Description. Roitt's Essential Immunology - the textbook of choice for students and instructors of immunology worldwide. Roitt's Essential Immunology clearly. Hazel M. Dockrell; Roitt's essential immunology, 10th edition. I. M. Roitt & P. J. Delves. Oxford: This content is only available as a PDF. Roitt's Essential Immunology Peter J. Delves Professor Delves obtained his PhD from the University of London in Roitt's Essential.
|Language:||English, Spanish, Dutch|
|ePub File Size:||27.79 MB|
|PDF File Size:||19.67 MB|
|Distribution:||Free* [*Register to download]|
PDF | 5+ minutes read | On Dec 12, , Ali Abdulhussain Mahdi and others published IMMUNOLOGY Roitt Preceded by Roitt's essential immunology / Peter J. Delves [et al.]. 12th ed. ISBN (pdf) | ISBN (epub). Subjects: | MESH. Chapter 13 Immunodeficiency · Chapter 14 Allergy and other hypersensitivities · Chapter 15 Transplantation · Chapter 16 Tumour immunology · Chapter
Neutrophils, eosinophils, and basophils are collectively known as polymorphonuclear granulocytes see Chapter 2. Complement is made primarily by the liver, though there is some synthesis by mononuclear phagocytes. Note that each cell produces and secretes only a particular set of cytokines or inflammatory mediators. In every case, the T cells recognize antigens present on the surface of other cells using a specific receptor the T cell antigen receptor TCR which is quite distinct from, but related in structure to, the antigen receptor antibody on B cells. T cells generate their effects either: by releasing soluble proteins, called cytokines, which signal to other cells; or by direct cellcell interactions. These cells are derived from blood monocytes and ultimately from stem cells in the bone marrow.
B cells and T cells are responsible for the specific recognition of antigens Lymphocytes are wholly responsible for the specific immune recognition of pathogens, so they initiate adaptive immune responses.
All lymphocytes are derived from bone marrow stem cells, but T lymphocytes T cells then develop in the thymus, while B lymphocytes B cells develop in the bone marrow in adult mammals. This antigen receptor molecule is called an antibody. If a B cell binds to its specific antigen, it will multiply and differentiate into plasma cells see Fig. Secreted antibody molecules are large glycoproteins found in the blood and tissue fluids. Because secreted Cytotoxic cells recognize and destroy other cells that have become infected Several cell types have the capacity to kill other cells should they become infected.
Of these, the CTL is especially important, but other cell types may be active against particular types of infection. All of these cell types damage their different targets by releasing the contents of their intracellular granules close to them. Cytokines secreted by the cytotoxic cells, but not stored in granules, contribute to the damage.
This action is sometimes called NK cell activity, so these cells are also described as NK cells. Auxiliary cells control inflammation The main purpose of inflammation is to attract leukocytes and the soluble mediators of immunity towards a site of infection. Inflammation is mediated by a variety of other cells including basophils, mast cells, and platelets. Basophils and mast cells can also synthesize and secrete a number of mediators that control the development of immune reactions.
Mast cells lie close to blood vessels in all tissues, and some of their mediators act on cells in the vessel walls.
Basophils are functionally similar to mast cells, but are mobile, circulating cells. The serum concentration of a number of these proteins increases rapidly during infection and they are therefore called acute phase proteins.
One example of an acute phase protein is C reactive protein CRP , so-called because of its ability to bind to the C protein of pneumococci.
This promotes the uptake of pneumococci by phagocytes, a process known as opsonization. Molecules such as antibody and CRP that promote phagocytosis are said to act as opsonins. Another important group of molecules that can act as opsonins are components of the complement system. Complement proteins mediate phagocytosis, control inflammation, and interact with antibodies in immune defense The complement system is a group of about 20 serum proteins whose overall function is the control of inflammation Fig.
The components interact with each other, and with other elements of the immune system. For example: a number of microorganisms spontaneously activate the complement system, via the so-called alternative pathway, which is an innate immune defense this results in the microorganism being opsonized i. Complement activation is a cascade reaction, where one component acts enzymatically on the next component in the cascade to generate an enzyme, which mediates the following step in the reaction sequence, and so on.
The blood clotting system also works as an enzyme cascade. Activation of the complement system generates protein molecules or peptide fragments, which have the following effects: Fig. 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.
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. Many of the secreted body fluids contain bactericidal components, such as acid in gastric juice, spermine and zinc in semen, lactoperoxidase in milk and lysozyme in tears, nasal secretions and saliva.
A totally different mechanism is that of microbial antago- nism associated with the normal bacterial flora of the body i. This suppresses the growth of many potentially pathogenic bacteria and fungi at superficial sites by competition for essential nutrients or by production of inhibitory substances. To give one example, pathogen invasion is limited by lactic acid produced by particular species of commensal bacteria that metabolize glycogen secreted by the vaginal epithelium.
When protective commensals are disturbed by antibiotics, susceptibility to opportunistic infections by Candida and Clostridium difficile is increased.
Even at this level, survival is a tough game. If microorganisms do penetrate the body, the innate immune system comes into play. Innate immunity involves two main defensive strategies to deal with a nascent infection: Before we discuss these strategies in more detail, let us first consider the stereotypical order of events that occur upon infection.
The beginnings of an immune response A major player in the initiation of immune responses is the macrophage. Tissue macrophages are relatively quiescent cells, biding their time sampling the environment around them through continuous phagocytosis. However, upon entry of a microorganism that engages one or more of their PRRs such as a Toll-like receptor or a NOD-like receptor , a startling transition occurs.
Submit Cancel. Thank you for submitting a comment on this article. Your comment will be reviewed and published at the journal's discretion. Please check for further notifications by email. Sign in. You could not be signed in.
Sign In Forgot password? Don't have an account? Sign in via your Institution Sign in. download Subscription prices and ordering Short-term Access To download short term access, please sign in to your Oxford Academic account above. This article is also available for rental through DeepDyve.
View Metrics. Email alerts New issue alert. Advance article alerts. Article activity alert. Receive exclusive offers and updates from Oxford Academic. Related articles in Google Scholar. Citing articles via Google Scholar.