On the occasion of the publication of the 8th edition of Kuby Immunology iii
Chapter 1
Overview of the Immune System 1
Historical Development of Immunology 2
The Birth of Immunology through Early Vaccination 2
Vaccination is a global initiative currently underway. 3
Immunology is a broader discipline than vaccine development for infectious diseases. 6
Immunity includes humoral immunity and cellular immunity 6
How does the immune system recognize foreign substances? 10
12 Key Concepts for Understanding the Mammalian Immune Response
Pathogens invade in many forms and break down natural defenses. 12
The immune response is immediately primed to prepare for an attack 12
Pathogen recognition molecules are generated by gene decoding or DNA rearrangement 14
Immune tolerance allows cells to avoid host attacks by the immune system 16
Immune responses occur through the interaction of innate and adaptive immunity 16
Immune cells and molecules are present throughout the body 17
Only adaptive immunity has a typical memory capacity 18
The Benefits, Disadvantages, and Harms of the Immune System 20
Inappropriate immune responses can cause many diseases 20
Immune responses make tissue transplantation difficult 24
Cancer also presents unique challenges to immunologists. 25
Conclusion 25
Reference 26
Recommended web address 26
Practice Problem 26

Chapter 2
Immune System Cells, Organs, and Microenvironment 29
30 cells that make up the hematopoietic and immune systems
Hematopoietic stem cells differentiate into various blood cells, including red blood cells and white blood cells. 31
Hematopoietic stem cells differentiate into myeloid and lymphoid cells 33
Myeloid cells are the first cells to respond to infection 37
Lymphocytes regulate the adaptive immune response 41
Primary lymphoid organs: Organs where immune cells are produced 46
The site of hematopoiesis changes during embryonic development 46
Bone marrow is the primary site of hematopoiesis in adults 48
The thymus is the primary lymphoid organ where T cells mature 50
Secondary lymphoid organs: organs where the immune response begins 52
Secondary lymphoid organs are distributed throughout the body and share anatomical features 52
The vascular and lymphatic systems connect lymphatic organs to infected tissues 53
Lymph nodes are highly specialized secondary lymphoid organs 54
The spleen regulates the immune response to blood-borne pathogens 57
Defense organs also have secondary lymphoid tissue 59
Tertiary lymphoid tissues are also involved in regulating and maintaining immune responses 59
Conclusion 62
Reference 63
Recommended web address 64
Practice Problem 64

Chapter 3
Immune Recognition and Response 67
General Properties of Immune Receptor-Ligand Interactions 68
Receptor-ligand binding consists of multiple noncovalent bonds 68
Method 69 of expressing receptor-ligand binding strength
Interactions between receptors and ligands can be multifactorial 69
Combinations of protein chain expression can increase the ligand binding diversity of a receptor 70
Adaptive immune receptor genes are rearranged in each lymphocyte 71
Expression levels of receptors and ligands can change during an immune response 71
During cell-cell interactions, local concentrations of ligands can be very high 72
Many immune receptors contain immunoglobulin domains 72
Immune antigen receptors can be present on the cell membrane, in the cytoplasm, or secreted 73__
Immune antigen receptor system 74
BCRs have the same antigen specificity as the antibodies they secrete 75
Antigen receptors on T cells recognize antigens accompanied by MHC proteins 81
Receptors of innate immunity bind to conserved molecules of pathogens 86
Cytokines and Receptors 87
Cytokines are described according to their function and distance of action 88
Cytokines exhibit multifaceted, redundant, synergistic, antagonistic, and cascade-inducing properties 89
Cytokines of the IL-1 family promote proinflammatory signals 91
Class 1 cytokines share common structural motifs but have diverse functions 91
Class 2 cytokines are divided into three interferon families 92
Cytokines of the tumor necrosis factor family are either soluble or membrane-bound 94
The IL-17 family of cytokines and their receptors were most recently identified 95
Chemokines induce leukocyte migration 95
A Conceptual Framework for Understanding Cell Signaling 97
Ligand binding can induce dimerization or multimerization of receptors 97
Ligand binding can induce phosphorylation of tyrosine residues on receptors or receptor-binding-associated molecules 97
Src-family kinases play a crucial role in the activation of many immune cells 99
Intracellular junction proteins assemble members of signaling pathways 100
The signal is relayed to the cell nucleus through a series of common downstream effectors 101
Not all ligand-receptor signals lead to transcriptional changes 102
Immune Response: The Output of Immune System Recognition 102
Changes in protein expression promote the migration of leukocytes into infected tissues 102
Activated macrophages and neutrophils can eliminate pathogens without adaptive immunity 103
Antigen activation induces optimized antigen presentation by dendritic cells 103
Cytokine secretion by dendritic cells and T cells induces additional immune responses 103
Antigen stimulation promotes long-term survival of T and B cells 104
Antigen binding promotes T cell division and differentiation 104
Antigen binding promotes B cell division and differentiation 104
Conclusion 106
Reference 106
Recommended Web Address 107
Practice Problem 107

