Author: F. Inman
Publisher: Springer Science & Business Media
ISBN: 1475713436
Category : Medical
Languages : en
Pages : 196
Book Description
In 1897, Ehrlich suggested that natural preformed receptors from the surface of cells provided immunity to various chemical substances. Many years later, in 1940, Pauling proffered the concept that antibodies comprised a single poly peptide chain and that each end of the protein could form an antigen-binding site. Burnet tried to explain the diversity of antibody specificity by hypothesizing that it was cell-derived. These hypotheses probably have led to as much or more experimentation and discussion than any other of the many conjectures set forth to explain immunity on a molecular and cellular basis. Extensive investigations, initially stimulated by these propositions, proved Pauling's notion incorrect. In its demise, however, the multichain structure of the immunoglobulins was realized. In retrospect it be comes obvious that Ehrlich's idea, though not correct, was borne of amazing logic and cognition. Expansion of Burnet's theory seems to be occurring presently; much excitement is engendered by the finding of cell-bound immunoglobulin receptors. Ouring the preceding dozen years, immunochemists have accumulated enormous quantities of data. Though there is so much yet to be done, as a result of this research one may now discuss antigen-binding sites in relation to the protein's primary structure. There is even considerable understanding of the cellular assembly of some immunoglobulins. Entire books can be written about the chemistry of antigens and of complement.
Contemporary Topics in Immunochemistry
Author: F. Inman
Publisher: Springer Science & Business Media
ISBN: 1475713436
Category : Medical
Languages : en
Pages : 196
Book Description
In 1897, Ehrlich suggested that natural preformed receptors from the surface of cells provided immunity to various chemical substances. Many years later, in 1940, Pauling proffered the concept that antibodies comprised a single poly peptide chain and that each end of the protein could form an antigen-binding site. Burnet tried to explain the diversity of antibody specificity by hypothesizing that it was cell-derived. These hypotheses probably have led to as much or more experimentation and discussion than any other of the many conjectures set forth to explain immunity on a molecular and cellular basis. Extensive investigations, initially stimulated by these propositions, proved Pauling's notion incorrect. In its demise, however, the multichain structure of the immunoglobulins was realized. In retrospect it be comes obvious that Ehrlich's idea, though not correct, was borne of amazing logic and cognition. Expansion of Burnet's theory seems to be occurring presently; much excitement is engendered by the finding of cell-bound immunoglobulin receptors. Ouring the preceding dozen years, immunochemists have accumulated enormous quantities of data. Though there is so much yet to be done, as a result of this research one may now discuss antigen-binding sites in relation to the protein's primary structure. There is even considerable understanding of the cellular assembly of some immunoglobulins. Entire books can be written about the chemistry of antigens and of complement.
Publisher: Springer Science & Business Media
ISBN: 1475713436
Category : Medical
Languages : en
Pages : 196
Book Description
In 1897, Ehrlich suggested that natural preformed receptors from the surface of cells provided immunity to various chemical substances. Many years later, in 1940, Pauling proffered the concept that antibodies comprised a single poly peptide chain and that each end of the protein could form an antigen-binding site. Burnet tried to explain the diversity of antibody specificity by hypothesizing that it was cell-derived. These hypotheses probably have led to as much or more experimentation and discussion than any other of the many conjectures set forth to explain immunity on a molecular and cellular basis. Extensive investigations, initially stimulated by these propositions, proved Pauling's notion incorrect. In its demise, however, the multichain structure of the immunoglobulins was realized. In retrospect it be comes obvious that Ehrlich's idea, though not correct, was borne of amazing logic and cognition. Expansion of Burnet's theory seems to be occurring presently; much excitement is engendered by the finding of cell-bound immunoglobulin receptors. Ouring the preceding dozen years, immunochemists have accumulated enormous quantities of data. Though there is so much yet to be done, as a result of this research one may now discuss antigen-binding sites in relation to the protein's primary structure. There is even considerable understanding of the cellular assembly of some immunoglobulins. Entire books can be written about the chemistry of antigens and of complement.
