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Reactive Oxygen and Nitrogen Intermediates in the Relationship Between Mammalian Hosts and Microbial Pathogens
Pages 90-97

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From page 90...
... Reflections on redundancy in immunity help explain an apparent paradox: the phagocyte oxidase and inducible nitric oxide synthase are each nonredundant, and yet also mutually redundant, in host defense. In combination, the contribution of these two enzymes appears to be greater than previously appreciated.
From page 91...
... , are susceptible to several inoculated pathogens. Finally, mice deficient in the high output pathway of nitric oxide production, catalyzed by NO synthase type 2 (NOS2 or iNOS)
From page 92...
... Thus, phox and NOS2 each appear to compensate in large part for isolated deficiency of the other. The relative futility of host defense against commensal organisms in
From page 93...
... Thus, the concept of microbial resistance is central not just to the pharmacology but also to the immunology of tuberculosis. Because RNI are essential for the control of murine tuberculosis and are produced in human tuberculosis, and control of the pathogen is imperfect in both species, tubercle bacilli may express mechanisms for RNI resistance.
From page 94...
... Differences in species, cell types, subcellular localization, and regulated expression help account for this multiplicity, but there is a more instructive explanation: chemical specificity. The earlier discussion of nonspecificity of chemically reactive micromolecules referred to the species of origin of their submolecular targets.
From page 95...
... An adaptation termed "differential" STM collects all of the bacterial clones that were negatively selected in wild-type mice and places them into new panels, together with a suitable number of control bacterial clones that had not displayed a survival disadvantage in vivo. These second-generation panels are used to repeat the selection in wild-type mice and simultaneously to extend the selection to mice genetically disrupted in a host defense pathway of interest: for example, `gp91Ph°X or NOS2.
From page 96...
... The distribution and diversity of RNI resistance genes suggest that RNI exert evolutionary pressure and that different RNI pose distinct biochemical challenges. Agents that inhibit pathogens' RNI resistance mechanisms may improve immunity in those diseases for which RNI represent an important but imperfect element of host control.
From page 97...
... (1999) in Nitric Oxide and Infection, ed.


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