Chapter 4
Innate Immunity 111
Anatomical Defenses Against Infection 113
The epithelial barrier prevents pathogens from entering the body 115
Antimicrobial proteins and peptides eliminate potential invaders 115
Cellular Innate Immune Response Receptors and Signaling Networks 117
Toll-like receptors (TLRs) induce responses to a variety of molecules in extracellular pathogens 118
C-type lectin receptors bind surface carbohydrates of extracellular pathogens 124
NOD-like receptors bind to cytoplasmic pathogen PAMPs 125
ALR binds to cytoplasmic DNA 126
RLR recognizes viral RNAs in the cytoplasm 129
cGAS and STING are activated by cytoplasmic DNA and dinucleotides 130
Mechanism of Innate Immunity 131
Expression of innate immune proteins induced by the PRR signaling pathway 131
Predation is an important mechanism for eliminating pathogens 136
Regulated cell death contributes to pathogen elimination 141
Induction of local inflammatory responses by innate immune responses 142
Innate lymphoid cells 143
NK cells are cytotoxic ILCs 144
Each ILC cell population produces unique cytokines and plays different roles 145
Regulation and Evasion of Innate Immunity and Inflammatory Responses 146
Innate and inflammatory responses can be harmful 146
Innate immunity and inflammatory responses are regulated both positively and negatively 149
Pathogens have evolved mechanisms to evade innate immunity and inflammatory responses. 150__
Interactions between the innate and adaptive immune systems 150
The innate immune system activates adaptive immune responses 151
Pathogen recognition by dendritic cells influences differentiation of helper T lymphocyte subsets 151
Some antigens, including PAMPs, can activate B cells independently of helper T lymphocytes 153
Adjuvants enhance the effectiveness of vaccines by activating innate immune responses. 153
Some pathogen clearance mechanisms are shared between innate and adaptive immune responses 154
The Universality of Innate Immunity 154
Some components of the innate immune system are common across the plant and animal kingdoms 154
The innate immune responses of invertebrates and vertebrates share both similarities and differences. 155
Conclusion 156
Reference 158
Recommended Web Address 159
Practice Problem 160

Chapter 5
Complement system 163
Major pathways of complement activation 164
The classical pathway is initiated by antibodies binding to antigens 166
The lectin pathway is initiated when a soluble protein recognizes a microbial antigen 171
Alternative routes begin in three ways: 172
The three complement activation pathways converge on the steps of C5 convertase formation and MAC generation 176
Various functions of complement 177
Complement receptors link complement-labeled pathogens to effector cells 177
Complement enhances host defense against infection 181
Complement plays a role in linking innate and adaptive immunity 184
The Role of Complement in the Contraction of the Immune Response 185
Regulation of complement activation 187
Complement activation is passively regulated by the short half-life of the protein and the composition of the host cell surface 187
C1 inhibitor C1INH promotes dissociation of C1 factor 187
A decay-promoting factor promotes the decay of C3 convertase 187
Factor I cleaves C3b and C4b 189
CD59 (protectin) inhibits MAC attacks 190
Carboxypeptidase inactivates anaphylaxis toxins C3a and C5a 190
Complement deficiency 190
Complement Evasion Strategies of Microorganisms 193
Evolutionary Origins of the Complement System 194
Conclusion 196
Reference 196
Recommended web address 197
Practice Problem 197

