Immune Response Ebook

How To Bolster Your Immune System

How To Bolster Your Immune System

All Natural Immune Boosters Proven To Fight Infection, Disease And More. Discover A Natural, Safe Effective Way To Boost Your Immune System Using Ingredients From Your Kitchen Cupboard. The only common sense, no holds barred guide to hit the market today no gimmicks, no pills, just old fashioned common sense remedies to cure colds, influenza, viral infections and more.

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The Immunity Crisis in America

Have you ever wondered WHY you get sick from different things, sometimes seemingly for no reason? Haven't you ever wished that you could find some way to stop yourself from getting sick and stay healthy all the time? Well, that might be more possible than you thought at first! Your immune system is an odd system, that many scientists are still struggling to understand. However, there have been some amazing breakthroughs! Once you get access to this detailed and helpful book, you will be able to find REAL and Applicable ways to improve your immune system and keep yourself from getting sick all of the time. This book teaches you everything that you never learned about your immune system Start learning what you can Really do to improve your immune system's health and keep your body healthier for longer! It's not hard at all Get started today!

Immunity Crisis Overview

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Overview of the Immune System

The immune system is a remarkably versatile defense system that has evolved to protect animals from invading pathogenic microorganisms and cancer. It is able to generate an enormous variety of cells and molecules capable of specifically recognizing and eliminating an apparently limitless variety of foreign invaders. These cells and molecules act together in a dynamic network whose complexity rivals that of the nervous system. Functionally, an immune response can be divided into two related activities recognition and response. Immune recognition is remarkable for its specificity. The immune system is able to recognize subtle chemical differences that distinguish one foreign pathogen from another. Furthermore, the system is able to discriminate between foreign molecules and the body's own cells and proteins. Once a foreign organism has been recognized, the immune system recruits a variety of cells and molecules to mount an appropriate response, called an effector response, to eliminate...

Cells And Tissues Of The Immune System

The immune system comprises a range of cells, tissues and chemicals that interact to overcome infection, repair tissue damage and maintain the integrity of the body. The immune response is affected by the food we eat, environmental, genetic, neurological and psychological influences. To understand how the immune system fights infection, you must be able to identify the cells involved and to associate the correct physical (phenotypic) and functional characteristics with them. These attributes (and many other aspects of the immune response) are described using specific terms that have precise meanings. So learning immunology is like learning a new language, once you have mastered the terminology and the basic structure, the rest falls into place quite easily The cells and tissues of the immune system provide part of the basic structure of immunology and these sections place special emphasis on introducing a number of relevant terms that you will come across again and again throughout...

Cells and Organs of the Immune System

The immune system consists of many different organs and tissues that are found throughout the body. These organs can be classified functionally into two main groups. The primary lymphoid organs provide appropriate microenvironments for the development and maturation of lymphocytes. The secondary lymphoid organs trap antigen from defined tissues or vascular spaces and are sites where mature lymphocytes can interact effectively with that antigen. Blood vessels and lymphatic systems connect these organs, uniting them into a functional whole. Carried within the blood and lymph and populating the lymphoid organs are various white blood cells, or leukocytes, that participate in the immune response. Of these cells, only the lymphocytes possess the attributes of diversity, specificity, memory, and self nonself recognition, the hallmarks of an adaptive immune response. All the other cells play accessory roles in adaptive immunity, serving to activate lymphocytes, to increase the effectiveness...

Ebv And The Immune System

EBV, a large (172,000 basepairs) herpesvirus, preferentially infects B lymphocytes in humans and causes lifelong infection. In developing countries, well over 90 of individuals are infected before the age of 2 yr (2,3). In industrialized countries, such as the United States, only 25-40 of children have been infected by the age of 2, but approx 75-90 of individuals will have acquired the infection by the age of 25 (4). Primary infection by EBV results in two main responses, depending on the age of the individual and the maturity of the immune system. If the primary infection occurs in early childhood, the immune response and clinical symptoms are almost always clinically silent, that is, quiescent seroconversion in contrast, about two-thirds of infected older children and adults will develop overt IM (2). The incubation period from infection to development of clinical symptoms of IM generally is 4-6 wk. During this time, increased numbers of B cells are infected and disseminate widely,...

Viruses and the immune system

The HIV virion consists of two single-stranded negative sense RNA sequences (about 9000 bases each) containing at least nine genes, plus three proteins - a reverse transcriptase, an integrase and a protease (Figure 2.10(a)). The HIV virion attaches itself to lymphocytes (helper and killer T cells) of the immune system through the CD4 and CCR5 receptors The human immune system has developed a number of methods for detecting and eradicating viruses and other pathogens (any disease-producing agent including bacteria) by activating both an innate and adaptive response. Innate responses are general responses to a limited number of pathogens and include phagocytes (scavenger cells) and macrophages (either fixed to specific locations in the body or circulating with the blood) that 'swallow' whole pathogens or clear up debris. Such cells are directed to pathogens through the stimulation of antibodies (immunoglobulins) in response to antigens and other substances produced by the pathogen. Also...

The Common Mucosal Immune System

The mucosal immune system can be divided into organized secondary lymphoid tissue (which allows antigen sampling, uptake, and presentation for initiation of the mucosal immune response) and more diffuse collections of lymphoid cells constituting mucosal effector sites (2). It now well established that Peyer's patches, appendix, and solitary lymphoid nodules in the gastrointestinal (GI) tract constitute the inductive sites of the gut-associated lymphoreticular tissues (GALT). Similarly, the tonsils and adenoids may represent the nasal-associated lymphoreticular tissues (NALT) in the upper airway and aerodigestive tracts. Organized bronchus-associated lymphoreticular tissues From Immunotherapy for Infectious Diseases Edited by J. M. Jacobson Humana Press Inc., Totowa, NJ (BALT) (3) were also described at airway branches of experimental animals such as rabbits, rats, and guinea pigs, but these structures rarely occur in humans (4). Collectively, GALT and NALT in humans and GALT, BALT,...

The Immune Response to Infectious Disease

You have an immune system for one reason and one reason only. In its absence, the human body would be a delightful place for microorganisms like bacteria, viruses, funguses, and parasites to live and raise their families. Your body is warm, wet, and chock full of the nutrients microbes need to survive and reproduce their own kind. There can be no doubt that this simple truth has played the major role in the evolutionary shaping of the immune system we have today. The failure of any individual part of our immune defense system leads to serious disease, and often death. Infectious disease was the leading disease of death in humans until just over a hundred years ago. A combination of public health measures and vaccination has greatly reduced the toll in human suffering and lives, but infectious disease is still out there and can wreak enormous harm, as HIV-induced AIDS constantly reminds us. More than 150,000 people in the United States still die each year from infectious disease 35,000...

The Immune Response To Bacteria

For large animals like humans, who produce small numbers of offspring over long periods of time, the protection provided by innate immunity alone would be insufficient to keep the species going. But during the two to three days required to mount a primary, fully adaptive immune response to bacterial infection, innate immune components provide our only defense, and it's enough to keep us alive until T cells and antibodies kick in. The innate immune system responds to the presence of bacteria using two major interconnected mechanisms microbial pattern recognition and inflammation. Microbial pattern recognition is the recognition arm of innate immunity, the means by which all multicellular organisms detect invasion of their bodies by micro-bial cells. Inflammation is the defense mounted by the innate immune system to control microbial invasion. Microbial pattern recognition in the innate immune system is thus based on the development, in us and our predecessors over evolutionary time, of...

Immune Response Viral Infections

Components of the Immune System 120 immune Responses to iViral Infection 129 In response to the constant threat of invasion by microorganisms and viruses, vertebrates have evolved an elaborate set of defensive measures, called, collectively, the immune system. During the initial encounter with a virus, the immune system of the host recognizes as foreign certain viral macromolecules (proteins, carbohydrates) called antigens, which elicit several kinds of responses to eliminate the virus and to prevent reinfection. Cells of the humoral immune system (B lymphocytes) respond to an antigenic stimulus by producing and secreting specific immunoglobulins called antibodies cells of the cell-mediated immune system (T lymphocytes) respond by secreting several cytokines which regulate the immune response by coordinating the activities of the various types of cells involved. These lymphocytes bear highly specific receptors that enable them to interface with discrete sites on the virion or on viral...

The Adaptive Immune Response

When the body is exposed to an antigen for the first time, a number of nonspecific (or innate) mechanisms are brought into play to restrict its spread and the accompanying tissue damage. They do not require specific identification of the invader, merely the recognition that something foreign has entered the system. These mechanisms are very efficient and manage to prevent infection by many organisms. However, the latter have been particularly adept in evolving ways to avoid destruction by these non-specific defence systems and as a result, the host has developed more complex immune mechanisms which specifically recognise the invader and invoke reactions to destroy it. This adaptive immunity is characterised by the development of both T and B lymphocyte memory cells, which allow a more rapid and effective response on second exposure to the eliciting antigen.

