Immunocompetent lymphocytes

The effectiveness of cyclosporine results from specific and reversible inhibition of immunocompetent lymphocytes in the Gq and G- -phase of the cell cycle. 

A patient suffers from adenosine deaminase (ADA) deficiency, an autosomal recessive immune deficiency in which bone marrow lymphoblasts cannot replicate to generate immunocompetent lymphocytes. The treatment option that would permanently cure the patient is... 

Cyclo- phosphamide (e.g., Cytoxan) PRODRUG is converted by liver to an alkylating agent which crosslinks DNA. Proliferation of B-cells is inhibited more than T-cells. May also attack immunocompetent lymphocytes to inhibit established immune respones. Drug of choice for Wegener s granulomatosis. Also used for severe rheumatoid arthritis autoimmune blood disorders. Alopecia, Gl distress, hemorrhagic cystitis of the bladder, bone marrow depression. 

T sodium retention T potassium excretion metabolic alkalosis i Gl calcium absorption J. antibody production 4. inflammatory reaction 4. immunocompetent lymphocytes 4. antigen processing t erythropoesis t neutrophils 4. lymphocytes... 

Sensitized lymphocytes stimulate the production of immunocompetent lymphocytes, and the effect of each sensitized cell lasts for a given period of time. For the purpose of the present analysis, it is assumed that the effect of each sensitized lymphocyte decays exponentially over a period of time. The production rate of blood lymphocytes at any time t due to the primary response (dLs/rfOprim would then be equal to the sum of the residual effect of all the lymphocytes sensitized between time 0 and time t — where 4>, is the time lag between sensitization and production of the lymphocytes. 

Ciclosporin binds to the cytosolic protein cyclophilin (immunophilin) of immunocompetent lymphocytes, especially T lymphocytes. This complex of ciclosporin and cyclophilin inhibits calcineurin, which activates transcription of interleukin-2 and inhibits lymphokine production and interleukin release, leading to reduced function of effector T cells [1 ]. 

In addition to the classical stress hormones already reviewed, several other hormones are augmented in response to stress. Stress-induced prolactin release is one of the most frequently studied examples. There is no doubt about the causal relationship between stress and increased pituitary prolactin release, but the biological meaning is much less clear (G2). This phylogenetically old hormone has been shown to have more than 85 different functions in all vertebrate species. However, besides its role in the induction of maternal lactogenesis, the physiological importance of prolactin is at present not fully established. Experimental and clinical evidence supports the view that prolactin is also an immunoregulating hormone (M44, R18). Prolactin receptors are present on human T and B lymphocytes (R18), and T lymphocytes depend on prolactin for maintenance of immunocompetence (B19). In addition, it has been shown that prolactin is able to influence the devel-... 

Ehrlich, J.P., Gunnison, A.F., and Burleson, G.R. 1989. Influenza virus-specific cytotoxic T-lymphocyte activity in Fischer 344 rat lungs as a method to assess pulmonary immunocompetence Effect of phosgene inhalation. Inhalation Toxicol. 1 129—138. 

Mixed Lymphocyte Response (MLR) Assay. This assay has been shown to be sensitive for the detection of chemical-induced immunosuppression and is a recommended Tier I assay by the NTP (Luster et al., 1988). In addition, it has been shown to be predictive of host response to transplantation and of general immunocompetence (Harmon et al., 1982). 

The corneal stroma also contains Schwann cells, surrounding the corneal axons, and immunocompetent cells (T andB lymphocytes, monocytes, and Langerhans cells). These latter cells are very numerous at the level of the limbus close to small vessels, but there are also a few of them at the level of the one third at the front of the central corneal stroma [4]. 

In order to study the immunostimulating effect of l-(chloromethyl)-3,7,10-trimethylsilatrane investigations were made of the weight coefficients of immunocompetent organs (thymus and spleen), the total leucocytes and erythrocytes in peripheral blood, titre of blood complement, the amount of antigen-reactive ro-sula-forming lymphocytes in spleen and thymus, microbial dissemination of skin as well as skin test with trypan blue. 

TCDD levels in the blood or the age of the person and the respective proliferative capacity of their lymphocytes. However, exposed subjects showed a reduced response to human lymphocyte antigen-allogeneic lymphocytes and interleukin-2-boosted proliferation. According to Tonn et al. (1996), this suppression is indicative of a reduced T-helper cell response, although the actual number of T-helper cells was not altered by 2,3,7,8-TCDD. The authors concluded that 2,3,7,8-TCDD immunosuppression is more likely mediated by a reduced functionality of individual cells rather than by a reduction in numbers of cells circulating in the blood. Tonn et al. (1996) further noted that the changes in immunocompetence observed did not correlate with obvious diseases related to severe immunodeficiency such as certain cancers and infections. 

Data on bioactivity on immunocompetent cells provide evidence that D-Ala-deltorphin-I potently (10-9 to 10-11 M) and persistently (up to 4 days) enhances Con A-induced mouse spleen cell proliferation [85]. The peptide increases uptake of thymidine and production of interferon--/ in phytohe-magglutinin-activated human lymphocytes [86] and is 100 times more potent than SNC80 in inhibiting the production of p24 antigen, an index of HIV-1 expression, in Jurkat cells stably transfected with a cDNA encoding for the delta-opiate receptor [87]. 

In summary, highly reactive metabolites of Cy disrupt DNA synthesis, thus inhibiting cell proliferation. As a result, production of lymphocytes and accessory cells is suppressed, and host immunocompetence is compromised. As noted below and summarized in Table 32.5, for a number of immunosuppressive compounds a metabolic product rather than the parent compound is responsible for the toxicity. 

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