Chapter 6
Structure and Expression of Lymphocyte Receptor Genes 201
The Mystery of Immunoglobulin Gene Structure 202
Scientists proposed two early theoretical models of antibody genetics.
A groundbreaking experiment identified several gene fragments encoding immunoglobulin light chains. 204
Multigene composition of immunoglobulin genes 207
The k light chain gene contains V, J, and C segments 207
The light chain gene contains paired J and C segments 209
The heavy chain gene structure includes VH, D, JH, and CH segments 210
Antibody genes found in mature B cells are the products of DNA recombination 210
Mechanism of V(D)J Recombination 210
V(D)J recombination in lymphocytes is a highly regulated sequential process 211
Recombination is induced by signal sequences 212
Gene fragments are linked by various types of proteins 214
V(D)J recombination occurs through a series of well-regulated events 216
Five Mechanisms for Generating Antibody Diversity in Naive B Cells 221
Regulation of V(D)J gene recombination involving chromatin changes 221
Expression of B cell receptor 226
Each B cell synthesizes only one heavy chain and one light chain 226
Receptor editing of potential autoreactive receptors occurs in the light chain 228
mRNA splicing regulates secretory and membrane-bound Ig expression 229
T cell receptor genes and expression 232
Understanding the structure of the TCR protein was crucial in the discovery of the TCR gene. 232
The B chain gene was discovered simultaneously in two different laboratories 232
While searching for A-chain genes, they found G-chain genes instead. 234
TCR genes are arranged into gene segments of clusters V, D, and J 234
Recombination of TCR gene fragments occurs at different rates, ab and
gd T cells are produced at different stages of differentiation 236
The process of rearrangement of TCR gene fragments is very similar to immunoglobulin gene recombination 236
TCR expression is regulated by allelic exclusion 239
Conclusion 239
References 240
Recommended web address 240
Practice Problem 241

Chapter 7
Major histocompatibility complex and antigen presentation 245
Structure and Function of MHC Class I and II Molecules 246
Type I MHC molecules consist of a large glycoprotein heavy chain and a small protein light chain 246
Class II MHC molecules consist of two non-identical membrane-bound glycoprotein chains 248
Class I and class II MHC molecules exhibit polymorphisms in their peptide binding sites 248
MHC Gene Structure and Inheritance 251
The MHC locus encodes three types of MHC molecules 251
Alleles of MHC genes are inherited in linked groups called haplotypes 254
MHC molecules are codominantly expressed 255
Type 1 and type 2 molecules exhibit diversity both within individuals and across species 255
MHC polymorphism is primarily restricted to the antigen-binding groove 258
Roles and Expression Patterns of MHC Molecules 260
MHC molecules present both endogenous and exogenous antigens 262
Type 1 MHC expression is found throughout the body 262
Expression of class II MHC molecules is primarily restricted to APCs 263
MHC expression varies depending on conditions 263
MHC alleles play a crucial role in immune responsiveness 265
T cells recognize peptides presented by self-MHC alleles 266
Evidence for distinct antigen processing and delivery routes 269
Intrinsic pathways of antigen processing and delivery 270
Peptides are produced by the proteasome, a protein-degrading enzyme complex 271
Peptides are transported from the cytoplasm to the rough endoplasmic reticulum (RER) 271
Chaperones help class I MHC molecules bind peptides 272
Extrinsic pathway of antigen processing and delivery 273
Peptides are generated from antigens that enter endocytic vesicles 274
The invariant chain transports class II MHC molecules into endocytic vesicles 274
The peptide binds to class II MHC molecules, expelling CLIP 275
Non-conventional antigen processing and delivery 276
Dendritic cells can cross-present exogenous antigens via class I MHC molecules 276
Cross-presentation by APCs is essential for the activation of naive CD81 T cells 278
Delivery of non-peptide antigens 278
Conclusion 281
Reference 281
Recommended web address 282
Practice Problem 282