Implication of HLA Class I Defects for Cancer Immunotherapy

Tumor peptide-based immunotherapy is an established approach of cancer treatment, with the aim of boosting anti-tumor T cell reactivity by stimulation with tumor-specific peptides. However, the overall clinical outcome of this type of treatment is poor. In many cases, the failure of this therapy and the progression of the cancer are associated with total loss of HLA class I tumor expression. Normal expression of HLA class I molecules on tumor cell surface is crucial for the successful outcome of peptide-based cancer therapy, since cytotoxic T cells can only recognize tumor-derived peptides in a complex with self-MHC class I molecules. Patients with HLA class I loss may not benefit from peptide-based immunotherapy, since peptide-mediated activation of cytotoxic T cells can occur only in complex with HLA class I molecules. In some cases, HLA class I downregulation can be restored by cytokine treatment. In cases of structural irreversible alterations, such as mutations in 2-microglobulin...

Specific Defenses The Immune System

Nonspecific defenses are numerous and effective, but some invaders elude them. Vertebrate animals deal with these pathogens by means of defenses targeted against specific threats. The recognition and destruction of specific nonself substances is an important function of an animal's immune system. In this section, we will first provide an overview of the main features of the immune response. We will then consider its two components the humoral immune response, which produces antibodies, and the cellular immune response, which destroys infected cells.

There are two interactive immune responses

The immune system has two responses against invaders the humoral immune response and the cellular immune response. These two responses operate in concert simultaneously and cooperatively, sharing mechanisms. HUMORAL IMMUNE RESPONSE. In the humoral immune CELLULAR IMMUNE RESPONSE. The cellular immune The cellular immune response is carried out by T cells within the lymph nodes, the bloodstream, and the intercellular spaces. These cells have integral membrane proteins T cell receptors that recognize and bind to antigenic determinants while remaining part of the cell's plasma membrane. T cell receptors are rather similar to antibodies in structure and function, each including specific molecular configurations that bind to specific antigenic determinants. Once a T cell is bound to an antigenic determinant, it initiates an immune response that typically results in the total destruction of a nonself or altered self cell.

The mucosal immune response

Most pathogenic organisms establish infection by attaching to, colonising and invading mucosal membranes, which line all the major internal surfaces of the body. Because they are moist, warm, and usually lubricated by nutrient-containing fluid, the mucosal membranes form an excellent environment for promoting the growth of bacteria. To limit infection, the large, complex, mucosal immune system has evolved which is anatomically and functionally distinct from that found elsewhere in the body. It comprises the gastrointestinal (GI) tract, upper and lower respiratory tracts and the urogenital tract. In addition, it may include the exocrine secretory glands such as the salivary, lachrymal, pancreatic and mammary glands.

Structure of the mucosal immune system

The largest part of the mucosal immune system comprises the immunological tissue in the GI tract, the surface area of which is about 400 square metres, approximately 200 times that of the skin. In evolution, the mucosal tissues were probably the first organs to require specific immune protection. The lymphoid tissues of the mucosae comprise the largest part of the immune system with 60 of all T cells being found in the epithelium of the small intestine. These tissues are particularly important in protection owing to their proximity to antigen. They consist of very organised collections of cells where antigen exposure and initiation of the immune response occurs, and effector Figure 4.10 Mucosal immune responses Figure 4.10 Mucosal immune responses

Impact Of Haart On Reconstitution Of Immune Responses

Prior to the inception of HAART, an individual's immune status and clinical prognosis was inferred from the CD4+ T-cell count, which provided the basis for recommendations for prophylaxis against OIs. This was based not only on clinical observations, but on laboratory data demonstrating that CD4+ T-cell declines paralleled the loss of a variety of immune functional responses (111,112). An important clinical question since the advent of HAART is whether the CD4+ T-cell count remains an accurate indicator of immune function and consequently clinical prognosis. cyte proliferative responses after 1 year of HAART therapy (77). The selective failure of tetanus responses to increase is probably owing to the infrequency of exposure to tetanus compared with Candida, CMV, MAC, and MTB, to which individuals are probably reex-posed endogenously. Indeed, a tetanus booster vaccination given to subjects after 1 year of HAART therapy resulted in reconstitution of tetanus-specific lymphocyte...

Primary and Secondary Immune Responses

The importance of the immune system is seen in humans who lack its function, those with acquired immunodeficiency syndrome (AIDS). Human immunodeficiency virus (HIV) is the causative agent of AIDS, and is similar to viruses that attack other species in the same way. Most who die with AIDS really succumb to one of many opportunistic infections that cause diseases in HIVpositive individuals, but which are eradicated by the immune system in normal individuals.

The innate immune system in infection

In order for an organism to cause infection it must first overcome a number of physical barriers, which are often considered to be part of the innate immune system. These barriers - the skin, the respiratory epithelium, the gastrointestinal epithelium, etc. - are largely non-specific and non-immunologic, but play a vital role in host defence (Figure 6.1).

Cancer Immunotherapy Via the Residual Repertoire

The available postthymic residual repertoire specific for self antigens, is, in part, comprised of clones that evaded negative selection, either because of their low affinity for antigen, or because their complementary self-determinant failed to gain access to the MHC to permit tolerance induction. This repertoire may serve as a convenient source of cells for generating an anticancer response, based on the contention that most tumor-associated antigens are actually highly expressed normal self-antigens. Most often, these clones will be directed against subdominant or cryptic determinants, and therefore attempts have been made to alter their target determinants to convert them into more effective immunogens, able to induce proinflammatory Th1 responses (29). Other approaches include the enhancement of costimulatory effects (30,31) and the neutralization of inhibitory elements such as CTLA-4 (32). It is evident that the interests of the autoimmunologist and the tumor immunologist merge...

Specific Immunotherapy

Specific immunotherapy to specific allergens induces allergen-specific anergy in peripheral T lymphocytes and this appears to be due to IL-10 production by Tr1 cells, followed by its production from monocytes.78 Endogenous IL-10 switches off the production of specific IgE and IgG4. IL-10 acts directly T cells by suppressing the CD28 co-stimulation signal transduction via tyrosine phosphorylation of CD28. Immunotherapy results in increased numbers ofTr1 cells that secrete both IL-10 and TGF-P, resulting in suppression of Th2-driven allergic inflammation.80 Grass pollen immunotherapy in seasonal rhinitis results in increased IL-10 production and this is expressed predominantly in CD4+CD25+ T cells that are a variant of regulatory T cells.81

Types of Immune Response

Immunity, which may be nonspecific or acquired, is a mechanism for the protection of the integrity of the body against foreign substances or agents. The theory of nonspecific immune response (which is innate) postulates a continuous immune surveillance by macrophages and natural killer cells that recognize as foreign cancer cells, which arise continually during lifetime, and destroy them. In contrast, acquired immunity takes weeks to mature, and its level of functioning declines with advancing age (a possible cause for the increased incidence of cancers in the elderly). Acquired immunity has two mechanisms of action, humoral and cell-mediated. In both types lymphocytes are the effector cells. Humoral immunity is elicited when an antigen triggers the immune system to rapidly produce B-cells which further differentiate into plasma cells (potentiated by T-helper cells and inhibited by T-suppressor cells) which, in turn, produce antibodies against the offending antigen. Cell-mediated...

Pain Stress And The Immune System

According to Melzack (1993), pain is a major stressor in human life and produces the classic physiological responses of all stressors. However, different pain stimuli or situations produce different perceived levels of stress, depending on the extent to which they are interpreted as life-threatening, so that physiological responses show great variability. There is convincing evidence on the damaging effects of pain-stress on the immune response, as described and evaluated by Liebeskind and others at the 1993 Padua Conference. A large body of evidence shows that stress suppresses immune function generally, suggesting that severe, prolonged pain can have serious, health-threatening consequences. Because it occurs more often in older people who are more likely to have severe postoperative and other kinds of pain, pain can no longer be brushed aside as 'well, it's just pain it can't kill you'.

Immunotherapy Of Specific Bacterial Infections

Much attention has been paid to the prevention and treatment of infections caused by enteric Gram-negative bacilli and Pseudomonas aeruginosa. Infections caused by these organisms have been of increasing importance as pathogens, especially in hospitals, causing significant morbidity and mortality (21). As more immunosuppressive treatments are used to control malignancies and other disorders, the incidence of secondary infections caused by Gram-negative bacilli increases. The ability of these organisms to become resistant to antibiotics over relatively short periods also presents a compelling argument for the development of effective prophylactic and therapeutic strategies to combat the frequently life-threatening infections associated with them. It would appear at times that significant progress has been made in this area, only to find evidence to the contrary. Nonetheless, the bulk of the evidence supports the idea that successful immunization against these organisms is possible and...

T Cell Tolerance to Tumors and Cancer Immunotherapy

It is widely recognized that the immune system plays a role in cancer progression and that some tumors are inherently immunogenic. The identification of tumor-associated antigens (TAAs) has stimulated research focused on immunotherapies to mediate the regression of established tumors. Cancer-specific immunity has traditionally been aimed at activating CD8+ cytotoxic T lymphocytes (CTLs) directed against major histocompatibility complex (MHC) class I-binding peptide epitopes. Other approaches utilize T cell adoptive therapy where autologous, tumor-specific T cells propagated in vitro are transferred back into recipients. However, these strategies have met with limited success in part due to the regulatory mechanisms of T cell tolerance, which poses a considerable challenge to cancer immunother-apy. Our laboratory utilizes the TRansgenic Adenocarcinoma of the Mouse Prostate (TRAMP) model, a murine model of prostate cancer, to study mechanisms of T cell tolerization to tumor...

