Hypersensitivity reactions Antibody-dependent

Larsen CG, Thomsen MK, Gesser B, Thomsen PD, Deleuran BW, Nowak J, Skodt V, Thomsen HK, Deleuran M, Thestmp-Pedersen K, et al The delayed-type hypersensitivity reaction is dependent on IL-8. Inhibition of a tuberculin skin reaction by an anti-IL-8 monoclonal antibody. J Immunol 1995 155 2151-2157. 

Rituximab is a monoclonal antibody to the CD20 receptor expressed on the surface of B lymphocytes the presence of the antibody is determined during flow cytometry of the tumor cells. Cell death results from antibody-dependent cellular cytotoxicity. The pharmacokinetics of rituximab are best described by a two-compartment model, with a terminal half-life of 76 hours after the first infusion and a terminal half-life of 205 hours after the fourth dose.36 Rituximab has shown clinical activity in the treatment of B-cell lymphomas that are CD20+. Side effects include hypersensitivity reactions, hypotension, fevers, chills, rash, headache, and mild nausea and vomiting. 

Most anaphylactoid reactions are due to a direct or chemical release of histamine, and other mediators, from mast cells and basophils. Immune-mediated hypersensitivity reactions have been classified as types I-IV. Type I, involving IgE or IgG antibodies, is the main mechanism involved in most anaphylactic or immediate hypersensitivity reactions to anaesthetic drugs. Type II, also known as antibody-dependent hypersensitivity or cytotoxic reactions are, for example, responsible for ABO-incompatible blood transfusion reactions. Type III, immune complex reactions, include classic serum sickness. Type IV, cellular responses mediated by sensitised lymphocytes, may account for as much as 80% of allergic reactions to local anaesthetic. 

The activation of mast cells and T cells results in late-phase reactions. Both immediate hypersensitivity and late-phase reactions are evident in the skin of atopic as well as nonatopic individuals after the cross-linking of IgE-bound mast cells with an antibody against IgE. The atopic asthmatic could develop late-phase reaction even in the absence of mast cell-related immediate hypersensitivity reaction, which is mast cell-independent and HLA-dependent, suggesting the role of T cells by themselves in causing asthma symptoms in atopic asthmatics. 

Immediate hypersensitivity Hay fever, urticaria, atopic asthma Antibody-dependent cytotoxic hypersensitivity Immune complex mediated hypersensitivity (Arthus reaction)... 

Biologies are sufficiently large and complex as to elicit immune responses directed to the protein. For the most part, the principal response elicited is a T cell-dependent humoral response. The development of an antibody response to a biologic in most cases has no adverse consequences (Schellekens 2002a Shankar et al. 2006). An antibody response is not an adverse event in itself. However, an antibody response to a biologic can have consequences that fall into three main categories hypersensitivity reactions, reduction in efficacy, and the induction of autoimmune disease (Schellekens 2002b). 

In contrast, infusion reactions, which are due to the nature of antibody production and structure, represent a class effect of monoclonal antibodies. To address these potentially fatal events, clinical researchers have examined such factors as duration of infusion [164] the role of premedication with antihistamines, acetaminophen, and/or corticosteroids and the molecular etiology of antibody infusion reactions. Infusion reactions may be broadly characterized as cytokine-dependent or hypersensitivity reactions [165]. Cytokine-dependent reactions arise from the interaction of a monoclonal antibody with molecular targets on tumor cells, blood cells, or effector cells, resulting in the release of inflammatory cytokines such as TNF a and interleukin (IL)-6 [166]. In a hypersensitivity reaction, the structure of a monoclonal antibody is recognized as an antigen by the patient s immune system. IgE is produced and... 

Since elicitation of antibody-mediated hypersensitivity reactions requires as a rule at least divalent or trivalent antigens, and is usually best achieved with multivalent conjugates, the specific inhibition of such reactions by monovalent haptens seems theoretically possible and depends primarily on the concentrations of inhibiting and eliciting haptens and on antibody affinity and concentration. It has been shown that anaphylactic reactions in vivo assessed by the PCA technique, or by observation of systemic shock or urticarial skin reactions, can be completely in-... 

Rand et al. (22) addressed the role of MCP-1 in a rat model of a cutaneous delayed-type hypersensitivity reaction. They observed MCP-1 expression by infiltrating neutrophils at early time points (4-8 h) following intradermal challenge and by epidermal and epithelial cells at later time points, with maximum expression at 24 h. Macrophage and T-cell recruitment peaked 2-3 d after challenge, and anti-MCP-1 antibodies inhibited the recruitment of T cells into the inflamed skin in a dose-dependent manner. In contrast, macrophage recruitment was inhibited only at the highest antibody dose. 

Coombs and Gell (1963) have classified all immunologic (allergic) reactions into four types (I to IV). The classification of Types I to III depends on whether antigen or antibody is cell-fixed or in solution. Type IV is cell-mediated and is typified in the skin by responses such as the tuberculin reaction which develops macroscopically over 36-48 hr and lasts for 72-96 hours. This is the classical delayed hypersensitivity reaction. 

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