Medical Immunology Fifth Edition Revised and Expanded edited by Gabriel Virella Medical University of South Carolina Charleston, South Carolina Marcel Dekker, Inc New York Basel TM Copyright â 2001 by Marcel Dekker, Inc All Rights Reserved ISBN: 0-8247-0550-5 This book is printed on acid-free paper Headquarters Marcel Dekker, Inc 270 Madison Avenue, New York, NY 10016 tel: 212-696-9000; fax: 212-685-4540 Eastern Hemisphere Distribution Marcel Dekker AG Hutgasse 4, Postfach 812, CH-4001 Basel, Switzerland tel: 41-61-261-8482; fax: 41-61-261-8896 World Wide Web http://www.dekker.com The publisher offers discounts on this book when ordered in bulk quantities For more information, write to Special Sales/Professional Marketing at the headquarters address above Copyright © 2001 by Marcel Dekker, Inc All Rights Reserved Neither this book nor any part may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopying, microfilming, and recording, or by any information storage and retrieval system, without permission in writing from the publisher Current printing (last digit): 10 PRINTED IN THE UNITED STATES OF AMERICA Preface In 1986, Marcel Dekker, Inc., published the first edition of Introduction to Medical Immunology It is remarkable that in 2001 the same publisher continues to enthusiastically back the publication of the fifth edition, now with the shorter title of Medical Immunology This is a book that goes against the grain Notes in the margins, boxes with correlations, or learning objectives will not challenge the reader What we try to provide is a classic text with updated information, written with a solid medical perspective We believe that this approach is the most appropriate one for the education of physicians of the 21st century Whether used by a medical student or by a resident, intern, or young specialist, the book will provide a good balance between basic and clinical science Of course, it is as true now as it was years ago that the field of immunology continues to grow at a brisk pace, and that many concepts are victims of constant revision It is very true of immunology that the more we know the greater is our ignorance But all of us involved in the fifth edition have enthusiastically undertaken the task of providing a general introductory book that should remain viable for half a decade If we use past editions as a yardstick, we have achieved this goal This new edition has been thoroughly revised and reorganized We have, obviously, maintained its emphasis on the clinical application of immunology We also remain faithful to our strong conviction that this textbook is written not to impress our peers with extraordinary insights or revolutionary knowledge, but rather to be helpful to medical students and young professionals who need an introduction to the field This means that the scientific basis of immunology needs to be clearly conveyed without allowing the detail to obscure the concept The application to medicine needs to be transparently obvious, but without unnecessary exaggeration The text must present a reasonably general and succinct overview, but needs to cover areas that appear likely to have a strong impact in the foreseeable future The book should stimulate students to seek more information and to develop his or her own “thinking” but cannot be a castle of theoretical dreams (and nightmares) With these goals in mind, one major change that we made in this edition was the redistribution of topics and rearrangement of chapters, to ensure a more logical and cohesive presentation The first part, “Basic Immunology,” includes a new chapter on phagocytic cells preceding “Infections and Immunity,” thus bringing to a close a logical sequence that starts with the discussion of the cells and tissues involved in the immune response The seciii iv Preface ond part, “Diagnostic Immunology,” consists of a single, new chapter in which the most modern aspects of diagnostic immunology are presented in a simple and effective fashion The chapters in Part III (“Clinical Immunology”) have been thoroughly revised, and are peppered with cases in order to provide a solid anchor between the discussion of concrete problems presented by patients with diseases of immunological basis and the relevant scientific principles A new part—”Immunodeficiency Diseases”—has been added to reflect the extraordinary significance of immunodeficiency diseases in clinical immunology, from providing experiments of nature that allow us to understand how the immune system is organized in humans to secondary immunodeficiencies (including those caused iatrogenically as well as the acquired immunodeficiency syndrome) encountered by physicians of all specialties with increasing frequency Part IV contains three important chapters: one dealing with the diagnosis of immunodeficiencies, the second dedicated to primary immunoeficiencies, and the last dedicated to secondary immunodeficiencies In preparing this new edition, I have been lucky in securing the continuing participation of many of the collaborators responsible for previous editions, and I was also able to recruit new blood, bringing new perspectives to some key chapters I also express our gratitude to Marcel Dekker for his continuing support, and to Ms Kerry Doyle for her editorial efforts We applied our best efforts to produce a concise textbook that should bring to the attention of our readers the intrinsic fascination of a discipline that seeks understanding of fundamental biological knowledge, with the goal of applying that knowledge to the diagnosis and treatment of human diseases We hope that this new edition will be a worthy successor to the previous four Gabriel Virella, M.D., Ph.D Contents Preface Contributors Part I iii ix Basic Immunology Introduction Gabriel Virella Cells and Tissues Involved in the Immune Response Gabriel Virella and Jean-Michel Goust 11 Major Histocompatibility Complex Jean-Michel Goust 31 The Induction of an Immune Response: Antigens, Lymphocytes, and Accessory Cells Gabriel Virella and Barbara E Bierer 51 Immunoglobulin Structure Gabriel Virella 77 Biosynthesis, Metabolism, and Biological Properties of Immunoglobulins Gabriel Virella 93 Genetics of Immunoglobulins Janardan P Pandey 105 Antigen-Antibody Reactions Gabriel Virella 119 The Complement System Robert Boackle 135 v vi Contents 10 