Notes: Abstract Immunity is the faculty to recognise foreign antigenic structures and to develop a specific response against them. This process is supported by the proliferation and the differentiation of immunocompetent cells. The immune system is now recognised as a target organ for the adverse effects of many agents. These agents include xenobiotics (drugs and chemicals). Immunotoxic agents may lead to two main types of effect: immunosuppressive effects which may result in an increased susceptibility to tumours or infectious diseases, or dysregulation of the immune response leading to hypersensitivity and autoimmunity. Two problems have to be considered when assessing the immunotoxicity of xenobiotics: (1) the screening of xenobiotic-induced immunotoxic effects by using the most predictive tests available, (2) the quantification of the occupational risk linked to immunotoxic compounds. For years, gross and histopathological evaluations of the lymphoreticular system provided the method for identifying agents which injure the immune system. It is now well recognised that determining the functional status of the immune system provides a greater sensitivity in terms of detecting an immunotoxic outcome. So, to evaluate the potential immunotoxic effects of drugs, it is important to use a panel of tests assessing: lymphoproliferation in response to T-(concanavalin A, phytohaemagglutinin, anti-CD3, allogeneic cells) and B-cells (lipopolysaccharide) mitogens, cytotoxic T-lymphocyte-mediated cytolysis (CTL), primary antibody response to specific antigens (PFC) and natural killer cell activity (NK). Recently, the ability of each test or combination of tests has been established when performed followingin vivo exposure to xenobiotics. It has been shown that the agreement between an immunotoxic outcome and the PFC assay was 78%. When this assay was used in association with NK activity the concordance reached 94%. These tests can be performed eitherex vivo followingin vivo exposure orin vitro.In vitro animal systems are potent tools to permit identification of a chemical's effect on isolated parts of the immune system and could be correlated with results obtained in humans using peripheral blood lymphocytes. Although these tests are predictive in relation to the detection of an immunosuppressive outcome, they are of no use to assess chemical-induced hypersensitivity. Immune responses to chemicals resulting in hypersensitivity, and the appearance of allergic reactions following subsequent reexposure are dependent on T lymphocyte activation. Following topical exposure to allergens, this activation is dependent on antigen presentation by Langerhans cells (LC). LC migrate from the skin to the lymph nodes under the influence of epidermal cytokines produced by keratinocytes (TNF-α, GM-CSF) and trigger T-lymphocyte thus leading to cell activation. Recently, the murine local lymph node assay, a predictive test for the identification of skin allergens has been developed. This assay measures the sensitisation potential of chemical as a function of lymph node cell proliferation induced in lymph nodes draining the site of exposure. In conclusion, immune response is the consequence of a series of events leading to lymphocyte proliferation and differentiation. This fact emphasises that the use of functional tests is an absolute requirement when doing immunotoxicity testing. In addition, the use of a single immune test should never be the rule.

Notes: Abstract Allergic contact dermatitis is induced by a wide variety of drugs that trigger specific immune responses following topical exposure. Identified chemical stuctures involved in such reactions include the mercuric and thiosalicylic acid groups of thimerosal, the diphenylketone group of the anti-inflammatory drug ketoprofen, the amide or ester structure of local anesthetics, and the side-chain and thiazolidine ring of β-lactams. The T cell responses to such compounds involve CD4+ and CD8+ αβ+ T lymphocytes and also CD4–/CD8– γδ+ T cells. Although "T helper 2" cytokine production by drug-specific human T cells from patients with allergic contact dermatitis has been described, T helper 1-like and T cytotoxic 1-like responses clearly play key roles in this cutaneous reaction.

Notes: Abstract Cell death is usually classified into two broad categories: apoptosis and necrosis. Necrosis is a passive, catabolic process, always pathological, that represents a cell's response to extreme accidental or toxic insults. Apoptosis, in contrast, occurs under normal physiological conditions and is an active process requiring energy. However, apoptosis can also be elicited in a pathological way by toxic injury or during disease processes. In these nonphysiological conditions, both types of cell death can be encountered following the same initial insult and the balance between death by apoptosis and by necrosis appears to depend upon the intensity of the injury and the level of available intracellular ATP. It is important, however, to discriminate between apoptosis and necrosis in pathological conditions, as therapeutic intervention could be considered in apoptotic cell death with putative new pharmacological agents aimed at interfering with the key molecular events involved. In most cases, none of the current laboratory techniques used alone allows for unambiguous identification of apoptotic cells. Some of the most common methods based on morphology, biochemistry, and plasma membrane changes are discussed in terms of specificity and possible sources of error in data interpretation. As a rule, classification of cell death in a given model should always include morphological examination coupled with at least one of the other assays.