Immunogenomics towards a digital immune system

One of the major differences that set apart vertebrates from non-vertebrates is the presence of a complex immune system. Over the past 400 500 million years, many novel immune genes and gene families have emerged and their products form sophisticated pathways providing protection against most pathogens. The Human Genome Project has laid the foundation to study these genes and pathways in unprecedented detail. Members of the immunoglobulin (Ig) superfamily alone were found to make up over 2 of human genes possibly constituting the largest gene family in the human genome. A subgroup of these human immune genes, those (among others) involved in antigen processing and presentation, are encoded in a single region, the major histocompatibility complex (MHC) on the short arm of chromosome 6. My laboratory has a long-standing interest in understanding the molecular organization and evolution of the MHC. To this end, we have been generating a range of MHC genomic resources that we...

Beginnings of the Immune Surveillance Theory

In the early 1900s, Ehrlich 1 proposed that a critical function of the immune system was to detect and eliminate carcinomas from the host. Thomas 2 and Burnet 3 developed the theory of immune surveillance proposing that tumor cells developed frequently and expressed tumor antigens that triggered the host to generate an immune-mediated response that eliminated the tumor. Studies by Old and Boyse 4 and Klein 5 in the 1960s confirmed the existence of tumor antigens on chemically or virally transformed murine tumors, and observed that tumors expressing these antigens were rapidly eliminated in syngeneic hosts. If the theory of immune surveillance was correct, then there would be an increase in spontaneous tumor incidence in immunocompromised hosts compared to tumor incidence in immunocompetent hosts. However, tumor studies in nude mice that lack functional T and B cells demonstrated no changes in the incidence of spontaneous tumor development compared to immunocompetent hosts 6 ....

Genomics of the immune response in Drosophila

In Chapter 3 we saw that the genomes of invertebrates, including the tunicate Ci. intestinalis, do not encode proteins of the adaptive immune system, which only evolved in the vertebrate lineage, to supplement the older innate immune system. The adaptive immune system is to be considered as a major evolutionary innovation it is specific to particular antigens, it shows an extremely large diversity, partly inherited and partly acquired during maturation of the system, and it builds up a memory of previous antigen encounters. The latter property implies that when an antigen reacts with a clone of cells with specificity for that antigen, these clones expand greatly and adapt to give the highest possible specificity for the antigen. All these properties are lacking in the innate immune system, which constitutes a general first-line defence with low specificity. The organization of the innate immune response of invertebrates shows many similarities with the vertebrate innate response,...

Approach To The Literature On Immunotherapy For Fungal Infections

The literature on immunotherapies for fungal infections consists of animal studies and human clinical data. In general, animal studies are usually well controlled and rigorously performed. In contrast, most of the information available about immunotherapy in humans comes from case reports and small studies. Hence, the reader must exercise caution when interpreting the human data and making inferences that are applicable to specific clinical situations. It is important to consider that the literature may be biased toward favorable outcomes since these are more likely to be reported than negative experiences. Firm conclusions about the value of specific types of immunotherapy for specific fungal infections must await the completion of well-controlled studies. Nevertheless, case reports and small studies provide important clinical information that can be used to design larger trials or guide heroic therapies in desperately ill patients with fungal infections refractory to standard...

Tumour cell evasion of the immune response

Tumours have been shown to possess the capability to avoid detection or destruction by the immune system (Table 8.9). The poor, or ineffective, immune response that occurs with particular tumours may be due to selective pressures within the tumour itself causing a reduction in (or loss of) expression of a tumour antigen, which might be capable of stimulating a good immune response (immunoselection). Such cells would not stimulate an antigen-specific response and thus would be unlikely to be recognised and destroyed. In other words, these tumour cells possess a selective advantage, which allows them to form the dominant population the resulting tumour being relatively resistant to immune attack. Table 8.9 Mechanisms of tumour cell evasion of the immune response Antigenic modulation (which is typically caused by antibodies) occurs when the immune response to a tumour antigen causes the loss of expression of that antigen. This process is similar to immunoselection except that when the...

Tolerance in the Mucosal Immune System

The immune system requires a mechanism for generating antigen specific tolerance to maintain immune homeostasis and control the harmful effects of auto-antigen reactive T lymphocytes. Several mechanisms have been proposed to allow the immune system to suppress the activity of certain T cell clones including clonal deletion, the induction of anergy and antigen specific suppression (reviewed in ref. 23). Recent experiments both in vitro and in animal models of autoimmune disease have characterised different populations of regulatory T lymphocytes that suppress antigen specific lymphocyte responses by the release of cytokines and also by cell cell interactions.

Elimination of superfluous antigenspecific lymphocytes at the termination of an immune response

After a transient stimulation of the immune system, such as an acute viral infection, most responding lymphocytes die, but some will survive as memory cells and maintain a state of equilibrium. There are two known mechanisms by which the superfluous lymphocytes are eliminated. The first mechanism is the loss of the antigenic stimulation that provides necessary survival and growth signals to lymphocytes this loss results in apoptosis. The second mechanism is known as activation-induced cell death. When T cells are exposed to repeated antigenic stimulation such as by self-antigen, activation of the T cell also leads to the co-expression of Fas and Fas-ligand, resulting in the death of the T cell and possibly of neighbouring cells (4).

The Intracellular Niche of L monocytogenes and Evasion of Immune Responses

The intracellular niche of L. monocytogenes allows it to evade some immune responses that otherwise are very effective against bacteria. As detailed below, L. monocytogenes has evolved to avoid macrophage- and B cell-mediated killing, as well as reducing immune surveillance by residing within nonprofessional antigen presenting cell subsets. L. monocytogenes that cannot maintain their intracellular niche are unable to survive and replicate within the host.

Mathematical models of HIV and the immune system

I describe how mathematical models have been used to elucidate the principles which govern HIV and immune system dynamics in relation to antiviral drug therapy. The review starts by introducing a basic model of virus infection and demonstrates how it was used to study HIV dynamics and to measure crucial parameters which lead to a new understanding of the disease process. Since this analysis indicates that eradication of the virus is not feasible during the lifetime of the patient, I continue to discuss mathematical models with the aim to explore how drug therapy can be used to induce long-term immunological control of the infection. 2003 Immunoinformatics bioinformatic strategies for better understanding of immune function. Wiley, Chichester (Novartis Foundation Symposium 254) p 193-215 The dynamics between viral infections and the immune system involve many different components and are multifactorial. Given such a scenario, the principles governing the dynamics and the...

How The Immune System Works

Immune System Health

What Is an Immune System You may not know it, but your immune system is huge. It's second in size only to your liver. But since it's spread throughout your body (Figure 1.1), you are probably only minimally aware of it. Lymph nodes are everywhere. The immune system has its own organs, like the thymus and the spleen. Its cells permeate your entire bloodstream. Your tonsils and adenoids and appendix are all part of the immune system, and so is the inside of your bones In just a moment we'll look at many of these components of the immune system, how they work, and how they fit together. WHY DO I NEED AN IMMUNE SYSTEM You have an immune system for one reason and one reason only. In its absence, the human body would be a delightful place for microorganisms like bacteria, viruses, funguses, and parasites to live and raise their families. Your body is warm, wet, and chock full of the nutrients microbes need to survive and reproduce their own kind. Compare that with other places microbes are...

Immune Surveillance Theory

The immune surveillance theory was first conceptualized in the early 1900s by Paul Ehrlich. He suggested that cancer cells frequently arise in the body but are recognized as foreign and eliminated by the immune system. Some 50 years later, Lewis Thomas suggested that the cell-mediated branch of the immune system had evolved to patrol the body and eliminate cancer cells. According to these concepts, tumors arise only if cancer cells are able to escape immune surveillance, either by reducing their expression of tumor antigens or by an impairment in the immune response to these cells. Among the early observations that seemed to support the immune surveillance theory was the increased incidence of cancer in transplantation patients on immunosuppressive drugs. Other findings, however, were difficult to reconcile with this theory. Nude mice, for example, lack a thymus and consequently lack functional T cells. According to the immune surveillance theory, these mice should show an increase in...

The Adaptive Immune System Requires Cooperation Between Lymphocytes and Antigen Presenting Cells

Membrane Bound Antigen Receptor

An effective immune response involves two major groups of cells T lymphocytes and antigen-presenting cells. Lymphocytes are one of many types of white blood cells produced in the bone marrow by the process of hematopoiesis (see Chapter 2). Lymphocytes leave the bone marrow, circulate in the blood and lymphatic systems, and reside in various lymphoid organs. Because they produce and display antigen-binding cell-surface receptors, lymphocytes mediate the defining immunologic attributes of specificity, diversity, memory, and self nonself recognition. The two major populations of lymphocytes B lymphocytes (B cells) and T lymphocytes (T cells) are described briefly here and in greater detail in later chapters. an important role in activating B cells, TC cells, macrophages, and various other cells that participate in the immune response. Differences in the pattern of cytokines produced by activated TH cells result in different types of immune response. Activation of both the humoral and...

The Innate and Adaptive Immune Systems Collaborate Increasing the Efficiency of Immune Responsiveness

An example of cooperation is seen in the encounter between macrophages and microbes. Interactions between receptors on macrophages and microbial components generate soluble proteins that stimulate and direct adaptive immune responses, facilitating the participation of the adap- immune response tive immune system in the elimination of the pathogen. Stimulated macrophages also secrete cytokines that can direct adaptive immune responses against particular intra-cellular pathogens. Just as important, the adaptive immune system produces signals and components that stimulate and increase the effectiveness of innate responses. Some T cells, when they encounter appropriately presented antigen, synthesize and secrete cytokines that increase the ability of macrophages to kill the microbes they have ingested. Also, antibodies produced against an invader bind to the pathogen, marking it as a target for attack by complement and serving as a potent activator of the attack. A major difference...