Contemporary Topics in Molecular Immunology
Author: R. Reisfeld
Publisher: Springer Science & Business Media
ISBN: 1468477730
Category : Medical
Languages : en
Pages : 286
Book Description
This series was originally entitled Contemporary Topics in Immunochemistry, and Volume 1 bearing that name was published. Upon its editorial review and while charting the development of future volumes, the editors began to sense that the word "Immunochemistry" was somewhat restrictive according to its present interpretation. Accompanying the expansion of knowledge in immuno biology is a demand for explanations in molecular terms. Since the intent of the series is to focus attention on research at the molecular level in any aspect of immunology, the editors and publisher felt the term "Immunochemistry" should be replaced with "Molecular Immunology." Thus, the series now bears a revised appellation, Contemporary Topics in Molecular Immunology. The editors feel this more accurately reflects the intended breath of the series. An apology is offered to writers, librarians, and other catalogers for the inconvenience this change will cause. F. P. Inman General Editor Athens, Georgia March,1973 vii Preface The earliest explorers into immunology were at once confronted by myriad molecular riddles which became increasingly complex as immunochemical tech niques resolved one question only to raise scores of others. Even as our knowledge of cellular immunology was growing remarkably fast, during the past two decades exciting experiments delineated the molecular structure of immuno globulins. These joint advances not only shaped the Gestalt of present-day immunology, but paved the way for an incisive molecular approach to the challenges of research.
Publisher: Springer Science & Business Media
ISBN: 1468477730
Category : Medical
Languages : en
Pages : 286
Book Description
This series was originally entitled Contemporary Topics in Immunochemistry, and Volume 1 bearing that name was published. Upon its editorial review and while charting the development of future volumes, the editors began to sense that the word "Immunochemistry" was somewhat restrictive according to its present interpretation. Accompanying the expansion of knowledge in immuno biology is a demand for explanations in molecular terms. Since the intent of the series is to focus attention on research at the molecular level in any aspect of immunology, the editors and publisher felt the term "Immunochemistry" should be replaced with "Molecular Immunology." Thus, the series now bears a revised appellation, Contemporary Topics in Molecular Immunology. The editors feel this more accurately reflects the intended breath of the series. An apology is offered to writers, librarians, and other catalogers for the inconvenience this change will cause. F. P. Inman General Editor Athens, Georgia March,1973 vii Preface The earliest explorers into immunology were at once confronted by myriad molecular riddles which became increasingly complex as immunochemical tech niques resolved one question only to raise scores of others. Even as our knowledge of cellular immunology was growing remarkably fast, during the past two decades exciting experiments delineated the molecular structure of immuno globulins. These joint advances not only shaped the Gestalt of present-day immunology, but paved the way for an incisive molecular approach to the challenges of research.
Contemporary Topics in Molecular Immunology
Author: Gordon Ada
Publisher: Springer Science & Business Media
ISBN: 1468428381
Category : Medical
Languages : en
Pages : 270
Book Description
A series of volumes devoted to molecular immunology will contain, for the most part, articles which attempt to explain immunological phenomena in terms of the behavior and properties of particular molecules. Many of the articles in this volume do this. At the same time, there are many instances-and this is particularly so in the case of immunology-where phenomena must first be described and interpreted in terms of the properties and behavior of cells. Most of us would hope that in due course a fuller understanding will be forthcoming. This volume starts off with such a contribution. Perhaps the most fascinat ing problem in immunology is how diversity is generated. There are two broad proposals: (1) that complete information exists ab initio (the germ-line theory), and (2) that there is initially a limited amount of information, and diversity is generated by somatic mutation. The issue is unresolved, but Cunningham has taken many of the data which have previously been used to support the germ-line theory and shows that the interpretations are not always clear-cut and can frequently be used to support another possibility-that new specificities may arise after stimulation of appropriate cells by antigens. And he has produced experimental evidence to support this notion. On the other hand, there can be little doubt that to a considerable degree the specificity of the immune response is determined by the selection by antigen of cells with receptors of appropriate specificity. This is essentially a surface phenomenon.