Lymphocyte Ontogeny and Membrane Markers Virginia M Litwin and Jean-Michel Goust 161 11 Cell-Mediated Immunity Barbara E Bierer, Jean-Michel Goust, and Gabriel Virella 193 12 The Humoral Immune Response and Its Induction by Active Immunization Gabriel Virella 225 13 Phagocytic Cells Gabriel Virella 245 14 Infections and Immunity Gabriel Virella 259 Part II 15 Diagnostic Immunology Diagnostic Immunology Gabriel Virella and Virginia M Litwin Part III 279 Clinical Immunology 16 Tolerance and Autoimmunity George C Tsokos, Jean-Michel Goust, and Gabriel Virella 313 17 Organ-Specific Autoimmune Diseases Gabriel Virella and Jean-Michel Goust 341 18 Systemic Lupus Erythematosus George C Tsokos and Jean-Michel Goust 361 19 Rheumatoid Arthritis Jean-Michel Goust and Gabriel Virella 377 20 Hypersensitivity Reactions Gabriel Virella 397 21 IgE-Mediated (Immediate) Hypersensitivity Jean-Michel Goust and Albert F Finn, Jr 411 22 Immunohematology Gabriel Virella and Mary Ann Spivey 431 23 Immune Complex Diseases Gabriel Virella and George C Tsokos 453 24 Immune System Modulators Philip D Hall, Jean-Michel Goust, and Gabriel Virella 473 Contents vii 25 Transplantation Immunology Gabriel Virella, Richard Knight, and Jonathan Bromberg 501 26 Tumor Immunology Sebastiano Gattoni-Celli 517 27 Malignancies of the Immune System Gabriel Virella and Jean-Michel Goust 529 Part IV Immunodeficiency Diseases 28 Diagnosis of Immunodeficiency Diseases Gabriel Virella and John Sleasman 555 29 Primary Immunodeficiency Diseases Gabriel Virella and John Sleasman 573 30 AIDS and Other Acquired Immunodeficiency Diseases Gabriel Virella 599 Index 631 Contributors Barbara E Bierer, M.D Chief, Laboratory of Lymphocyte Biology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland Robert J Boackle, Ph.D Professor and Director of Oral Biology and Professor of Immunology, Medical University of South Carolina, Charleston, South Carolina Jonathan S Bromberg, M.D., Ph.D Professor of Surgery, Gene Therapy, Molecular Medicine, and Chief, Kidney/Pancreas Transplantation and Transplant Research, RecanatiMiller Transplant Institute, Mount Sinai School of Medicine, New York, New York Albert F Finn, Jr., M.D Clinical Associate Professor of Medicine, Department of Medicine and Department of Microbiology, and Immunology, Medical University of South Carolina, Charleston, South Carolina Sebastiano Gattoni-Celli, M.D Professor, Department of Radiation Oncology and Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, South Carolina Jean-Michel Goust, M.D Professor, Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, South Carolina Philip D Hall, Pharm.D Associate Professor, College of Pharmacy, Medical University of South Carolina, Charleston, South Carolina Richard Knight, M.D Associate Professor of Surgery, Recanati-Miller Transplant Institute, Mount Sinai School of Medicine, New York, New York Virginia M Litwin, Ph.D Senior Research Investigator, Clinical Pharmacology/ Experimental Medicine, Bristol-Myers Squibb Company, Hamilton Square, New Jersey Janardan P Pandey, Ph.D Professor, Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, South Carolina ix 642 [Hypersensitivity] diseases, use of immunosuppressive drugs in, 485 immediate (see Type I hypersensitivity reactions) immune complex-induced hypersensitivity reactions, 402–405 Arthus reaction, 403 serum sickness, 404–405 immunoglobulin E-mediated, 411–430 case study, 413, 426–427 drug therapy, 424–426 early, late phases in type I hypersensitivity, 420–423 eosinophils, in late phase, 422–423 genetic control, immunoglobulin E synthesis, 416–417 immunoglobulin E antibodies, 414–418 quantitative assay, 414–415 skin tests, 415–416 interaction of immunoglobulin E with cell surface receptors, 418–420 pathogenesis, 413–423 prevention, 423–424 T-B cell cooperation in, 417–418 reactions, 397–410 type I hypersensitivity reactions, 398–400 clinical expression, 399 historical overview, 398–399 pathogenesis, 400 Hyperviscosity syndrome, 534, 535, 536 Hypoadrenalism, primary, chronic, 344–345 Hypocomplementemia, clearance of immune complexes, 155–156 Hypogammaglobulinemia acquired, 578–579 clinical presentation, 579 diagnosis, 579 physiopathology, 578 therapy, 579 of infancy, transient, 574–576 Hyposensitization, 423–424 Iatrogenically induced immune deficiencies, 603–605 neutropenia, 603 causes of, 603 postsurgery immunodeficiency, 603–604 splenectomy, 604–605 thymectomy, 605 ICA (anti-islet cell antibodes), 345 Index IDDM (see Insulin-dependent diabetes mellitus) Idiopathic monoclonal gammopathies, 540–541 Idiopathic thrombocytopenic purpura, 356–357 Idiotypes, 110 Ig (see Immunoglobulin) IL (see Interleukins) IL-2 receptors, expression, 195–196 Immediate hypersensitivity (see Type I hypersensitivity reactions) Immune complex diseases, 453–472 adsorption, transfer of immune complexes, 456 classification, immune complex disease, 465–466 clinical expression, 466–467 immune complex formation, cell interactions, 455–456 circulating immune complexes, 455 physicochemical characteristics, 454–455 physiopathology, 454–461 soluble immune complexes, detection of, 462–465 cryoglobulins, 462–464 interactions with complement, 464–465 polyethylene glycol, precipitation of soluble immune complexes, 464 specific immune-complex-screening tests, 465 therapeutic approaches to, 467 Immune complex-induced hypersensitivity reactions, 402–405 Arthus reaction, 403 serum sickness, 404–405 Immune complex-induced inflammation, postinfectious, 272–273 Immune complexes, systemic lupus erythematosus, 368–369 Immune elimination, 231 Immune hemolytic anemias, 444–449 autoimmune hemolytic anemia, 444–446 case study, 444, 449 cold agglutinin disease, 446 diagnosis, 444–446 drug-induced hemolytic anemia, 446–448 autoimmunity induction mechanism, 448 drug adsorption mechanism, 447–448 immune complex mechanism, 447 treatment, 448–449 Immune recognition, 60–61 Index Immune response abnormal consequences of, 271–273 antigen-antibody complexes, 272 autoimmunity, 273 bacterial “superantigens,” 271–272 postinfectious tissue damage, 272–273 cross-reactions with tissue antigens, 273 immune complex-induced inflammation, 272–273 immune destruction, infected cells, 273 induction of, 51–76 antigen processing, presentation, 62 antigen receptor, on T lymphocytes, B lymphocytes, 61–62 cytotoxic T