Roitt's Essential Immunology - the textbook of choice for students and Also available as a FREE enhanced Wiley Desktop Edition (upon purchase of the book), Fully downloadable figures and illustrations, further reading and useful links. Post-C3 pathway generating C5a 22 / Fundamentals of Immunology Figure The mast cell. (a) A Roitt's essential immunology 12th ed. p. Buy Roitt's Essential Immunology: Includes Free Desktop Edition (Essentials) 12th ed. by Peter Get your Kindle here, or download a FREE Kindle Reading App. Product details. Paperback: pages; Publisher: Wiley-Blackwell; 12th ed. edition (18 April ) . out of 5 starsLove the accompaning free eBook version.
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Read "Roitt's Essential Immunology" by Peter J. Delves available from Basic and Clinical Pharmacology 14th Edition ebook by Bertram G. Katzung and Gilman's The Pharmacological Basis of Therapeutics, Twelfth Edition . ISBN: ; Language: English; Download options: EPUB 2 Get the Free App. [Peter J Delves; Ivan M Roitt;] -- "Roitt's Essential Immunology - the textbook Create lists, bibliographies and reviews: Sign in or create a free account Kindle eBook Edition/Format: Print book: English: 12th edView all editions and formats Fully downloadable figures and illustrations, further reading and useful links. (Essentials ; 16). Rev. ed. of: Roitt's essential immunology / Ivan M. Roitt, Peter J. Delves. Set in 10/12 pt Adobe Garamond Pro by Toppan Best-set Premedia Limited. 1 Fully downloadable figures and illustrations, further reading and useful links. • Extracts from .. free access to a Wiley DeskTop Edition – a digital.
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He has authored and edited a number of immunology books, and teaches the subject at a broad range of levels. Seamus J. His research is focused on various aspects of programmed cell death apoptosis in the immune system and in cancer and he has received several awards for his work in this area.
Dennis R. His research interests include antibodies, antibody responses to pathogens and vaccine design, particularly in relation to HIV. Ivan M. The work was extended to an intensive study of autoimmune phenomena in pernicious anaemia and primary biliary cirrhosis. Martin, Dennis R. Burton, Ivan M. Registered office: All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, recording or otherwise, except as permitted by the UK Copyright, Designs and Patents Act , without the prior permission of the publisher.
Designations used by companies to distinguish their products are often claimed as trademarks. All brand names and product names used in this book are trade names, service marks, trademarks or registered trademarks of their respective owners. The publisher is not associated with any product or vendor mentioned in this book. This publication is designed to provide accurate and authoritative information in regard to the subject matter covered. It is sold on the understanding that the publisher is not engaged in rendering professional services.
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The contents of this work are intended to further general scientific research, understanding, and discussion only and are not intended and should not be relied upon as recommending or promoting a specific method, diagnosis, or treatment by physicians for any particular patient. The publisher and the author make no representations or warranties with respect to the accuracy or completeness of the contents of this work and specifically disclaim all warranties, including without limitation any implied warranties of fitness for a particular purpose.
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Roitt, Peter J. Includes bibliographical references and index.
ISBN pbk. Delves, Peter J. Roitt, Ivan M. Essential immunology. R57 Fundamentals of Immunology 1. Innate immunity 3 2. Antibodies 53 4. Membrane receptors for antigen 79 5. The primary interaction with antigen 6. Immunological methods and applications 7.
The anatomy of the immune response 8. Lymphocyte activation 9. The production of effectors Control mechanisms Ontogeny and phylogeny PART 2: Applied Immunology Adversarial strategies during infection Vaccines Allergy and other hypersensitivities Transplantation Tumor immunology Autoimmune diseases Glossary Index Companion website www.
We are much indebted to the co-editors of Immunology, J. Brostoff, D. Roth and D. Male, together with the publishers, Mosby, and the following individuals for permission to utilize or modify their figures: Brostoff and A. Hall for figure Horton for figure Taverne for figures IMR would like to acknowledge the indefatigable secretarial assistance of Christine Griffin.
He would also like to thank Mia, Madeleine and Jamie for their support and indulgence. Every effort has been made by the authors and the publisher to contact all the copyright holders to obtain their permission to reproduce copyright material. However, if any have been inadvertently overlooked, the publisher will be pleased to make the necessary arrangements at the first opportunity. A number of scientists very generously provided illustrations for inclusion in this edition, and we have acknowledged our gratitude to them in the relevant figure legends.