Publisher: Springer Science & Business Media
ISBN: 1468428381
Category : Medical
Languages : en
Pages : 270
Book Description
A series of volumes devoted to molecular immunology will contain, for the most part, articles which attempt to explain immunological phenomena in terms of the behavior and properties of particular molecules. Many of the articles in this volume do this. At the same time, there are many instances-and this is particularly so in the case of immunology-where phenomena must first be described and interpreted in terms of the properties and behavior of cells. Most of us would hope that in due course a fuller understanding will be forthcoming. This volume starts off with such a contribution. Perhaps the most fascinat ing problem in immunology is how diversity is generated. There are two broad proposals: (1) that complete information exists ab initio (the germ-line theory), and (2) that there is initially a limited amount of information, and diversity is generated by somatic mutation. The issue is unresolved, but Cunningham has taken many of the data which have previously been used to support the germ-line theory and shows that the interpretations are not always clear-cut and can frequently be used to support another possibility-that new specificities may arise after stimulation of appropriate cells by antigens. And he has produced experimental evidence to support this notion. On the other hand, there can be little doubt that to a considerable degree the specificity of the immune response is determined by the selection by antigen of cells with receptors of appropriate specificity. This is essentially a surface phenomenon.
Contemporary Topics in Molecular Immunology
Author: F. P. Inman
Publisher: Springer Science & Business Media
ISBN: 1468439170
Category : Medical
Languages : en
Pages : 238
Book Description
Included in this volume is a broad range of topics. Immunology is such a diverse field that many of the subspecialties overlap, and one finds it convenient and necessary to integrate information from several of them. We try to focus on the molecular aspects of immunology as much as is reasonable, but some con tributions consist of ablend of molecular and cellular immunology and even immunopathology. This is as it should be, since information at the molecular level often provides an explanation of phenomena observed at other levels. Myelin basic protein holds the interest of immunologists because it is impli cated in the induction of the autoimmune disease called experimental allergie encephalomyelitis (EAE). Although much biochemical and immunological information about this protein has been uncovered, it is not understood how such an inaccessible self-antigen can serve as the focal point in the central ner vous system for myelin basic protein-specific EAE-inducing T cells. Day dis cusses the problem by first reviewing the sequences of the proteins from several species and the antigenicity of the proteins and peptides derived from them. The reader is then led into a thorough discussion of the immunological relation ships that do and do not influence development of the encephalitis. From this discussion, the author promulgates the bystander model as the best overall mechanism to explain why different fragments of the highly conserved protein are needed by various species to give rise to the same type of localized central nervous system disease.
Publisher: Springer Science & Business Media
ISBN: 1468439170
Category : Medical
Languages : en
Pages : 238
Book Description
Included in this volume is a broad range of topics. Immunology is such a diverse field that many of the subspecialties overlap, and one finds it convenient and necessary to integrate information from several of them. We try to focus on the molecular aspects of immunology as much as is reasonable, but some con tributions consist of ablend of molecular and cellular immunology and even immunopathology. This is as it should be, since information at the molecular level often provides an explanation of phenomena observed at other levels. Myelin basic protein holds the interest of immunologists because it is impli cated in the induction of the autoimmune disease called experimental allergie encephalomyelitis (EAE). Although much biochemical and immunological information about this protein has been uncovered, it is not understood how such an inaccessible self-antigen can serve as the focal point in the central ner vous system for myelin basic protein-specific EAE-inducing T cells. Day dis cusses the problem by first reviewing the sequences of the proteins from several species and the antigenicity of the proteins and peptides derived from them. The reader is then led into a thorough discussion of the immunological relation ships that do and do not influence development of the encephalitis. From this discussion, the author promulgates the bystander model as the best overall mechanism to explain why different fragments of the highly conserved protein are needed by various species to give rise to the same type of localized central nervous system disease.
Contemporary Topics in Molecular Immunology
Author: R. A. Reisfeld
Publisher: Springer Science & Business Media
ISBN: 1475707797
Category : Medical
Languages : en
Pages : 439
Book Description
New information is developing so rapidly in the entire field of immunology that one is unable to remain abreast of all advancing fronts. In many cases, consider able information has accumulated as the result of the efforts of many investigators, but the conclusions from the various laboratories have not been summarized recently in a comprehensible manner. One such situation has to do with work on IgD. An up-to-date report on this immunoglobulin was included in Volume 10f this series, but since that time there has been considerable progress in the deter mination of its structure and function. In the present volume Leslie and Martin have reviewed the accomplishments of recent years and the problems remaining to be solved. New information regarding the concentration of IgD in body fluids in normal and disease states is presented. Studies of the ontogeny of surface IgD in animals are described, and the fmdings imply that it may be important in the primary immune response. The role of IgD on lymphocyte surfaces is thoroughly discussed especially in terms of stimulating or suppressive combinations of signals delivered to the lymphocyte by agents which bind or alter the surface rt:ceptors. The authors conclude by proposing a model for plasma-cell differentiation which accounts fo~ the existence of triple Ig-bearing cells, many IgM-IgD-bearing cells, and the low percentage of cells bearing a single isotype. Sometimes the serum of an individual contains abnormally large amounts of two distinct, homogeneous populations of immunoglobulins.
