Host resistance

Levamisole [14769-73-9] (6-phenyl-2,3,5,6-tetrahydroimida2o[2,l- ]thia2ole, 8) C22H22N2S, was found to be effective against herpes vims infections in humans (15,16). It acts as a modulator of host resistance mechanisms, especially as an enhancer of cellular immunity. 

Plants are continually exposed to a vast array of potential phytopathogenic fungi nevertheless, plants resist to most of them by blocking fungal development soon after penetration. Resistance against pathogens can be distinguished in resistance at the species level (non-host resistance) and resistance at the cultivar level (race-cultivar resistance). Plants lack a circulatory system and antibodies and have evolved a defense mechanism that is distinct from the vertebrate immune... 

Newkirk MM. Rheumatoid factors host resistance or autoimmunity Clin Immunol 2002 104(1) 1-13. 

Miskin EM, Cabral GA. Delta-9-tetrahydrocannabinol decreases host resistance to herpes simplex virus type 2 vaginal infection in B6C3F mice. J Gen Virol 1985 66 2539-2549. 

Virus restriction and modification by the host We have already seen that one form of host resistance to virus arises when there is no receptor site on the cell surface to which the virus can attach. Another and more specific kind of host resistance involves destruction of the viral nucleic acid after it has been injected. This destruction is brought about by host enzymes that cleave the viral DNA at one or several places, thus preventing its replication. This phenomenon is called restriction, and is part of a general host mechanism to prevent the invasion of foreign nucleic acid. 

Host-range mutations are those that change the range of hosts that the virus can infect. Host resistance to phage infection can be due to an alteration in receptor sites on the surface of the host cell, so that the virus can no longer attach, and host-range mutations of... 

Nematode-host interactions are complex and poorly understood. The relationship between cyst nematodes and their hosts appears to have co-evolved, and as a result there are numerous genes for host resistance that are complemented by nematode parasitism genes (Triantaphyllou, 1987). Different alleles of these genes may interact in various combinations to give... 

Host resistance is the most environmentally and economically sound approach for nematode management, and in those crops where resistance pertains it has proved to be an extremely valuable commodity. For example, the introduction of the Heterodera glycinm-rcsistant cultivar Forrest saved soybean growers in the southern USA over US 400 million during a 5-year period (Bradley and Duffy, 1982). Regrettably, nematode resistance is yet to be identified for many crop plants, although several naturally... 

The in vivo manipulation of specific type 2 cytokines using anticytokine monoclonal antibodies, or mouse strains with targeted deletions in cytokine and/or cytokine receptor genes, has proved a fruitful approach in identifying the importance of individual cytokines and the responses that they control in contributing to host resistance. These studies have identified important roles for IL-4, IL-9 and IL-13 in host protection against nematode infection, though the relative importance of each cytokine appears to be nematode-species dependent. 

A critical and IL-4-independent role for IL-13 has also been identified in host resistance to T. muris. Despite generating strong and equivalent type 2 responses to wild-type mice, mice deficient in IL-13 production failed to clear infection (Bancroft et al., 1998). Expulsion in BALB/c IL-4 KO mice was completely blocked following treatment with A25, confirming an important role for IL-13 in resistance to 1. muris (A.J. Bancroft et al., unpublished observations) (Table 17.1). In addition, IL-4 receptor KO mice (lacking IL-4 and IL-13 functions) are completely susceptible to T. muris (A.J. Bancroft, unpublished observations). 

It is clear that the type 2 cytokines IL-4, IL-9 and IL-13 play an obligatory role in host resistance to nematode infection whereas type 1 responses promote host susceptibility. Therefore, given that susceptibility to nematode infection is not due to a lack of responsiveness perse, but rather the development of an inappropriate response, it is important to understand the factors that influence the induction and expansion of Th subset responses and so control infection outcome. Studies in nematode models and other systems have addressed these questions and identified the importance of host genetic factors, the nature of the antigen and the antigen presenting cell, co-stimulatory molecules on these cells, and the cytokine and chemokine environment immediately following induction of the response. 

Lawrence, R.A., Allen, J.E., Gregory, W.F., Kopf, M. and Maizels, R.M. (1995) Infection of IL-4-deficient mice with the parasitic nematode Brugia malayi demonstrates that host resistance is not dependent on a T helper 2-dominated immune response. Journal of Immunology 154, 5995-6001. 

Rosenthal, G.J., M.M.Fort, D.R.Germolec, M.F.Ackermann, K.R.Lamm, P.C.Blair, B.AFowler, and M.I.Luster. 1989. Effect of subchronic arsine inhalation on immune function and host resistance. Inhal. Toxicol. 1 113-127. 

The majority of early publications that can be reasonably identified as comprising immunotoxicology reported altered resistance to infection in animals exposed to various environmental or industrial chemicals. Authors logically concluded that xenobiotic exposure suppressed immune function since the immune system is ultimately responsible for this resistance to infection. Subsequent studies demonstrated that suppression of various cellular and functional endpoints accompanied or preceded increased sensitivity to infection, and that administration of known immunosuppressants likewise decreased host resistance. The human health implications of these studies, that chemical exposure reduced resistance to infection, drove the initial focus of many immunotoxicologists on functional suppression, and provided the theoretical and practical underpinnings of immunotoxicity testing. 

Luster, M.L et al., Risk assessment in immunotoxicology. II. Relationships between immune and host resistance tests, Fund. Appl. Toxicol., 21, 71, 1993. 

Keil, D., Luebke, R.W. and Pruett, S.B., Quantifying the relationship between multiple immunological parameters and host resistance probing the limits of reductionism, J. Immunol., 167, 4543, 2001. 

Follow-on studies are also recommended as needed. These include determination of potential test article effects on blood or tissue immunophenotypes (by flow cytometry or immunohistochemistry), natural killer cell, macrophage, or neutrophil function, host resistance to infection or tumors, and cell-mediated immunity. The important issue in all of these guidelines is this do not ignore signs of immunotoxicity, and assess these findings when observed. 

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