Chapter 8
T cell development 287
Early thymocyte development 289
Thymocytes develop through four double-negative stages 289
Thymocytes express the ab or gd T cell receptor 290
DN thymocytes undergo b-selection to proliferate and differentiate 292
Positive and Negative Selection 293
Thymocytes “learn” MHC restriction in the thymus 294
T cells undergo positive and negative selection 296
Positive selection ensures MHC restriction 297
Negative selection (central immune tolerance) ensures self-tolerance 300
The Paradox of Selection: Why Not Eliminate All Positively Selected Cells? 302
An alternative model can explain the thymic selection paradox 304
Do positive and negative selection occur simultaneously or sequentially? 304
System Decision 305
Several models have been proposed to explain the systematic decision 305
Transcription factors Th-POK and Runx3 regulate lineage determination 307
Double-positive thymocytes may be determined to be different cell types 307
Exit from the thymus and final maturation 307
Other Mechanisms for Maintaining Self-Tolerance 308
TREG cells regulate the suppression of immune responses 308
Peripheral mechanisms of immune tolerance also protect against autoreactive thymocytes 309
Conclusion 310
Reference 310
Recommended web address 312
Practice Problem 312

Chapter 9
B cell development 315
B cell development in the bone marrow 317
B cell developmental stages involve changes in cell surface markers, gene expression, and immunoglobulin gene rearrangement 317
The first step in lymphocyte differentiation is the generation of common lymphoid progenitor cells 319
In the later stages of B cell development, a stepwise rearrangement of the B cell phenotype and immunoglobulin genes occurs 322
Immature B cells in the bone marrow are highly sensitive to tolerance induction, and self-reactive cells are eliminated 327
Completion of B cell development in the spleen 330
T1 and T2 transitional B cells are formed in the spleen and undergo selection for survival and autoreactivity 330
T2 B cells give rise to mature follicular B-2 B cells 333
T3 B cells primarily exhibit autoreactivity and anergy 333
Development and Characterization of B-1 and Marginal Zone B Cells 335
B-1a, B-1b, and marginal zone B cells differ phenotypically and functionally from B-2 B cells 336
B-1a B cells originate from a distinct developmental lineage 337
Comparison of B and T cell development 338
Conclusion 340
Reference 342
Recommended web address 343
Practice Problem 343

Chapter 10
T cell activation, helper subpopulation differentiation, and memory 345
T Cell Activation and the Two-Signal Hypothesis 346
TCR signaling provides the 'primary signal' to establish T cell activation 346
Costimulatory signals are required for T cell activation and differentiation 350
Clonal immune anergy occurs in the absence of costimulatory signals 352
Cytokines provide a 'tertiary signal' 354
APCs provide costimulatory ligands and cytokines to naive T cells 354
T cell activation by superantigens 355
Helper T cell differentiation 356
Helper T cells are divided into several subpopulations 357
Helper T cell subpopulation differentiation is determined by polarizing cytokines 359
Each effector T cell has unique characteristics 360
Helper T cell subpopulation differentiation is flexible 366
Helper T cell subsets are crucial for normal immune responses and immune diseases 367
T cell memory 369
Naive T cells, effector T cells, and memory T cells express different cell membrane molecules 369
Memory cell subpopulations differ in distribution, organization, and function. 370
There are many questions about the origin and function of memory cells. 370
Conclusion 371
Reference 372
Recommended web address 373
Practice Problem 374

Chapter 11
B cell activation, differentiation, and memory development 377
T cell-dependent B cell response 379
Unsensitized B cells encounter antigens in the lymph nodes and spleen 381
When a B cell recognizes an antigen bound to a cell, immune synapse formation reaches its maximum level 383
Antigen binding to the BCR activates signaling pathways within B cells 384
B cells also receive and transmit signals through coreceptors 386
B cells use more than one method to obtain antigen from antigen-presenting cells 387
Antigen receptor binding induces internalization and antigen presentation 388
The early phase of the T cell-dependent response is characterized by chemokine-driven B cell migration 388
Fate specificity of stimulated B cells depends on the expression of transcription factors 392
T Cell-Dependent B Cell Responses: Differentiation and Memory Generation 393
Some activated B cells differentiate into plasma cells that form primary foci 393
Other activated B cells migrate to the follicle and initiate the germinal center reaction 394
Principles of Somatic Hypermutation and Class-Switch Recombination 398
Memory B cells that recognize T-dependent antigens are generated both inside and outside the germinal center 401
Most newly generated B cells are lost at the end of the primary immune response 405
T cell-independent B cell response 406
T-cell-independent antigens stimulate antibody production without T-cell assistance 406
Two novel B cell subclasses mediate responses to T cell-independent antigens 407
Negative regulation of B cells 410
Negative signals via CD22 are balanced by positive BCR-mediated signals 411
Negative signaling via the FcgRIIb receptor inhibits B cell activation 411
CD5 acts as a negative regulator of B cell signaling 411
B-10 B cells act as negative regulators by secreting IL-10 412
Conclusion 412
Reference 413
Recommended web address 414
Practice Problem 414