lymphocytes, antigen presentation, activation of, 66–68 factors associated with, 54–56 helper T lymphocytes, activation of, 62–66 immune recognition, clonal restriction, expansion, 60–61 MHC complex and, 40–44 primary, 249 antigen fate and, 231–232 description of, 227–229 secondary, 230–231 antigen fate and, 231, 232 sequence of events in, 228 stages of, 2–3, Immune system modulators, 473–500 anti-inflammatory drugs, 474 cytokine modifiers, 487–488 hypersensitivity, autoimmune diseases, immunosuppressive drugs in, 485 immunopotentiation, 488–496 active immunization, 494–495 bacterial, chemical immunomodulators, 496 biological response modifiers, 488–492 dialyzable leukocyte extracts, 495 intravenous immunoglobulins, 492–494 thymic hormones, 495–496 immunosuppression, 474–488 drugs, 474–484 prolonged immunosuppression, adverse consequences of, 485–487 Immunization, 234–240 attenuated vaccines, 238–239 recombinant organisms, 238–239 historical background, 234–235 643 [Immunization] immunotherapeutic agents, vaccines as, 240 recommended immunizations, 239–240 types of vaccines, 235–238 component vaccines, 236–238 bacterial polysaccharides, 236 conjugate vaccines, 236–237 DNA vaccines, 237–238 inactivated toxins, 236 mixed component vaccines, 236 recombinant bacterial antigens, 236 synthetic peptide vaccines, 237 viral component vaccines, 237 killed vaccines, 236 Immunoblotting (see Immunofixation) Immunodeficiency acquired, 600–607 with ataxia-telangiectasia, 588 clinical presentation, 588 genetics and physiopathology, 588 with thrombocytopenia, eczema, 590 clinical presentation, 590 genetics and pathogenesis, 590 laboratory findings, 590 therapy, 590 Immunodeficiency diseases diagnosis, 555–572 B-lymphocyte membrane markers, 562–564 cell-mediated immunity, diagnostic evaluation, 564–569 cytokine assays, 568–569 delayed-type hypersensitivity, in vivo testing of, 564–566 mitogenic stimulation assays, 567 natural killer cells, 566 response to antigenic stimulation, 567–568 T-lymphocyte membrane markers, 566 T-lymphocyte mitogens, 567 complement function, diagnostic evaluation of, 569 humoral immunity, diagnostic evaluation, 557 immunoglobulins, antibodies, quantitative assay of, 557–562 molecular genetic studies, 569 phagocytic cell function, diagnostic evaluation of, 569 serum immunoglobulin levels, 557–559 644 [Immunodeficiency diseases] primary, 573–598 cellular immunodeficiencies, 583–585 combined immunodeficiencies, 585–590 humoral immunodeficiencies, 574–583 phagocytic cell deficiencies, 590–593 Immunodiffusion, radial, 280–282 Immunoelectrophoresis, 283 quantitative, 282 Immunofixation, 283 Immunofluorescence, 290–297 autoantibody detection, 292 flow cytometry, 293–297 cytoplasmic staining, 296 DNA analysis, 296 sorting, 296–297 surface staining, 293–296 in microbiology, 291–292 quantitative immunofluorescence assays, 292 tissue-fixed antigen-antibody complex detection, 292–293 Immunogenicity, 51–52 characteristics of, 54 Immunoglobulin A, 87–88 deficiency, selective, 579–581 clinical presentation, 580 diagnosis, 580 physiopathology, 579–580 therapy, 580–581 subclasses, 82 secretory, 87–88 biosynthesis of, 94 transport, 95 Immunoglobulin D, 88 Immunoglobulin E, 88 hypersensitivity mediated by, 411–430 case study, 413, 426–427 drug therapy, 424–426 early, late phases in type I hypersensitivity, 420–423 eosinophils, in late phase, 422–423 genetic control, immunoglobulin E synthesis, 416–417 immunoglobulin E antibodies, 414–416 quantitative assay, 414–415 response, 416, 417–418 skin tests, 415–416 interaction of immunoglobulin E with cell surface receptors, 418–420 Index [Immunoglobulin E] pathogenesis, 413–423 prevention, 423–424 T-B cell cooperation in, 417–418 Immunnoglobulin G (IgG) characteristics, 81 complement-binding sequences, 129 functional topography, 78 half-life, 97 placental transfer, 99 proteolytic digestion, 78 structural model, 78–79 structure, 83 subclasses, 81–82 Immunoglobulin M, 87 Immunoglobulin molecules, immunoglobulin heavy-chain allotypes, 111–112 Immunoglobulin superfamily, 26 Immunoglobulin structure, 77–92 antibody-combining site, 86–87 characteristics of immunoglobulins, 81 disulfide bonds, reduction of, 78–80 domains, 82–85 heavy, light chains, structural, antigenic heterogeneity of, 81–82 immunoglobulin A, 87–88 subclasses, 82 immunoglobulin D, 88 immunoglobulin E, 88 immunoglobulin M, 87 immunoglobulin superfamily of proteins, 85–86 proteolytic digestion, 78 prototype immunoglobulin molecule, 77–80 regions, 82–85 variable, constant, 82–84 subclasses, 82 Immunoglobulins, 93–104 biological properties, 98–102 complement activation, 99–100 Fc receptors binding to, 100–102 types of, 100 placental transfer, 99 biosynthesis, 93–96 combined immunodeficiency with, 588 genetics, 105–118 allelic exclusion, 113 allotypes, 114 antibody diversity, genetic basis of, 109–110 Index [Immunoglobulins] antigenic determinants, immunoglobulin molecules, 110–112 allotypes, 110–112 heavy-chain V-region allotype, 112 immunoglobulin A heavy-chain allotypes, 112 immunoglobulin E heavy-chain allotypes, 112 immunoglobulin heavy-chain allotypes, 111–112 K-type light-chain allotypes, 112 idiotypes, 110 isotypes, 110 diseases, 114 DNA polymorphisms, restriction fragment length polymorphisms, 112–113 gene rearrangement, 105–109 GM allotypes, immunoglobulin subclass concentrations, 114 immune response, 114 restriction fragment length polymorphisms, 112–113 immunoglobulins, 112–113 intravenous, 492–494 metabolism, 96–98 quantitative assay of, 557–562 Immunohematology, 431–452 ABO system, 431–432 autoimmune hemolytic anemia, warm antibody type, 444–446 blood groups, 431–433 blood transfusion reactions, 437–440 serological principles of, 434–437 blood types, laboratory determination of, 434 cold agglutinin disease, syndrome, 446 drug-induced hemolytic anemia, 446–448 extravascular hemolytic reactions, 438 hemolytic disease of newborn, 440–443 immune hemolytic anemias, 444–449 immunological diagnosis, 442 intravascular hemolytic reactions, 437–438 nonhemolytic immune transfusion reactions, 439–440 reagents, 434 Rh system, 432 sensitization, mechanisms of, 441 tube testing, alternatives to, 437 Immunonephelometry, 282–283 645 Immunophilins, 479 Immunopotentiation, 488–496 active immunization, 494–495 bacterial immunomodulators, 496 biological response