Publisher: Springer Science & Business Media
ISBN: 1475707797
Category : Medical
Languages : en
Pages : 439
Book Description
New information is developing so rapidly in the entire field of immunology that one is unable to remain abreast of all advancing fronts. In many cases, consider able information has accumulated as the result of the efforts of many investigators, but the conclusions from the various laboratories have not been summarized recently in a comprehensible manner. One such situation has to do with work on IgD. An up-to-date report on this immunoglobulin was included in Volume 10f this series, but since that time there has been considerable progress in the deter mination of its structure and function. In the present volume Leslie and Martin have reviewed the accomplishments of recent years and the problems remaining to be solved. New information regarding the concentration of IgD in body fluids in normal and disease states is presented. Studies of the ontogeny of surface IgD in animals are described, and the fmdings imply that it may be important in the primary immune response. The role of IgD on lymphocyte surfaces is thoroughly discussed especially in terms of stimulating or suppressive combinations of signals delivered to the lymphocyte by agents which bind or alter the surface rt:ceptors. The authors conclude by proposing a model for plasma-cell differentiation which accounts fo~ the existence of triple Ig-bearing cells, many IgM-IgD-bearing cells, and the low percentage of cells bearing a single isotype. Sometimes the serum of an individual contains abnormally large amounts of two distinct, homogeneous populations of immunoglobulins.
Contemporary Topics in Molecular Immunology
Author: H. Eisen
Publisher: Springer Science & Business Media
ISBN: 1468481428
Category : Medical
Languages : en
Pages : 246
Book Description
Immunochemistry, recently rechristened molecular immunology, has been pre occupied throughout its long history with the structure and function of antibodies and the specificity of antibody-antigen reactions. With the recent X-ray diffrac of several crystallized immunoglobulin (Ig) fragments and a whole tion analyses Ig molecule, the three-dimensional structure of antibodies and their ligand combining sites has been realized, marking the concluding stages of a phase of immunological research that can be traced back at least 75 years. At the same time chemically minded immunologists have been moving in new directions. A substantial beginning in one direction has been made with the purification of messenger RNAs (mRNAs) for Ig chains. Hybridization of these RNAs (or their DNA copies made with the enzyme reverse transcriptase) to cell DNA is beginning to provide convincing estimates of the number of germ-line Ig genes. And some hybridization studies have already yielded suggestive evidence for translocation of V and C genes from separate to contiguous positions in DNA isolated from cells at different stages of differentiation. Moreover, in vitro trans lation of Ig mRNAs has revealed a remarkably hydrophobic stretch of about 20 amino acids at the N-terminus of the nascent Ig chain. This extra piece is absent in the Ig extracted from or secreted by plasma cells, presumably because it is rapidly cleaved from the "preimmunoglobulin" chain within the cell, but the extra piece probably plays a key role in directing the synthesis of prelg to the cell's secretory pathway.
Publisher: Springer Science & Business Media
ISBN: 1468481428
Category : Medical
Languages : en
Pages : 246
Book Description
Immunochemistry, recently rechristened molecular immunology, has been pre occupied throughout its long history with the structure and function of antibodies and the specificity of antibody-antigen reactions. With the recent X-ray diffrac of several crystallized immunoglobulin (Ig) fragments and a whole tion analyses Ig molecule, the three-dimensional structure of antibodies and their ligand combining sites has been realized, marking the concluding stages of a phase of immunological research that can be traced back at least 75 years. At the same time chemically minded immunologists have been moving in new directions. A substantial beginning in one direction has been made with the purification of messenger RNAs (mRNAs) for Ig chains. Hybridization of these RNAs (or their DNA copies made with the enzyme reverse transcriptase) to cell DNA is beginning to provide convincing estimates of the number of germ-line Ig genes. And some hybridization studies have already yielded suggestive evidence for translocation of V and C genes from separate to contiguous positions in DNA isolated from cells at different stages of differentiation. Moreover, in vitro trans lation of Ig mRNAs has revealed a remarkably hydrophobic stretch of about 20 amino acids at the N-terminus of the nascent Ig chain. This extra piece is absent in the Ig extracted from or secreted by plasma cells, presumably because it is rapidly cleaved from the "preimmunoglobulin" chain within the cell, but the extra piece probably plays a key role in directing the synthesis of prelg to the cell's secretory pathway.