Chapter 12
Effector Cell Responses: Antibody-Mediated and Cell-Mediated Immune Responses 417
Antibody-mediated effector function 418
Antibodies protect against pathogens, toxins, and harmful cells in a variety of ways. 418
Different antibody types mediate different effector functions 421
Fc receptors mediate various effector functions of antibodies 424
Defensive function varies depending on the antibody class 427
The Role of Antibodies in Disease Treatment 428
Cell-mediated immune response 428
CTLs recognize and eliminate infected or tumor cells through TCR activation 428
Natural killer cell activity depends on the balance of activating and inhibitory signals 441
NKT cells serve as a bridge between the innate and adaptive immune systems. 447
Conclusion 447
References 450
Recommended web address 451
Practice Problem 451

Chapter 13
Barrier Immunity: Immunology of the Mucosa and Skin 455
Common Themes in the Barrier Immune System 457
The surface of every barrier is lined with one or more layers of epithelial cells 457
Barrier organs are home to innate and adaptive immune cells that interact with epithelial cells and secondary lymphoid tissues. 461
The barrier immune system induces both tolerance and inflammatory responses to the microbiota 462
Jangmyeon Station 463
The intestine is organized into different anatomical sections and tissue layers 464
Intestinal epithelial cells are diverse in phenotype and function 467
Setting the Stage: Maintaining Gut Immune Homeostasis 469
The intestinal barrier maintains a barrier between the microbiota and epithelial cells 469
Antigens are delivered from the intestinal lumen to antigen-presenting cells in a variety of ways. 470
Immune homeostasis in the gut is promoted by several types of innate and adaptive immune cells 470
The small and large intestines have different immune systems 475
Commensal microbes help maintain an immunotolerant environment in the gut 476
Sudden Operation: The Scene System's Response to Intrusion 477
The immune system recognizes and responds to harmful pathogens 477
The scene system can initiate both type 1 and type 2 reactions 479
Dysbiosis, inflammatory bowel disease, and chronic digestive disorders 482
Other barrier immune system 483
The respiratory immune system shares many characteristics with the intestinal immune system. 484
Intranasal vaccine 487
The skin is a unique barrier immune system 488
Conclusion 490
References 490
Recommended web address 491
Practice Problem 492

Chapter 14
Adaptive Immune Response in Space and Time 495
Immune Cells in Healthy Tissues: Maintaining Homeostasis 496
496 unsensitized lymphocytes circulating between primary and secondary lymphoid organs
For extravasation to occur, each characteristic molecule is involved.
There are four steps to go through 499
503 unprimed lymphocytes searching for antigens by scanning the network structure of the lymph node
Immune Response to Antigens: Innate Immune Response 504
Innate immune cells are activated by binding to antigens through pattern recognition receptors 505
Antigens travel to secondary immune organs through the lymphatic vessels in two different forms 505
APCs migrate to the T lymphocyte zone of secondary lymphoid organs with processed antigens 507
Unprocessed antigens arrive at the B cell zone 508
Antigens that enter the bloodstream are captured by unique APCs in the marginal zone of the spleen 509
The First Encounter Between Antigen and Lymphocyte 509
Unprimed CD4+ T lymphocytes stop moving after binding to antigen 509
B lymphocytes receive assistance from CD4+ T lymphocytes at the border between the follicles and the periphery of the lymph node 510
Dynamic image analysis provides new insights into B and T lymphocytes in the germinal center. 511
In lymph nodes, CD8+ T lymphocytes are activated through interactions with various cells 512
Summary of the Primary Immune Response 514
Differentiation into central memory T lymphocytes begins early in the primary immune response 514
The immune response declines after 10 to 14 days 516
Function of effector and memory cells 517
Activated lymphocytes leave the lymph nodes and circulate to various tissues 517
Chemokine receptors and adhesion molecules enable memory/effector lymphocytes to migrate to peripheral tissues 518
Example 520 of an immune response
CD8+ T lymphocyte response in toxoplasmosis 520
Immune response of resident memory T lymphocytes to herpes simplex virus infection 521
Host immune cell response to tissue grafts 522
Relationship between Listeria infection and DC 524
T lymphocyte response to tumors 524
Regulatory T lymphocytes suppress immune responses in various ways 524
Conclusion 525
Reference 525
Recommended web address 526
Practice Problem 526

