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1
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0004291826
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X. Schaechter, M. G. Medoff, B. J. Eisenstein, Eds. Williams & Wilkins, Baltimore, MD, ed. 2
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For a population biologist-friendly review of these defenses, see J. K. Spitznagel, in Mechanisms of Microbiat Disease, X. Schaechter, M. G. Medoff, B. J. Eisenstein, Eds. (Williams & Wilkins, Baltimore, MD, ed. 2, 1993), pp. 90-114; H. K. Zeigler, in Mechanisms of Microbial Disease, M. Schaechter, G. Medoff, B. I. Eisenstein, Eds. (Williams & Wilkins, Baltimore, ed. 2, 1993), pp. 114-153; W. E. Paul, Ed., Fundamentals of Immunology (Lippincott, Williams & Wilkins, Baltimore, MD, ed. 4, 1999).
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(1993)
Mechanisms of Microbiat Disease
, pp. 90-114
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Spitznagel, J.K.1
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2
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0004291826
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M. Schaechter, G. Medoff, B. I. Eisenstein, Eds. Williams & Wilkins, Baltimore, ed. 2
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For a population biologist-friendly review of these defenses, see J. K. Spitznagel, in Mechanisms of Microbiat Disease, X. Schaechter, M. G. Medoff, B. J. Eisenstein, Eds. (Williams & Wilkins, Baltimore, MD, ed. 2, 1993), pp. 90-114; H. K. Zeigler, in Mechanisms of Microbial Disease, M. Schaechter, G. Medoff, B. I. Eisenstein, Eds. (Williams & Wilkins, Baltimore, ed. 2, 1993), pp. 114-153; W. E. Paul, Ed., Fundamentals of Immunology (Lippincott, Williams & Wilkins, Baltimore, MD, ed. 4, 1999).
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(1993)
Mechanisms of Microbial Disease
, pp. 114-153
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Zeigler, H.K.1
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3
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0004257938
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Lippincott, Williams & Wilkins, Baltimore, MD, ed. 4
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For a population biologist-friendly review of these defenses, see J. K. Spitznagel, in Mechanisms of Microbiat Disease, X. Schaechter, M. G. Medoff, B. J. Eisenstein, Eds. (Williams & Wilkins, Baltimore, MD, ed. 2, 1993), pp. 90-114; H. K. Zeigler, in Mechanisms of Microbial Disease, M. Schaechter, G. Medoff, B. I. Eisenstein, Eds. (Williams & Wilkins, Baltimore, ed. 2, 1993), pp. 114-153; W. E. Paul, Ed., Fundamentals of Immunology (Lippincott, Williams & Wilkins, Baltimore, MD, ed. 4, 1999).
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(1999)
Fundamentals of Immunology
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Paul, W.E.1
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7
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0032475822
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A. U. Neumann et al., Science 282, 103 (1998).
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(1998)
Science
, vol.282
, pp. 103
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Neumann, A.U.1
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13
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0342900472
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note
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"I often say that when you can measure what you are speaking about, and express it in numbers, you know something about it: but when you cannot express it in numbers, your knowledge is of a meager and unsatisfactory kind: it may be the beginning of knowledge, but you have scarcely, in your thoughts, advanced to the stage of Science, whatever the matter may be." William Thompson (Lord Kelvin) (1824-1907). Of course, we wouldn't say that.
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14
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0343771393
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note
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In itself this is a considerable achievement. The integument of a mammal and the associated fluids and cilia are formidable defenses in their own right and are, doubtless, the primary reason that the bacteria and other microparasites that abound in the world around us, on us, and within us rarely cause disease. Save for trauma including the proboscis of biting arthropods, it is difficult for a microbe to get through the skin of a mammal. Although not as impermeable as skin, the mucosa of the alimentary tract and nasal pharyngeal passages and other orifices have formidable defenses of their own. Included among these are our microbial allies, the established populations of our commensal bacteria in these habitats. Their communities, and by default the mucosa in which they reside, are protected from colonization by potential pathogens by a home team advantage in the competition for space and nutrients and a variety of competitive allelopathic mechanisms, such as bacteriocins and microcins and predation by phage, protozoa, and nemotodes.
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16
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0342900465
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F. P. DeVries, A. VanDerEden, J. P. M. Putten, J. Dankert, Infect. Immun. 64, 2999 (1996).
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(1996)
Infect. Immun.
, vol.64
, pp. 2999
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DeVries, F.P.1
VanDerEden, A.2
Putten, J.P.M.3
Dankert, J.4
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18
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0343771391
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note
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If the colonizing population of the ancestral capsulated strains is too small, a sufficient number of unencapsulated variants (mutants) may not be generated and invasion will not take place. This indeed, may well be one of the reasons for the observations that systemic infections are caused by very few of the colonizing bacteria (42-44). These situations where a genetic change in the microparasite population is needed to establish systemic infection virulence could well be a consequence of short-sighted evolution of the microparasite in the host, rather than an adaptation for the maintenance of the microparasite in the community of hosts (45).
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19
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0342900470
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note
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It has been suggested that because of the stochastic nature of the early phase of infections, vaccines that are only partially effective could reduce the probability of infection (46).
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20
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0343771390
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note
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It may well be that although the infection is cleared by the constitutive defenses, an adequate specific immune response may be induced to generate immune memory. This, for example, may account for why older adults who have never experienced invasive diseases by commensal organisms such as H. influenzae and N. meningititis are much less susceptible to bacterial meningitis than younger individuals.
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21
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0342900468
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For an example of a mathematical model of this type and a consideration of the motivation for its development, its predictions, and its role in an experimental study of a bacterial infection, see www.eclf.net/ phagocyte.html.
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26
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0030980891
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A. R. McLean, M. M. Rosado, F. Agenes, R. Vasconcello, A. A. Freitas, Proc. Natl. Acad. Sci. U.S.A. 94, 5792 (1997).
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(1997)
Proc. Natl. Acad. Sci. U.S.A.
, vol.94
, pp. 5792
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McLean, A.R.1
Rosado, M.M.2
Agenes, F.3
Vasconcello, R.4
Freitas, A.A.5
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33
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0033615678
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T. P. Arstila et al., Science 286, 958 (1999).
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(1999)
Science
, vol.286
, pp. 958
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Arstila, T.P.1
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49
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0343771381
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The authors wish to thank F. Baquero, J. Bull, D. Generaux, D. Relman, I. Stojilkovick, and R. Zappala for useful comments and suggestions, most of which we agree with but lament in not having the space to develop them here. This endeavor was supported by grants from the U.S. National Institutes of Health GM33782 and AI40662 (B.R.L) and GM 54268 (R.A.) and from the Wellcome Trust (B.R.L)
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The authors wish to thank F. Baquero, J. Bull, D. Generaux, D. Relman, I. Stojilkovick, and R. Zappala for useful comments and suggestions, most of which we agree with but lament in not having the space to develop them here. This endeavor was supported by grants from the U.S. National Institutes of Health GM33782 and AI40662 (B.R.L) and GM 54268 (R.A.) and from the Wellcome Trust (B.R.L).
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