Classical response antibodies

Interestingly, all these monoclonal antibodies have a poor antitumor activity when used as single agents, with overall response rates of about 10%. Thereby, these monoclonal antibodies have all been approved in combination with classical cytotoxic agents or radiation therapy. 

A classic drug associated with hepatotoxicity is halothane. It is associated with antibodies against trifluoroacetylated protein due to the binding of the reactive metabolite of halothane [59,60], However, in addition, it is also associated with autoantibodies, such as antibodies against Cyp 2E1, the major P450 responsible for oxidation of halothane [61]. 

The development of respiratory hypersensitivity requires an induction phase where exposures to the sensitizer lead to an interaction with immune cells and the eventual development of specific effecter immune molecules (e.g., antibodies) and cells (e.g., T lymphocytes) [5], The induction phase can require months to years of exposure before there is a detectable immune response and/or onset of symptoms typical of respiratory hypersensitivity, including asthma. Classic IgE mediated responses have been described as Th2 cell dominant responses. A subset of CD4+ T cells known as Th2 cells push the immune response to the development of IgE and IgG4 antibodies in humans along with secretion of cytokines that attract and activate inflammatory cells such as eosinophils. 

First, based on the concept of catalytic antibodies as first described by Jencks, the use of a TSA of the target reaction to elicit antibodies during an immune response has been developed and identified as a classic strategy in the search for catalytic antibodies. Structural studies have in particular shown that this strategy has led to... 

Cotton dust activates complement vitro by both the classical (antibody dependent) and alternative (antibody independent) pathways (12,47,48). It is proposed that endotoxins may be the agents responsible for complement activation (49). Cotton dust extractions maximizing endotoxin content are 10 times more potent than other extracts in activating complement (12). Activation of complement via the alternative pathway has also been... 

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. 

This pathway of complement activation, which starts when antibody has bound to antigen on the microbe surface, is called the classical pathway. An alternative pathway of activation also exists which is activated directly by polysaccharides in the cell wall of microorganisms even in the absence of antibody. The alternative pathway therefore defends the body against attack in the early stages before an immune response can occur and also augments the effects of the classical pathway of complement activation when the immune response has occurred. 

There are two mechanisms by which therapeutic proteins induce antibodies the classical activation of the immune system by foreign proteins and the breaking of B cell tolerance by human proteins. The two mechanisms differ in time of onset and response level as we have described extensively previously [2]- Also the immunological mechanisms behind the two types of immune activation differ fundamentally and therefore also the characteristics of the product that are involved in induction of antibodies. 

The classical complement pathway reqnires activation by circulating antibodies, IgM or IgG (specific immnne response), while the alternative and lectin pathways can be activated in the absence of antibody (non-specific immnne response). 

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