Immunotherapy Ebook

Immunity Crisis

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! Continue reading...

Immunity Crisis Summary


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Clinical examples of free radical antioxidant and immune function interactions

Examples of immune dysfunction associated with increased oxidative stress exemplify the interactions between the immune system and the oxidant anti-oxidant status of the individual. Rheumatoid arthritis (RA), an autoimmune disease of unknown cause, is characterized by a chronic inappropriate immune response in articular joints, resulting in inflammation and destruction of joint tissues. At some point, the initial insult and inflammation becomes a chronic process. Infiltration of the fluid-filled joint space (synovium) with inflammatory neutrophils occurs and structural changes appear in the synovium, forming an inflamed layer called a pannus. Oxidative products reduce the viscosity of the synovial fluid, thus hindering joint movement further. The cumulative effects of free radical damage throughout the lifespan are seen in the pigmented age spots of the elderly, which are a consequence of lipid oxidation. The overall increased oxidative stress associated with aging also adversely...

Cytokines In Immune Response To Infections

As discoveries and comprehension of cytokine biology continue to increase, the complexity of the cytokine network has become overwhelming. Despite the complexity of cytokine activity, it is important to appreciate the role of the interplay of the cytokines with their various target cells in the immune response to an inflammatory agent. The immune response during the early stages will either eradicate the infectious agent or set the stage for the type of chronic immune response. When the control mechanism for the type of cytokine response is dysfunctional, the result may be the development of a chronic or progressive infection rather than eradication or containment of the infectious agent, e.g., the development of miliary tuberculosis, lepromatous leprosy, visceral leishmaniasis, and sepsis. The host's genetic background is also a factor in the development of chronic inflammatory response and pathology. Autoimmune diseases result from perturbation of the immune system either...

Antibodydependent immunotherapy

The capacity to use antibodies for immunotherapy has been reported by a number of groups, and provides a very flexible and specific approach. This approach has been used in a wide spectrum of diseases, in transplantation and cancer, as well as autoimmunity. One of the virtues of antibody-mediated therapy is its molecular specificity, which, unlike the case with organic chemical drugs, is precisely known. Thus, cross-reactions can be readily monitored and therapeutic trials offer insight into pathophysiology. Subsequent developments have altered the structure of murine antibodies so that they more closely resemble human antibodies in order to reduce immunogenicity. Replacement of the Fc and hinge regions leads to 'chimeric' antibodies, retaining the murine Fv, and more recently only the murine hyper-variable regions have been 'grafted' on to a human Ig backbone, forming 'humanized' antibodies. With the generation of transgenic mice with a considerable part of the functional human Ig...

The Cost of the Immune System Autoimmunity and Transplant Rejection

The complexity of the immune system undoubtedly reflects its great survival value. Microbial invaders and their toxins are rapidly neutralized and destroyed, using flexible combinations of antibody, phagocytosis, and T cellmediated killing of cells supporting the growth of viruses or other intracellular pathogens. Although the immune system uses thousands of genes and many different cell types, this is a small price for immediate, short-term and long-term defences that can deal with any external threat, as long as it can be recognized as nonself. In nature, there is generally little pressure for economy of genes or cells. There are two much more important prices for having a good immune system. First, the protection against infectious disease given by the immune system makes transplantation between unrelated individuals impossible without the use of immunosuppressive drugs. Second, in a few individuals, the immune system turns its attack to the host. Paroxysmal cold haemoglobinuria is...

Effect of Specific Medicinal Herbs on Immune System and Immune Cells

Systematic studies on the effect of specific medicinal herbs on immune system are designed to obtain evidence-based scientific knowledge on the appropriate use of traditional medicinal herbs. The development of immunology has resulted in further complexity by combining external (environment and pathogens) and internal (neuroendocrine-immune system) factors in the pathogenesis of infectious diseases. The most important thing is to learn how to modulate the immune response to external conditions with powerful new techniques and drugs. Immunopharmacol-ogy is still a young science, and the molecular complexity of the immune system is not yet fully understood. Nevertheless, along with Metchnikoff, we can say, we therefore have the right to hope that in the future, medicine will find more than one way to bring phagocytes into play for the benefit of health 1-3 . Traditional herbal medicine provides several remedies for strengthening the body's resistance to illness through effects on immune...

