Introductory Immunology: Basic Concepts for Interdisciplinary Applications
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Introductory Immunology: Basic Concepts for Interdisciplinary Applications, 3rd Edition, is a completely updated, revised, and expanded concise, conceptual approach to understanding the immune systems as a primary defense to maintain health and homeostasis. This expanded version includes the aspects of microbiology and related immune defense mechanisms important in combating disease, as well critical components related to the field of vaccine development.
Immunology as a subject is no longer confined to the realms of "immunology" or "microbiology" studies. Indeed, the subject matter has become increasingly important to understand complex mechanisms found within a wider range of biological systems. This book aims specifically at educated audiences who do not have a deep understanding of medical, biochemical, or cellular knowledge. The overall text will present concepts that portray a comprehensive picture of the natural defenses to infectious agents as well as provide an introduction to mechanisms that lead to autoimmune dysfunction. In addition, immunological diseases will be detailed, with the goal of allowing the readers to gain sufficient knowledge to make sound choices for clinical decisions to affect treatment outcomes.
This new edition expands on the existing chapters, focusing on updating the previous text. It has been expanded to include knowledge on effector mechanisms addressing components inherent within cellular responses that are either newly discovered, or missing from the previous edition. It has an extra emphasis on aspects related to mechanisms important in combating microbial agents and critical sections on how vaccines protect against pathogenic invaders to limit associated pathology.
The goal is that Introductory Immunology will become the preferred provider of core knowledge in immunology to build a foundation to explore components of the human immune system that work together to confer and understand dysregulation that causes clinical diseases. This book serves as a basic platform to define therapeutic interventions by:
- creating appreciation for components of the human immune system to work together to confer lifelong protection;
- providing a core knowledge in immunology to build a foundation to explore mechanisms involved in clinical disease, and defining functional aspects of immunological terms to permit the reader easy access to comprehend specific topics;
- presenting introduction to complex immunological concepts in a concise and easy manner that relates to clinical disease;
- breaking down all of immunology into manageable, logically digestible building blocks, and providing a map to explore overlapping mechanisms of immune protective responses;
- providing a platform to readers without medical, biochemical, or cellular expertise to understand and appreciate how immunology controls homeostasis and protects against pathogens.
Jeffrey K. Actor
Jeffrey K. Actor, PhD, is a professor and Medical Immunology Course Director in the Department of Pathology and Laboratory Medicine at the McGovern Medical School at the University of Texas Health Center at Houston. Dr. Actor received his PhD degree from the University of Massachusetts. His research interests include examination of host immune responses during pathogenic disease, understanding proinflammatory and regulatory cytokines during mycobacterial infections, vaccine development, and molecular mechanisms of adjuvant-induced immunomodulation. Professor Actor has established himself as a productive educator-scientist with a strong background in immunology and molecular biology with a broad range of expertise in pathobiology. He has shown his commitment to education and excellence, at both the Medical School and Graduate School levels.
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Introductory Immunology - Jeffrey K. Actor
Introductory Immunology
Basic Concepts for Interdisciplinary Applications
Third Edition
Jeffrey K Actor
Department of Pathology and Laboratory Medicine, University of Texas McGovern Medical School, Houston, TX, United States
Table of Contents
Cover Image
Title page
Copyright
Dedication
Preface
Acknowledgments
Chapter 1. A functional overview of the immune system and components
Abstract
Chapter focus
Immune homeostasis
Self versus nonself
Innate and adaptive immunity
Anatomy of the immune system
Cells of the immune system
First-line defenders: the myeloid cells
Adaptive avengers: the lymphoid cells
Lymphocytes
Cluster of differentiation
Summary
Chapter 2. The inflammatory response
Abstract
Chapter focus
Inflammation
Initiation of the inflammatory response
The role of antibodies in inflammation
Biological functions of complement
Activation and directed migration of leukocytes
Pathogen recognition and cytokine signaling
Feedback and adaptation from a distance
Pathological consequences of the inflammatory Response
Summary
Chapter 3. The B lymphocyte: antibodies and how they function