Chapter 15
Allergies, hypersensitivity, and chronic inflammation 529
Allergy: Type 1 hypersensitivity 531
IgE antibodies are associated with type 1 hypersensitivity reactions 531
Various allergens trigger type 1 hypersensitivity reactions 531
IgE antibodies act by binding antigens as a result of cross-linking of Fc´ receptors 533
IgE receptor signaling is tightly regulated 537
Granulocytes produce molecules associated with type 1 hypersensitivity reactions 537
Type 1 hypersensitivity reactions are characterized by early and late reactions 539
There are different categories of type 1 hypersensitivity reactions 539
Susceptibility to type 1 hypersensitivity is influenced by environmental and genetic factors 543
Diagnostic testing and treatment for allergic reactions are available 548
Development of allergic reactions 550
Antibody-mediated (type 2) hypersensitivity 551
Transfusion reactions are an example of type 2 reactions 551
Neonatal hemolysis occurs as a type 2 reaction 553
Drugs can cause hemolytic anemia 554
Immune complex-mediated (type III) hypersensitivity reaction 555
Immune complexes can damage various tissues 555
Immune complex-mediated hypersensitivity reactions may resolve spontaneously 555
Autoantigens may be involved in immune complex-mediated responses 556
Arthus reaction is a local type 3 hypersensitivity reaction 556
Delayed (Type IV) hypersensitivity 557
Type IV DTH response begins with antigen sensitization 557
Secondary exposure to a sensitizing antigen induces a DTH response 557
DTH response can be detected by skin testing 559
Contact dermatitis is a type IV hypersensitivity reaction 559
Chronic inflammation 560
Infection causes chronic inflammation 561
There are non-infectious causes of chronic inflammation 562
Obesity is associated with chronic inflammation 563
Chronic inflammation can lead to systemic diseases 563
Conclusion 565
Reference 566
Recommended web address 567
Practice Problem 567

Chapter 16
Immune Tolerance, Autoimmunity, and Organ Transplantation 571
Formation and Maintenance of Immune Tolerance 572
Antigen sequestration, or evasion, is one way to protect self-antigens from attack. 573
The development of central immune tolerance occurs in primary lymphoid organs 573
Cells that mediate peripheral immune tolerance arise outside of primary lymphoid organs 575
Many immune cell types operate in the periphery to suppress anti-self reactions 576
Autoimmunity 580
Autoimmune diseases targeting specific organs 581
Some autoimmune diseases are systemic 585
Both internal and external factors can promote susceptibility to autoimmune diseases. 588
What Causes Autoimmunity? 590
Treatment of Autoimmune Diseases from General Immunosuppression to Targeted Immunotherapy 591
Transplant Immunology 594
Demand for transplants is high, but the supply of organs remains low 594
Antigenic similarity between donor and recipient improves transplant success 597
Some organs are more suitable for transplantation than others 597
Finding suitable donors and recipients requires a pre-assessment of histocompatibility. 600
Allogeneic transplant rejection follows the rules of immunospecificity and immune memory 601
Graft rejection follows a predictable clinical course 601
Immunosuppressive therapy can be general or target-specific 606
Immune tolerance of allogeneic transplantation is preferred in certain cases 608
Conclusion 610
Reference 610
Recommended web address 611
Practice Problem 611__