Immune Responses To Reaassociated Bacteria

There are at least two important properties of the principal ReA-associated infections which have implications for the immune response directed against them. First, these organisms are first encountered at mucosal surfaces. Second, the organisms are either obligate or facultative intracellular parasites, so that the organism may be compelled to alter its antigenic structure in order to survive intracellularly. A. Mucosal Immune Responses to ReA-Associated Bacteria In view of our lack of knowledge of the role of mucosal T cells in the normal immune response to ReA-associated pathogens, it is idle to speculate how this might be abnormal in B27+ individuals. In the HLA-B27 transgenic rat, B27 need only be present on bone marrow-derived cells, immunocytes, and not on the enterocytes (35). Therefore, in this model, it is less likely that B27 plays its role by affecting antigen presentation to intraepithelial lymphocytes. Likewise, since neither y8 T cells nor intraepithelial CD8+ cells...

Hsp 60 In Autoimmune Responses

According to the molecular mimicry theory (2,3), it is possible that antibodies and or T lymphocytes made in the immune response to a specific epitope found on a component of the pathogen may also bind to a structurally similar host determinant, thereby leading to autoimmune damage. This mimicry may be due to the presence of a common epitope in homologous proteins, such as the host and pathogen members of the hsp 60 family. Because of their high degree of homology across the broad stretches of phylogeny and their ubiquity, heat shock proteins represent a logical protein family in which to seek examples of molecular mimicry. As previously reviewed (4), it has been hypothesized that molecular mimicry between host and pathogen heat shock proteins constitutes an important physiological element of the protective immune response, which for unknown reasons may go awry in some individuals and may contribute to autoimmune disease. Another possibility, presented below, is molecular mimicry...

Effects of Antioxidant Deficiency on Immune Function

One of the most obvious factors that could reduce antioxidant status is a dietary deficiency. Jacob et al. (1991) examined the effects of marginal vitamin C deficiency on immune and other parameters in healthy males. Serum, white blood cell and sperm vitamin C levels were significantly reduced when the daily diet contained 5, 10 or 20 mg of vitamin C for 2 months. DTH responses to seven antigens were also significantly depressed during the period of low vitamin C intake. In fact, when subjects initially consumed 250 mg day-1 of vitamin C, they responded to 3.3 out of seven antigens, which were reduced to less than one antigen after only 1 month at 5 mg day-1 of vitamin C. Even when intakes were increased back to 250 mg day-1 for 1 month, the average number of DTH responses did not increase above one out of seven antigens. The robustness of the responses (i.e. the diameter of the induration) was 35 mm at baseline, dropped to 11 mm when vitamin C intakes were 5, 10 or 20 mg for 2 months...

The Immune System An Overview

When considered in the broadest sense as the process whereby organisms maintain functional and organizational integrity against foreign encroachment, immunity is clearly a prerequisite to life itself. Given this, it is not surprising that even the simplest of organisms demonstrate immune functioning, which is consistent with the notion that immunity arose early in the evolution of life on earth (Maier and Watkins 1998). In vertebrates, the immune system has evolved a wide array of separate, but cooperative, mechanisms that serve to attack invading pathogens, destroy tumor cells, and remove and repair damaged tissue. From an evolutionary perspective, the high rate of autoimmune disorders, such as multiple sclerosis and rheumatoid arthritis, suggests that the adaptive advantages of robust immune system functioning outweigh the frequently disastrous consequences engendered when the immune system overreacts and begins attacking the self (Nesse and Williams 1994). The immune system review...

Interaction of the Nervous System and the Immune System

In the past, little interaction was thought to occur between the nervous system and the immune system. However, recent studies demonstrate that there are ways in which the nervous system and the immune system communicate with each other. The placebo effects observed in people with MS and other diseases may be examples of this process. The field of study that examines immune system-nervous system interactions has been termed psychoneuroimmunology. The brain may communicate with the immune system in many different ways. The brain influences the production of hormones, which then may affect the function of the immune system. In addition, nerve fibers have connections with immune organs. The chemical messengers used by the nervous and immune systems appear to be involved in cross-communication. Nerve cells communicate with each other by releasing chemicals known as neurotransmitters, whereas immune cells communicate with each other by secreting different chemicals, known as cytokines....

