Immune Responses: Adverse Versus Non-Adverse Effects

Abstract

The adaptive immune system in vertebrates has evolved to provide host resistance to infectious microorganism s and malignant disease. Normal immune function and the induction of speci c immune responses require the orchestrated interaction between cells and molecules both within and outside the lymphoid system. Immunotoxicolog y can be de ned as the study of adverse health effects that may result from the interaction of xenobiotics with the immune system. In general terms such effects can take one of two forms. The rst of these is immunotoxicity (or immunosuppressio n) where there is a perturbation of, or damage to, one or more component s of the immune system resulting in impaired immune function and reduced host resistance. The design and interpretation of experimental immunotoxicity studies and the investigation of clinical immunosuppressio n require consideration of the relationship between changes in the structure and/or function of discrete component s of the immune system and holistic changes in the susceptibility to infectious and malignant disease. The other main way in which chemicals may cause adverse health effects secondary to interaction with the immune system is through stimulation of speci c immune responses that result in allergic disease. Allergy to chemicals and proteins can take many forms, including allergic contact dermatitis, allergic sensitization of the respiratory tract (associated with rhinitis and/or asthma), systemic allergic reactions (associated frequently with drug treatment), and gastrointestinal disease. Here there is a need to distinguish between immunogeni c responses per se and those immune responses that are of suf cient vigor and of the quality necessary to provoke allergic sensitization. The purpose of this article is to explore the extent to which distinctions can be drawn between adverse and nonadverse effects in the context of immunotoxicit y and allergy.

20 Years of fish immunotoxicology – what we know and where we are

“…A chemically induced modulation of an immune parameter is not per se adverse, but it may lead to immunosuppression, increased susceptibility to infectious and malignant disease, hypersensitivity like allergy, or autoimmune disease (Kimber & Dearman 2002). Immunotoxicology is the study of chemical impacts on the immune system.…”

“…The third challenge is the interpretation of the toxicant-induced immunomodulation. A toxicant-induced alteration of a molecular or cellular immune parameter does not always lead to an adverse response such as reduced immunocompetence, but it may also represent an immunostimulation (Kimber & Dearman 2002). The fourth challenge in assessing immunotoxic effects is the diversity of potential targets, as well as possible effects.…”

Regulatory immunotoxicology: does the published evidence support mandatory nonclinical immune function screening in drug development?

“…The translation of small changes in immunological function to an assessment of health risks for man remains problematic and there currently exists no clear consensus on what magnitude of change can be defined as being adverse, or whether immunotoxicants generally follow linear or threshold-based dose relationships (Kimber and Dearman, 2002). Similar concerns were expressed by Descotes (1996).…”

“…On the other hand, the reverse was not true: for some compounds there were changes in IFTs but not in respect of host resistance, leading to the conclusion that IFTs are, in general, more sensitive than host-resistance assays . An alternative explanation is that a small change in immune status can be tolerated without an increase in host susceptibility due to functional redundancy in the immune system and the existence of compensatory and complementary mechanisms (Kimber and Dearman, 2002). In terms of correlations between NK-cell activity and host resistance in animal models, Wilson et al (2001) reported that a significant decrease (typically P50-60%) in spontaneous NK-cell activity is normally required before any decrease in host resistance is observed.…”

Interactions between Infections, Nutrients and Xenobiotics

“…However, it is important to distinguish between small and biologically unimportant changes in immune parameters presumed to be without health consequences and those changes that may jeopardise our host defence. In many studies an alteration in immune function has been observed in the absence of a demonstrable change in host resistance (Kimber and Dearman, 2002).…”