modifiers, 488–492 cellular sources, 489–490 clinical applications, 490–492 function, 489 structure, 489 cancer, 495 chemical immunomodulators, 496 dialyzable leukocyte extracts, 495 transfer factor, 495 HIV infection, 494 intravenous immunoglobulins, 492–494 thymic hormones, 495–496 Immunoserology, 279–301 agglutination, 286–289 bacterial agglutination, 286–287 hemagglutination, 288–289 of inert particles coated with antigen, antibody, 287 complement fixation, 289–290 enzyme immunoassay, 299–301 immunofluorescence, 290–297 autoantibody detection, 292 flow cytometry, 293–297 cytoplasmic staining, 296 DNA analysis, 296 sorting, 296–297 surface staining, 293–296 in microbiology, 291–292 quantitative immunofluorescence assays, 292 tissue-fixed antigen-antibody complex detection, 292–293 precipitation assays, 280–286 counterimmunoelectrophoresis, 280 double diffusion method, 280 immunoelectrophoresis, 283 immunofixation, 283 immunonephelometry, 282–283 quantitative immunoelectrophoresis, 282 radial immunodiffusion, 280–282 western blot, 283–286 radioimmunoassay, 297–299 Immunosuppression, 474–488, 506–511 biological response modifiers, 507–508 anti-T-cell monoclonal antibodies, 507–508 antihymocyte, antilymphocyte globulins, 507 646 [Immunosuppression] chemical immunosuppression, 506–507 antimetabolites, 506 calcineurin inhibitors, 506–507 glucocorticoids, 506 rapamune, 507 rapamycin, 507 sirolimus, 507 side effects, 510–511 malignancies, 511 opportunistic infections, 510–511 total lymphoid irradiation, 508 transfusion effect, 509–510 Immunosuppressive drugs, 474–484 alkylating agents, 477–479 anti-inflammatory effects, 475–476 antimetabolites, 477–479 apoptosis, induction of, 475 co-stimulatory signals, monoclonal antibodies blocking, 483–484 cyclosporine A, 479–482 cytokine synthesis, downregulation of, 475 glucocorticoids, 475–477 immunosuppressive monoclonal antibodies, 483–484 immunosuppressive polyclonal antibody preparations, 482–483 inhibitory signals, monoclonal antibodies delivering, 484 interleukin-2 receptor, monoclonal antibodies blocking, 484 nonsteroidal anti-inflammatory drugs, 476–477 sirolimus, 479–482 tacrolimus, 479–482 Immunotherapeutic agents, vaccines as, 240 Inactivated toxins, 236 Inactivation of T-cell responses, 207–208 Induction of immune response, factors associated with, 54–56 adjuvants, use of, 55–56 antigen administration, method, 55 genetic background, 55 Ineffective immune responses, 269–270 Infantile agammaglobulinemia, 577–578 clinical presentation, 577 diagnosis, 577–578 therapy, 578 Infection immunodeficiency, 606–607 bacterial infections, 606 parasitic infections, 606–607 Index [Infection] viral infections, 607 AIDS, 607–626 immunosuppressive effects of, 270–271 Infectious agents, immune elimination of, 5–6 Inflammation cell-mediated immunity and, 267–268 helper T-lymphocyte role in, 209–210 immune-complex-induced, 272–273 immune reactions and, 28 Ingestion, phagocytic, 253–254 Insulin-dependent diabetes mellitus (IDDM) DQ molecules and, 44 MHC markers, 347–348 pancreatic tissue and, 342 pathogenesis, 345–346 Insulitis, 346 Integrins, 25, 26, 28 Intercellular adhesion molecules, (ICAMs) extravascular emigratin of leukocytes and, 459 functions, 25, 26, 172 interaction with LFA-1, 215 Interleukins (ILs), biological effects, 203 cellular sources, 203 central nervous system effects, 203 hematopoietic effects, 205 vascular effects, 202–203 Interleukin-1 antagonists, 488 Interleukin-2 synthesis deficiency, 588–589 clinical presentation, 589 diagnosis, 589 genetics and physiopathology, 588–589 Interleukins, released by TH1, TH2 lymphocytes, 71 Intracellular infectious agents, immune elimination of, 5–6 Intracellular killing, phagocytic cells and, 249–251 Intravascular hemolytic reactions, 437–438 Intravenous immunoglobulins, 492–494 Intrinsic association constant, 122 Irradiation, lymphoid, total, 508 Ischemia, cold-induced, 536 Isoniazide, induction of systemic lupus-like syndrome, 371 J chain, 87 Job’s syndrome, 591 Jones-Mote reaction, 407 Index Kernicterus, 441 K-type light-chain allotypes, immunoglobulin molecules, 112 Killed vaccines, 236 Killing assays, phagocytic function, 255–256 KM allotypes (K-type light-chain allotypes), 112, 114 Kupffer’s cells, 23 Langerhans cells, 14 Late complement component deficiencies, 595 LATS (long-acting thyroid stimulator), 342 Lectin pathway, complement activation, 149–150 Leukemia, 543–550 defined, 543–544 hairy cell, 545–546 lymphocytic acute, 546–550 B-cell acute lymphocytic leukemia, 546–547 classification, 546 enzymatic markers of acute lymphocytic leukemia, 546 T-cell acute lymphocytic leukemia, 547–548 T-cell leukemia associated with HTLV-1, 548–549 chronic, 545 plasma cell, 540 Leukocyte common antigen (LCA; CD45), 180–181 Leukocyte extracts, dialyzable, 495 Leukocyte function antigen (LFA) (CD11a) functions interaction with ICAM-1 Leukocyte markers, lymphocyte ontogeny, 187–190 Leukocytes adherence, disorders of, 591 polymorphonuclear macrophages, comparison, 251 monocytes, comparison, 251 physiology of, 245–251 Leukostasis, vascular, pulmonary, hemodialysis and, 154 Light-chain allotypes, immunoglobulin, Ktype, 112 Light-chain disease, 530, 538 647 Light chains, heavy chains, immunoglobulin, structural, antigenic heterogeneity of, 81–82 Linkage disequilibrium, 39 Liver, autoimmune diseases of, 350–353 Long-acting thyroid stimulator (LATS), 342 L-selectin (leukocyte adhesion molecule-1), 26 LTB4 (leukotriene B4), 421 Lupoid hepatitis, 352 Lupus erythematosus, systemic, 334 Lymph nodes anatomical organization, 16,18 circulation, 19 physiological role, 18–19 Lymphocyte diversity, ontogeny, study of, 163–166 genetic approaches, 166 lymphocyte membrane markers, 163–166 CD nomenclature, 165–166 monoclonal antibodies, 164–165 Lymphocyte function, laboratory assessment, 301–307 antigenic stimulation, response to, 304 cytokines, cytokine receptors, in plasma, urine, assay of, 304–305 cytotoxic effector cells, assays for, 305–306 mitogenic stimulation assays, 302–303 mixed lymphocyte reaction, 307 mononuclear cells, isolation of, 302 tetramer assays, 304 Lymphocyte ontogeny B-lymphocyte ontogeny, 167–172 B-cell activation regulation, surface molecules involved in, 169–172 surface molecules involved in, 169–171 B-cell maturation, 168–169 isotype switching, 168 B-lineage