Immunological tolerance induced

There exists direct evidence that the immune system mounts an immune response against most cancer types. Virtually all transformed cells express (a) novel surface antigens not expressed by normal cells or (b) express, at greatly elevated levels, certain antigens present normally on the cell at extremely low levels. These normal expression levels may be so low that they have gone unnoticed by immune surveillance (and thus have not induced immunological tolerance). 

The transformation of a cell to the cancerous state is normally associated with increased surface expression of antigens recognized as foreign by the host immune system. These surface antigens, often termed tumour antigens or tumour surface antigens, are either not expressed at all by the untransformed cell or are expressed at such low levels that they fail to induce immunological tolerance. 

Cohn, L. 2001. Food for thought. Can immunological tolerance be induced to treat asthma Am J Respir Cell Mol Biol 24 509-512. 

Immunologists have for several decades used globular proteins as model antigens to study experimental immunological tolerance in vivo. To induce tolerance, the proteins can be administered orally ( oral tolerance ) or by injection either intravenously or intraperitoneally. The protein must be delivered in the absence of adjuvants, which would otherwise activate the antigen-presenting... 

Importantly, in the absence of co-stimulatory help, signal 1 is known to induce a state of immunological tolerance, whereas signal 2 alone will not elicit any response. In other words, signal 2 can be considered to be more decisive than signal 1 for inducing an immune response. 

Immunosuppression has concomitant risks of opportunistic infections and secondary tumors. Therefore, the ultimate goal of research on organ transplantation and autoimmune diseases is to induce and maintain immunologic tolerance, the active state of antigen-specific nonresponsiveness. If attainable, tolerance would represent a true cure for conditions discussed above without the side effects of the various immunosuppressive therapies. The calcineurin inhibitors prevent tolerance induction in some, but not aU, preclinical models. In these same model systems, sirolimus does not prevent tolerance and may even promote tolerance induction. 

The main safety issues for DNA vaccines include integration of the plasmid into the host genomic DNA, production of pathogenic anti-DNA antibodies to the plasmid that could induce or exacerbate diseases such as systemic lupus erythematosus, or immunologic tolerance to the antigen being expressed [147]. As a result. 

Mitchell GF, Humphrey JH, Williamson AR (1972) B cell tolerance induced by polymeric antigens I. Comparison of the dose and epitope density requirements for inactivation of primed and unprimed B cells in vivo. Eur J Immunol 5 361 Mota I (1964) The mechanism of anaphylaxis I. Production and biological properties of mast cell sensitizing antibody. Immunology 7 681 Neftel KA Waelti M Spengler H Von Felten A Weitzman SA Buergi H de Week AL (1981) Neutropenia after penicillins Toxic or immune-mediated Klin Wochenschr 59 877... 

Mechlorethamine is a nitrogen mustard which is used in psoriasis. Taylor and Halprin (1972) sensitized 34 of 57 patients treated attempts to induce immunologic tolerance were unsuccessful. A woman with mycosis fungoides developed an urticarial and anaphylactoid reaction inunediately after a total body surface application of nitrogen mustard (Daughters et al. 1973). She received at least 100 applications prior to this reaction, which waned after an antihistamine injection. Immediate sensitivity to nitrogen mustard may not be rare (Grunnet 1976). 

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