Abstract
Chapter focus
B lymphocytes produce antibodies
Structural characteristics of immunoglobulins
Immunoglobulin nomenclature
Biologic properties of antibody isotypes
Kinetics of antibody response
Membrane-bound immunoglobulin
Development of B cells
Antibody gene recombination
Development and selection of mature B cells
Activation and differentiation of B cells
Summary
Chapter 4. T lymphocytes: ringleaders of adaptive immune function
Abstract
Chapter focus
T lymphocytes: specific and long-lasting immunity
The T cell receptor
T-cell development
Antigen recognition by T cells: requirement of major histocompatibility molecules
The HLA locus
MHC class I
MHC class II
T lymphocyte functions
Events involved in T lymphocyte activation
Role of T cells in B-cell activation
Cytotoxic T-cell effectors
Other lymphocyte phenotypes
Superantigens
Summary
Chapter 5. How we defend against infectious agents
Abstract
Chapter focus
Immune homeostasis and pathogenic organisms
Major immune defense mechanisms against pathogens
Physical barriers to infection
Bacterial infections
Mycobacterial infections
Viral infections
Parasitic infections (helminths)
Fungal infections
Evasion of immune response
Summary
Chapter 6. Basic disorders of immune function
Abstract
Chapter focus
Immunodeficiency disorders
Genetic basis for primary immunodeficiency
Innate deficiencies
Complement disorders
Innate pattern-recognition receptor disorders
Adaptive immune disorders
Treatment of immunodeficiency diseases
Immunodeficiency as a predisposition to disease
Summary
Chapter 7. Autoimmunity: regulation of response to self
Abstract
Chapter focus
Homeostasis, immune regulation, and autoimmunity
Tolerance to self
Etiology of autoimmune disease
Role of autoantibodies and self-reactive T lymphocytes in autoimmune disorders
Laboratory tests for autoimmunity
Targeted therapeutics
Summary
Chapter 8. Immune hypersensitivities
Abstract
Chapter focus
Hypersensitive disorders
Type I hypersensitivity: immunoglobulin E–mediated immediate hypersensitivity
Type II hypersensitivity: antibody-mediated cytotoxic hypersensitivity
Type III hypersensitivity: immune complex-mediated hypersensitivity
Type IV hypersensitivity: delayed-type (cell-mediated) hypersensitivity
Alternative hypersensitivity classifications
Summary
Chapter 9. Vaccines and immunotherapy
Abstract
Chapter focus
Principles of vaccination
Basic concepts of protective immunization
Types of immunizations
Age and timing of immunizations
Vaccine types and components
Immunologic adjuvants
Passive immunization
Therapeutic uses of immunoglobulins
Other ways to modify immunity
Summary
Chapter 10. Cancer immunology
Abstract
Chapter focus
Understanding immune defenses against cancers
Tumor antigens
Effector mechanisms in tumor immunity
Natural killer cells and innate response to tumor cells
Adaptive response to tumor cells
Escape mechanisms of tumor elimination
Tumors of the immune system
Immunodiagnosis and immunotherapy
Summary
Chapter 11. Transplantation immunology
Abstract
Chapter focus
Transplantation defined
Tissue histocompatibility
Natural isohemagglutinins
Human leukocyte antigens
Allograft rejection
Hyperacute rejection
Accelerated rejection
Acute rejection
Chronic rejection
Graft-versus-host disease
Pretransplantation histocompatibility evaluation
Immunosuppressive drugs to prevent allograft rejection
Immunosuppressive therapy
Summary
Chapter 12. Assessment of immune parameters and immunodiagnostics
Abstract
Chapter focus
Antibody–antigen reactions
Affinity
Secondary manifestations of antibody–antigen binding
Solid-phase precipitation assays
Radial immunodiffusion
The Ouchterlony assay
Immunoelectrophoresis
Latex agglutination
Lateral flow
Western blot
Immunoassays
Enzyme-linked immunoadsorbent assay
Detection of cellular antigens
Immunohistochemistry
Fluorescence-activated cell sorting analysis
Multiplex bead arrays
Assays to determine immune function
Other tools to measure immunological status
Summary
Glossary
Index
Copyright
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Notices
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Dedication
Jeffrey K. Actor
This book is dedicated with gratitude to all the students mentored during my tenure at the McGovern Medical School, for their feedback and suggestions toward the completion of this project. In addition, thanks goes to my children, Jonas and Amanda, for sharing a thirst for knowledge and for continuing to ask scientific questions; and to my wife, Lori, for her love and patience and for understanding my desire to complete this project. I also wish to specially recognize my father, Paul Actor, PhD, who instilled in me a sense of excitement about the wonders of science and the curiosity to seek questions about how biological systems function; and to my mother, Ruthe Actor, who taught me to seek value in everything I accomplish and to approach all challenges with an open mind. Finally, I extend gratitude to Linda Versteeg-Buschman at Elsevier for her continued support and encouragement on this endeavor.