Inflammation Represents a Complex Sequence of Events That Stimulates Immune Responses

Vasoactive Hormones Blood Pressure

Tissue damage caused by a wound or by an invading pathogenic microorganism induces a complex sequence of events collectively known as the inflammatory response. As described above, a molecular component of a microbe, such as LPS, may trigger an inflammatory response via interaction with cell surface receptors. The end result of inflammation may be the marshalling of a specific immune response to the invasion or clearance of the invader by components of the innate immune system. Many of the classic features of the inflammatory response were described as early as 1600 bc, in Egyptian papyrus writings. In the first century ad, the Roman physician Celsus described the four cardinal signs

The Revival of Immune Surveillance

Experimental support of immune surveillance began to emerge in the middle 1990s with the development and testing of a variety of mutant mice that were deficient in one or more components of innate or adaptive immune systems. The first evidence came from a series of experimental models that eliminated interferon (IFN)-7, an important cytokine produced mainly by T cells, natural killer (NK) cells, and NKT cells. Mice treated with neutralizing antibodies for IFN-7 and then given transplanted fibrosarcoma tumors exhibited a significant incidence of tumor growth 8 . Kaplan et al. 9 demonstrated that at least one effect of IFN-7 was to directly inhibit tumor growth. They expressed dominant-negative IFN-7 receptors in fibrosarcomas that were then transplanted into recipient mice. Tumors that could not respond to IFN-7 grew significantly faster than tumors with functional IFN-7 receptors. The most convincing evidence for an important role of IFN-7 in protecting the host from developing tumors...

Immunotherapy With Ebv As A Therapeutic Target

HD is curable in 80 of cases with combination chemotherapy and or radiation therapy. In those cases where cure is not achieved or patients are unable or unwilling to accept the risks associated with standard therapy, immunotherapy may provide an alternative therapeutic option. Immunotherapy is any treatment that exploits the specificity of the immune system to limit disease progression or effect cure. It may be active as in the case of vaccines or passive as in the case of infused CTLs. Its toxicity generally does not overlap that caused by standard therapies. EBV, which is present in 40 of HD cases in the West and virtually all HIV-associated HD cases, is an attractive immunotherapy target given its immunogenicity, genetic stability, and constant presence within H-RS cells. Adoptive Immunotherapy Cellular immune responses are the key to limiting primary and latent EBV infection. When that control is lost lymphoproliferative states such as HD may occur. Adoptive immunotherapy, the...

Regulators That Control Genes Of The Vertebrate Immune Systems

Lymphoid Development And Ikaros

The adaptive immune system, with its B- and T-lymphocytes, antigen-dependent clonal selection mechanisms, and antigen-specific immunologic memory, is found only in vertebrates within the chordate assemblage of deuterostomes (56-60). Supplementing the innate immune system, this results in a layered system of innate and adaptive responses, interconnected and cemented by many potent regulatory links between the two kinds of response (61). In evolutionary terms, lymphocytes presumably arose by the modification of developmental pathways, leading to more basal hematopoietic cell types. In this section, we consider the relationships between the innovations required for the adaptive immune system and the underlying regulatory structures of deuterostome innate immunity. 4.1. Immune System Innovations of Jawed Vertebrates Two innovations are conspicuous in this comparison. One, of course, is the elaborate recombinase system, which rearranges antigen receptor gene segments in vertebrates to...

Bacterial Evasion Of The Immune System

Other bacterial species such as Trypanosoma cruzi, listeria, and salmonella have developed alternate methods to evade the immune system. These microorganisms escape from the phagosomes and live within the cytoplasm of cells. Ultimately, some antigenic fragments are produced and the host responds with the production of CD8 cells that lyse the infected cells.

Adaptive Immunity to L pneumophila Infection

Cannabinoid And Adaptive Immunity

The adaptive immune response to bacterial infection follows initial exposure to microbes, not necessarily active infection, and is transferable to naive recipients by lymphocytes. The humoral antibody response to bacterial infection is a typical adaptive immune response when an individual is exposed to bacterial antigens and a heightened specific antibody response then occurs after secondary stimulation by antigens from the same microbe or active infection. The role of antibodies in resistance to infection varies according to the bacterium. In the case of Legionella infection, various specific virulence factors and specific components or antigens have been elucidated20. However, the importance of these antigens for the humoral immune response in humans has not yet been clearly defined. In contrast, the role of many immune factors involved in Legionella immunopathogene-sis in experimental animals has been characterized. Antibodies to Legionella antigens and other components promote...

Immunotherapy for Cancer

Besides interleukin-2 and gamma interferon, other cy-tokines may be useful in the treatment of cancer and are currently undergoing experimental investigations. Interleukin-12, for example, seems promising because it is needed for the changing of uncommitted helper T lymphocytes into the TH1 subtype that bolsters cell-mediated immunity. Scientists are also attempting to identify specific antigens that may be uniquely expressed in cancer cells in an effort to help the immune system target cancer cells for destruction.

Multiple Sclerosis As A Disease Of Miscommunication Between The Central Nervous System And Immune System

In the time frame immediately following Medwar's seminal experiments defining immune privilege, CNS function was thought to be dependent on successful isolation of the CNS from the immune system. Numerous in vivo and in vitro studies confirmed the neurotoxic potential of the products produced by activated immune cells (including nitric oxide, prostaglandins, cytokines). Furthermore, therapeutic interventions such as nonsteroidal anti-inflammatory drugs and steroids aimed at suppressing the immune system showed moderate, if incomplete success, at limiting the progression of secondary neurodegeneration in both humans and rodent models (3). In this context, the very existence of a resident population of macrophages (microglia) stably distributed throughout the CNS appeared nonsensical at best and maladaptive at worst. Even more puzzling was the almost universal response of microglia to nearly all pathological insults (from the mildest to the most severe) the rapid induction of the...

Aberrant Adaptive Immunity in Lupus

Vertebrates acquire adaptive immunity after birth, which is a response to specific antigens that involves B and T cells of the immune system and frequently leads to a state of immune memory (Iwasaki and Medzhitov 2004). The adaptive immune system produces antibodies and T cells that are highly specific for a particular pathogen (or antigen). The relative specificity of SLE sera to a selected subset of nuclear antigens (as opposed to reacting to the whole universe of antigens) suggests that lupus genes must be impacting adaptive immunity at some level. Our recent genetic dissection studies have indicated that Sle1z may be one such locus gene (Figure. 1). Collectively, the above studies reveal that a mutant form of the SLAM gamily gene, Ly108, can profoundly impact key checkpoints in early B cell tolerance, hence leading to the emergence of self-reactive antibodies. Since a similar locus (Tsao et al. 1999) and gene(s) (unpublished observations) are also at play in human SLE,...

Disorders of the Immune System

Sometimes the immune system fails us in one way or another. It may overreact, as in an allergic reaction it may attack self antigens, as in an autoimmune disease or it may function weakly or not at all, as in an immune deficiency disease. After a look at allergies and autoimmune diseases, we will examine the acquired immune deficiency that characterizes AIDS. hypersensitivity. A common type of condition arises when the human immune system overreacts to (is hypersensitive to) a dose of antigen. Although the antigen itself may present no danger to the host, the inappropriate immune response may produce inflammation and other symptoms, which can cause serious illness or death. Allergic reactions are the most familiar examples of this phenomenon. There are two types of allergic reactions AIDS is an immune deficiency disorder People are subject to various immune deficiency disorders, such as those in which T or B cells never form and others in which

Four features characterize the immune system

Antigen And Antibody Symbols

The characteristic features of the immune system are specificity, the ability to respond to an enormous diversity of foreign molecules and organisms, the ability to distinguish self from nonself, and immunological memory. specificity. As we saw above, the lymphocytes (B cells and T cells) are involved in specific defense mechanisms. T cell receptors and the antibodies produced by B cells recognize and bind to specific nonself substances. Organisms or molecules that are recognized by and interact with these cells to initiate an immune response are called antigens. The specific sites on antigens that the immune system recognizes are called antigenic determinants or epitopes (Figure 18.6). Chemically, an antigenic determinant is a specific portion of a large molecule, such as a certain sequence of amino acids that may be present in several proteins. A large antigen, such as a whole cell, may have many different antigenic determinants on its surface, each capable of being bound by a...

Cytokine Therapy Can Augment Immune Responses to Tumors

The isolation and cloning of the various cytokine genes has facilitated their large-scale production. A variety of experimental and clinical approaches have been developed to use recombinant cytokines, either singly or in combination, to augment the immune response against cancer. Among the cytokines that have been evaluated in cancer immunother-apy are IFN-a, p, and 7 IL-1, IL-2, IL-4, IL-5, and IL-12 GM-CSF and TNF. Although these trials have produced occasional encouraging results, many obstacles remain to the successful use of this type of cancer immunotherapy. The most notable obstacle is the complexity of the cytokine network itself. This complexity makes it very difficult to know precisely how intervention with a given recombinant cytokine will affect the production of other cytokines. And since some cytokines act antagonistically, it is possible that intervention with a recombinant cytokine designed to enhance a particular branch of the immune response may actually lead to...