Contemporary Topics in Molecular Immunology
Author: R. Porter
Publisher: Springer Science & Business Media
ISBN: 1468428411
Category : Medical
Languages : en
Pages : 265
Book Description
The distinction between molecular immunology and immunobiology is neces sarily arbitrary. The most rapid progress is usually made in the blurred area between the two, when the chemist is aware of the full significance of the biological problems, and the biologist is alert to the contribution that a knowl edge of molecular structure can be made to their solution. The range of scientific disciplines able to contribute to research in immunology, which this approach brings, is reflected in the present volume. Protein chemists worked out the arrangement of the polypeptide chains and the amino acid sequences of antibodies and X-ray crystallographers the three dimensional structure, but more precise definition of the amino acid side chain positions in the combining site is required for an understanding of the subtleties of antibody specificity. That this can be achieved with physical techniques such as nuclear magnetic resonance has been shown by R. A. Dwek, and in his chapter he summarizes these results with a minimum of technical detail. The immune response has been shown to be dependent on complex cellular interactions and further progress will be facilitated by investigation of the molecular basis of these interactions. This necessitates study of the structure and organization of the molecules in the surfaces of lymphocytes and other cells.
Publisher: Springer Science & Business Media
ISBN: 1468428411
Category : Medical
Languages : en
Pages : 265
Book Description
The distinction between molecular immunology and immunobiology is neces sarily arbitrary. The most rapid progress is usually made in the blurred area between the two, when the chemist is aware of the full significance of the biological problems, and the biologist is alert to the contribution that a knowl edge of molecular structure can be made to their solution. The range of scientific disciplines able to contribute to research in immunology, which this approach brings, is reflected in the present volume. Protein chemists worked out the arrangement of the polypeptide chains and the amino acid sequences of antibodies and X-ray crystallographers the three dimensional structure, but more precise definition of the amino acid side chain positions in the combining site is required for an understanding of the subtleties of antibody specificity. That this can be achieved with physical techniques such as nuclear magnetic resonance has been shown by R. A. Dwek, and in his chapter he summarizes these results with a minimum of technical detail. The immune response has been shown to be dependent on complex cellular interactions and further progress will be facilitated by investigation of the molecular basis of these interactions. This necessitates study of the structure and organization of the molecules in the surfaces of lymphocytes and other cells.
Contemporary Topics in Molecular Immunology
Author: F. Inman
Publisher: Springer Science & Business Media
ISBN: 1468445170
Category : Medical
Languages : en
Pages : 256
Book Description
recipients and acceptance of allografts can be made. The authors have the experi ence and ability to bridge the entire field of transplantation and their article encompasses both clinical and immunochemical data in this area. Their data show clearly that matches for the DR antigens are more important than those at the ABC loci in determination of graft survival. Additional relevant factors, in cluding autoimmunity and other B-cell antigens, are discussed and correlated with graft survival. The authors also present pathology data concerning the distribution of HLA-DR antigens in various tissues. These data indicate a fruitful area for future investigations on the chemical aspects of the various antigens encoded within the human MHC. Do changes in the structure of lymphocyte surface glycoproteins, especially changes in their carbohydrate portions, occur during normal lymphoid differen tiation? Information about this question is limited, and pertinent data are avail able for only a few proteins. Three of the proteins are major glycoprotein con stituents of rodent thymocyte membranes: the Thy-! antigen, a glycosylated leukocyte sialoglycoprotein called W3/13, and a high-molecular-weight glycopro tein known as the leukocyte-common antigen. In his contribution, Pink thor oughly characterizes these glycoproteins and discusses the evidence that the structures change when a thymocyte differentiates into a mature, peripheral T cell. A comparison is drawn between lymphocyte glycoprotein changes and those that occur during red blood cell differentiation. The reader will find Pink's discourse informative and provocative. Mast cells, basophils, and related tumor lines bind IgE with very high affinity.
