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Biomedical subjects

G B MACKANESS

Publications and source records attributed to G B MACKANESS.

At least 19 recordsLinked to original sources

THE IMMUNOLOGICAL BASIS OF ACQUIRED CELLULAR RESISTANCE.

The resistance developed by mice during infection with Listeria monocytogenes, Brucella abortus, or Mycobacterium tuberculosis is not specifically directed against the infecting organism. The processes involved in the induction of acquired resistance, however, are highly specific and seem to depend upon two factors: a state of immunological reactivity of the host and the presence of the specific microbial antigens to which the host has become reactive. When these two coexist in the tissues the host is found to be non-specifically resistant. It is suggested that resistance, which was shown to depend upon an altered state of host macrophages, may be due to the interaction of antigen and a specific antibody adsorbed to the surface of host macrophages; and that the antibody involved in the reaction is perhaps identical with the antibody which confers the state of delayed-type hypersensitivity. The results are discussed in relation to the question of latent infection and infection immunity.

Allergy and Immunology↗

THE PASSIVE TRANSFER OF ACQUIRED RESISTANCE TO LISTERIA MONOCYTOGENES.

Five methods have been used in an effort to reveal an antibody that could account for the features of acquired resistance to Listeria monocytogenes: (a) a comparison of the growth rates of Listeria in the spleens of mice infused repeatedly with normal or immune mouse serum; (b) measurement of peritoneal clearance of Listeria in the presence of normal or immune mouse serum; (c) the survival rate of Listeria in monolayers of mouse macrophages infected in the presence of normal or immune mouse serum; (d) the effect of injecting urea extracts of spleens and peritoneal macrophages of normal or immune mice on the survival and growth of Listeria in recipient animals; (e) a comparison of survival rates in lethally infected mice following the passive transfer of cells and serum from normal or immune donors. The only evidence of passive protection was obtained when intact living cells from immune donors were used for transfer under conditions which permitted them to interact with the parasite population.

Allergy and Immunology↗

Cellular resistance to infection.

The mouse was found to be natively susceptible to Listeria monocytogenes. Its susceptibility was attributed to the capacity of the organism to survive and multiplying in host macrophages. During the first 3 days of a primary infection the bacterial populations of spleen and liver were found to increase at a constant rate. On the 4th day of infection the host became hypersensitive to Listeria antigens and at the same time bacterial growth ceased. A rapid inactivation of the organism ensued. Convalescent mice were resistant to challenge, but no protective factor could be found in their serum. Histological evidence suggested that acquired resistance was the result of a change occurring in the host's mononuclear phagocytes. When challenged in vitro, the macrophages of convalescent mice were found to resist infection with Listeria monocytogenes. Listeria-resistant cells appeared during the course of infection at a time which corresponded with the development of the antibacterial mechanism in the spleen. They persisted for as long as the antibacterial mechanism remained intact in this organ. This period of absolute resistance to Listeria lasted about 3 weeks. Thereafter, the host remained hypersensitive but unable to inactivate a challenge inoculum of Listeria. However, it remained capable of producing an accelerated response to reinfection. This was thought to depend upon an ability to generate a new population of resistant cells from a residuum of specifically sensitized macrophages or macrophage precursors still surviving in the tissues as a result of the immunological activation which occurred during the primary infection.

Animals↗

The phagocytosis and inactivation of staphylococci by macrophages of normal rabbits.

The phagocytosis and survival of staphylococci in the presence of rabbit macrophages has been studied quantitatively. The method permitted an independent measurement to be made of intracellular and extracellular bacteria during the course of phagocytosis. It was found that S. aureus was relatively resistant to phagocytosis. In the presence of specific immune serum, however, it was ingested at a rate comparable with that of S. albus in normal serum; under these conditions more than 90 per cent of bacteria of either strain were inactivated within 60 minutes. Since immune serum did not alter the susceptibility of S. aureus to inactivation within macrophages, it is concluded that S. aureus and S. albus are similar in respect to their ability to survive within macrophages. The inactivation of staphylococci occurred more slowly, and a greater percentage survived incubation for 180 minutes, in macrophages than in polymorphonuclear leucocytes. Moreover, they retained their morphology for many hours within the former cell, but disappeared rapidly from the cytoplasm of granulocytes. It is suggested that the antibacterial mechanisms of the two cell types are fundamentally different. When studied over a prolonged period the staphylococci which survived early inactivation within macrophages were observed to die slowly over many hours. When they were recovered from cells and exposed to fresh macrophages, however, they were ingested and inactivated as readily as bacteria of the original population. It is suggested, therefore, that the prolonged survival in vitro of some staphylococci is due to variation in the efficiency of the antibacterial mechanism of exudative mononuclear phagocytes.

Animals↗