Preface
Our bodies have evolved a protective set of mechanisms, comprising cells and organs, as a primary defense to maintain health. In essence, we have developed internal tools to preserve health and homeostasis. Indeed, a working definition of health embraces the effective elimination or control of life-threatening agents. This includes both infectious agents attacking from the outside and internal threats, such as tumors. Immune responses are therefore specifically designed to interact with, and respond to, the environment to protect the host against pathogenic invaders and internal dangers. The goal of this book is to appreciate the components of the human immune system that work together to confer protection and prevent clinical disease.
We will begin our discussion by establishing a foundation for subsequent chapters, through the presentation of the systems and cells involved in immune responses. Chapter 1 will give a general overview of the mechanisms in place to fight against disease. Components and pathways will be defined to allow the presentation of concepts of innate (always present) and adaptive (inducible and specific) responses, and how these responses interact with one another to form the basis for everyday protection. This edition expands concepts of innate immune function, and phenotypic cellular subsets, reflecting the discoveries that link innate and adaptive immunity. These concepts will form the foundation to examine the process of defense against various classes of pathogens. Chapter 2 will examine the coordinated effort of cells and blood components in the development of inflammation as it is related to protection against infection. Chapter 3 will introduce the basis for the function of adaptive components, exploring the generation of B lymphocytes and the nature of antibodies. Chapter 4 will extend this discussion to T-lymphocyte populations and examine how they serve as ringleaders for immune function. Chapter 5 will discuss immune responses, with an element of detail focused on commonly encountered infectious organisms. This overview also will include how the initial engagement of pathogens by innate components triggers pathways that cause inflammation. A section of this chapter will introduce the concept of opportunistic infections and diminished response when individuals are immunocompromised.
Effective immune surveillance is paramount to maintaining health. Chapter 6 will examine the basic disorders of immune function. Too little of a response results in an inability to control threats, which thus is ineffective toward the elimination of infectious agents. This lack of reactivity (hyporeactivity) leads to holes in our immune repertoire. This may be the result of genetic deficiencies or acquired compromise of immune function. In the same manner, responses representing excessive activity also can lead to damage to the host. This overaggressive response, a state of hyperreactivity, may reflect a productive response that increases in intensity and duration without effective control. The dysregulation leads to tissue-damaging events and eventual states of disease.
The chief function of the immune system is to distinguish between what is you (self) and what constitutes external threats. When the ability to distinguish these elements is compromised, autoimmunity may arise. In Chapter 7, autoimmune dysfunction will be addressed, moving from basic concepts to the specific mechanisms involved in major clinical disorders. This includes a detailed discussion of how the self is recognized, as well as the mechanisms involved in tolerance that limit reactivity to our own tissues. The goals here are to present the clinical manifestation of autoimmunity in such a manner that outward symptoms are understood through investigation of the molecular targets involved in the host immune self-recognition response. At other times, misdirected recognition of nonself elements, such as environmental allergens that typically are considered harmless, results in the development of clinical presentations. Therefore Chapter 8 will examine the processes involved in the manifestation of immune dysfunction, including the concepts of immune hypersensitivities that lead to clinical disease.
The general topic of vaccines will be addressed in Chapter 9, including both how they work and a frank discussion of the relative truths surrounding their use. Novel methodologies related to vaccine components and composition that are now globally adopted for clinical use will be detailed. This chapter will also contain information on newly developed therapeutics that are grounded in methods that lead to immune modification and factors that promote a healthy immune response (e.g., lifestyle activities and good common practices). Indeed, it is critical that we maintain a healthy balance throughout our lives to ensure functional immune response as we age. The challenges faced at each stage of our lives, from that found in the prenatal/newborn period, to midlife, to so-called maturity, are mentioned in a way that encourages a healthy condition to allow the optimization of immune function.
A discussion of natural (effective) response to tumor development in Chapter 10 will lead to an investigation into the components of immune function to eliminate potentially dangerous precancerous events naturally. This will be followed by coverage of the challenges that we face when protective responses fail and tumors develop. A section also will contain information on cancers of the immune system and the problems that arise when the protective cells themselves become the cause of tumorigenic activity. Advances in immune-based cancer therapies will be described that include subjects such as CAR-T therapy, directed monoclonal treatments, and pathway inhibitors.
Chapter 11 will delve once more into details underlying the concepts of self
versus nonself
and blood types, with the goal to present genetic relationships (similarities as well as differences) between individuals. The mechanisms of the immunobiology of transplantation will be discussed, with details about the contributing cells and factors involved in transplant acceptance and rejection. The challenge is to appreciate the importance of innate and adaptive components in graft recognition, as well as to recognize the clinical consequences of transplantation that affect aspects of daily activities. Rejection topics will be discussed, including graft-versus-host disease, as well as modern immune-based therapeutics designed to alter immune function to limit graft rejection.