Companion website This book is accompanied by a companion website: Preface Welcome to this new edition! When Ivan wrote the first edition some 40 years ago, he wanted to feel that he was chatting to the reader almost informally, rather than preaching, and it has been our intention to maintain this style.
As a subject, immunol- ogy is exciting and dynamic and to persuade you that it is absolutely worthwhile for you to tackle this new edition we have made very extensive changes to update the previous edition.
Accordingly, apart from the introduction of numerous new illustra- tions, we have: It is our fond expectation that you will enjoy and benefit from a reading of our offering. Delves Seamus J. Martin Dennis R. Burton Ivan M. Roitt 8. Staphylococcus aureus enterotoxin A B etc. Over the next two pages you will be shown how to make the most of the learning features included in the textbook. Your Wiley DeskTop Edition allows you to: Keep books, notes and class materials organized in folders inside the application Share: Exchange notes and highlights with friends, classmates and study groups.
Your textbook can be transferred when you need to change or upgrade computers Link: Your textbook is full of useful photographs, illustrations and tables. The DeskTop Edition version of your textbook will allow you to copy and paste any photograph or illustration into assignments, presentations and your own notes.
The photographs and illustrations are also available to download from the companion website. Self-assessment multiple choice and single best answer questions and answers are available on the companion website: You may also wish to use the short podcasts available online for revision, once you have read through the chapters. You can access any of these features by clicking on the icon in your Desk Top Edition.
A key to these is given in the figure below. Good luck with your studies! Part1 Fundamentalsof Immunology Delves, Seamus J. Published by Blackwell Publishing Ltd. Fungi adopt many forms and approximate values for some of the smallest forms are given. Figure 1. The formidable range of infectious agents that confronts the immune system.
Knowing when to make an immune response The ability to recognize and respond to foreign entities is central to the operation of the immune system The vertebrate immune system is a conglomeration of cells and molecules that cooperate to protect us from infectious agents and also provides us with a surveillance system to monitor the integrity of host tissues.
Although the immune system is quite elaborate, as we shall see, its function can be boiled down to two basic roles; recognition of foreign substances and organ- isms that have entered the body, and removal of such agents by a diverse repertoire of cells and molecules that act in concert to eliminate the potential threat. The cells and molecules that comprise the innate immune system are preoccupied with detecting the presence of particular molecular patterns that are typically associated with infectious agents Figure 1.
Tissue damage can also instigate an immune response Aside from infection, there is a growing recognition that tissue damage, leading to nonphysiological cell death, can also provoke activation of the immune system Figure 1.
In this situation, the molecules that activate the immune system are derived from self but are not normally present within the extracellular space. Necrosis is typically caused by tissue trauma, burns, certain toxins, as well as other non-physiological stimuli and is characterized by rapid swelling and rupture of the plasma membranes of damaged cells.
Chapter 1: PRRs can be either soluble or cell- associated and can instigate a range of responses upon encountering their appropriate ligands. Necrotic cells release danger- associated molecular patterns DAMPs , whereas apoptotic cells typically do not.
Stimuli that induce necrosis frequently cause severe cellular damage, which leads to rapid cell rupture with consequent release of intracellular DAMPs.
On the other hand, because stimuli that initiate apoptosis are typically physiological and relatively mild, apoptotic cells do not rupture and their removal is coordinated by macrophages and other cells of the innate immune system, before release of DAMPs can occur.
For this reason, apoptosis is not typically associated with activation of the immune system. It might seem surprising that the immune system can also be activated by self-derived molecules, however, this makes good sense when one considers that events leading to necrotic cell death are often rapidly followed or accompanied by infection.
Furthermore, if a pathogen manages to evade direct detection by the immune system, its presence will be betrayed if it provokes necrosis within the tissue it has invaded.
Before moving on, we should also note that there is another mode of cell death that frequently occurs in the body that is both natural and highly controlled and is not associated with plasma membrane rupture and release of intracellular contents.
This mode of cell death, called apoptosis see Videoclip 2 , is under complex molecular control and is used to eliminate cells that have reached the end of their natural lifespans. Apoptotic cells do not activate the immune system because cells dying in this manner display molecules on their plasma membranes e. In this way, DAMPs remain hidden Recognition of nonself entities is achieved by means of an array of pattern recogni- tion receptors and proteins collectively called pattern recog- nition molecules that have evolved to detect conserved i.