Pathophysiology of Immune Response

The immune system (the cells and the molecules responsible for immunity) is defined as part of the host's defence against destructive forces either from outside the body (e.g., bacteria, viruses and parasites) or from within (e.g., malignant and autoreactive cells). Innate (natural) immune defences are those components of the immune system (macrophages, monocytes and neu-trophils) that function without relying on prior exposure to a particular antigen. They are the early phases of the host defence that protect the organism during the 4-5 days it takes for lymphocytes to become activated. Adaptive or acquired immune responses develop over the lifetime of a human being in response to environmental challenges (pathogens or antigens). Lymphocytes are the primary cells of the aquired immune system. The T lymphocytes can both modulate the function of other immune cells and directly destroy cells infected with intracellular pathogens. During development, each T cell generates a unique...

Activated B Cells May Bridge the Innate and Adaptive Immune System

The cross-talk between the innate and adaptive immune systems in general as well as in rheumatoid arthritis has regained significant attention (Corr and Firestein 2002) with the one-way concept of activation of the adaptive by the innate path less likely. In this regard, there is a general perception of three stages in the course of rheumatoid arthritis disease initiation, perpetuation and a terminal destructive process (Corr and Firestein 2002 Firestein and Zvaifler 2002 Kouskoff et al. 1996 Mangialaio et al. 1999). However, the distinct role of antigen-specific lymphocytes remains a matter of debate. Recent concepts (Mangialaio et al. 1999) repostulated that the initiation of RA may be antigen-independent by involving joint constituents. Secondly, the inflammatory phase appears to be driven by specific antigens either foreign or native and either integral to the joint or presented in the periphery. In the third stage, however, destruction of the synovium seems to be again...

Aging Decreases Humoral Immune Responses

In humans, aging affects antibody production both quantitatively and qualitatively with reduced serum concentrations of antigen-specific immunoglobulin (Ig), antibody specificity, affinity and CSR (Frasca et al., 2008a Frasca et al., 2008b). There are decreased numbers of total B cells (Chong et al., 2005 Shi et al., 2005 Frasca et al., 2008a) as well as, specifically, switch memory B cells in aged individuals (Frasca et al., 2008a). Antibodies made by B lymphocytes prevent colonization by pathogens and provide immunity against invading pathogens. In the elderly and in patients with weakened immune systems, vaccines and therapeutic agents are likely to be not as effective because the number of functional B lymphocytes are fewer and Ig levels are reduced compared to healthy people. The changes in the humoral immune response during aging significantly contribute to the increased susceptibility of the elderly to infectious diseases and reduced response to vaccination (Gardner et al.,...

Modulation of mCRPs for Immunotherapy

Since mCRPs can prevent efficient complement activation, inhibit complement-mediated killing mechanisms such as CDC, ADCC, CR3-DCC, and also down-regulate effector T cell responses, it is therefore hypothesized that blockade or neutralizing mCRPs would significantly improve anti-tumor mAb-based tumor immunotherapy or vaccine-mediated anti-tumor immune responses. These strategies include neutralizing mAbs against mCRPs, small interfering RNAs or anti-sense oligos to knockdown mCRPs, utilization of chemotherapeutic drugs or cytokines to downregulate mCRPs, and a recently proposed new approach for suppression of expression of membrane-bound complement regulator (mCR) genes. RNA interference (RNAi) can be induced by synthetic siRNA or by vector-driven expression of shRNA. Vectors are usually delivered by viruses resulting in incorporation of the vector into the host genome and a long-term gene silencing. However, this induces unwanted immune response and possible toxic effects. In...

Heat Shock Proteins And The Adaptive Immune System

Heat shock proteins (HSP) are highly conserved proteins induced in response to cellular stress, such as heat shock or nutrient deprivation (Lindquist and Craig 1988) (Ferm et al. 1992). HSP assist the folding of newly synthesized proteins, participate in protein transport across membranes and refold proteins denatured during cell stress (Jindal et al. 1989). However, HSPs, and in particular, HSP60 interests immunologists because, in addition to serving as a chaperone inside the cell, HSP60 also functions as an antigen in host defense. It was discovered that variants of HSP60 were common bacterial antigens dominant in the immune response to many infectious agents (Young 1992). Later, HSP60 became a subject for autoimmunity research by the finding that a peptide epitope of Mycobacterial HSP60 was recognized by a clone of T cells capable of mediating arthritis in the adjuvant arthritis model (Cohen 1991 van Eden et al. 1988). Soon afterwards, mammalian HSP60 was found to be a target of T...

