Immune system humoral aspects

Bone marrow suppression that affects white blood cells more than platelets is the major dose-limiting toxicity. Maximal suppression of blood cell count occurs 10 to 14 days after drug administration recovery is generally seen 21 to 28 days after injection. Cyclophosphamide reduces the number of circulating lymphocytes and impairs the function of both humoral and cellular (i.e., B and T cell) aspects of the immune system. Chronic therapy increases the risk of infections. Nausea may occur a few hours after administration. Alopecia is more common than with other mustards. 

The treatment of a PID is based on the aspect of the immune system that is lacking. For those with dehcien-cies in humoral immunity, the only effective treatment available is antibody replacement (e.g., immune globulin) and medical management of infections. For those with dehciencies in cell-mediated immunity, there is no effective pharmacological treatment. 

The clinical manifestations of PIDs vary with the aspect of the immune system affected. In general, because of the role of antibodies in protection against bacterial infections, individuals with deficiencies in humoral immunity are particularly prone to infections from Streptococcus pneumoniae and Haemophilus influenzae. These individuals are also prone to infections of the respiratory, gastrointestinal, and urinary tracts because of the protective role of IgA in secretions. 

Halothane-induced hepatitis seems to be mediated by both humoral and cell-mediated aspects of the immune system. Thus, both specific circulating antibodies and cytotoxic T lymphocytes are involved. One suggestion is that the mechanism involves antibody-dependent cell cytotoxicity (ADCC). 

Secondly, the various humoral and cell-mediated responses operating at the interface of the innate and acquired arms of the immune system are activated and coordinated by pharmacologically active components that are released at certain steps along the complement cascade. These proteolytic byproducts, which are independent of the components that comprise the MAC, induce the various humoral and cell-mediated aspects of the innate and acquired arms of immunity, all of w hich are necessary for the concerted elimination of the microorganism. 

Methods for assessing or modeling of the responses of the human immune system to vaccines are critical components of any effort to understand the relationship between immunogenicity and either a positive or a negative outcome of vaccination. Decades of research have yielded many useful in vitro methods that enable the isolation and molecular dissection of selected components (modulators or cell types) of an immune system, whether mouse or human. While of hmited scope biologically, these systems have elucidated the modulators and cell types responsible for certain facets of humoral or cellular immunity. These systems have also been employed to define the roles that modulators and specific cell types play in particular aspects of an immune response. Missing, until recently, was an in vivo setting in which to study the human immune system. 

Unlike most ADRs that are mediated by the adaptive immune system, there are some very good animal models of systemic DIAI involving autoantibody production. While these models have revealed that there are multiple mechanisms by which drugs initiate autoimmunity, it is clear that Th2 cytokines, such as IL-4 and lL-6, play an important role in all types of systemic DlAl (Kroemer et al. 1996 Qasim et al. 1997 Yung et al. 1995). These cytokines mediate the humoral aspects of DlAl, including autoantibody production and B cell proliferation and differentiation. Neutrahzing either lL-4 (Ochel et al. 1991) or lL-6 (Finck et al. 1994) decreases the severity of DlAl in animal models. In contrast, treatments that enhance Th2 immunity by inhibiting Thl cytokines such as TNF-a increase the severity of DlAl (Ishida et al. 1994). 

The majority of patients with Burkitt s lymphoma showed an intact delayed hypersensitivity response to DCNB and lymphocyte transformation to phytohemagglutinin was also normal in the majority of patients (Z3). Fass et al. (F2) reported that 12 patients with Burkitt s lymphoma when tested with autologous tumor extracts showed measurable cellular responses of the host against his own tumor. In contrast to patients with Burkitt s lymphoma who have impaired antibody production but normal cellular immunity, patients with other forms of neoplasia of the reticuloendothelial system frequently have impairment of both the humoral and cellular aspects of immunity. 

Cannabinoids are able to cause different effects at the level of various systems and/or organs the most important effects occur on the central nervous system and on the cardiovascular system. In fact, they are able to affect mood, memory, motor coordination and cognition, and they increase heart rate and variate the systemic arterial pressure. Furthermore, it is well known the capability of cannabinoids to reduce intraocular pressure and to affect the respiratory and endocrine systems (L. E. Hollister, Health Aspects of Cannabis, Pharmacological Reviews, 38,1-20,1986). More recently, it was found that they suppress the cellular and humoral immune response and have antiinflammatory properties (A. W. Wirth et al.. Antiinflammatory Properties of Cannabichromene, Life Science, 26,1991-1995,1980). 

Immunotoxicity. The results from the available human and animal studies indicate that di- -butyl phthalate is not a skin-sensitizing agent following dermal exposure (Lehman 1955 Schulsinger and Mollgaard 1980). These studies did not assess other aspects of immunotoxicity. Additionally, immunotoxicity has not been adequately assessed following inhalation or oral exposure. Tests of several additional end points of humoral and cell-mediated immune function are needed to assess the sensitivity of this system to di- -butyl phthalate. 

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