subpopulations, developmental order of, 167–168 downregulatory molecules on B cells, 171–172 ontogenic development, immunoglobulin synthesis, 169 cytokines, in lymphocyte ontogeny, 161–162 dendritic cells, 183 leukocyte markers, 187–190 membrane markers, 161–192 648 [Lymphocyte ontogeny] natural killer cells, 181–183 activation, 183 inhibitory molecules, 182–183 ontogeny, 181–182 receptors, 182–183 ontogeny, by opposing signaling events, regulation of, 162 stem cell differentiation, 161 T lymphocyte B lymphocyte differentiation, 166–167 coreceptors, 166 gene arrangement, 166 receptors, selection of, 166–167 differentiation of, 166–167 ontogeny, 173–181 coreceptors, 175 markers, T-cell activation, 180–181 inhibition of, 181 membrane markers, mature T lymphocytes, 179–181 pre-T lymphocytes enzymatic activity in, 173 markers, 173 receptor selection, 175–178 negative selection, 175–176 positive selection, 176–178 T-cell differentiation after birth, 178 TcR genes, rearrangement of, 173–175 TcR structure, 178–179 Lymphocytes, 11–13, 51–76 (see also B lymphocyte; T lymphocyte) cell-mediated immunity and, 5–6 Lymphocytic leukemia acute, 546–550 B-cell acute lymphocytic leukemia, 546–547 classification, 546 enzymatic markers of acute lymphocytic leukemia, 546 T-cell acute lymphocytic leukemia, 547–548 T-cell leukemia associated with HTLV1, 548–549 chronic, 545 Lymphoid development, during fetal life, 162–163 Lymphoid irradiation, total, 508 Lymphoid organs, 16, 17 Lymphoid tissues, 16, 17 Index Lymphomas, 543–550 Epstein-Barr virus-associated B-cell lymphomas, 549–550 B-cell lymphomas, in immunocompromised patients, 549 Burkitt’s lymphoma, 549 Hodgkin’s disease, 550 Mediterranean-type abdominal, 542 Lymphotoxin (tumor necrosis factor-), 202 Mac-1 (CD11b), 26–27 MAC (membrane attack complex), 144–145 Macroglobulinemia, Waldenstrom’s, 541–542 clinical features, 541 diagnosis, 541 management, 541–542 Macrophages, 14 comparison of polymorphonuclear leukocytes and, 251 lymphocyte-mediated activation, 267–268 physiology of, 251–252 Macrophage chemotactic protein (MCP), 204, 267 Macrophage inflammatory proteins (MIPs), 204, 219–220 Major histocompatibility complex, 31–50 antigens classes, characteristics of, 34 complexity, 43 structure of, 34–36 class I MHC molecules, 34 class II MHC molecules, 35–36 binding, immune response and, 42 cellular distribution, MHC antigens, 37 chromosomal localization, arrangement, MHC genes, 37–38 classification, human leukocyte antigen genes, gene products, 33–37 cytotoxic T lymphocytes, MHC restriction of, 40–41 deficient expression of molecules, 589–590 detection of human leukocyte antigen genes, gene products, 33–37 disease associations, 44–47 autoimmune diseases, 44–47 malaria, 44 expression, regulation of, 41–42 genetics, 38–40 helper T lymphocytes, antigen presentation to, MHC-II, 41 heterozygosity, 43 Index [Major histocompatibility complex] human leukocyte antigens, 33 classes, 33–34 identification, human leukocyte antigen antigens, 36–37 immune response and, 40–44 MHC-II diversity, 42 overview, 33 peptide-carrying proteins, 43–44 restriction, cytotoxic T lymphocytes, 40–41 restrictive role, MHC-CD interactions, 42 structure, human leukocyte antigen genes, gene products, 33–37 Major histocompatibility complex-CD interactions, restrictive role, 42 Major histocompatibility complex–II diversity, 42 helper T lymphocytes, antigen presentation to, 41 Malaria, major histocompatibility complex, 44 Malignancies (see also Cancer; Tumor) B-cell dyscrasias, 529–543 immune system, 529–554 leukemias, 543–550 lymphomas, 543–550 Malignant transformation, natural killer cells, 218 Malnutrition, immunodeficiency, 600–601 MALT (mucosa-associated lymphoid tissues), 21–22 Mannose-binding protein, 260 Mannose receptors, 260 Mast cells Fc receptors, 88 mediator-release, 424, 425 tissue-fixed, 15 type I hypersensitivity and, 400 Masugi nephritis (see Nephrotoxic nephritis) Materno-fetal transmission, HIV, 623 MCP (macrophage chemotactic protein), 204, 267 M-CSF (monocyte colony-stimulating factor), 490 Measles, 270 Mediterranean-type abddominal lymphoma, 542 Membrane attack complex (MAC), 144–145 Membranoproliferative glomerulonephritis, 327 Memory, immunological, 2, 13 Memory cells, expanded population of, consequences of existence of, 230 649 6-Mercaptopurine (6-MP), 477, 478, 479 Meta-aminobenzene sulfonic acid, antigens tested with immune serum for, 120 Metanilic acid, 120 Methotrexate, 477, 478 ␣-Methyldopa-induced hemolytic anemia, 447, 448–449 Microbial anticomplementary mechanisms, 156 Michrochimerism, 510 2-Microgloubulin, 34 MIF (migration-inhibition factor), 200, 204, 267 Migration-inhibition factor (MIF), 200,204,267 MIP (macrophage inflammatory protein), 204 Mitogenic stimulation assays, 302–303, 567 Mixed component vaccines, 236 Mixed lymphocyte reaction, 307 Molecular genetic studies, 569 Molecular mimicry, in onset of autoimmune diseases, 332 Monoclonal antibodies, production, 164–165 Monoclonal immunoglobulins, 81 Monoclonal gammopathies, idiopathic, 540–541 Monoclonal proteins (paraproteins), 529, 537 Monocytes, 14 comparison of polymorphonuclear leukocytes and, 251 physiology of, 251–252 Mononuclear cells, isolation of, 302 Mu-chain disease, 543 Mucocutaneous candidiasis, chronic, 585 Mucosa-associated lymphoid tissues (MALT), 21–22 Mucosal humoral immune response, 232–234 Mucosal immunity passive transfer, 233–234 physiological significance of, 234 Mucosal levels cell-mediated immune mechanisms, 233 humoral immunity at, 233 Mucosal tolerance, 323–324 anti-idiotypic immune responses, 324 Multiple myeloma, 537–540 clinical features, 77, 537 laboratory diagnosis, 537–538 management, 538–540 Multiple sclerosis, 354–356 Myasthenia gravis, 353–354 Mycophenolate mofetil (CellCept), 506 650 Myelin basic protein (MBP), 354 Myocarditis, autoimmune, 332 Narcolepsy, 45, 47 Natural antibodies, 262–264 Natural killer cells, 13–14, 217–218, 262, 566 activation of, 217–218 antibody-dependent cellular cytotoxicity, 218 lymphocyte ontogeny, 181–183 activation, 183 inhibitory molecules, 182–183 ontogeny, 181–182 receptors, 182–183 target recognition by, 217–218 viral infection, malignant transformation, 218 Nephritis, nephrotoxic, 401–402 lupus, 327 nephrotoxic or Masugi, 401–402 Nephrotoxic nephritis, 401–402 Neuromuscular systems, autoimmune