Publisher: Springer Science & Business Media
ISBN: 1468445170
Category : Medical
Languages : en
Pages : 256
Book Description
recipients and acceptance of allografts can be made. The authors have the experi ence and ability to bridge the entire field of transplantation and their article encompasses both clinical and immunochemical data in this area. Their data show clearly that matches for the DR antigens are more important than those at the ABC loci in determination of graft survival. Additional relevant factors, in cluding autoimmunity and other B-cell antigens, are discussed and correlated with graft survival. The authors also present pathology data concerning the distribution of HLA-DR antigens in various tissues. These data indicate a fruitful area for future investigations on the chemical aspects of the various antigens encoded within the human MHC. Do changes in the structure of lymphocyte surface glycoproteins, especially changes in their carbohydrate portions, occur during normal lymphoid differen tiation? Information about this question is limited, and pertinent data are avail able for only a few proteins. Three of the proteins are major glycoprotein con stituents of rodent thymocyte membranes: the Thy-! antigen, a glycosylated leukocyte sialoglycoprotein called W3/13, and a high-molecular-weight glycopro tein known as the leukocyte-common antigen. In his contribution, Pink thor oughly characterizes these glycoproteins and discusses the evidence that the structures change when a thymocyte differentiates into a mature, peripheral T cell. A comparison is drawn between lymphocyte glycoprotein changes and those that occur during red blood cell differentiation. The reader will find Pink's discourse informative and provocative. Mast cells, basophils, and related tumor lines bind IgE with very high affinity.
Contemporary Topics in Molecular Immunology
Author:
Publisher:
ISBN:
Category : Immunochemistry
Languages : en
Pages : 322
Book Description
Publisher:
ISBN:
Category : Immunochemistry
Languages : en
Pages : 322
Book Description
A Historical Perspective on Evidence-Based Immunology
Author: Edward J. Moticka
Publisher: Newnes
ISBN: 0123983754
Category : Medical
Languages : en
Pages : 396
Book Description
A Historical Perspective on Evidence-Based Immunology focuses on the results of hypothesis-driven, controlled scientific experiments that have led to the current understanding of immunological principles. The text helps beginning students in biomedical disciplines understand the basis of immunologic knowledge, while also helping more advanced students gain further insights. The book serves as a crucial reference for researchers studying the evolution of ideas and scientific methods, including fundamental insights on immunologic tolerance, interactions of lymphocytes with antigen TCR and BCR, the generation of diversity and mechanism of tolerance of T cells and B cells, the first cytokines, the concept of autoimmunity, the identification of NK cells as a unique cell type, the structure of antibody molecules and identification of Fab and Fc regions, and dendritic cells. - Provides a complete review of the hypothesis-driven, controlled scientific experiments that have led to our current understanding of immunological principles - Explains the types of experiments that were performed and how the interpretation of the experiments altered the understanding of immunology - Presents concepts such as the division of lymphocytes into functionally different populations in their historical context - Includes fundamental insights on immunologic tolerance, interactions of lymphocytes with antigen TCR and BCR, and the generation of diversity and mechanism of tolerance of T and B cells
Publisher: Newnes
ISBN: 0123983754
Category : Medical
Languages : en
Pages : 396
Book Description
A Historical Perspective on Evidence-Based Immunology focuses on the results of hypothesis-driven, controlled scientific experiments that have led to the current understanding of immunological principles. The text helps beginning students in biomedical disciplines understand the basis of immunologic knowledge, while also helping more advanced students gain further insights. The book serves as a crucial reference for researchers studying the evolution of ideas and scientific methods, including fundamental insights on immunologic tolerance, interactions of lymphocytes with antigen TCR and BCR, the generation of diversity and mechanism of tolerance of T cells and B cells, the first cytokines, the concept of autoimmunity, the identification of NK cells as a unique cell type, the structure of antibody molecules and identification of Fab and Fc regions, and dendritic cells. - Provides a complete review of the hypothesis-driven, controlled scientific experiments that have led to our current understanding of immunological principles - Explains the types of experiments that were performed and how the interpretation of the experiments altered the understanding of immunology - Presents concepts such as the division of lymphocytes into functionally different populations in their historical context - Includes fundamental insights on immunologic tolerance, interactions of lymphocytes with antigen TCR and BCR, and the generation of diversity and mechanism of tolerance of T and B cells