Delayed-type hypersensitivity DTH

It is also more or less accepted that T-cells, in particular T-helper cells (CD4+), may develop into either Thl cells or Th2 cells. By doing so, T-helper cells orchestrate the ensuing immune response by the types of cytokines they produce. Thl cells, by producing IL-12 and y-IFN, stimulate macrophages and/or cytotoxic T-cells to kill and destroy infected or malignant cells, or to initiate a delayed type hypersensitivity (DTH) reaction Th2 cells, by producing IL-4, IL-5, IL-10, IL-13, trigger B-cells to initiate antibody production. 

Ingested arsenic localizes to the skin [2, 7], where it may alter cutaneous immune responses. The delayed type hypersensitivity (DTH) response to 2,4-dinitrochlorobenzene (DNCB) was suppressed in Bowen s disease patients [8], Langerhans cells (LC) in skin lesions and perilesioned skin from arsenic-induced Bowen s disease and carcinomas were reduced in number and were morphologically altered, having a notable loss of dendrites [9], These data suggest that chronic exposure to arsenic in drinking water may... 

Prenatal exposure of mice to the fungicide hexachlorobenzene (HCB) resulted in suppression of the delayed type hypersensitivity (DTH) response to oxazolone. Similar to the DTH response, the in vitro mixed lymphocyte response (MLR) was also suppressed by in utero exposure.101... 

Another question is whether an endpoint reflecting the status of CMI should be included in any DIT protocol.1719 For the measurement of CMI, roundtable participants suggested that a validated DTH or T-cell responses to anti-CD3 be evaluated.38 The DTH assay is considered by the NTP as part of the Tier II test panel.3 Although reports indicate that the delayed-type hypersensitivity (DTH) response can be assessed in weanling rats.41 roundtable participants agreed that data are lacking as to whether cell-mediated immune (CMI) assessments in younger animals are feasible.38 Ultimately, the characterization of a validated endpoint which measures CMI, and the determination of whether such an endpoint should be an essential part of a DIT framework remain critical research needs. 

Type IV Delayed-type Hypersensitivity (DTH). Delayed-type hypersensitivity reactions are T-cell mediated with no involvement of antibodies. However, these reactions are controlled through accessory cells, suppressor T cells, and monokine-secreting macrophages, which regulate the proliferation and differentiation of T cells. The most frequent form of DTH manifests itself as contact dermatitis. The drug or metabolite binds to a protein in the skin or the Langerhans cell membrane... 

Delayed-type Hypersensitivity (DTH) Response. The DTH response assay is considered by the NTP to be a comprehensive Tier II assay for cell-mediated immunity. 

Toxicology. NRL causes allergic skin reactions of type I (immediate-type) and type IV [delayed-type hypersensitivity (DTH)]. 

For keyhole limpet hemocyanine (KLH) both antibody responses and delayed type hypersensitivity (DTH) reactions can be determined [43—45]. In addition several infectious models, including bacterial, viral and parasitic infections may be used to challenge the immune system [18,46]. As survival and eradication of the infections is the primary function of the immune system, these models provide direct information on the functional status of the immune system. Direct immunotoxic compounds will induce immunosuppression and thus an increase in infection rate and/or severity of the infection. The number of infectious agents (bacteria, parasites, or viral colonyforming units), increased morbidity and mortality are indications for an immunotoxic effect. Also a reduction in specific antibody levels in animals treated with the test compound compared to nontreated controls indicates immunosuppression. 

Chemicals and pharmaceuticals may be tested for their capacity to induce skin sensitization [49]. The potency of a xenobiotic or pharmaceutical compound to induce delayed type hypersensitivity (DTH) or contact dermatitis (CD) may be tested in the so called local lymph node assay (LENA) in which the induction of an immune response in lymph nodes is determined after local (skin) exposure [49-51]. The induction of cellular proliferation in draining lymph nodes is measured by determining the... 

In experimental mouse studies, TCDD exposure results in thymic atrophy and alterations in an array of adaptive immune responses including delayed-type hypersensitivity (DTH), cytotoxic T lymphocyte (CTL) activity, and T-cell-dependent antibody responses. In contrast, TCDD enhances neutrophil recruitment to the site of antigen challenge. Because both cell-mediated and humoral immunity are suppressed by TCDD and related HAHs, it is not surprising that administration of these compounds to mice results in increased susceptibility to challenge with viral, bacterial, or parasitic diseases, as well as syngeneic tumors. 

However, there are times when the immune system acts in an exaggerated manner leading to tissue damage. This is referred to as hypersensitivity. In the classic Coombs and Cell classification system, there are four types of hypersensitivity reactions. The first three (types 1-3) are mediated by antibody (e.g., IgG, IgE). The fourth type (type 4) is mediated by antigen-specific T cells and is also known broadly as delayed-type hypersensitivity (DTH). It is delayed because the reaction appears hours to days after antigen crosses into the skin. Though often thought of as... 

Although supplementation with to-3 fatty acids did not significantly alter the humoral immune response to keyhole limpet hemocyanin (KLH) in geriatric beagles (Wander et al., 1997), it significantly suppressed the cell-mediated immune response based on results of a delayed-type hypersensitivity (DTH) skin test. After consumption of the 1.4 1 diet, stimulated mononuclear cells produced 52% less PGE2 than those from dogs fed the 31 1 diet. 

At the same time that CMl occurs, delayed-type hypersensitivity (DTH) also develops through the activation and multiplication of T-lymphocytes. DTH refers to the cytotoxic immune process that kills nonactivated immature macrophages that are permitting intracellular bacillary replication. These immature macrophages are killed when the T-lymphocytes initiate Fas-mediated apoptosis (programmed cell death). The bacilli released from the immature macrophages then are killed by the activated macrophages. ... 

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