diseases of, 353–356 multiple sclerosis, 354–356 myasthenia gravis, 353–354 Neutropenia, 603 autoimmune, 356 causes of, 356, 603 Neutrophil count, phagocytic function and, 252 Newborn, hemolytic disease of, 440–443 Nezelof syndrome, 588 NK cells (see Natural killer cells) Nocturnal hemoglobinuria, paroxysmal, 153–154 Nonhemolytic immune transfusion reactions, 439–440 Nonsecretory myeloma, 530,538 Nonself discrimination, vs self discrimination, 6–7 Nonspecific anti-infectious defense mechanisms, 259–262 acute phase reaction, 261–262 complement system activation, 260–261 constitutive nonspecific defense mechanisms, 259–260 inducible nonspecific responses, 260 leukocyte chemotaxis, 261–262 natural killer cells, 262 phagocytosis, 260 T lymphocytes, 262 Index Nonsteroidal anti-inflammatory drugs (NSAIDs), rheumatoid arthritis, 390 Nuclear factor-kappa B (NF-B),65, 69, 197, 198 Nuclear factor of activated T cells (NF-AT), 69,197, 198 Nucleoside analogs, 619 OKT3, 507 Ontogeny natural killer cells, 181–182 study approaches, 163–166 T lymphocytes, 173–181 Opiates, immunodeficiency, 606 Opportunistic infections, with immunosuppression, 510–511 Opsonins, 100, 129, 264 Opsonization, antigen-antibody reactions, 128 Organ-specific autoimmune diseases, 341–360 Addison’s disease, 344–345 blood cells, autoimmune diseases of, 356–357 autoimmune neutropenia, 356 idiopathic thrombocytopenic purpura, 356–357 chronic active hepatitis, 352–353 gastrointestinal tract, autoimmune diseases of, 350–353 liver, autoimmune diseases of, 350–353 neuromuscular systems, autoimmune diseases of, 353–356 multiple sclerosis, 354–356 myasthenia gravis, 353–354 neutropenia, causes of, 356 pancreas, autoimmune diseases of, 345–350 acanthosis nigricans, 350 diabetes mellitus, 345–349 development of, pathogenic events leading to, 349 genetic factors, 347–348 pathogenesis, 345–347 immunotherapy, 349–350 pernicious anemia, 350–351 primary biliary cirrhosis, 351 thyroid gland, autoimmune diseases of, 341–344 Graves’ disease, 341–343 Hashimoto’s disease, 342–344 Ouchterlony technique, precipitation assay, 280 Overlap syndrome, 362–363 Index Oxidative burst, phagocytic function and, 254–255 PAF (platelet-activating factor), 421, 422, 459–460 Pancreas, autoimmune diseases of, 345–350 acanthosis nigricans, 350 diabetes mellitus, 345–349 development of, pathogenic events leading to, 349 genetic factors, 347–348 pathogenesis, 345–347 immunotherapy, 349–350 Pancreatitis, 154 Paper disk radioimmnosorbent test (PRIST), 414 Paraproteins (monoclonal proteins), 529–530, 535 Parasitic infections, immunodeficiency, 606–607 Paroxysmal nocturnal hemoglobinuria, 153–154 Passive transfer, mucosal immunity, 233–234 of anaphylactic reactions, 398–399 Penicillin-induced hemolytic anemia, 447 Peptide-carrying proteins, major histocompatibility complex, 43–44 Peptide vaccines, synthetic, 237 Perforins, 13, 215 Periarteriolar lymphatic sheath, of spleen, 19 Peripheral blood cells, receptors on, 151 Pernicious anemia, 350–351 Persistent B-cell stimulation, prolonged retention of antigen and, consequences of, 231 Peyer’s patches, 22, 23, 24 PGE2 (prostaglandin E2), 387 Phagocytic cell, 245–278 activated macrophage, 251–252 chemotaxis, migration to extravascular compartment, 245–247 deficiencies, 590–593 intracellular killing, 249–251 macrophage comparison of polymorphonuclear leukocytes and, 251 physiology of, 251–252 monocyte comparison of polymorphonuclear leukocytes and, 251 physiology of, 251–252 651 [Phagocytic cell] phagocytic function, laboratory evaluation of, 252–256 adherence, 252 chemotaxis, migration, 252–253 degranulation, 254 ingestion, 253–254 killing assays, 255–256 neutrophil count, 252 oxidative burst, measurement of, 254–255 phagocytosis, 247–249, 252 polymorphonuclear leukocytes, physiology of, 245–251 Phagocytosis, 141–143, 247–249, 260 PKC (protein kinase C), 65, 196 Placental transfer, immunoglobulins, 99 Plasma cell dyscrasias, 529 Plasma cell leukemia, 540 Plasma cells differentiatin, 8, 11 immunoglobulin synthesis, 77, 93 morphology, 12, 13 submucosal, 94 switching, 107 ultrastructure, 94 Platelet-activating factor (PAF), 421, 422, 459–460 PMN (see Polymorphonuclear leukocytes) Pokeweed mitogen (PWM), 302, 303 Polyimmunoglobulin receptor (poly-IgR), 94–94, 95 Polymorphonuclear leukocytes macrophages, comparison, 251 monocytes, comparison, 251 physiology of, 245–251 Polysaccharides, bacterial, 236 immunogenicity, 54 Postinfectious tissue damage, 272–273 cross-reactions with tissue antigens, 273 immune complex-induced inflammation, 272–273 immune destruction, infected cells, 273 Postsurgery immunodeficiency, 603–604 Prausnitz-Kustnner reaction, 399 Precipitation, antigen-antibody reactions, 125–127 Precipitation assays, 280–286 counterimmunoelectrophoresis, 280 double diffusion method, 280 immunoelectrophoresis, 283 immunofixation, 283 652 [Precipitation assays] immunonephelometry, 282–283 quantitative immunoelectrophoresis, 282 radial immunodiffusion, 280–282 western blot, 283–286 Pricipitin curve, 125 Primary biliary cirrhosis, 351 Primary hypoadrenalism, chronic, 344–345 Primary immunodeficiency diseases, 573–598 cellular immunodeficiencies, 583–585 combined immunodeficiencies, 585–590 humoral immunodeficiencies, 574–583 phagocytic cell deficiencies, 590–593 Prolonged immunosuppression, adverse consequences of, 485–487 Prolonged retention of antigen, B-cell stimulation and, consequences of, 231 Properdin, 148 Prostaglandin E2 (PGE2), 387, 603 Prostate-specific antigen (PSA), 520–521 Proteasome, 66 Protein kinase C (PKC), 65, 196 Proteins fractionation, 77 immunogenicity, 54 Proteolytic digestion, immunoglobulin, 78 Proteolytic enzymes, 149 Prototype immunoglobulin molecule, 77–80 Prozone, 127 P-selectin, 202 Pulmonary distress syndrome, 154 Pulmonary vascular leukostasis, hemodialysis and, 154 Pyrogenic factor, 407–408 Quantitative immunoelectrophoresis, 282 Quantitative immunofluorescence assays, 292 Radial immunodiffusion, 280–282 Radioallergosorbent test (RAST), 415–416 Radioimmunoassay, 297–299 RAG gene products, 110 RANTES, 204, 267 Rapamune, 507 Rapamycin, 507 Rapid diagnosis tests, 287 Recombinant bacterial antigens, 236 Recommended immunizations, 239–240 Regulatory cells immune response, 218–220 nature of, 219 Index Reiter’s syndrome, 45, 46 Rejection (see Transplantation) Renal