Host immune system, suppression

The active immunotherapeutic approach is specific and based on the premise that tumor antigens are immunogenic and the host is sufficientiy immunocompetent to mount an effective immune response to an autologous tumor. Theoretically, a weak or suppressed host immune system that had allowed the formation of a tumor may be overridden by active immunization or immunostimulation. In practice, vaccines composed of so-called autologous tumor extracts have been used to treat patients with malignant melanoma (73), and purified melanoma tumor-associated antigens have been used to ehcit antibody responses in melanoma patients (74). 

The effect of PDT on the host immune system is dichotomous, resulting in immune suppression or immune activation. Although the mechanism leading to immune activation or suppression is unclear, recent studies indicated that the nature and extent of the tissue treated and the dose play a major role. >" Cutaneous PDT suppresses allograft rejection and contact hypersensitivity (CHS) reactions. - " PDT suppression of CHS in murine models was demonstrated with a number of different photosensitizers " and is antigen specific. The kinetics of CHS suppression is photosensitizer dependent. TPPS4 and HpD-PDT induce immediate CHS suppression, while m-THPC and Photofrin-PDT suppression require 72 h to develop. Kinetic differences were linked to photosensitizer... 

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. 

In utero exposure of mice to benzo(a)pyrene (B[a]P) resulted in suppression of the antibody response to SRBC, which persisted for up to 78 weeks in the offspring.102 In a follow up study, injection of B[a]P from gestation day 11 to 17 resulted in suppressed antibody responses to SRBC, MLR and graft versus host responses (GvH). It was suggested that lesions caused by B[a]P in the developing immune system may predispose the host to the growth of neoplasms.103... 

A drawback for stem cell therapy is the problem of cell rejection due to the host s immune system recognizing the cells as foreign. This rejection issue has to be overcome to ensure stem cell therapy is a viable treatment. Recently, French scientists reported on research progress in stem cell transplants for curing children with sickle cell anemia. A mix of antirejection drugs was used to suppress rejection of the new stem cells. 

Tier 2 also include host resistance models, tests in which an animal is exposed to a xenobiotic and then challenged with an infectious agent or tumor cells. This is considered the ultimate test for an adverse effect on the immune system. However, it should be noted that the amount of immune suppression that can be tolerated is greatly dependent on the dose and virulence of the challenging agent, as well as the genetics of the host. Manipulation of these variables can affect greatly results obtained in host resistance tests. 

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... 

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