Immune specific

Svensson, C. and Lundberg, K., Immune-specific up-regulation of adseverin gene expression by 2,3,7,8-tetrachlorodibenzo-p-dioxin, Molec. Pharmacol., 60, 135, 2001. 

In general, a well-conducted long-term study in two species, with no indication of immunotoxicity, based on the considerations outlined above, should be adequate to evaluate the potential for drug-induced immunotoxicity. If the results from these studies do not produce evidence of immune-specific toxicity after examination of standard and/or additional hematologic, serum chemical, and histopathologic parameters, then additional testing should not be indicated. However, if there are structure-activity considerations that may indicate a potential for concern, of if... 

Abbas AR, Baldwin D, Ma Y et al (2005) Immune response in silico (IBIS) immune-specific genes identified from a compendium of microarray expression data. Genes Immun 6 319-331... 

Binder CJ, Hartvigsen K, Chang MK, et al. (2004) lL-5 links adaptive and natural immunity specific for epitopes of oxidized LDL and protects from atherosclerosis. J CUn Invest 114 427 37... 

To determine what cells make the immune-specific RNA we inoculated mid-third instar Drosophila larvae with bacteria and six hours later dissected them into fat bodies and fat body-free carcass. Total RNA was collected, separated by electrophoresis, transfered to nitrocellulose, and probed with labelled Pool 1 oligonucleotide. The results showed (Fig. 5) that intact inoculated larvae accumulate the immune-specific transcript while intact control larvae do not. The tissue dissection experiment showed that fat body cells of inoculated larvae contain transcripts homologous to the immune-specific probe, but the carcass does not. We conclude that fat body cells in Drosophila larvae accumulate a transcript that has homology to sarcotoxin when they have been inoculated with bacteria. We are currently cloning the responsible immune gene. 

Figure 4. The oligonucleotide recognizes an immune-specific transcript. melanogaster were inoculated with bacteria or left as controls and incubated for 11 or 30 hours as indicated. RNA was collected and separated on the gel shown at the right stained with ethidium bromide and then hybridized to the oligonucleotide probe in a northern blot on the left.

Figure 5. Drosophila fat body cells accumulate immune-specific RNA. Drosophila larvae were inoculated with bacteria and six hours later RNA was extracted from either whole larvae, from fat body, or from the carcasses minus fat body. These RNAs were separated on the gel shown on the right stained with ethidium bromide, then northern blotted and probed with the oligonucleotide on the left.

Some of the ABs may have structural homology to antibacterial proteins isolated from the flesh fly (20,21) since an oligonucleotide probe that can encode a portion of the sarcotoxin protein recognizes an immune-specific RNA in Drosophila fat body cells, the cellular origin of Drosophila s ABs (unpubl.). The induction mechanism must work relatively rapidly since we found immune-specific RNA in fat body cells within 6 hours after inoculation. Because of its homology to sarcotoxin, we assume that the immune-specific transcript detected by the oligonucleotide probe encodes an antibacterial protein. 

AID was first discovered using a subtracdve hybridization screen for genes activated on induction of GSR(Muramatsu et al, 1999) and has since been shown to serve highly critical roles in a number of immune-specific processes. AID expression is restricted to activated B cells (Muramatsu etal, 1999) and is required for SHM in mice (Muramatsu et al, 2000). AID was also found to be the culprit in a human immune disorder, Hyper-IgM-2 syndrome, in which some patients exhibited AID deficiency, resulting in the abolishment of both GSR and SHM (Revy et al, 2000). Hyper-IgM syndrome (HIGM) is characterized by normal or elevated serum IgM levels associated with the absence of IgG, IgA, and IgE isotypes as a result of defective GSR (Notarangelo et al, 1992). Additional experiments in mice and B cell lines have verified this AID requirement (Martin and Scharff, 2002 Muramatsu et al, 2000 Revy et al, 2000). 

Vaccine A substance that contains an antigen to which the immune system responds. See also immunization, specific types of vaccines. 

Antibodies have been raised against 5 -nucleotidase of mouse liver plasma membranes by using purified membrane preparations from the same source (GURD EVANS, 1974) and the antiserum inhibited enzyme activity. Antisera raised against rat liver as well as rat fat cell plasma membranes inhibited ecto-5 -nucleotidase in isolated rat fat cells (NEWBY al., 1975). However, it is not known whether the immune-specific and the catalytic site of the enzyme are identical. 

Interferons and interleukins either directly or indirectly affect some aspect of the immune system. Potential immunotoxicity is monitored by a variety of endpoints of the host response including natural immunity, specific cytotoxic T-cell immunity, delayed-type hypersensitivity, antibody production and secondary production of cytokines. In addition it is important to identify relevant laboratory tests, e.g. cytotoxicity, proliferation, cytokine levels, antibody... 

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