Lymphocyte response to mitogens

Chloroquine and hydroxychloroquine are used mainly in malaria (see Chapter 52) and in the rheumatic diseases. The mechanism of the antiinflammatory action of these drugs in rheumatic diseases is unclear. The following mechanisms have been proposed suppression of T-lymphocyte responses to mitogens, decreased leukocyte chemotaxis, stabilization of lysosomal enzymes, inhibition of DNA and RNA synthesis, and the trapping of free radicals. 

Andreesen R, Modolell M, Weltzien HU, Munder PG. 1980. Alkyl-lysophos-pholipid induced suppression of human lymphocyte response to mitogens and selective killing of lymphoblasts. Immunobiology 156 498-508... 

Dibenzodioxins, including TCDD (dioxin), have been demonstrated to cause severe thymic atrophy with resulting effects on the immune system. The target seems to be the epithelial cells in the thymus, and it is interesting that thymus cells contain the TCDD receptor. Thymic atrophy correlates with the presence of this receptor, and other compounds which compete with TCDD for this receptor also cause thymic atrophy. The basis of the toxicity of TCDD to the thymus may be an effect on T-cell maturation and differentiation. The result of exposure of animals to TCDD is depressed antibody responses, increased susceptibility to infectious agents, and depressed T-cell function. In humans exposed to TCDD occupationally, decreased serum levels of some immunoglobulins and depressed lymphocyte responses to mitogens were reported. 

Manzella, J. P., and Roberts, N. J., 1979, Human macrophage and lymphocyte responses to mitogen stimulation after exposure to influenza virus, ascorbic acid, and hyperthermia, J. Immunol. 123 1940. 

In a report on an isolated case of peripheral lymphocyte response to mitogenic (PHA) stimulation from a patient with megaloblastic anemia due to folate deficiency. Das and Hoffbrand (1970) found a depressed incorporation of H-Thymidine, In a more extensive study, Gross et al. (1975) studied cell mediated immune function in twenty three Bantu patients in South Africa where there is a high incidence of megaloblastic anemia due to nutritional... 

Laoetera N., D. Scalia, D.G. Mashek, U. Bemabucci and R.R. Grummer, 2007. Effects of intravenous triacylglycerol emulsions on lymphocyte responses to mitogens in fasted dairy cows undergoing intense lipomobilization. J. Dairy Res. 74, 323-328. 

Mutchnick, M.G. and Lee, H.H., Impaired lymphocyte proliferative response to mitogen in alcoholic patients. Absence of a relation to liver disease activity, Alcohol Clin. Exp. Res., 12, 155, 1988. 

Nickel salts have also been reported to have immunosuppressive properties in rodents, including giving acute thymic involution [389, 390], suppression of T lymphocyte response to T cell mitogens [389], suppression of antibody [389, 391, 392] and interferon production [393] and suppression of natural killer (NK) cell activity [389, 394-397]. 

Cell-mediated immunity Lymphocyte mitogenic response to concanavalin A and mixed lymphocyte response to allogeneic lymphocytes local lymph node assay. 

Exposure of rats to carbon tetrachloride (up to 160 mg/kg/day for 10 days) by gavage did not alter the primary antibody response to sheep red blood cells, lymphoproliferative responses to mitogen or mixed leukocytes, natural killer cell activity, or cytotoxic T lymphocyte responses also, spleen and thymus weights were comparable to controls (Smialowicz et al. 1991). In rats exposed twice weekly for 4-12 weeks to 3,688 mg/kg/day, there was histologic evidence of hemorrhage, hemosiderin deposition, and lymphocyte depletion in the pancreaticoduodenal lymph node (Doi et al. 1991), an effect which may be secondary to induced hepatic damage. 

The opioids modulate the immune system by effects on lymphocyte proliferation, antibody production, and chemotaxis. In addition, leucocytes migrate to the site of tissue injury and release opioid peptides, which in turn help counter inflammatory pain. However, natural killer cell cytolytic activity and lymphocyte proliferative responses to mitogens are usually inhibited by opioids. Although the mechanisms involved are complex, activation of central opioid receptors could... 

Mycophenolate mofetil (MMF) is a semisynthetic derivative of mycophenolic acid, isolated from the mold Penicillium glaucus. In vitro, it inhibits T- and B-lymphocyte responses, including mitogen and mixed lymphocyte responses, probably by inhibition of de novo synthesis of purines. Mycophenolate mofetil is hydrolyzed to mycophenolic acid, the active immunosuppressive moiety it is synthesized and administered as MMF to enhance bioavailability. 

Surprisingly, no difference in immune function as measured by spleen cell counts, in vitro lymphocyte proliferation responses to mitogens, and in vitro and in vivo plaque-forming cell responses to antigens was observed (30). However, human studies have shown changes in natural killer cell activity after TSD and during RS (31,32). 

In vitro lymphocyte proliferative responses to mitogens such as phytohemagglutinin, concanavalin A, and pokeweed mitogen or to specific antigens of interest. The response may be measured by tritiated thymidine incorporation or by cytokine production (IFN-r, IL-2, TNF, and others). 

T lymphocyte antigen receptor (TCI signalling in isolation is not sufficient to activate T lymphocytes, since purified T lymphocytes do not secrete IL-2 in response to mitogenic lectins or anti-TCR antibodies in the absence of viable accessory cells, despite the feet that under these conditions TCR-associated second... 

Macrophages play an important ro g in the initiation and modulation of lymphocyte responses to antigen. They secrete factogg which enhance the resp ys of both T lymphocytes and B lymphocytes to mitogenic stimuli. ... 

Mercaptopyrldoxine (62) was reported to enhance the intensity of the secondary reaction in adjuvant arthritic rats and to augment pertussis vaccine edema. Also, it stimulated lymphocyte responses to Concanavalin A.203 Another sulfhydryl compound, a-mercaptoproplonylglyclne (64), enhanced antibody formation to SRBC in mice when given for five days before immunization. T- and B-cell mitogen reactivity of lymphoid cells from EL4 leukemia-bearing mice was restored and production of cytotoxic antibody to EL4 increased by the administration of 64.204... 

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