Generation Of Cellmediated Immune Responses

Cytokine Network

The design of successful immunologic strategies to treat human virus-associated malignancies requires an understanding of the effector processes that control viral infection and the mechanisms viruses use to evade such responses. Immune responses against viruses are mediated by nonspecific effector cells, such as natural killers and macrophages, and antigen-specific T- and B-lymphocytes. Fig. 1. Generation of cell-mediated immune response. For activation of naive T-helper (Th) and cytotoxic T-lymphocytes (CTLs), professional antigen-presenting cells (e.g., dendritic cells DCs ) are required. DCs process the antigens and present the immunogenic peptides in an MHC context with simultaneous delivery of costimulatory signals (e.g., B7 CD28 or CD40 CD40 ligand signals) to activate T-lymphocytes. Two antigen-processing pathways are generally accepted. In the cytosolic pathway, endogenously synthesized antigens (cytoplasmic proteins) are digested in proteosomes and transported into the...

Immune Responses to Extracellular and Intracellular Bacteria Can Differ

Infection by extracellular bacteria induces production of humoral antibodies, which are ordinarily secreted by plasma cells in regional lymph nodes and the submucosa of the respiratory and gastrointestinal tracts. The humoral immune response is the main protective response against extracellular bacteria. The antibodies act in several ways to protect the host from the invading organisms, including removal of the bacteria and inactivation of bacterial toxins (Figure 17-8). Extracellular bacteria can be pathogenic because they induce a localized inflammatory response or because they produce toxins. The toxins, endotoxin or exotoxin, can be cytotoxic but also may cause pathogenesis in other ways. An excellent example of this is the toxin produced by diphtheria, which exerts a toxic effect on the cell by blocking protein synthesis. Endotoxins, such as lipopolysaccharides (LPS), are generally components of bacterial cell walls, while exotoxins, such as diphtheria toxin, are secreted by the...

Introduction Evasion and Modulation of the Immune Response by Pathogens

As organisms evolved into multicellular life forms and devoted more time, resources, and energy to life, they needed to insure their investment with a system that could differentiate foreign invaders from self. The immune system allows for recognition of pathogens, in turn leading to an evaluation of the pathogen and then the appropriate response to control or eliminate the pathogen. However, pathogens have also been evolving alongside their hosts. In order to improve their odds for survival, pathogens often evade or modulate the immune response to create a more favorable host environment. Avoiding immune recognition by evading the immune response is the most effective way for the pathogen to survive in a host. Examples of pathogen evasion include latency, antigenic variation, or sequestration in immune-privileged sites. Modulation of the immune response by pathogenic bacteria can be attributed to virulence factors, proteins, or other molecules that bacteria produce in order to...

Systemic Function of the Immune System

The many different cells, organs, and tissues of the immune system are dispersed throughout the body, yet the various components communicate and collaborate to produce an ef The tissue damage associated with the injury and infection results in an inflammatory response that causes increased blood flow, vasodilation, and an increase in capillary permeability. Chemotactic signals are generated that can cause phagocytes and lymphocytes to leave the blood stream and enter the affected area. Factors generated during these early stages of the infection stimulate the capacity of the adaptive immune system to respond. Langerhans cells (dendritic cells found throughout the epithelial layers of the skin and the respiratory, gastrointestinal, urinary, and genital tracts) can capture antigens from invading pathogens and migrate into a nearby lymphatic vessel, where the flow of lymph carries them to nearby lymph nodes. In the lymph nodes these class II MHC-bearing cells can become members of the...

Clinical Trials Of Dendritic Cell Immunotherapy

Numerous studies in animal models have documented that ex vivo antigen-pulsed DCs are effective inducers of pathogen-specific immunity (59,63,66,67). However, the utility of ex vivo antigen-pulsed DCs for the prophylaxis or therapy of infection has not yet been extensively studied in humans. In the first reported DC clinical trial in HIV-infected patients, the safety and antigen-presenting properties of allogeneic or autologous DCs were investigated in seven HLA-A2 + , HIV-infected patients (46). Allogeneic DCs, obtained from the peripheral blood of HLA-identical, HIV-seronegative siblings using the density gradient procedure described earlier, were pulsed with recombinant HIV-1 MN gp160 or synthetic peptides corresponding to HLA-A*0201-restricted cytotoxic epitopes of envelope, Gag and Pol proteins. The antigen-pulsed cells were infused intravenously six to nine times at monthly intervals, and HIV-spe-cific immune responses were monitored. proliferative responses. A recipient of...

Cancer And The Immune System

What if the immune system could respond to tumors, could recognize them as somehow aberrant, like a virally infected cell or a transplant What if those tumors that do develop in us are just the rare renegades that manage somehow to slip past our immune defenses Would that mean we could then somehow pump up the immune system to increase its search and destroy function as a means of combating cancer Interest in immune responses to tumors was rekindled in the 1950s, when people began studying cancers induced by chemicals. For example, the highly carcinogenic chemical methylcholan-threne, when painted on the skin of a mouse, will cause a sarcoma almost every time. These experiments were done in inbred strains of mice. Inbred strains are strains produced by repeated brother-sister matings. After 20 or so generations, all the members of the same sex of an inbred strain are essentially genetically identical twins. And just as with human identical twins, they can exchange cells, tissues, and...

Mucosal Immune System

The tear film that coats the ocular surface and the mucus layer of the GI and respiratory tracts are richly endowed with secretory IgA antibodies, which are secreted by B cells of the common mucosal immune system 4, 5 . The importance of IgA antibody is reflected by the commitment of the immune system to its production. IgA accounts for 70 of all the immunoglobulin secreted by the mammalian immune system and more IgA is produced each day than all of the other immunoglobulin isotypes combined 2, 6 . Secretory IgA antibody seems to be ideally suited for the protection of mucosal surfaces, as it is highly effective in blocking adhesion of pathogens to epithelial surfaces 2, 4, 7 . Moreover, IgA is a poor activator of the complement system and does not provoke inflammation. This in turn reduces the risk of chronic inflammation in organs such as the GI tract that are repeatedly exposed to foreign molecules present in foods. Each day our GI and respiratory tracts are exposed to a...

T Cells The Cellular Immune Response

Cell Helper Immune Response

Thus far we have been concerned primarily with the humoral immune response, whose effector molecules are the antibodies secreted by plasma cells that develop from activated B cells. T cells, as we have seen, are involved in the humoral immune response, but they are also the effectors of the cellular immune response, which is directed against any factor, such as a virus or mutation, that changes a normal cell into an abnormal cell. In this section, we will describe two types of effector T cells (helper T cells and cytotoxic T cells). We will also describe the MHC (major histocompatibility complex) proteins, which underlie the immune system's tolerance for the cells of its own body. Helper T cells, or TH cells, assist both the cellular and humoral immune responses. The major histocompatibility complex encodes proteins that present antigens to the immune system We have seen that an animal's immune system recognizes its own cells by their surface proteins. Several types of mammalian cell...

Diseases Caused by the Immune System

Immune mechanisms that normally protect the body are very complex and subject to errors that can result in diseases. Autoimmune diseases and allergies are two categories of disease that are not caused by an invading pathogen, but rather by a derangement in the normal functions of the immune system. The ability of the normal immune system to tolerate self-antigens while it identifies and attacks foreign antigens provides a specific defense against invading pathogens. In every individual, however, this system of defense against invaders at times commits domestic offenses. This can result in diseases that range in severity from the sniffles to sudden death. Diseases caused by the immune system can be grouped into three interrelated categories (1) autoimmune diseases, (2) immune complex diseases, and (3) allergy, or hypersensitivity. It is important to remember that these diseases are not caused by foreign pathogens but by abnormal responses of the immune system. Autoimmune diseases are...

Immune Responses In Mucosal Surfaces

Mucosal Innate Immune Responses Epithelial cells also secrete antimicrobial peptides such as defensins, inflammatory cytokines, and chemokines, which contribute to mucosal innate immune responses. In this regard, the human intestinal a-defensins (HDs) HD-5 and HD-6 were identified in intestinal Paneth cells and in the human reproductive tract (58). The a-Defensin are also secreted by tracheal epithelial cells, and they are homologous to peptides that function as mediators of nonoxidative microbial cell killing in human neutrophils (termed human neutrophil petide HNPs ) (59,60). The p-defensins, and in particular human p-defensin-1 (hBD-1), are expressed in the epithelial cells of the oral mucosa, trachea, and bronchi, as well as mammary and salivary glands in humans (61-63). Human intestinal epithelial cells were reported to express hBD-1 constitutively, whereas hBD-2 was only seen in inflamed colon or after bacterial infection of a colonic epithelial cell line (64). Secretory...

Regulation of Immune Surveillance Effectors within the

Although there are no conclusive data on the role of immune surveillance in the eye, there are substantial data on the immune response against tumors transplanted or injected into the anterior chamber, and these data are useful in making predictions about whether or not immune surveillance occurs. The argument that immune surveillance does not occur in the eye is supported by data indicating that both innate and adaptive immune effector cells responsible for mediating surveillance are all negatively regulated within the eye. The effect of the ocular environment on each of these effector cell subpopulations is summarized below. A number of researchers have reported the inhibitory effects of the ocular environment on DCs macrophages that prevent the development of both innate and adaptive immunity. For example, a-melanocyte-stimulating hormone inhibits the ability of DCs macrophages to release nitric oxide, an important pro-inflammatory cytokine in innate immunity 36 . Transforming...

