Disease resistance models

Commonly Employed Experimental Disease Resistance Models. ... 

Selgrade, M.K., Daniels, M.J. and Dean, J.H., Correlation between chemical suppression of natural killer cell activity in mice and susceptibility to cytomegalovirus rationale for applying murine cytomegalovirus as a host resistance model and for interpreting immunotoxicity testing in terms of risk of disease, J. Toxicol. Environ. Flealth, 37, 123, 1992. 

A glucocorticoid-resistance model has been proposed to provide an explanation for how stress might influence diseases in which excessive inflammation is observed (e.g., allergies, autoimmune diseases, rheumatoid arthritis, and cardiovascular disease). In these cases, chronic stress diminishes the immune system s sensitivity to glucocorticoids that normally terminate the inflammatory response. For example, in a study of a group of 50 parents caring for a child undergoing treatment for pediatric cancer, whole blood of parents of cancer patients exhibited a lesser dexamethasone-dependent suppression of IL-6 production in vitro compared to parents of medically healthy children.94... 

Extensive evidence suggests that the immune system is a sensitive target for toxicity of 2,3,7,8-TCDD and structurally related halogenated aromatic hydrocarbons (Kerkvliet 1995). Exposure to 2,3,7,8-TCDD can increase susceptibility to bacterial (Thigpen et al. 1975 Thomas and Hinsdill 1979 White et al. 1986), viral (Clark et al. 1983 House et al. 1990), parasitic (Tucker et al. 1986), and neoplastic disease (Luster et al. 1980). However, the specific immunological functions affected by 2,3,7,8-TCDD in most of the host-resistance models have not been fully defined. Thymic involution is characteristic of exposure to 2,3,7,8-TCDD and structurally related chemicals in all species examined. There is experimental evidence showing that immune suppression in rodents occurs at lower doses of... 

Integrate resistance models with other systems that predict disease, pests, plant growth, etc. (i.e., an IPM system incorporating resistance management). 

Biological engineering. Once a system is modeled and understood, the pathway or network can be reengineered to produce a better outcome (e.g., disease-resistant crop) or to identify the optimal therapeutic agent. 

Infectious Diseases. Resistance to a variety of organisms, including BCG, cryptococcus, and Candida, has been shown to be increased in immunosuppressed animals following in vivo treatment with TF5 (Collins and Auclair, 1979 Collins and Morrison, 1979 Bistoni et al., 1982 Ishitsuka et al, 1983). The basis for this increased resistance may be explained by studies showing that mouse strains with low resistance to Candida or BCG have increased resistance and elevated production of two lymphokines, MIF and 7 interferon following in vivo treatment with TF5 (Neta and Salvin, 1983 Salvin and Neta, 1983). Similar results were seen with Taj. In another model, interferon production in response to Newcastle s disease virus infection was also increased by in vivo treatment with TF5 or Ta (Huang et al., 1982). 

Therapeutic Agents Targeting TNF-oc. The Streptococcus pneumoniae host resistance model is also valuable for evaluating the importance of macrophage cytokines on bacterial host resistance. Human biological therapeutics targeting inhibition of TNF-a have been used to treat inflammatory autoimmune diseases such as rheumatoid arthritis. Decreased TNFa as a result of treatment with monoclonal antibodies (mAb) to TNF-a has an effect on several biomarkers of infection (Takashima et al, 1997 van der Poll et al, 1997 Benton et al., 1998 O Brien et al, 1999). These studies have reported that treatment of mice with a mAb to TNF-a results in altered levels of TNF-a in the lungs... 

Abstract This chapter describes what is known about the main components and responses of the innate and adaptive immune system of fish. The chapter first reviews the organs, cells and molecules of the immune system known in a few economically important or model fish species. Molecular evidence suggests a similar immune system exists throughout the jawed vertebrates yet marked differences are also apparent. The innate parameters are at the forefront of fish immune defence and are a crucial factor in disease resistance. The adaptive response of fish is commonly delayed but is essential for long lasting immunity and a key factor in successful vaccination. 

Some metabolites of curcumin (particularly tetrahydrocurcumin) may also participate in producing the observed effects of curcumin in different models because these metabolites display greater stabilities than the parent curcumin molecule at physiological pH. Recent data show similar modes of action of curcumin metabolites regarding antioxidant enzyme induction and inhibition of multidrug-resistant proteins. " Additional data indicate that curcumin may even act against other types of diseases such as atherosclerosis " " and Alzheimer s disease. " - " ... 

---