Modulation and Regulation of Immune Responses

From an epidemiological point of view, very interesting studies argue in favor of the important role of the bacterial environment in the first year of life in order to ensure the good orientation of immune responses preventing the short- and long-term development of atopic diseases (13,101,103,109-111). Recent comparative studies have been conducted in children living in the same allergenic environment but under different life-style conditions, urban and farming environments. Results showed that substantial protection against development of asthma, hay fever, and allergic sensitization was seen only in children exposed to stables, farm raw milk, or both in their first year of life (103). Authors also found that prenatal exposure of women had a substantial protective effect. Clinical trials using probiotics to treat or prevent atopic eczema in infants have also generated arguments suggesting that the infantile intestinal microbiota balance plays an important role in the good...

Endocrine Functions of Adipose Tissue in the Immune System

It is now well recognized that adipose tissue secretes many autocrine, paracrine, and endocrine factors (adipokines) that have wide ranging effects in metabolism including satiety, regulation of energy expenditure and energy storage. However in addition to roles directly related to metabolism, adipokines are also involved in regulation of the following immune function cytokine induction, macrophage activation, neutrophil activation, recruitment of macrophage and T cells to adipose tissue (Lago et al. 2007 Guzik et al. 2006), and inflammatory diseases such as rheumatoid arthritis, osteoarthritis, sepsis, atherosclerosis, insulin resistance and obesity (Lago et al. 2007 Trayhurn and Wood 2004). The list of these adipokines is now extensive and growing every day. Readers are referred to the following detailed reviews (Lago et al. 2007 Bouloumie et al. 2005 Trayhurn and Wood 2004, 2005 Fain 2006). The most recent adipokines identified include examples such as visfatin, apelin, vaspin,...

Humoral Immune Responses

Hypersensitivity reactions occur when the body mounts an excessive immune response to a typically innocuous antigen resulting in tissue damage. Hypersensitiv-ity reactions require a sensitizing exposure so the excessive response does not occur with the initial exposure. There are four classic hypersensitivity reactions. Types I, II, and III occur shortly after reexposure to the antigen and are therefore called Type I reactions occur within seconds or minutes after exposure to the antigen. Antigens that provoke this type of reaction are usually small, soluble proteins capable of eliciting an immune response at low doses (examples pollen, pet dander, penicillin). After the initial exposure to the antigen, Th2 helper cells direct B cells to become IgE producing plasma cells. Monomers of IgE antibody specific to the inciting antigen then bind to FceRI on mast cells with high affinity. Upon reexposure to the antigen the IgE on the mast cell binds to the antigen causing aggregation and...

Effect of Antipsychotic Drugs on the Immune Response in Schizophrenic Patients

Both in vitro and in vivo studies have suggested that effective antipsychotic treatment corrects the imbalance between the cellular and humoral arms of the adaptive immune system 4, 27 . Both haloperidol and clozapine, for example, have been shown to increase the release of IL-2 and IFN from whole blood cultures in vitro, whereas the antidepressant amitriptyline was ineffective 28 . In vivo, IL-18, a cytokine that also originates from activated Th-1 cells, is also increased following effective antipsychotic treatment, while the blunted reaction of patients to a salmonella vaccine challenge is reversed following effective drug treatment. In addition, the Th-3 cells have recently been implicated in correcting the imbalance between the Th-1 and Th-2 arms of the adaptive immune system. The Th-3 cells secrete transforming growth factors (TGF) of which serum TGF-1 has been reported to be elevated in schizophrenia 29 . This suggests that antipsychotic drug-induced changes in the...

Brief Survey Of The Immune System

The immune system plays a crucial role in human health, but one that has two sides. On the one hand, it is absolutely indispensable for protection against pathogens on the other, malfunctions in the immune system can result in serious disease. Earlier sections of this book have mentioned the involvement of the immune system in inflammatory diseases such as arthritis and asthma, and also in autoimmune diseases such as type 1 diabetes (diabetes mellitus) and Addison's disease. As medicine becomes more molecular in character, the cellular and molecular details of immunity must be clarified if truly effective treatments are to be discovered. Human life and health depend on the ability of the immune system to distinguish between self and non-self and selectively to destroy viruses, bacteria, fungi, multicellular parasites, or other foreign invaders. That discrimination involves the sensing of foreign matter by receptors on the surface of various immune cells. Such receptors can detect...