Immune Response to Infectious Diseases

Earthworm Ureathral Pictures

Circumvent both innate and adaptive immunity. One of the first and most important features of host innate immunity is the barrier provided by the epithelial surfaces of the skin and the lining of the gut. The difficulty of penetrating these epithelial barriers ensures that most pathogens never gain productive entry into the host. In addition to providing a physical barrier to infection, the epithelia also produce chemicals that are useful in preventing infection. The secretion of gastric enzymes by specialized epithelial cells lowers the pH of the stomach and upper gastrointestinal tract, and other specialized cells in the gut produce antibacterial peptides. Generally, pathogens use a variety of strategies to escape destruction by the adaptive immune system. Many pathogens reduce their own antigenicity either by growing within host cells, where they are sequestered from immune attack, or by shedding their membrane antigens. Other pathogens camouflage themselves by mimicking the...

Evaluation ofthe Immune System

The choice for experimental animal is the species that absorbs, metabolizes, distributes, and excretes (ADME) the test chemical in a manner similar to humans. Often, the ADME ofthe test chemical is unknown before testing. Here, mice, rats, or dogs are used because there are methods available to detect effects on the immune response. Regulatory agencies require testing in both the rat and the mouse because validated testing methods are available. Route and Duration. It seems obvious that xenobiotics should be tested in protocols in which the route of administration and duration are similar to the human situation. For example, animal studies on dioxin have used acute highdose protocols inducing adverse effects whereas the human experience is chronic low-dose exposure with no effects on the immune system. For target organ toxicity studies, the study duration may be much shorter. When antigen is used to stimulate the immune system in the presence of maximal...

Dr Jekyll MUC1 is a Tumor Antigen Targeted by Immune Surveillance

Structures that can comprise up to 16 monosaccharide units 42, 43 . During malignant transformation the core2 forming p6-glucosaminyltransferase level is low or not expressed and leads to the accumulation of corel structures 41 that now serve as substrates of Gal-specific a3-sialyltransferase and GalNAc-specific p6-sialyltransferases. In addition, the increased presence of may compete with the core2 enzyme for substrate 44 . Thus, the length of O-linked glycans on tumor MUC1 is restricted by a high degree of sialic acid that dominates over neutral carbohydrates 19, 45 . This underglycosylation results in unmasking of previously cryptic protein core epitopes and short carbohydrate epitopes. This is important for the humoral and cellular immune response, because the peptide core is more accessible for peptide specific anti-MUCl antibodies and for enzymatic processing into peptides for presentation to T cells, compared to MUC1 on normal epithelia. Considering the undesirable Mr. Hyde...

Mechanisms of the Effects of Fermentable Fibers on immune Functions

Even though the mechanism for the effect of fermentable dietary fibers on immune function in the intestine has not been fully established, interesting hypotheses have been proposed that include 12.3.2 Probiotics, Immune Functions, and the Risk of Immune-Associated Diseases In contrast to work on fermentable dietary fibers, many more studies have documented effects of feeding probiotics and especially lactic acid bacteria (i.e., lacto-bacilli and bifidobacteria) on various parameters of immune function, as well as on risk of miscellaneous diseases that are causally linked to a dysfunctioning of the defenses. Reports on the effects of probiotics on immune functions and on the risk of immune-associated diseases often give conflicting results, probably because different species, genera, or strains of microorganisms have different properties and consequently different effects. In addition, their effects also depend on the degree of contact with the intestinal mucosa and the intestinal...

Evaluating Immune System Status Immunotoxicity

Because xenobiotics have multiple effects on the immune system, it is difficult to arrive at a concise definition for immunotoxicity. However, the U.S. FDA considers an immunotoxic effect to be any change in the structure or function of the immune system that is permanent or reversible. This definition has been embraced by most immunotoxicologists because it considers all possible outcomes of interactions between the immune system and xenobiotics. The interaction between xenobiotics (e.g., chemicals or pharmaceuticals) and the immune system has four possible outcomes (1) the xenobiotic may directly interact with the immune system to suppress or enhance the response to exogenous agents, (2) the xenobiotic may interact with host tissue and initiate hypersensitivity or autoimmune reactions, (3) the xenobiotic may not react di rectly with the immune system but initiate effects in other organs that influence the immune system, and (4) the xenobiotic may have no effect on the immune system...

Immunotherapy for Virus Associated Malignancies

Much of the evidence for the association of viruses with human cancer comes from epidemiologic data (2). EBV and HPV have a high prevalence in most populations, but only a small proportion of infected persons develops a virus-associated cancer. The period of latency between primary infection and tumor outgrowth underscores the mul-tifactorial origins of human tumors. Further evidence for the association of viruses with cancer comes from the detection of viral DNA in tumor tissue, the ability of viruses to transform cells in vitro, and the expression of viral proteins with oncogenic potential or the ability to inactivate tumor suppressor genes. Regardless of their precise role in oncogenesis, viral tumor-associated antigens can serve as targets for immunotherapy. The cytotoxic T-lymphocyte (CTL) arm of the cellular immune response is thought to be the most important defense against tumors and virus-infected cells. In this chapter, we discuss the use of EBV-specific CTLs as...

Immune Response Against Herpes Virus Infection

Mechanisms of innate immune are characterized by rapid induction and relatively undiversified response. The initial recognition is aimed to limit virus replication and spread to uninfected cells and involves additional cellular effectors in the infection control. Innate responses to the virus infection are composed of humoral components, including complement, natural antibodies, cytokines (IFN-a p, TNF-a, IL-12, etc.), and antimicrobial peptides (defensins), and recruited cellular effectors (neutrophils, macrophages, resident dendritic cells, y 8 T cells, natural killer (NK), and NKT cells). This mechanism restricts the number of infected cells. HSV replication in epithelial cells may stimulate the complement system and production of chemokines and IFN-a p. These molecules may activate capillary endothelia, which begins expression of adhesion molecules, which alert dendritic cells (DCs) and resident macrophages to the presence of a pathogen (Duerst and Morrison 2003). Immature DCs...

Tumors of the Immune System

Tumors of the immune system are classified as lymphomas or leukemias. Lymphomas proliferate as solid tumors within a lymphoid tissue such as the bone marrow, lymph nodes, or thymus they include Hodgkin's and non-Hodgkin's lymphomas. Leukemias tend to proliferate as single cells and are detected by increased cell numbers in the blood or lymph. Leukemia can develop in lymphoid or myeloid lineages.

Cytokines In Immunity To Infection

Apart from cytotoxic effector function, T cells play another important regulatory role in immunity to infection through the production of cytokines. These affect the activity of a wide range of cells, enhancing the function of some, The immune response to viral infections may be divided into separate stages, each being associated with a particular pattern of cytokine secretion. In the first stage, IFNa b production causes the activation of NK cells (Table 6.7). This may be accompanied by IFNg and or IL-12 production. Interferon production is one of the earliest host responses to viral infection, which commences within the first 24 hours after invasion. Different types of interferon are produced depending upon the site of infection and the cells affected. If fibroblasts are among the infected cells, interferon-b is produced. If the site of infection is populated by leukocytes or if the virus spreads to the blood or lymphoid tissue, interferon-a is produced. Finally, if T lymphocytes...

Components of the immune system and their functional assessment

Lipids may be involved in immunity in several ways. The role of some glycosphingolipids in cell-surface antigens is discussed later in Section 4.4.2. The following deals only with the contributions of dietary lipids. Because of their importance as a source of dietary energy, triacylglycerols may contribute to the enhancement of immune function in malnourished individuals. Individual lipids, including some fat-soluble vitamins and different types of fatty acids, play more specific roles through their contribution to membrane structure and integrity (Section 6.5), their metabolism to eicosanoids (Section 2.4), their participation in processes of lipid peroxidation (Box 4.3), or their influence on gene expression (Section 5.3). The immune system has evolved to protect the body from constant attack by infectious organisms and other non-self molecules that could have detrimental effects on the host. It involves complex interactions between different types of cells, which produce substances...

Components of the Immune System

The immune system comprtses several kinds ot lymphocytes as well as cells of the monocyte macrophage lineage, dendritic cells, and NK cells. Lymphocytes, with their specific surface receptors, are the key to immunologic specificity Any given 1 or B lymphocyte possesses receptors with specificity for a particular epitope. When T or B lymphocytes bind antigen they respond by dividing to form an expanded clone of cells (clonal expansion) The B lymphocytes differentiate into plasma cells, which secrete specific antibody. The T lymphocytes secrete soluble factors known as lymphokines or interleukins, which are representatives of a large family of hormones, known generically as cytokines, that modulate the activities of other cells involved in the immune response. Some of the T and B cells revert to long-lived small lymphocytes responsible for immunologic metnoiy. Whereas antibodies and the receptors on B cells recognize epitopes on foreign antigens in their native conformation, T-cell...