In practice, PAMPs can be anything from carbohydrates that are not normally exposed in vertebrates, proteins only found in bacteria such as flagellin a component of the bacterial flagellum that is used for swimming , double-stranded RNA that is typical of RNA viruses, as well as many other molecules that betray the presence of microbial agents.
The cardinal rule is that a PAMP is not normally found in the body but is a common feature of many frequently encountered pathogens. Pattern recognition molecules also appear to be involved in the recognition of DAMPs released from necrotic cells. Fortunately, we have many ways in which an impending infection can be dealt with, and indeed it is a testament to the efficiency of our immune systems that the majority of us spend most of our lives rela- tively untroubled by infectious disease.
One way of dealing with unwelcome intruders involves the binding of soluble humoral pattern recognition mole- cules, such as complement a series of molecules we will deal with later in this chapter , mannose-binding lectin, C-reactive protein, or lysozyme, to the infectious agent and this can lead directly to killing through destruction of microbial cell wall constituents and breaching of the plasma membrane due to the actions of such proteins.
The latter humoral factors are also adept at coating microorganisms and enhancing their uptake and subsequent destruction by phagocytic cells. Other pattern recognition receptors are cell associated and engage- ment of such receptors can lead to phagocytosis of the micro- organism followed by its destruction within phagocytic vesicles. Just as importantly, cellular PRR engagement also results in the activation of signal transduction pathways that culminate in the release of soluble messenger proteins cytokines, chemokines and other molecules, see below that mobilize other components of the immune system.
Cells of the immune system release messenger proteins that amplify immune responses An important feature of the immune system is the ability of its constituent cells to communicate with each other upon Figure 1. Cytokines and chemokines can have pleiotrophic effects. Note that the effects of chemokines and cytokines shown are not exhaustive. Although cells of the immune system are capable of releasing numerous biologically active molecules with diverse functions, two major categories of proteins— cytokines and chemokines—have particularly important roles in immunity.
Cytokines are a diverse group of proteins that have pleiotropic effects, including the ability to activate other cells, induce differentiation and enhance microbicidal activity Figure 1. Cytokines are commonly released by cells of the immune system in response to PAMPs and DAMPs, and this has the effect of altering the activation state and behaviour of other cells to galvanise them into joining the fight.
Both types of messenger proteins act by dif- fusing away from the cells secreting them and binding to cells equipped with the appropriate plasma membrane recep- tors to receive such signals. Cytokines, chemokines and their respective receptors are discussed at length in Chapter 9. Innate versus adaptive immunity Three levels of immune defense Before we get into the details, we will first take a look at how the immune system works in broad brushstrokes.
The verte- brate immune system comprises three levels of defense Figure 1. First, there is a physical barrier to infection that is pro- vided by the skin on the outer surfaces of the body, along with the mucous secretions covering the epidermal layers of the The vertebrate immune system comprises three levels of defense. Infectious agents that successfully penetrate the physical barriers are then engaged by the cells and soluble factors of the innate immune system.
The innate immune system is also responsible for triggering activation of the adaptive immune system, as we will discuss later in this chapter. The cells and products of the adaptive immune system reinforce the defense mounted by the innate immune system.
Any infectious agent attempting to gain entry to the body must first breach these surfaces that are largely imperme- able to microorganisms; this is why cuts and scrapes that breach these physical barriers are often followed by infection.
Roitt's Essential Immunology, 12th Edition
The second level of defense is provided by the innate immune system, a relatively broad-acting but highly effective defense layer that is largely preoccupied with trying to kill infectious agents from the moment they enter the body. The actions of the innate immune system are also responsible for alerting the cells that operate the third level of defense: The latter cells represent the elite troops of the immune system and can launch an attack that has been specifically adapted to the nature of the infectious agent using sophisticated weapons such as antibodies.
Innate immune responses are immediate and relatively broad acting Upon entry of a foreign entity into the body, the innate immune response occurs almost immediately. Innate immune responses do not improve upon frequent encounter with the same infectious agent.
The innate immune system recognizes broadly conserved components of infectious agents, the afore- mentioned PAMPs, that are not normally present in the body. Upon detecting a PAMP, the innate immune system mounts an immediate attack on anything displaying such molecules by either engulfing such entities or through attacking them with destructive enzymes, such as proteases or membrane attacking proteins Figure 1.