Chapter 17
Infectious Diseases and Vaccines 615
The Importance of Barriers and Vectors in Preventing Infection 616
Link between infection site and immune response 618
Infections of the mucosa or barrier are usually regulated by TH2 responses 618
Extracellular pathogens are recognized and attacked as extracellular tools 618
Recognition of infected cells is necessary to prevent intracellular infection 620
Virus infection 620
The antiviral innate immune response is crucial for inducing the adaptive immune response. 621
Many viruses are neutralized by antibodies 622
Cell-mediated immunity is crucial for viral suppression 622
Viruses can evade their host's defenses 623
Imprinting of immune memory influences future susceptibility to viruses 623
Bacterial infection 626
Immune responses to intracellular and extracellular bacteria differ 626
Bacteria can evade defense mechanisms 626
Parasitic infection 628
Protozoan parasites include a variety of unicellular eukaryotes 628
Helminths often induce only a mild immune response 629
Fungal infection 629
Innate immunity protects against most fungal infections 629
Immunity against pathogenic fungi can also be acquired 631
New infectious disease 632
Recently emerged new infectious disease 632
Infectious diseases re-emerge due to various factors. 634
Vaccine 634
Basic Research and Effective Vaccine Design 634
Protective immunity is acquired through active or passive immunization 635
Passive immunization involves administering antibodies that have been produced. 635
Strategies for Effective Vaccines 637
Conjugate and multivalent vaccines increase antigenicity and vaccination efficacy. 642
Adjuvants are used to increase the effectiveness of vaccines 644
Conclusion 644
Reference 645
Recommended web address 645
Practice Problem 645

Chapter 18
Immunodeficiency Disorder 651
Primary immunodeficiency 652
Primary immunodeficiency can be detected early in life 652
Combined immunodeficiency impairs adaptive immunity 655
B-cell immunodeficiency suppresses the production of one or more antibody isotypes 659
Disruption of the innate immune system affects the adaptive immune response. 660
Complement defects are common in general 662
NK cell deficiency increases susceptibility to viral infections and cancer 662
Immunodeficiency disorders that impair immune regulation can manifest as autoimmunity 662
Immunodeficiency disorders are treated with replacement therapies 663
Immunodeficient animal models are used to study basic immune function. 664
Secondary immunodeficiency 665
Secondary immunodeficiency can be caused by a variety of factors 666
HIV/AIDS threatens many lives worldwide. 666
The retrovirus HIV-1 is the causative agent of AIDS. 668
HIV-1 is transmitted through close contact with the body fluids of an infected person 670
In vitro studies reveal the structure and life cycle of HIV 672
HIV variants with a preference for CCR5 or CXCR4 coreceptors
Plays a different role in infection 674
HIV infection causes progressive immune dysfunction 675
Changes over time lead to the progression of AIDS 676
Antiretroviral therapy prevents HIV replication, disease progression, and transmission of infection. 679
A vaccine may be the only way to stop the HIV/AIDS pandemic. 683
Conclusion 684
Reference 687
Recommended web address 687
Practice Problem 688__

Chapter 19
Cancer and the Immune System 691
Terminology and Cancer Development 692
Accumulation of DNA mutations or genetic translocations can lead to cancer 693
Cancer-related genes regulate cell proliferation and survival 693
Malignant transformation occurs through a multistep process 696
Tumor antigen 699
Tumor-specific antigens have unique protein sequences 699
Normal cell proteins with unique expression patterns can become tumor-associated antigens 700
Immune Response to Cancer 702
Both inhibition and promotion of tumor growth are possible through immunoediting 702
Innate and adaptive immune pathways participate in cancer recognition and elimination. 703
Immune response factors that promote cancer survival 707
Tumor cells have evolved to evade immune recognition and apoptosis. 708
Anticancer Immunotherapy 709
Monoclonal antibody 710 targeting tumor cells
Proliferation and production of tumor-specific T cells 713
Therapeutic tumor vaccine 713 that enhances antitumor immune response
Manipulation of auxiliary control signals using gate blocking 715
Conclusion 718
Reference 718
Recommended web address 718
Practice Problem 719