Rationale for Immune Response and the

The second edition of Immune Response and the Eye was originally conceived to be an update to the first edition, which was published in 1999 and was edited by the late J. Wayne Streilein. At the time of his death, Wayne had set into motion plans to update the first edition and to introduce exciting new developments in the field of ocular immunology to the readers of this book. He recognized the enormous number of advances that had occurred since the publication of the previous edition and it was with great enthusiasm that he enlisted the authors of this edition to prepare their respective chapters. His untimely death in 2004 not only put this project on hold but robbed the world of a remarkable mentor, scientist, and role model. It has been a bittersweet experience for us to resume what Wayne started and to try to mold this edition of Immune Response and the Eye into a fitting tribute to his vision. We have attempted to retain the original roster of authors. It is noteworthy that,...

Pathology caused by the cellmediated immune response

The mere expression of a cell-mediated immune response involves some degree of inflammation, lymphocyte infiltration, macrophage accumulation and activation and can therefore by itself cause pathological changes. This type of response predominates in the pathogenesis of tuberculosis, with mononuclear cell infiltration, degeneration of parasitised macrophages, and the formation of giant cells as central features. In chronic mycobacterial infection, the continuous release of microbial antigens leads to a chronic inflammatory response and the formation of granulomas. This particular pathological feature is also associated with a range of other chronic microbial and parasitic diseases including bacterial (leprosy and syphilis), chlamydial (lymphogranuloma inguinale), and fungal (coccidiomycosis) infections. One human virus infection in which a cell-mediated immune response appears to contribute greatly to the pathology of the disease is measles. This is evidenced by the fact that children...

Immune System

The immune system is an integrated system of organs, tissues, cells, and cell by-products (such as antibodies) that differentiates self from non-self and neutralizes potentially pathogenic organisms or substances. The body defends itself against foreign proteins and infectious microorganisms by means of a complex dual system that depends on

The Immune System

Immunity or resistance to infection derives from the activity and intact functioning of two tightly interrelated systems, the innate immune system and the adaptive immune system. Elements of the innate or natural immune system include exterior defenses, such as skin and mucous membranes phagocytic leukocytes and serum proteins, which act nonspecifically and quickly against microbial invaders. Microbes that escape the onslaught of cells and molecules of the innate immune system face destruction by T cells and B cells of the adaptive immune system. Activation of the adaptive immune system results in the generation of antibodies and cells that specifically target the inducing organism or foreign molecule. Unlike the innate system, adaptive or acquired immune responses develop gradually but exhibit memory. Therefore, repeat exposure to the same infectious agent results in improved resistance mediated by the specific aspects of the adaptive immune system. Work ing together, elements of the...

Immunotherapy

The goal of immunotherapy is to overcome the deficits of the host or the tumor itself and activate an effective immune response to the tumor. In the case of virus-associated malignancies, immunotherapeutic strategies can be either prophylactic (prevention of infection or prevention of tumor outgrowth in already infected individuals) or therapeutic (targeting the immune response against viral proteins expressed in tumor cells). In both applications, CTLs are regarded as the most important effector arm of the immune response against tumor or virus-infected cells, and they may be activated in vivo or ex vivo (Fig. 2). In vivo approaches such as vaccination aim to evoke an immune response by administration of an immunogen such as a peptide or DNA directly into patient. In the ex vivo approach, CTLs are activated and expanded in vitro, in a culture environment conducive to CTL growth, and then adoptively transferred into a recipient. A tumor cell may fail to activate an effective immune...

Immune Surveillance

Innate immunity provides effective first-line immune responses against invading pathogens and consists of NK cells, dendritic cells (DCs), mast cells, macrophages, and natural IgM antibody-producing B cells 17 . Cells involved in innate immunity recognize conserved glycolipid or glycoprotein patterns rather than individual specific cell surface determinants to distinguish between self and non-self. Recent studies have demonstrated that the innate immune system has the capacity to discriminate between malignant cells and normal cells suggesting that innate immunity mediates tumor immune surveillance. Abnormal glycolipids and glycoproteins are frequently synthesized and expressed on the tumor cell surface, and many of these structures elicit strong IgM production by CD5+ B cells of the innate immune system. Tumor-reactive IgM antibodies that recognize abnormal carbohydrates expressed by mutated epithelial cells have been identified and isolated in patients with gastric cancer 18 . These...

Cancer Immunotherapy

Cancer immunotherapies fight against billions of tumor cells in a dynamic process that involves downregulation of tumor major histocompatibility complex (MHC) and or TAA, selection of resistant tumor clones, and other mechanisms of escape as well as local systemic immunodepression (6). Moreover, TAA are frequently also expressed in nontransformed cells. Thus, the immune system is likely to have developed some degree of tolerance toward TAA. Furthermore, nearly all preventive vaccines developed for infectious diseases are effective in that they induce an antibody response, unfit to target TAA mostly expressed intracellularly, which rely on the induction of antigen-specific cytotoxic T lymphocytes (CTL). Finally, alum, the adjuvant commonly included in commercial vaccines, is unable to support CTL generation (7). Peculiar to antigens recognized by CTL is that they are produced inside the cells, then physiologically degraded in peptidic fragments ( epitopes) and presented on cell...

Antigens And Their Receptors

An important characteristic of the immune system is that the cells are able to distinguish between those molecules that are normally present in the body, i.e. self and those that are not, i.e. non-self. This is a vital distinction. The term non-self may mean a foreign invader such as a microorganism or a protein expressed on a cell in an abnormal way. This chapter is designed to introduce you to the terms used to describe those substances which stimulate an immune response - immunogens. It will discuss those characteristics which make a molecule a good immunogen and will distinguish between an immunogen and an antigen - a molecule or group of molecules which bind specific receptors but may not alone induce an immune response. We will look at an important group of self-antigens, which are coded for by genes of the major histocompatibility complex. In addition, we will examine the structure and function of those molecules on cells that are capable of recognising antigens. An immunogen...

Generation of antigen receptor diversity

The effectiveness of the specific immune response is dependent in part on its ability to develop memory, allowing a rapid response upon subsequent exposure to antigen. However, the real key is the ability of the specific immune response to distinguish between different antigenic epitopes. The immune system is exposed to an enormous variety of antigens in the form of infectious agents or chemicals and must be able to respond to such a challenge. However, the number of genes required to code for every possible antigenic determinant would be enormous. Thus, logically, a balance is required. Since it is important that the immune system does not react to self-antigens, the range of possible antibody specificities (the antibody repertoire) must be great enough to prevent extensive cross-reactivity between self-antigens and those on infectious agents but small enough that there is space for the genetic material required. This logic must also be extended to the T cell antigen receptor where...

Which of the following statements is TRUE

(a) An antigen can interact specifically with the immune system but requires other stimuli in order to initiate an immune response. (b) An antigen is any molecule or group of molecules, which can induce an immune response. (d) An immunogen can interact specifically with the immune system but cannot itself stimulate an immune response.

The mucosae and their role in immunity

The mucosal immune system is constantly exposed to antigens (derived from food or the normal microbial flora) to which an immune response would be inappropriate. However, its structure is such that these antigens are usually not exposed to the systemic immune system. In addition, a state of unresponsiveness or tolerance to such antigens may prevail. This may be due to antigen being presented by dendritic cells that lack the necessary co-stimulatory molecules, resulting in tolerance rather than immunity. In addition, antigens presented by epithelial cells appear to preferentially stimulate CD8 + T cells, which have been implicated in down-regulating immune responses to mucosal antigens.

Mechanisms of tolerance induction

The theory of clonal deletion was proposed first by Burnett to explain the lack of self-reactivity in the immune system. This suggested that all cells bearing receptors which recognise self-antigen were destroyed, thus preventing the development of an autoimmune response. Death usually results from the induction of apoptosis (often referred to as cellular suicide or programmed cell death) in the self-reactive cells.

Contact hypersensitivity

Contact hypersensitivity is a cutaneous reaction involving the dendritic cells of the skin - Langerhans cells. Contact allergens bind to particular amino acids on proteins. Thus, the allergen (which normally alone may not stimulate an immune response) becomes a hapten on a carrier protein. This hapten is then seen by the immune system as an antigenic determinant on the larger protein. Langerhans cells are able to process these haptenated proteins and present antigen to T cells in the local cutaneous lymph nodes. Once activated, the T cells produce cytokines and chemokines that encourage the migration and activation of local macrophages initiating a local, cutaneous inflammatory response. Critical in the induction and initiation of the response are IL-12 (from Langerhans cells) and IL-4, IL-10 and IFNg (from T cells).

Autoimmunity and autoimmune diseases

Autoimmunity, as opposed to autoimmune disease, is vital to the development of a normal immune response. As we discussed previously, T cells recognise antigen only in association with self-MHC molecules they will not respond if the antigen is presented by foreign MHC molecules, thus confirming that the reaction involves specific recognition of self molecules. This is an example of autoimmunity which is productive. A further example is the recognition of self-idiotypes by anti-idiotypic antibodies, which is essential for the diversification and regulation of immune responses. Apart from these instances, the immune system does not normally react to itself, i.e. it is tolerant to self. Self-tolerance occurs early in foetal development and is vital for health and the normal functioning of the immune response its breakdown resulting in autoimmune disease which may be debilitating or even fatal. How can such autoimmunity develop One suggestion is that an antigen may be hidden from the...