The clear intent is to bludgeon the unwanted intruder into submission as quickly as possible. This makes sense when one considers the prodigious rates of prolif- eration that bacteria can achieve—many bacterial species are capable of dividing every 20 minutes or so—particularly in the nutrient-rich environment our bodies provide.
Key players in the innate immune response include macrophages, neu- trophils and soluble bactericidal i. Although highly effective, innate immune responses are not always sufficient to com- pletely deal with the threat, particularly if the infectious agent is well adapted to avoid the initial attack.
Importantly, adaptive immune responses improve upon each encounter with a particular infectious agent, a feature called immunological memory, which underpins the concept of vaccination.
The adaptive immune response is mediated primarily by T- and B-lymphocytes and these cells display specific receptors on their plasma membranes that can be tailored to recognize an almost limitless range of structures. By definition, molecules that are recognized by T- and B-lymphocytes are called antigens.
Recognition of antigen by a lymphocyte triggers proliferation and differentiation of such cells and this has the effect of greatly increasing the numbers of lymphocytes capable of recognizing the particular antigen that triggered the response in the first place. This rapidly swells the ranks of lymphocytes capable of dealing with the infectious agent bearing the specific antigen and results in a memory response if the same antigen is encountered at some time in the future. We will look in detail at the receptors used by T- and B-cells to see antigen in Chapter 4.
Innate and adaptive immune responses are interdependent The innate and adaptive immune systems work in tandem to identify and kill infectious agents Figure 1.
The innate immune system uses hard-wired i. PAMPs that are commonly expressed on microorganisms. Because the recep- tors of the innate immune system are encoded by the germline, innate immune responses are quite similar between individuals of the same species.
In contrast, the adaptive immune system uses randomly generated receptors that are highly specific for each infectious agent that the immune system comes into Physical barriers Innate immune system Adaptive immune system Therefore, adaptive immune responses are highly variable between individuals within a species and reflect the range of pathogens a particular individual has encountered.
Thus, when an infection occurs, the innate immune system serves as a rapid reaction force that deploys a range of relatively nonspecific weapons to eradicate the infectious agent, or at the very least to keep the infection contained. This gives time for the initially sluggish adaptive immune system to select and clonally expand cells with receptors that are capable of making a much more specific response that is uniquely tailored to the infectious agent.
The adaptive immune response to an infectious agent reinforces and adds new weapons to the attack mounted by the innate immune system. While it was once fashionable to view the innate immune system as somewhat crude and clumsy when compared to the relative sophistication of the adaptive immune system, an explosion of new discoveries over the past 5—10 years has revealed that the innate immune system is just as highly adapted and sophisticated as the adaptive immune system.
Moreover, it has also become abundantly clear that the adaptive immune system is highly dependent on cells of the innate immune system for the purposes of knowing when to respond, how to respond and for how long. Exactly why this is so will be discussed later in this chapter, but for now let us consider the external barriers to infection in a little more detail.
External barriers against infection As mentioned above, the simplest way to avoid infection is to prevent the microorganisms from gaining access to the body Figure 1. When intact, the skin is impermeable to most infectious agents; when there is skin loss, as for example in burns, infection becomes a major problem.
Additionally, most bacteria fail to survive for long on the skin because of the direct inhibitory effects of lactic acid and fatty acids in sweat and sebaceous secretions and the low pH that they generate. An exception is Staphylococcus aureus, which often infects the relatively vulnerable hair follicles and glands.
Mucus, secreted by the membranes lining the inner sur- faces of the body, acts as a protective barrier to block the adherence of bacteria to epithelial cells. Microbial and other foreign particles trapped within the adhesive mucus are removed by mechanical stratagems such as ciliary movement, coughing and sneezing. Among other mechanical factors that help protect the epithelial surfaces, one should also include the washing action of tears, saliva and urine. A brand new introduction sets the scene to section 1, Fundamentals of Immunology, introducing the microbial world and the strategies the body employs to defend itself.
Each chapter then guides the reader through a different part of the immune system, and explains the role of each cell or molecule individually, and then as a whole. Section 2, Applied Immunology, discusses what happens when things go wrong, and the role the immune system plays alongside the damaging effects of a disease, including cancer, immunodeficiency, allergies and transplantation and the beneficial effects of vaccines. The 13 th edition continues to be a user-friendly and engaging introduction to the workings of the immune system, whilst supporting those who require a slightly more detailed understanding of the key developments in immunology.
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