Mechanism of virulence and inhibition of influenza type (A) virus during mouse and egg adaptation.
Creators: name: Woodie, James David
Publisher: name: University of Utah
Year: 2012
Subjects: subject: Mice
subject: Microbiology
subject: FOS: Biological sciences

description: Several methods were used to study the host-parasite relationships in Pasteurella tularensis infections.  These included: 1) susceptibilities of normal and immunized mice, rabbits and guinea pigs to various strains of the organism; 2) determination of susceptibilities after x-irradiation; 3) in vitro phagocytosis using a standard bacteriological plate count and a radioisotope labeling method; 4) in vivo phagocytosis by the reticulo-endothelial system; 5) bactericidal activities in vitro of normal and immune sera; 6) passive transfer of normal and immune phagocytic cells and 7) passive transfer of normal and immune sera.  Rabbits, guinea pigs and mice were immunized by infecting with an LD25 of the moderately virulent strain Jap 4, followed in three weeds by an LD25 of the virulent strain 425 F4G.  The first group of immunized animals were found capable of surviving 10[3] times and LD100 challenge of a fully virulent strain of the organism, (LD100 = one organism).  The latter group were able to survive challenges of 10[4] times of normal LD100.  Similar protection was manifest when the animals were challenged with strains of lesser virulence.  A comparison was made of the vitro phagocytic capacities of alveolar and peritoneal macrophages taken from the normal and immunized groups of the three animal species mentioned.  Pasteurella tularensis strains 38, Jap 4, 425 F4G and 9K 161T ranging from avirulent to fully virulent were used in these phagocytic studies.  It was found that the immune phagocytes from all animals had significantly enhanced intracellular destructive capacities for all strains of the organism.  The effects of 30% autologous, homologous and heterologous normal and immune sera in the media were studied. It was observed that neither ingestion nor intracellular digestions were influenced by any of these types of sera in any of the experiments.  Extracellular specific antibodies were not found to influence the course of events when present with either normal or immune phagocytes.  Streptomycin was not found to affect intracellular organisms in these studies.  Passive transfer studies were conducted using alveolar macrophages from rabbits and guinea pigs, peritoneal microphages from rabbits, guinea pigs and mice, and peritoneal polylmorphonuclears from mice.  These cells were injected intraperitoneally into the animals which were challenged in the same manner at various time intervals before and after cell transfers were made.  It was found that immune phagocytes from all three species were capable of protecting each of the others if the cells were given at the time of challenge or before, but not if given 24 hours after challenge.  Normal cells from the naturally resistant rabbits (to strain 425 F4) were found capable of protecting normal mice challenged with the same strain.  Passive normal and immune serum transfers were also conducted in these three animal species. It was found in these studies that homologous or heterologous immune sera were able to increase the time of survival of all animals challenged with small numbers of a fully virulent strain of the bacterium, but did not decrease the mortalities of these animals.  Those animals challenged with strains of lesser virulence had decreased mortalities, as well as increased survival times.  These results were also evident using homologous or heterologous sera.  No relationships between agglutinin titers and protection were evident.  Further studies conducted showed that normal sera from rabbits, guinea pigs and mice had significant bactericidal activities upon all strains of the organisms ranging from 3 to 15 percent.  Immune sera did not have additional bactericidal activities.  In other studies it was found that the organs of the reticuloendothelial systems of mice and rabbits had increased intracellular cytopeptic abilities as compared to those from normal animals.  Increased ingestive abilities were not observed.  It was confirmed that a critical age exists in the three animal species, under which immunization was not as effective as in older animals.  This age was near 30 days for each of the species.  The effects of x-irradiation on normal and immunized mice and guinea pigs challenged before and after irradiation were examined.  It was found that immunization protected these animals against sub-lethal numbers of bacteria.  Immunized animals challenged 48 hours after irradiation were found to have increased mortalities and decreased survival times as compared to those challenged before and at the time of irradiation.  Similar results were observed with non-immunized animals.  It was concluded from these studies that cellular factors are paramount in host resistance to P. tularensis infections in both normal and immune rabbits, mice and guinea pigs.  Enhanced intracellular destructive capacities of the phagocytes are primarily responsible for the increase of resistance in immunized animals.  The exact mechanisms involved are unknown as are the roles of specific antibodies and other humoral factors.  These humors, however, do have some influence on the infections as it shown by the bactericidal activities of the serum and the increased survival time of the challenged animal when immune serum therapy was used.