Immunodeficiency diseases

This section concerns those diseases which directly affect the normal functioning of the immune system. Immunodeficiency diseases were first described in the 1950s when the use of antibiotics and passive immunisation increased the survival of individuals with recurrent infections. Immunodeficiency diseases (IDs) are characterised by infections caused by organisms, which are easily overcome and eliminated in healthy persons. In addition, individuals with immunodeficiency diseases tend to contract infections very easily, have aggressive disease and respond poorly to therapy. The diseases can be broadly segregated into primary and acquired. Individuals are born with primary immunodeficiency diseases either as a result of genetic or developmental abnormalities. Acquired immunodeficiencies are those which result from infection or clinical treatment (iatrogenic immunodeficiency), e.g. damage to the immune system as a result of radiotherapy for cancer.

Severe combined immunodeficiency disease SCID

Due to the T cell abnormality, shortly after birth affected babies may develop disseminated yeast infections (usually caused by Monilia spp.), severe pneumonia (caused by Pneumocystis carinii) and recurrent infections caused by other opportunistic pathogens (organisms which, in healthy individuals, are normally prevented from causing disease by the immune system). Since these infections usually affect the skin and the pulmonary and gastrointestinal tracts, their prevalence in patients with SCID suggests that the defect also affects the immune mechanisms normally involved in surface and mucosal immunity. Since both the cell-mediated and humoral systems are affected, patients may die as a result of infection with common viruses such as varicella, herpes and cytomegalovirus. In addition, affected children often have chronic diarrhoea and malabsorption of nutrients from the gut, resulting in a failure to thrive. In ADA-deficient individuals, adenosine and dAdo accumulate intra-cellularly...

Iatrogenic immunodeficiencies

Infection may indirectly cause proliferation of potentially harmful bacteria or fungi by altering the intestinal flora of the host part of the innate immune system Autoimmune diseases may cause alterations in the haemopoietic system, producing anaemia, granulocytopenia, thrombocytopenia or immune deficiency

Infection Immunity Immunopathogenesis

Having discussed how both the innate and specific immune responses develop, we will now examine how they act to prevent or overcome infection. Every day we are exposed to an enormous number of bacteria, viruses, fungi and parasites. However, most of us are usually quite healthy. Relatively few of these organisms cause infection but when they do so, they may cause tissue damage in the host. If these organisms are allowed to grow unchecked, they will cause the death of the host either directly or indirectly. However, most infections do not have such a terminal outcome and in people who are generally healthy, infection is usually confined and any tissue damage easily repaired. This ''damage limitation'' is brought about by the cellular and chemical components of the immune system acting together to limit the spread of the infection, kill the microorganisms, and repair the tissue damage. The ability of different organisms to cause disease (their pathogenicity) varies greatly and is...

Bone marrow transplantation

The immune system of most recipients must be destroyed in order to prevent rejection of the marrow and to allow the development of a new haemapoietic system. This is achieved by treating with cyclophosphamide (50-60 mg kg, for 2 or 4 days) and by total body irradiation (7.5-15 Gy administered over 3-5 days a single dose of radiation would damage the lungs and eyes). This combination of therapies eliminates the immune system and has an anti-neoplastic effect in most cancer patients. Obviously, patients undergoing bone marrow transplantation to combat severe combined immunodeficiency disease do not require this treatment since they lack a functioning immune system.

Female reproductive immunology

Half the chromosome complement of the foetus is derived from the father and molecules encoded by paternal genes theoretically could be recognised as foreign by the maternal immune system. Importantly, the maternal and foetal immune systems coexist for a period of time and so the potential exists for either to reject the other. However, the mother and foetus appear to have a symbiotic relationship. This mutual state of tolerance is critical for a healthy delivery. Several mechanisms exist that may explain this mutual acceptance. Foetal tissues may lack MHC Class I antigens (trophoblast cells) or express non-classical members of this family (extravillous trophoblast cells), the maternal immune system may be non-specifically suppressed, blocking antibodies may be produced and or complement regulatory protein expression may be altered. The first exposure of the female to paternal antigens (that may be expressed by the foetus) occurs after sexual intercourse. Although sperm bear foreign...

Recurrent spontaneous abortion

The minor histocompatibility antigens TA1 and TLX appear to be important in preventing recognition of foetally expressed paternal antigens. If these antigens are not matched in the male and female, the pregnant female may recognise the paternal TLX as foreign thereby being stimulated to produce an immune response. This may result in the production of an antibody that prevents a response to the foreign TA1, thus preventing rejection. If mates are matched for TLX, the maternal immune system cannot recognise the paternal TLX antigen and antibody, which prevents a response to TA1 will not be produced. Thus, an immune response to TA1, may occur leading to rejection of the foetus. Since the male immune system is not exposed to antigens from the female during intercourse, any immunological abnormalities affecting the male reproductive system are likely to be autoimmune. Autoimmune recognition of sperm antigens is frequently reported in infertile couples and in individuals who have undergone...

Spermspecific antigens

Since tolerisation to spermatozoa does not normally occur, vasectomy may lead to exposure of the immune system to sperm-associated antigens and the development of autoimmune disease. An association has been demonstrated between the expression of HLA-A28 and the development of anti-sperm antibodies in vasectomised men. These antibodies have been shown to form circulating immune complexes which, in monkeys, have been implicated in the rapid onset of atherosclerosis.

Immune complex formation

Red Blood Cells And Immune Complexes

Immune complexes that localise in the kidney glomeruli can activate complement and induce an inflammatory response. This results in poly-morphonuclear leukocyte infiltration, glomerular basement membrane swelling, and albumin and red blood cells in the urine. This acute glomerulonephritis may be seen mainly in children as a post-infection complication with Streptococcus spp. When the immune system has eliminated the infection, immune complexes are no longer formed and any pathological changes are usually reversed, leading to complete recovery. However, repeated infection or the persistent deposition of complexes leads to irreversible damage. This happens in certain persistent infections in which microbial

Maternalfoetal exchange

Syncytial trophoblast cells are continuously released from the placenta and from the 18th week of gestation, can be found circulating in the mother's blood. This may allow recognition of foetal antigens by the mother's immune system and may protect the mother from the extensive and otherwise unchecked growth and invasion of the trophoblast, as occurs in choriocarcinoma. 7.2.4 Effect of pregnancy on the maternal immune response

Classification of immunodeficiency diseases

Immunodeficiency diseases fall into two principal categories - primary and acquired. The causes of primary immunodeficiency diseases may be congenital (due to developmental or genetic abnormalities occurring during pregnancy) or genetic (due to the inheritance of an abnormal gene from one or both parents Table 5.11). Acquired immunodeficiency disease may result from exposure to chemicals, drugs, irradiation or microorganisms. In recent years, AIDS (the acquired immune deficiency syndrome) has received much attention, but other acquired diseases are becoming more common due to the use of chemo- and radiotherapy. These are known as iatrogenic immunodeficiencies, i.e. acquired as a result of treatment for another clinical condition. The resulting diseases may be classified according to which part of the immune system is affected, i.e. B cells, T cells, B and T cells, phagocytes, complement or a combination of these.

Which of the following statements concerning the immunology of male reproduction is Incorrect

(a) Since the male immune system is not exposed to antigens from the female during intercourse, any immunological abnormalities affecting the male reproductive system are likely to be autoimmune. (b) Immune responses to sperm antigens are frequently reported in infertile couples. (c) Individuals who have undergone vasectomy often demonstrate anti-sperm antigen immune responses.

THE bloodtestis barrier

During development, the male immune system may not be tolerised to sperm-specific antigens due to the fact that they are sequestered behind a blood-testis barrier. However, this same barrier may be effective enough to prevent subsequent development of autoimmune diseases affecting the sperm or testicular cells by maintaining a partition between the spermatozoa and the host immune system. Unfortunately, evidence exists to suggest that this barrier is not totally exclusive since some sperm-specific antigens have been detected in the seminiferous tubules. Reaction to these antigens may be prevented in a number of ways, e.g. suppressor cells, non-specific suppressive mechanisms, lack of antigen presentation and lack of lymphocyte trafficking through the testes.

Cytolysis

1.1.4 Cells involved in the specific immune response Most of us are aware that the immune system works by recognising unusual molecules that are not usually found in the body (i.e. they are non-self). These chemicals may be complex (in the form of microorganisms) or simple (such as minor changes in molecules usually present in the body - altered-self). This ability to discriminate between what are sometimes very small differences in chemical structure is a property of the specific or adaptive immune response and is dependent upon the activity of a particular group of cells, the lymphocytes. Many molecules in the immune system interact with other molecules known as receptors. This ligand-receptor interaction is often likened to the interaction between a lock and key. The key for any particular lock is shaped intricately so that it fits that one lock and no other. However, master keys may fit many different locks because they share the important common features with the different keys...

Lymphocyte memory

Generally, the rapidity of secondary responses is a reflection, in part, of an increase in the number of antigen-specific precursor cells. However, this precursor frequency must be carefully regulated in order to limit the response to that required to eliminate a pathogen without causing incidental damage to the host. In order to understand how this regulation works, we must consider the cellular responses that occur during a primary immune response. Briefly, antigen localises in the lymphoid tissues (particularly in the paracortex of the lymph nodes and the periarteriolar lymphocyte sheaths of the spleen) where T and B cell primary responses are initiated. Naive lymphocytes recirculate through these areas and upon recognition of antigen, the reactive cells are stimulated by lymphokines and rapidly proliferate in situ. The level of proliferation is dependent upon the concentration of antigen and the affinity of the receptors on the responding cells. Having acquired specific effector...