Clonal selection

Clonal Selection Clostridial Neurotoxins Clostridium Botulinum Toxin Clotting CNTF... 

Remy, I., and Michnick, S. W. (1999). Clonal selection and in vivo quantitation of protein interactions with protein-fragment complementation assays. Proc. Natl. Acad. Sci. USA 96, 5394-5399. 

Zlokamik G, Negulescu PA, Knapp TE et al (1998) Quantitation of transcription and clonal selection of single living cells with P-lactamase as reporter. Science 279 84-88... 

Podolsky, S. H. and Tauber, A. I. (1997), The Generation of Diversity, Clonal Selection and the Rise of Molecular Immunology, Harvard University Press, Harvard, MA, p. 508. 

Zlokarnik, G., Negulescu, P. A., Knapp, T. E., Mere, L., Burres, N., Feng, L., Whitney, M., Roemer, K. and Tsien, R. Y. (1998). Quantitation of transcription and clonal selection of single living cells with beta-lactamase as reporter. Science 279, 84-88. 

Some xenobiotics may have divergent mechanisms of autoimmune responses. For example, hydralazine demonstrates adduct reactivity as well as inhibition of DNA methylation [68,73], while procainamide inhibits DNA methylation, forms immunogenic NPA, and disrupts clonal selection in the thymus [68, 72, 74], It is this complicated pattern of effects that makes assessment of autoimmune potential in the laboratory for new xenobiotics almost impossible. Animal models can sometimes be recreated to resemble human disease [74], and thus may be useful for therapy considerations, but are difficult to utilize for screening chemicals for hazard potential due to the diverse nature of autoimmunity mechanisms and physiological presentation. While evidence supports many different mechanisms for xenobiotic-induced autoimmune reactions, none have conclusively demonstrated the critical events necessary to lead to the development of autoimmune disease. Therefore, it is difficult to predict or identify xenobiotics that might possess the potential to elicit autoimmune disorders. 

Clonal selection is the process by which only a limited number of lymphocytes are stimulated to replicate by an antigen. 

Immunologically competent cells, whether they are T or B lymphocytes, have membrane receptors that are specific for an antigen. It is basically the binding of the antigen to the specific receptor on the appropriate lymphocyte which initiates the whole process, stimulating the cell to proliferate and producing a clone of identical cells, a process known as clonal selection . The nature of the secondary response is due in the main to this large number of cells now available. 

Along with mese genetic features, a low growm rate and a low blood supply (conditions often present m sohd mmors) can affect sensitivity to ionizing radiation wim me following mechanisms (Brown, 1999) reduction of me rate of cells m me most sensitive phases of me cell cycle low efficiency of ROS formation wimm me irradiated mmor due to hypoxia clonal selection of cancer cells highly resistant to oxidative stress/apoptosis and wim efficient anaerobic metabolism. 

Williams AC, Collard TJ, Paraskeva C (1999) An acidic environment leads to p53 dependent induction of apoptosis in human adenoma and carcinoma cell lines implications for clonal selection during colorectal carcinogenesis. Oncogene 18 3199-3204... 

F. M. Burnet, The Clonal Selection Theory of Acquired Immunity, Vanderbilt Univ. Press, 1959. 

The immune response is mediated by interactions among an array of specialized leukocytes and their associated proteins. T lymphocytes produce T-cell receptors. B lymphocytes produce immunoglobulins. All cells produce MHC proteins, which display host (self) or antigenic (nonself) peptides on the cell surface. In a process called clonal selection, helper T cells induce the proliferation of B cells and cytotoxic T cells that produce immunoglobulins or of T-cell receptors that bind to a specific antigen. 

Burnet FM (1959) The clonal selection theory of acquired immunity. Cambridge University Press, Cambridge... 

The second half of the chapter considers restrictions on and elaborations of the process of gene rearrangement. Allelic exclusion—the expression of an allele from only one chromosome of a pair—assures that each antibody-forming cell will produce antibodies of only a single specificity, as postulated by the clonal selection hypothesis. The preimmune repertoire is modified after exposure to antigen an... 

A key feature of the clonal selection theory is that each antibody-forming cell or clone is committed to the expression of one antibody. The diversity in the response is a consequence of the great variety of distinct clones. Initially, Burnet (1957) assumed that antibody diversification occurs exclusively early in life, by a random... 

As described in Part I, increases in affinity or avidity for antigen are characteristic features of the immune response. In antibody responses to well-defined haptenic determinants, the affinity of the antibodies for the hapten had been shown to increase during the period after immunization this was interpreted in terms of clonal selection, cells with antibody-receptors of higher affinity successfully competing for antigen against cells with receptors of lower affinity. 

In Part I, some of the early evidence for the existence of the receptor and for its identity in specificity to the antibody produced by the cell on which it resides was presented (see section, Clonal Selection Prevails). However, it was realized that the C region of the receptor is unlikely to be completely identical to antibody since... 

Burnet, F.M. (1957). A modification of Jeme s theory of antibody production using the concept of clonal selection. Aust. J. Sci. 20,67-69. 

Burnet, M. (1964). The clonal selection theory of immunity—A Darwinian modification. Aust. J. Sci. 27,6-7. 

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