The Physical Examination In Cases Of Suspected Immune Deficiency

The physical examination often provides important evidence for or against immune deficiency and may also allow the physician to assess critically the cumulative morbidity due to infection. Most importantly, the presence or absence of lymphoid tissue should be carefully documented. The absence of visible tonsils in patients who have not had them surgically removed and the absence of palpable cervical or inguinal lymph nodes should promote a strong suspicion of a significant antibody deficiency because the bulk of these tissues is composed of B-lineage lymphoid cells involved in antibody synthesis. Conversely, the presence of palpable lymph nodes and easily visible tonsils essentially excludes Bruton agammaglobulinemia and may suggest the absence of SCID but does not help one way or the other with the diagnosis of CVID or X-linked hyper-IgM syndrome. The presence of cervical or peripheral adenopathy, splenomegaly, or hepatomegaly may suggest HIV, CGD, or other abnormalities. Many...

Primate Nonhuman Immune System

Immune response to pathogens that infect humans. The use of nonhuman primates in such studies is largely due to the similarity between their immune systems and that of their human counterparts. In particular, the lymphocyte markers, major histocompatibility complex (MHC) molecules, and T cell receptors (TCRs) of Old World primates and great apes are very similar to those of humans. In this entry we will describe several animal models of human diseases and the similarities between the immune systems, MHC genes and TCR genes of nonhuman primates and humans.

Effects of Mercury on the Immune System

The internal damage caused by mercury exposure is not limited to the nervous system. The immune system can also suffer severe injury.64 Like the nervous system, the immune system is highly complex and involves many elements, including cellular components, cytokines, special hormones, and antibodies. It is also important to remember that the immune and nervous systems are intimately connected, both directly and indirectly, a connection that is especially important during development. Low levels of mercury have several significant effects on the immune system. For example, one study involving eighty-one males occupationally exposed to mercury vapor, as compared to thirty-six controls, found that mercury stimulated T-lymphocytes including T-helper and T-suppressor cells in the exposed workers.65 In another study of forty-four workers exposed to mercury vapor, the majority with levels below the accepted toxicity limit of 50 ug gram of creatinine, demonstrated increased levels of several...

Abnormalities Of The Immune System

The purpose of this chapter is to introduce you to a range of conditions, which may be described as abnormalities of the immune system. When an antigen is introduced into an individual, the immune response recognises it as foreign and eliminates the invader in the most appropriate way, i.e. it limits any potential spread and destroys the antigen efficiently. The response is controlled such that only those mechanisms required are brought into play and there is little resulting tissue damage. However, in certain individuals the response to particular antigens may result in extensive tissue damage. It is accompanied by a massive inflammatory response, which results in the signs and symptoms that are classified as hypersensitivity. Some people refer to this type of response as uncontrolled or harmful, but these are misnomers. It may be that in certain cases, e.g. in an infectious disease, the hypersensitivity response is vital to preventing the spread of the agent. Although tissue damage...

Pregnancy And The Altered Immune Response

It is well documented that there are significant changes in immune function during normal pregnancy. Many immunologically based diseases improve or deteriorate dramatically during pregnancy. Specific examples include the disease flares that frequently characterize ulcerative colitis, rheumatoid arthritis, and multiple sclerosis in pregnant patients. Thus, many researchers have suggested that the cause of PPCM lies in a similar immunologic disturbance. It has been postulated that the maternal immune system forms antibodies to the myometrium, placenta, or fetus that cross-react with myocardial antigens. Some patients with PPCM develop antibodies to smooth muscle and actin. However, there is little direct evidence for an autoimmune etiology of PPCM. A novel speculation on the causation of PPCM is the migration into the maternal myocardium of fetal stem cells, which provoke maternal autoantibodies that induce an autoimmune myocarditis. This theory postulates that fetal cells cross the...