Finally, additional information and resources will be provided in Chapter 12 to allow readers to develop an immune-based foundation of knowledge to understand the clinical tests associated with identifying immune parameters that arise during the development of disease states. As such, this includes an introduction to mechanisms that form the basis of immune-related diagnostics and identification of immune properties of the blood during disorders and how immune factors influence outcomes of disease states.
All in all, the hope is that this book will present the concept of the immune system in a holistic manner so that readers may better understand immune-based diseases resulting from either immune system component deficiencies or excess activity. This book is aimed at those who want to know more to encourage readers to explore deeper. It is aimed at the curious who have never previously considered the underlying facets of effective immune function, students who wish to expand their basic knowledge of biological systems, physicians seeking to refresh their understanding of the immune concepts that cause clinical disease, nurses who desire to expand their view of symptom development in patients, patients who want a simple explanation for the complex way that their bodies respond in the context of the world they live in, and, finally, all who seek to find out how the body confers protection against infectious agents, maintain everyday homeostasis, and guard against dysregulation of the normal response to confer health and control the development of disease.
Acknowledgments
I would like to give special credit to Keri C. Smith, PhD, for academic contribution to the chapters on inflammation, antibodies, and immunoassays; and to Robert L. Hunter, MD, PhD, for sharing his positive outlook on life and showing me the joy of embracing scientific thought. In addition, I would like to acknowledge Jonas A. Actor, PhD; Jun Liu, PhD; and Angel Paredes, PhD, for the front cover 3D scanning electron micrograph of Mycobacterium tuberculosis–infected macrophages.
Chapter 1
A functional overview of the immune system and components
Abstract
This chapter establishes a foundation to appreciate how components of the immune system work together to protect against the development of clinical disease. The basic systems and cells involved in immune responses are presented as a general overview of functional immunity. Components and systems presented include concepts of innate (always present) and adaptive (inducible and specific) responses, myeloid and lymphoid cell types, and an introduction to immune anatomy.
Keywords
Innate immunity; adaptive immunity; myeloid; lymphoid; lymphocyte; leukocyte; lymphoid organs; lymph node; thymus; spleen; cluster of differentiation (CD)
Chapter focus
To establish a foundation to appreciate how components of the immune system work together to protect against the development of clinical disease. The basic systems and cells involved in immune responses will be presented in this chapter to give a general overview of functional immunity. Components and systems will be defined to allow an understanding of concepts of innate (always present) and adaptive (inducible and specific) responses, and how these responses interact with one another to form the basis for protection against disease.
Immune homeostasis
A functional immune system offers constant surveillance of human beings in relationship to the world. It confers a balanced state of health through effective elimination of infectious agents (bacteria, viruses, fungi, and parasites) and through control of malignancies. Indeed, the immune system has evolved to allow cells and organs to interact with the environment to protect against harmful invaders. At the same time, mechanisms are in place to instill tolerance toward the naturally occurring microbiome (i.e., microbial and viral agents) that reside within us in symbiotic ways. Taken together, these responses represent a balance of components that ward off the development of clinical disease.
Self versus nonself
Discrimination between the self and the nonself is considered the chief function of the immune system. We are under constant assault by invaders. Our bodies represent prime substrates for organisms to grow and reside, with an abundance of nutrients, warmth, and protection from the outside elements. The immune system is basically a series of obstacles to limit and inhibit pathogen entry and then to attack and destroy those organisms once they enter the body. The immune response is exquisitely designed to recognize these invaders as foreign.
In fact, the major feature that renders our immune system so effective is its ability to distinguish our body’s own cells (the self) from that which it considers foreign (termed the nonself). Each of our cells carries specific tags, or molecular markers, that label it as self.
These markers are important, as they not only determine what is unique about us but also distinguish one person from another.
Almost anything and everything that registers as nonself
will trigger an immune response. An intricate system of molecular communication and cellular interactions allows immune components to function in concert to combat disease-causing organisms. The foreign agent (microbe, virus, parasite, etc.), or any part of it that can be specifically recognized, is called an antigen. Simply put, an antigen is defined as any substance or physical structure that can be recognized by the immune system. Major classes of antigens include proteins, carbohydrates, lipids, and nucleic acids. If an antigen is of high complexity and weight, it can trigger full immune activity and become immunogenic.
The ability to distinguish our own cells from the outside world is critical to maintain functional protection. If this ability is lost (e.g., when self
tissue is seen as foreign), then our immune system launches an aggressive response against our own tissues. This is what happens during autoimmunity, where destruction of the self leads to clinical disease.
The immune system maintains a balance of responsiveness. Too little a response is ineffective, while too aggressive a response can lead