In-vitro immunization

Me Cabe MJ Jr. Metropolitan Center for Higher Technology, Detroit, Ml Mechanisms and consequences of Pb modulation of cell-mediated and humoral immunity (in vitro culture system mice in vivo) National Institute of Environmental Health Sciences... 

Cytokines and chemokines made by cells such as keratinocytes, macrophages and LC might be expected to recruit and activate leukocytes, which have the potential to kill schistosomula before the development of any adaptive immunity. In vitro, schistosomula have been shown to be susceptible to a wide array of immune effector mechanisms mediated by eosinophils and neutrophils (Butterworth, 1984 Capron and Capron,... 

Test on cellular immunity in vitro assays for lymphocyte and eosinophil activation it is performed for distinguishing between children with and without food allergy, based on determination of Th2 type cytokines (11-4), as compared to nonallergic children producing predominately Thl cytokines (interferon-y) (Nowak-Wegrzyn, 2003). 

One fairly new system is the Modular Immune in vitro Construct technology system (MIMIC), which can measure innate and adaptive immune responses and evaluate cytokines, antibodies, and chemokines in vitro. The system is based on a multidimensional interrogation of quiescent primary human cells mainly of blood origin that can reproduce immune responses in a cell-based high-throughput screen and rapidly capture the effect of an immunoresponsive agent (e.g.,... 

Kopecky J, Kuthejiova M. Suppressive effect of Ixodes ricinus salivary gland extract on mechanisms of natural immunity in vitro. Parasite Immunol 1998 20(4) 169-174. 

An advantage of immunization in vitro is that the activation of B-lymphocytes takes 3 to 4 days rather than a few weeks as is the case with immunization in vivo. Furthermore, weak antigens at low concentrations can be used. A disadvantage is that certain immunoglobulin isotypes tend to be produced preferentially (usually IgM) although refinement of the techniques during cell activation can stimulate the production of other isotypes. 

BiY JE, CLEM Lw. Temperaturc-mediated processes in teleost immunity in vitro immunosuppression induced by in vivo low temperature in channel catfish. Vet Immunol Immunopathol 1991 Jul 28(3-4) 365-77. 

The class II cytokine receptor family includes receptors for interferon a/P (lEN a/P) and y (lENy) and IL-10. lEN-y immunoreactivity has been found in neurons in the hypothalamus, cerebral cortex, mammilary nuclei, and dorsal tegmentum. Astrocytes and microglia in vitro can be stimulated to express class II histocompatibiHty complex (MHC-II) antigens by lEN-y, which may be involved in the presentation of antigen to T-ceUs by astrocytes. Thus lEN-y may be critical in CNS-immune function and dysfunction especially in regard to neuronal and gHal apoptotic processes. 

One component of the age-ielated decline in immune function is decreased production of the lymphokine that promotes the growth of T-ceUs, interleukin 2 (IL-2). Administration of recombinant-derived IL-2, both in vitro and in vivo, appears to restore certain immune functions in aged mice. Recovery of T-regulatory effects on B-ceU differentiation has been reported in human cells from elderly patients treated with IL-1 and/or IL-2 (42). Similar effects have been observed in the presence of the pentapeptide thymopentin [69558-55-0] (Arg Lys Asp Val Tyr), a weU-known IL-2 inducer. Recombinant IL-2 adrninistered to aged mice for three weeks has been shown to correct the T-ceU functional deficiency associated with antigen-specific immunoglobulin production by certain lymphoid tissue (43). 

Chinese Herbal Medicines. Many traditional Chinese medicines have been screened for radioprotective activity in experimental animals. In one study of more than a thousand Chinese herbs, a number of agents increased the survival rate of dogs exposed to a lethal dose of y-rays by 30—40%, and some symptoms of radiation injury were ameHorated. These effects are potentially related to stimulation of the hemopoietic and immune systems (130). Extracts of five Chinese dmg plants, as weU as aspirin, effectively protected mice exposed to 7.5—8.0 Gy (750—800 rad) of y-radiation, and increased survival rates by 8—50% (131). Several Chinese traditional medicines, adininistered ip before or after irradiation, protected against Hpid peroxidation in a variety of mouse tissues, including BM, Hver, and spleen, as weU as in mouse Hver microsomal suspensions irradiated in vitro (132). 

In-vitro models can provide preliminary insights into some pharmacodynamic aspects. For example, cultured Caco 2 cell lines (derived from a human colorectal carcinoma) may be used to simulate intestinal absorption behaviour, while cultured hepatic cell lines are available for metabolic studies. However, a comprehensive understanding of the pharmacokinetic effects vfill require the use of in-vivo animal studies, where the drug levels in various tissues can be measured after different dosages and time intervals. Radioactively labelled drugs (carbon-14) may be used to facilitate detection. Animal model studies of human biopharmaceutical products may be compromised by immune responses that would not be expected when actually treating human subjects. 

Redwood City, California, and Roche) and two clones have been selected for their improved in vitro activity relative to human IFN-a. One of them has been pegylated but its development has been halted because of strong immune reaction. 

Immunotoxicity. Limited information is available regarding the effects of endosulfan on the human immune system. However, specially designed studies using rats indicate that both humoral and cellular immune responses are depressed by ingested endosulfan at doses that do not induce any overt signs of toxicity (Banerjee and Hussain 1986,1987). In vitro studies support the possibility that endosulfan affects immune system function (Das et al. 1988). These results demonstrate that immunotoxicity may be a more sensitive end point of endosulfan-induced toxicity than other end points, and humans may be at risk for adverse immune effects following exposure to endosulfan. An intermediate-duration oral MRL was derived based on the observation of depressed immune responses (Banerjee and Hussain 1987). 

Since the limited information available on the effects of dermally administered endosulfan suggests that this chemical behaves similarly across both routes of exposure and that adverse effects on immune function end points have also been observed in vitro, there is no reason to suspect that the immunotoxic effects observed following oral exposure are route-specific. Tests of immunologic function in exposed human populations would provide information as to whether immunosuppression also occurs in humans... 

Hoschele D (2006) Cell culture models for the investigation of NRTI-induced mitochondrial toxicity. Relevance for the prediction of clinical toxicity. Toxicol In Vitro 20(5) 535-546 Itescu S, Brancato LJ et al (1989) A sicca syndrome in HIV infection association with HLA-DR5 and CDS lymphocytosis. Lancet 2(8661) 466 68 Itescu S, Brancato LJ et al (1990) A diffuse infiltrative CDS lymphocytosis syndrome in human immunodeficiency virus (HIV) infection a host immune response associated with HLA-DR5. Ann Intern Med 112(1) 3-10... 

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