Key Characteristics Of The Immune System

The innate immune system also acts to recruit antigen-specific immune responses, not only by attracting cells of the immune system to the site of the infection, but also through the uptake of antigen by dendritic cells that transport antigen to lymphoid tissue where primary immune responses are initiated. Dendritic cells also produce cytokines that can regulate the quality of the immune response so that it is most appropriate to combating the pathogen. Primary immune responses are initiated when a foreign antigenic substance interacts with antigen-specific lymphocytes under appropriate circumstances. The response generally consists of the production of antibody molecules specific for the antigenic determinants of the immunogen and of the expansion and differentiation of antigen-specific helper and effector T-lymphocytes. The latter include cells that produce cytokines and killer T cells, capable of lysing infected cells. Generally, the combination of the innate immune response and the...

Immune responses of the host

Yersiniosis elicits both humoral and cell-mediated immune responses in the host. It appears that most of the antibody response is directed toward the lipopolysaccharide. Follow-up studies have, however, demonstrated that patients with Yersinia infection produce antibodies directed towards a multitude of antigenic determinants, both plasmid and chromo-somally encoded ones. The antibodies often persist for several months and in the case of postinfection complications even years. As yersiniosis is fairly common in some parts of the world it is thus not surprising that, for example in northern Europe, the sera of 10-30 of healthy blood donors indicate previous Y. enterocolitica or Y. pseudotuberculosis infection. A remarkable feature of Yersinia infection is that it may pass quite unnoticed. This is illustrated by occasional severe reactions upon transfusion of blood, the donor of which, unaware of it, has carried Yersinia in the blood. During preservation at refrigerator temperature the...

Arthropathies Associated With Cancer Immunotherapy

The immunotherapy of malignancy utilises the hosts immune system to destroy neoplastic cells. Polyarthritis may evolve or reappear as a result of this therapy. In a report of 3 patients receiving IL-2 immunotherapy for metastatic melanoma and renal-cell carcinoma, 2 patients developed a clinical picture resembling rheumatoid arthritis. A third patient, who had a remote history of Reiters syndrome, developed symmetric oligoarthritis 67 . The authors postulated induction of an autoimmune arthritis via an IL-2 induced T-cell mechanism, based on the inflammatory histologic findings, elevated levels of rheumatoid factor, positive antinuclear antibodies and positive HLA-DR4 genotype. Patients receiving IL-2 also developed spondiloarthritis with peripheral involvement and psoriatic arthritis 68 . The arthritis was self-limited, with improvement when immunotherapy was stopped but could be reproducibly induced by successive treatment cycles. HLA typing of these patients showed the presence of...

Stress and the Immune System

Physical and psychosocial stressors have been shown to compromise immune function (Ader et al., 1991 Kielcolt-Glaser and Glaser, 1995). The immune suppressive effects of stress may be more pronounced in individuals that already have limited immune competence, such as infants, individuals with a predisposition to autoimmune disease, and the elderly (Kielcolt-Glaser and Glaser, 1995). An individual's response to a stressor is manifested in physiological, hormonal, behavioral, and immunological changes. These stress-induced responses are initiated by the hypothalamus and translated into action by the hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic nervous system. Products from these two systems (e.g., corticoid hormones and catecholamines) can directly modulate the activity of various immune effector cells (Ader et al., 1991). Stress has a bidirectional effect on the immune system depending on whether it is acute or chronic. Acute stress enhances antigen-specific...

The Immune System

The nervous system is not the only system in the body that talks to other systems and to itself. Many parts of the body communicate with each other. This is especially true for the immune system, which is responsible for destroying foreign substances such as viruses and bacteria. Most people know about the immune system because they are familiar with the acquired immunodeficiency syndrome (AIDS), in which a virus attacks the immune system and makes it inactive. In MS the picture is different in that the immune system appears to be too active. It sends out messengers in the form of specific types of white blood cells that attack myelin as if it were a foreign substance. The immune system is made up of many different cells that function to protect the body. These cells are made and stored in different parts of the body and make a large number of immunomod-ulating substances. The combinations of cells and substances that may be formed are essentially unlimited, which adds to the...

