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.
The Relationship Between Antigenic Structure and Immune Specificity.- I. Introduction.- II. Antigens.- A. Poly-?-D-Glutamyl Capsule of Bacillus anthraces.- B. Adrenocorticotropic Hormone (ACTH).- C. Angiotensin.- D. Bradykinin.- E. Gastrin.- F. Glucagon.- G. Ferredoxin.- H. Insulin.- I. Cytochrome c.- J. Ribonuclease.- K. Lysozyme.- L. Myoglobin.- M. Hemoglobin.- N. Tobacco Mosaic Virus and Its Protein Subunit.- III. Discussion.- A. Reaction with Circulating Antibodies.- B. Specificity of Cellular Immune Reactions.- IV. Concluding Remarks.- References.- Human Histocompatibility Antigens.- I. Introduction.- II. Extraction of Histocompatibility Antigens.- III. Solubilization and Purification of HL-A Antigens.- A. Antigen Source Material.- B. KCl Extraction Technique.- C. Purification with Polyacrylamide Gel Electrophoresis.- IV. Biological Evaluation of Soluble HL-A Antigens.- V. Chemical Characterization of HL-A Antigens.- A. Antigens Prepared from Spleen Cells.- B. HL-A Antigens from Lymphocytes in Culture.- VI. Chemical Nature of HL-A Alloantigens.- VII. Summary.- Acknowledgment.- References.- Bacterial Flagellin as an Antigen and Immunogen.- I. Introduction.- II. Properties of Flagellin from Salmonella Organisms.- A. Physical and Chemical Properties.- B. Antigenic Properties.- III. Degradation and Modification of Flagellin.- A. Antigenic Properties of Fragments Released from Flagellin.- B. Antigenic Properties of Chemically Modified Flagellin.- IV. In Vivo Immunogenicity of Flagellin and Its Derivatives.- A. Immunogenicity of Flagellin and Polymerized Flagellin.- B. Immunogenicity of Fragmented Flagellin.- C. Immunogenicity of Chemically Modified Flagellin.- V. In Vivo Localization Patterns of Flagellin and Its Derivatives.- VI. In Vitro Behavior of Flagellin and Its Derivatives.- A. Induction of Immune Responses.- B. Reaction Between Antigen and Lymphocytes.- VII. Antigen as a Regulator of Cell Behavior.- VIII. Discussion and Conclusions.- References.- The Transfer of Immunity with Macrophage RNA.- I. Introduction.- II. The Heightened Immunogenicity of Antigens Associated with Macrophages.- A. Immune Responses of Fractionated Cell Populations.- B. Retention and Localization of Antigen by Macrophages.- III. RNA-Antigen Complexes.- A. Assessment of the Requirement for Macrophages.- B. Assessment of the Existence of Antigen-Specific RNAs.- C. Assessment of the Requirement for an Enzyme.- D. Relationship Between the Capacity to Complex with RNA and Immunogenicity.- E. The Nature of the RNA-Antigen Chemical Bond.- F. Are RNA-Antigen Complexes Laboratory Artifacts?.- IV. The Transfer of Cellular Immunity with RNA.- V. Informational RNA.- VI. Conclusions.- Acknowledgment.- References.- Relationship of Events at the Lymphocyte Cell Surface to Gene Expression: Approaches to the Problem.- I. Introduction.- II. General Properties of Continuously Growing Cultured Human Lymphocytes.- III. Control of Synthesis of Membrane-Associated Immunoglobulin.- A. Quantitative Aspects.- B. Half-Disappearance of M-Ig in Logarithmically Growing Cells Treated with Inhibitors of Protein Synthesis.- C. Amount and Half-Disappearance of M-Ig and Cytoplasmic Ig in Synchronized “G0” Cells.- D. Half-Disappearance of M-Ig and Cytoplasmic Ig in Logarithmically Growing Cells Treated With Actinomycin D.- IV. Molecular Events During the Rest to Proliferation Transition in Lymphocytes.- A. Synchronization of Cultured Lymphocytes.- B. Phenotypic Expression in Stationary Phase (“G0”) and Logarithmically Growing Cells.- C. Polypeptide Synthesis in the “G0” to G1 Transition.- D. Perturbations Using Actinomycin D and Cyclic AMP.- V. Studies on the “Linkage” Between the Plasma Membrane and Cellular Genes.- A. Nature of Cytoplasmic DNA.- B. Association of DNA with Cytoplasmic Membranes.- C. Synthesis of Membrane-Associated DNA in Synchronized Cells.- D. Electron Microscopic Studies of Plasma Membrane-Associated DNA.- VI. Summary and Prospects for the Future.- Acknowledgment.- References.- The Antigen-Binding Sites of Immunoglobulins.- I. Introduction.- II. Size and General Features of the Antibody Combining Site.- III. Structural Studies.- IV. Sequence of the Variable Regions of Heavy and Light Chains.- V. Affinity-Labeling Studies.- VI. Conclusion.- References.- ?D Immunoglobulin.- I. Introduction.- II. Isolation of ?D.- III. Structure of ?D.- A. Physical Properties.- B. Chemical Properties.- IV. Biological Properties of ?D.- A. ?D Concentration in Body Fluids.- B. Antibody Activity.- C. Metabolic Properties.- D. Other Biological Activities.- E. ?D Multiple Myeloma.- V. Prospects.- Acknowledgment.- References.