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Activated T cells release cytokines that cause accumulation and activation of macrophages, which in turn cause local damage This type of reaction is very important in defense against intracellular infections such as tuberculosis, but is also responsible for contact hypersensitivity responses (allergic contact dermatitis) such as the response to poison ivy Inhalation of beryllium can result in a range of pathologies, including acute pneumonitis, tracheobronchitis, and chronic beryllium disease, all of which appear to be due to type IV berylliumspeci c immune responses The expression of type IV responses following challenge is delayed, occurring 24 to 48 hours after exposure The different types of immune-mediated injury are not mutually exclusive More than one hypersensitivity mechanism may be involved in the response to a particular antigen.

The lipid envelope is embedded with HBV surface antigen (HBsAg) proteins, which are provided by a coinfecting HBV14 The HBV proteins present in the lipid envelope provide the means for HDV particle exit and entry into the cell This dependence on HBV for a source of envelope proteins provides the molecular explanation for why HDV infection is always accompanied by HBV coinfection Although identical over most of their length, SHDAg and LHDAg differ in their function in a variety of ways For example, while SHDAg is crucial for RNA replication the LHDAg can trans-dominantly inhibit this process15,16 Large delta antigen can also trans activate a variety of different genes17 Perhaps the most dramatic difference between the delta antigen isoforms is observed during virus assembly Although both isoforms are found in HDV particles, only the large delta antigen can promote virus assembly in conjunction with HBsAg.

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The rst quantity of interest is the shape and the characteristics of the empirical cumulative distribution of all interarrival times. Figure 15.7 shows the empirical density function for the CMU trace from 29 to 30 June 1995 and for the external AT&T trace from 18 November to 8 December 1995. Although the empirical density is fairly smooth, there are quite a few spikes, especially for the small interarrival times. The spikes in the small interarrival times are due to timer resolution problems and simultaneous arrival of connections.

Also the resulting pathology, particularly that caused by type III and IV, reactions may appear very similar, although the mechanisms leading to the effect are different..

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Transport through circulatory system in association with binding proteins Passive diffusion, carrier-mediated uptake, active uptake, filtration in elimination organs Biotransformation

An important clue as to what feature of large delta antigen is required for its role in particle assembly was revealed by a closer examination of the 19 amino acids unique to the larger isoform In particular, it was noted that the last four amino acids of LHDAg, Cys-Arg-Pro-Gln-COOH, constitute a CXXX box motif that is highly conserved in all HDV isolates This observation suggested that LHDAg is subject to prenylation and indeed this was shown to be the case18 Subsequent studies demonstrated that the speci c type of prenyl lipid added to delta antigen is farnesyl19 That large delta antigen prenylation is required for HDV particle assembly was shown by mutation of the large delta antigen CXXX box18 Mutation of cysteine to serine abolished both prenylation and assembly of HDV virus-like particles (VLPs) (Figure 111).

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Figure 10.5 Processes involved in the vectorial transport of xenobiotics from the whole body point of origin to the speci c site of elimination.

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This was the rst demonstration that viral proteins can undergo prenylation and exploit this modi cation to mediate a critical aspect of the corresponding virus life cycle For HDV, the apparent crucial role of prenylation in virus assembly may be to target the thus lipid-modi ed large delta antigen to the membranes that contain the HBsAg envelope proteins Alternatively, the attached farnesyl moiety could act as a ligand speci cally recognized by a receptor in those membranes, such as HBsAg, somewhat analogous to the interaction of the geranylgeranylated Rab3 with GDI7 In either case, these results suggested the hypothesis that inhibition of LHDAg prenylation by pharmacologic means might similarly prevent virus particle formation and thereby represent the basis for.

LeBlanc, G. A., and W. C. Dauterman. Conjugation and elimination of toxicants. In Introduction to Biochemical Toxicology, E. Hodgson and R. C. Smart, eds. New York: Wiley-Interscience, 2001, pp. 115 136. Kester, J. E. Liver. In Encyclopedia of Toxicology, vol. 2, P. Wexler, ed. New York: Academic Press, 1998, pp. 253 261. Rankin, G. O. Kidney. In Encyclopedia of Toxicology, vol. 2, P. Wexler, ed. New York: Academic Press, 1998, pp. 198 225. Klaassen, C. D. ed. Casarett and Doull s Toxicology: The Basic Science of Poisons, 6th ed. New York: McGraw-Hill, 2001.

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