The Immune Response

The immune system evolved to discriminate self from nonself. Innate, or natural, immunity is broadly reactive, does not require priming, and is of relatively low affinity. Adaptive, or learned, immunity is antigen-specific, depends upon antigen exposure or priming, and can be of very high affinity. The two arms of immunity work closely together, with the innate immune system being more active early in an immune response and adaptive immunity becoming progressively dominant over time. The major effectors of innate immunity are complement, granulocytes, monocytes macrophages, natural killer cells, mast cells, and basophils. The major effectors of adaptive immunity are B and T lymphocytes. B lymphocytes make antibodies T lymphocytes function as helper, cytolytic, and regulatory (suppressor) cells. These cells are important in the normal immune response to infection and tumors but also mediate transplant rejection and autoimmunity. Immunoglobulins (antibodies) on the B lymphocyte surface...

Immune System

The immune system is the body's defense against biological systems that would harm it. The most obvious of these consist of infectious agents, such as viruses or bacteria. Also included are neoplastic cells, which give rise to cancerous tissue. The immune system produces immunoglobin, a substance consisting of proteins bound to carbohydrates. This material functions as antibodies against immunogen or antigen macromolecules of polysaccharides, nucleic acids, or proteins characteristic of invasive foreign virus, bacteria, or other biological materials. The cells that the immune system uses to provide protection are called leukocytes. The immune system response to toxicants is called immunogenesis and can occur in several ways. Immunosuppression occurs when the body's natural defense mechanisms are impaired by agents such as toxicants. Radiation and drugs such as chemotherapeutic agents, anticonvulsants, and corticosteroids can have immunosuppressive effects. Immunosuppressants are...

Antioxidant Defences Following Infection and Injury

Although pro-inflammatory cytokines are essential for the normal operation of the immune system, they play a major damaging role in many inflammatory diseases, such as rheumatoid arthritis, inflammatory bowel disease, asthma, psoriasis and multiple sclerosis, and in cancer (Tracey and Cerami, 1993 Grimble, 1996). They are also thought to be important in the development of atheromatous plaques in cardiovascular disease (Ross, 1993). In conditions such as cerebral malaria, meningitis and sepsis, they are produced in excessive amounts and are an important factor in increased mortality (Tracey and Cerami, 1993). Clearly, in these diseases, the cytokines are being produced in the wrong biological context. In malaria, tuberculosis, sepsis, cancer, HIV infection and rheumatoid arthritis, inflammatory cytokines bring about a loss of lean tissue, which is associated with depleted tissue GSH content and an increased output of nitrogenous and sulphur-containing excretion products in the urine...

Effector mechanisms of Thmediated immunity

Th1 cells appear to be critical in effecting an antigen-specific phagocytic-mediated defence against microorganisms, principally bacteria, fungi and some parasites. If, however, Thl-biased immunity is directed against self-antigens, extensive tissue destruction and autoimmune disease may ensue. Common autoimmune diseases resulting from inappropriate Th1 responses include autoimmune haemolytic anaemia, autoimmune thrombocytopenic purpura, Goodpasture's syndrome, type I insulin-dependent diabetes mellitus, rheumatoid arthritis and multiple sclerosis. Disease may also ensue if a Thl-biased immune response is inappropriately directed against innocuous antigens, such as occurs in coeliac disease. The effector mechanisms of Thl-biased immune responses include activation of macrophages that have phagocytosed microorganisms normally resistant to lysosomal destruction. Thl cytokines direct isotype switching of B-cells towards IgG production. In mice, Thl cytokines promote secretion of the...

Adhesion molecules and disease

The in vivo relevance of adhesion molecules in the immune response has also been demonstrated experimentally in a variety of ways. Altered expression and or function of adhesion molecules has been noted in various disease states. The functional relevance of these findings has been demonstrated by in vivo blocking studies using antibodies specific for adhesion molecules, soluble adhesion receptors, blocking peptides or carbohydrates, and antisense oligonucleotides. Thus, targeting of adhesion molecules with these reagents has been shown to be effective in many different animal models of human disease, including models of ischemia reperfusion injury, acute inflammation, allograft rejection during organ transplantation and various chronic inflammatory disorders such as rheumatoid arthritis. In most of these studies, the primary focus has been on blocking or modulating leukocyte or lymphocyte attachment to endothelial cells. Modulation of adhesion molecule expression has also been shown...