failure, immunodeficiency, 601–602 Restriction fragment length polymorphisms (RFLP), immunoglobulins, 112–113 genetics, 112–113 Rh system, 432 antigens of, 432 Rheumatic fever, acute, 331–332 Rheumatic heart disease, 331 Rheumatoid arthritis, 377–396 anti-immunoglobulin antibodies diagnostic specificity of, 381 physiological role of, 381 anticollagen antibodies, 383 antigen presentation, dendritic cells, 386–387 antinuclear antibodies, 383 autoantibodies in, 380–383 B-cell precursors, RF-producing plasmablasts, phenotype, 382 B cells, as local amplificators of autoimmune response, 387 case study, 377–378, 391–392 cell-mediated immunity abnormalities in, 385–388 genetic factors, 388 genetic factors in, 383–385 hormonal factors, 388–389 human leukocyte antigen associations, 383 DR4 subtypes, 383–385 initiating factors, 389–390 localized disease clinical presentation, 378 pathological manifestations of, 378–379 pathogenesis, 388–390 pathological aspects of, 378–380 precipitating factors, 389 predisposing factors, 388–389 related diseases, 380 rheumatoid factor anti-immunoglobulin antibodies, 380–382 methods used for detection of, 380 pathogenic role, 382 self-perpetuating mechanisms, 389 seronegative rheumatoid arthritis, 382 synovium macrophages, 387–388 systemic involvement clinical presentation, 379 pathological manifestations, 379 Index [Rheumatoid arthritis] T lymphocytes, 385–386 therapy, 390–392 biological response modifiers, 391 disease-modifying drugs, 390 glucocorticoids, 390 nonsteroidal anti-inflammatory drugs, 390 reinduction of tolerance, 391 Rheumatoid factor anti-immunoglobulin antibodies, 380–382 methods used for detection of, 380 pathogenic role, 382 Rh immune globulin, 442 Scatchard plot, 122–123 Scleroderma, 383 Sclerosing panencephalitis (SSPE), 496 Secondary immunodeficiencies, 600–607 burn-associated immunodeficiency, 602–603 causes of, 600 with drug abuse, 605–606 alcohol, 605 cannabinoids, 605 opiates, 606 iatrogenically induced immune deficiencies, 603–605 neutropenia, 603 causes of, 603 postsurgery immunodeficiency, 603–604 splenectomy, 604–605 thymectomy, 605 with infections, 606–607 bacterial infections, 606 parasitic infections, 606–607 viral infections, 607 AIDS, 607–626 with malnutrition, 600–601 with renal failure, 601–602 with vitamin deficiencies, 601 with zinc deficiency, 601 Secretory component (SC), 87–88, 94–95 Sedimentation coefficient, 77 Selectins E (endothelial-leukocte adhesion molecule), 26, 202 L (leukocyte adhesion molecule-1), 26 P, 202 Selective immunoglobulin A deficiency, 579–581 clinical presentation, 580 diagnosis, 580 653 [Selective immunoglobulin A deficiency] physiopathology, 579–580 therapy, 580–581 Self discrimination, vs nonself discrimination, 6–7 Septic shock, C1-INH depletion and, 154 Seroconversion, HIV, acute illness associated with, 616 Seronegative rheumatoid arthritis, 382 Serum immunoglobulin levels, in diagnosis, 557–559 Serum sickness, 404–405 Severe, combined immunodeficiency, 585–588 clinical presentation, 586 diagnosis, 586–587 pathogenesis, 585–586 therapy, 587–588 Sézary syndrome, 549 Sirolimus, 479–482, 507 Slow-reacting substance of anaphylaxis (SRSA), 400, 421, 422 Soluble immune complexes, detection of, 462–465 Somatic mutations, affinity maturation and, 110 Specific defenses, overview, Spleen, 19 Splenectomy, 604–605 Stages of immune response, 2–3 Stem cell differentiation, lymphocyte ontogeny, 161 Subacute sclerosing panencephalitis, 273 Superantigens, bacterial, 271–272 Suppressor T lymphocytes, 323 Surface staining, 293–296 Swiss-type agammaglobulinemia, 585–588 Sympathetic ophthalmia, 332 Synovium macrophages, rheumatoid arthritis, 387–388 Synthetic peptide vaccines, 237 Systemic lupus erythematosus, 334, 361–376 case study, 361, 371–372 clinical manifestations, 362–363 course, 362 diagnosis, 362 genetic factors, 366–367 glomerulonephritis, 369–370 immune complexes in, 368–369 immune response abnormalities, 367–368 B-cell abnormalities, 367 T-cell abnormalities, 367–368 654 [Systemic lupus erythematosus] immunological abnormalities in, 363–366 autoantibodies, 363–365 diagnostic value of autoantibodies, 366 pathogenic role of autoantibodies in SLE, 365 nonimmune factors influencing course of, 370–371 environmental factors, 370–371 hormonal effects, 370 overlap syndromes, 362–363 pathogenesis of, 366–372 treatment, 372–373 Tacrolimus (Profgraf; FK506), 479–482 T-cell abnormalities, systemic lupus erythematosus, 367–368 T-cell activation, 193–207 antigen-derived peptide recognition, by Tcell receptors, 193–194 CD4ϩT lymphocytes, 195–200 central nervous system effects, 203 chemokines, 200–207 co-stimulatory signals, 194–195, 200 cytokines, 200–207, 203–204 hematopoiesis, 205 interleukin-1, 203 interleukin-2 autocrine, paracrine effects of, 199 binding, 199–200 gene expression, 195–199 receptor, 199 synthesis, 199–200 interleukins, 201–202 pro-inflammatory cytokines, 200–203 T-lymphocyte proliferation, 199–200 TcR occupancy, 195–199 vascular effects, 202–203 T-cell acute lymphocytic leukemia, 547–548 T-cell anergy, mechanisms of, 321–322 T-cell/B-cell, cooperation, immunoglobulin Emediated hypersensitivity, 417–418 T-cell-dependent, T-independent antigens, 59–60 T-cell-independent antigens, characteristics of immune response to, 60 T-cell leukemia associated with HTLV-1, 548–549 T-cell receptor genes, T-lymphocyte ontogeny, rearrangement of, 173–175 structure, T-lymphocyte ontogeny, 178–179 TcR (see T-cell receptor) Index T-dependent antigens, in humoral immune response, 210 T-dependent areas, 17, 18 Terminal deoxyribonucleotidyl transferase (Tdt) in acute lymphocytic leukemias, 547 fow cytometry detection, 295 Tetramer assays, 304 Thalidomide, 512 TH2 lymphocytes, interleukins released by, 71 TH2 subpopulations, signals involved in control of differentiation of, 72 Thrombocytopenia, immunodeficiency with, eczema, 590 clinical presentation, 590 drug-induced, 447 genetics and pathogenesis, 590 in idiopathic thrombocytic purpura, 356 laboratory findings, 590 therapy, 590 Thrombocytopenic purpura, idiopathic, 356–357 Thymectomy, 605 Thymic hormones, 495–496 immunopotentiation, 495–496 Thymus aplasia, congenital, 584–585 clinical presentation, 584 diagnosis of immunological abnormalities, 584 etiology and pathogenesis, 584 therapy, 584–585 Thyroid gland, autoimmune