminated from the site of inoculation, at a time when high antibody levels exist (8).…”

“…Seed 2, prepared from embryonated chicken eggs (12EP/15GP/5EP), was used for challenge infections (see below). Some characteristics of these seed preparations and the method employed for their production and characterization have been published (8,10). Guinea pigs infected with the seed prepared from monkey kidney cell cultures did not develop hypersen-sitivity to normal yolk sac components.…”