Antibodies dependent hypersensitivity

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. 

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. 

Figure 7.81 Antibody-dependent phagocyte-mediated lysis of red cells in penicillin immunotoxicity (type II hypersensitivity). Abbreviation NK, natural killer cell.

In humans, there are five isotypes of antibodies, IgG, IgA, IgD, IgE, and IgM, which are defined by the structures of their heavy chains and their abilities to form multimers (Figure 10.1) [8], IgG is the most abundant isotype present in serum with average serum concentrations ranging from 0.5 to 9mg/ml depending on the IgG subtype. This is followed by IgA (3mg/ml), IgM (1.5mg/ml), IgE (0.05 mg/ml), and IgD (trace). Each antibody isotype has unique functions. Critical functions of IgG include opsonization, complement activation, antibody-dependent cell-mediated cytotoxicity (ADCC), passive immunity, and regulation of B cells. Both IgM and IgD act as antigen receptors on naive B cells, and soluble, multimeric forms of IgM are involved in complement activation. IgA is involved in mucosal and passive neonatal immunity, while IgE is involved in immediate hypersensitivity [8],... 

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

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-... 

Antilymphocyte antibody acts primarily on the small, long-lived peripheral lymphocytes that circulate between the blood and lymph. With continued administration, "thymus-dependent" lymphocytes from lymphoid follicles are also depleted, as they normally participate in the recirculating pool. As a result of the destruction or inactivation of T cells, an impairment of delayed hypersensitivity and cellular immunity occurs while humoral antibody formation remains relatively intact. ALG and ATG are useful for suppressing certain major compartments (ie, T cells) of the immune system and play a definite role in the management of solid organ and bone marrow transplantation. 

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. 

TDAR = T cell dependent antibody response, DTH (=delayed-type hypersensitivity test) is problematic in NHP. 

In experimental mouse studies, TCDD exposure results in thymic atrophy and alterations in an array of adaptive immune responses including delayed-type hypersensitivity (DTH), cytotoxic T lymphocyte (CTL) activity, and T-cell-dependent antibody responses. In contrast, TCDD enhances neutrophil recruitment to the site of antigen challenge. Because both cell-mediated and humoral immunity are suppressed by TCDD and related HAHs, it is not surprising that administration of these compounds to mice results in increased susceptibility to challenge with viral, bacterial, or parasitic diseases, as well as syngeneic tumors. 

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