diseases of, 341–344 Graves’ disease, 341–343 Hashimoto’s disease, 342–344 Thyroiditis, autoimmune (Hashimoto’s thyroiditis), 342, 343–344 Thyroid receptor antibodies, 342 Thyroid-stimulating immunoglobulin (TSI), 342 Thyrotoxicosis (Graves’ disease), 341–343 T-independent antigens, in humoral immune response, 210 Tissue-fixed antigen-antibody complex detection, 292–293 Tissues in immune response, 11–30 adhesion molecules, ligands, 26–27 B lymphocytes, distribution of, 17 cells of immune system, macrophages, 14 lymph nodes, 17–19 anatomical organization, 17–18 physiological role, 18–19 Index [Tissues in immune response] lymphocyte traffic, 23–28 cell adhesion molecules, 25 homing, 25–28 lymphocyte recirculation, extravascular migration, 23–25 regulation of, 25–28 lymphocytes, distribution of, 17 lymphoid tissues, organs, 16–23 mucosal-associated lymphoid tissues, 21–23 spleen, 19–20 anatomical organization, 19 physiological role, 19 thymus, 20–21 anatomical organization, 20 physiological role, 20–21 T lymphocytes (T cells), 262 anergy, models for, 321 B-cell cooperation, in antibody responses, 56–59 B-lymphocyte differentiation, 166–167 coreceptors, 166 gene arrangement, 166 receptors, selection of, 166–167 helper activation of, 62–66 antigen presentation to, MHC-II, 41 cell subsets, regulatory roles, 208–209 humoral immune response, 210–213 in inflammatory responses, 209–210 major histocompatibility complex, antigen presentation to, major histocompatibility complex–II, 41 TH1, TH2 subpopulations (subsets), regulatory roles, 208–209 TH1, TH2 subpopulations, signals involved in control of differentiation of, 72 membrane markers, 566 mitogens, 567 ontogeny, 173–181 coreceptors, 175 markers, T-cell activation, 180–181 inhibition, 181 membrane markers, mature T lymphocytes, 179–181 pre–T lymphocyte enzymatic activity in, 173 markers, 173 receptor selection, 175–178 negative selection, 175–176 positive selection, 176–178 T-cell differentiation after birth, 178 655 [T lymphocytes (T cells)] TcR genes, rearrangement of, 173–175 TcR structure, 178–179 rheumatoid arthritis, 385–386 tolerance models, 320–322 clonal deletion experimental models, 320–322 mechanisms of, 321 T-cell anergy, mechanisms of, 321–322 Tolerance acquired, 315–317 autoimmune diseases, treatment, 334–336 autoimmunity, 325–334 B-cell anergy models for, 318–319 reversibility of, 319 B-lymphocyte clonal deletion, models for, 319 characteristics of, 314–315 defined, 314–315 downregulation of immune response, 322–324 mechanisms of, 318 experimental approaches, 318 models, 318–320 reinduction of, rheumatoid arthritis, 391 termination of, 324–325 transgenic mice, 318 Tolerogenic conditions, 315–317 Tonsils, 22 Total lymphoid irradiation, 508 Transfusion effect, 509–510 nonhemolytic immune reactions, 439–440 reactions, 437–440 serological principles of, 434–437 Transforming growth factor- (TGF-), 219–220 Transgenice mice models B-lymphocyte tolerance, 317 T-lymphocyte tolerance, 320–322 Transient hypogammaglobulinemia of infancy, 574–576 Transplantation immunology, 501–516 donor-recipient matching, 502–503 graft rejection, 503–506 acute rejection, 504–505 case study, 505–506 delayed or chronic rejection, 505 hyperacute (early) rejection, 503–504 graft-versus-host reaction, 511–513 case study, 513 656 Index [Transplantation] pathogenesis, 512 pathology, 512 prevention, 512–513 treatment, 512 immunosuppression, 506–511 biological response modifiers, 507–508 anti-T-cell monoclonal antibodies, 507–508 antihymocyte, antilymphocyte globulins, 507 other monoclonal antibodies, 508 chemical, 506–507 antimetabolites, 506 calcineurin inhibitors, 506–507 glucocorticoids, 506 rapamycin, 507 side effects, 510–511 malignancies, 511 opportunistic infections, 510–511 total lymphoid irradiation, 508 transfusion effect, 509–510 rejection antigens, 518–519 overview, Tuberculin test, 405 Tumor immunology, 517–528 cancer immunity, effector mechanisms, 521–522 immunogenicity of tumors, 518–521 immunotherapy, 524–525 rejection antigens, 518–519 tumor-associated antigens, 519–521 Tumor necrosis factor, 200–201 , 202, 490, 611 Type I hypersensitivity reactions, 398–400 clinical expression, 399 historical overview, 398–399 pathogenesis, 400 Type II hypersensitivity (see Cytotoxic reactions) Type III hypersensitivity (see Immune complex-induced hypersensitivity reactions) Type IV hypersensitivity reactions (see Delayed hypersensitivity reactions) Vaccines attenuated, 238–239 recombinant organisms, 238–239 types of, 235–238 component vaccines, 236–238 bacterial polysaccharides, 236 conjugate vaccines, 236–237 DNA vaccines, 237–238 inactivated toxins, 236 mixed component vaccines, 236 recombinant bacterial antigens, 236 synthetic peptide vaccines, 237 viral component vaccines, 237 killed vaccines, 236 Vascular leukostasis, pulmonary, hemodialysis and, 154 VCAMs (vascular intercellular adhesion molecules), 26, 28, 460 VDJ segment, 106–108 Viral component vaccines, 237 Viral infection (see also under specific infection) immunodeficiency, 607 AIDS, 607–626 natural killer cells, malignant transformation, 218 Vitamin deficiencies, 601 V-region genes, 109 Urticaria, 399 Uveitis, acute anterior, 46 Yersinia pseudotuberculosis, 46 V-region allotype, heavy-chain, immunoglobulin molecules, 112 Waldenstrom’s macroglobulinemia, 541–542 clinical features, 541 diagnosis, 541 management, 541–542 Western blot, 283–286 Wiskott-Aldrich syndrome, 590 clinical presentation, 590 genetics and pathogenesis, 590 laboratory findings, 590 therapy, 590 X-linked hyper-immunoglobulin M syndrome, 581–582 clinical presentation, 581 diagnosis, 581 genetics and physiopathology, 581 therapy, 582 ZAP70 kinase, 196, 586 Zidovudine, 623 Zinc deficiency, 601 .. .Medical Immunology Fifth Edition Revised and Expanded edited by Gabriel Virella Medical University of South Carolina Charleston, South Carolina Marcel Dekker, Inc New York Basel TM Copyright... Immunity Gabriel Virella 259 Part II 15 Diagnostic Immunology Diagnostic Immunology Gabriel Virella and Virginia M Litwin Part III 279 Clinical Immunology 16 Tolerance and Autoimmunity George C Tsokos,... Transplantation Immunology Gabriel Virella, Richard Knight, and Jonathan Bromberg 501 26 Tumor Immunology Sebastiano Gattoni-Celli 517 27 Malignancies of the Immune System Gabriel Virella and Jean-Michel Goust