Chapter 20
Immunology Research Techniques 721
Antibody production 721
Polyclonal antibodies are secreted by multiple clones of antigen-specific B lymphocytes 721
Monoclonal antibodies are derived from a single B lymphocyte 722
Monoclonal antibodies can be modified for specific purposes in a laboratory or hospital laboratory. 723
Experimental technique based on immunoprecipitation 724
Immunoprecipitation can be performed in solution 724
Immunoprecipitation can also be achieved within a gel matrix 725
Immunoprecipitation can be used to isolate specific proteins from cells and tissues 725
Hemagglutination is used to detect antigens attached to the surface of red blood cells 726
Hemagglutination is used to detect viruses or antiviral antibodies 727
Bacterial agglutination is used to detect antibodies against bacteria 727
Antibody testing using molecules attached to a solid support 727
Radioimmunoassay is used to measure important proteins and hormones in the body. 727
ELISA tests use enzyme-labeled antigens or antibodies 728
Indirect ELISA 728
ELISPOT measurement method 731
Western blotting can be used to detect specific proteins in a protein mixture 731
Method for measuring the affinity of antigen-antibody reactions 732
Equilibrium dialysis is used to measure the affinity of antibodies for antigens 732
Surface plasmon resonance (SPR) is the most commonly used method for measuring antibody affinity 733
Antibody staining for microscopic observation of cells and intracellular structures 735
Immunocytochemistry and immunohistochemistry use enzyme-labeled antibodies to image fixed tissues. 735
Electron microscopy observes antigens bound to antibodies using gold beads 735
Immunofluorescence-based imaging technology 735
Fluorescence is used to visualize cells and molecules 735
Confocal fluorescence microscopy can produce sharp three-dimensional images 737
Multiphoton fluorescence microscopy is a modified confocal microscope 738
In vivo imaging allows observation of immune responses in vivo 739
DNA Sequence Analysis and Visualization of Intact Chromatin 740
Flow Cytometry and Cell Sorting 740
Sophisticated software can identify individual cell populations in a sample 743
Flow cytometers and FACS are clinically important tools. 744
Analysis of multicolor fluorescence data requires very sophisticated software 744
CyTOF uses antibodies for mass spectrometry 745
Magnetism allows for easy and aseptic cell sorting 746
Cell Cycle Analysis 746
Cell division was first measured by the titrimetric thymidine uptake method 746
The chromogenic assay for cell division is rapid and avoids the use of radioactive materials. 746
BrdU-based cell division assay detects de novo DNA synthesis via antibodies 747
PI can analyze the cell cycle pattern of a cell population 747
CFSE is used to track cell division 748
Analysis of Apoptosis 748
Apoptosis was first measured using the 51Cr release assay 748
Fluorescent annexin A5 measures phosphatidylserine located on the outer membrane of apoptotic cells 748
The TUNEL assay can measure DNA fragmentation in apoptotic cells 749
Caspase assay measures the activity of enzymes involved in cell death 750
Structural Analysis of Chromatin 750
Chromatin immunoprecipitation assays analyze protein-DNA interactions 750
Chromosome structure capture technology analyzes long-distance interactions between chromosomal DNA 751
CRISPR-Cas9 751
Laboratory Animal Research Techniques 753
Animal experiments must be conducted in accordance with animal protection laws 753
Pure breeding minimizes inter-experimental variation 753
Pseudogenetic mice are used to study the function of specific genes in the immune response. 754
Adoptive transfer is a biomedical experiment that studies the properties of isolated cell populations. 755
Transgenic animals are animals into which genes have been artificially injected. 755
Gene insertion and gene deletion techniques can replace endogenous genes with dysfunctional or genetically modified genes. 755
The Cre/lox system enables inducible gene deletion in specific tissues 757
Reference 759
Recommended web address 760
Practice Problem 761

Appendix 1 CD Antigen 763
Appendix 2 Cytokines and Related JAK-STAT Signaling Molecules 770
Appendix 3 Chemokines and Chemokine Receptors 776
Glossary 779
Problem 805
Search 841