Biological actions and possible physiological roles

Immune system Most annexins are localized intracellularly, particularly in the cytosol. However, various stimuli including increased intracellular Ca2+ are known to translocate annexins to plasma membranes and other subcellular vesicles including chromaffin granules. Glycosylation and acylation of annexins is thought to be important for such insertion and or attachment to membranes. Some annexins are known to be extracellularly released. Autoantibodies against annexins in patients with rheumatoid arthritis and systemic lupus erythematosus (SLE) neutralize these annexins, thereby augmenting inflammatory responses in these diseases. Similar observations have been extended to inflammatory diseases such as asthma, psoriasis, and ulcerative colitis. Among these diseases, SLE may involve dysfunction of suppressor T cells in the immune system. During immunoglobulin E (IgE) synthesis in vitro annexin I enhances suppressor function by inhibiting the glycosylation of IgE-binding factor.

Natural and diseaseassociated lymphocytespecific antibodies

Specific antibodies in human immunodeficiency virus (HIV) infection is associated with increased risk for developing acquired immune deficiency syndrome (AIDS). Such antibodies may have been produced as a result of an immune response against lymphocyte-bound HIV determinants (such as gp41) and may directly cause the lymphopenia in AIDS patients. Autoantibodies to CD4, found in some HIV patients, do not however appear to have a prognostic significance. Autoantibodies to the GM3 ganglioside on AIDS patients' lymphocytes have been detected which do not bind to normal GM3.

Methods of experimentally inducing autoimmunity

Tomy of 3-week-old Wistar rats followed by repeated low-dose irradiation. In a similar vein, Nishizuka and colleagues made the observation that thyroiditis spontaneously developed in mice following thymectomy alone, provided that this was carried out in the neonatal period. The autoimmune basis of these conditions was evident from the presence of infiltrating lymphocytes in the target tissue, circulating tissue-specific autoantibodies and the ability to transfer the disease to naive recipients with lymphocytes from affected animals. From 1975 onwards a number of other manipulations and treatments involving the immune system were shown to induce organ-specific autoimmune disease in rodents. A feature of all these procedures is either a deficiency of circulating T lymphocytes or their functional impairment as, for example, by a reduction in the range of the T cell receptor (TCR) repertoire. The spectrum of autoimmune diseases induced by this means is now impressive and includes...

Modulating factors in autoimmune disease

Immune responses in general are not only regulated by mechanisms intrinsic to the immune system, but also by endocrine and neuroendocrine signals. It has Hormones involved in stress responses, such as glucocorticoids, catecholamines, endogenous opiates and most of the anterior pituitary hormones, have strong effects on specific and natural immune functions. It is well known that acute or chronic stress can exacerbate certain autoimmune diseases in humans. Chemical sympathectomy (by means of 6-OH-dopamine) has been shown to influence the course of experimental autoimmune disease in animals. Obese strain chickens were found to have enhanced plasma levels of corticoid-binding globulin leading to a diminished availability of free glucocorticoids. Early in vivo supplementation with free corticosterone prevented the onset of thyroiditis. Further to this, obese strain chickens were shown to have a central defect in the responsiveness of the hypothalamo-pituitary-adrenal axis to signals of...

Intervention in autoimmunity

Immune system rather than control the specific autoimmune response. More rational approaches to ther apy are now beginning to emerge based upon, for example, oral or nasal tolerance induction, the use of cytokine antagonists, and intervention using peptide-based therapeutics to directly block T cell activation. See also Adhesion molecules Autoantigens Autoimmune diseases Cytokines Idiotype network Oral tolerance Privileged sites T cell vaccination Tolerance, peripheral Tolerance, central Immunotherapy of autoimmune diseases Relative risk.

Functions of H2 class II molecules

Study of the class II molecules of the mouse MHC has provided a great deal of the current information on the functional roles played by class II molecules in the immune system. Genetic manipulations which are feasible in defined inbred mouse strains have allowed investigators to examine in great detail how class II molecules regulate responses to antigen. The advent of transgenic and knockout mouse technology in more recent years has created additional opportunities for studying the roles of class II molecules, in both immune system development and function. Following the development of inbred, genetically defined strains of rodents, it was observed that the allelic forms of class II molecules expressed by an animal determine its responsiveness to certain soluble antigens. In fact, it was this property of mouse class II genes which was the basis for their early designation as immune response (lr) genes. However, it was not until decades later that details of how class II molecules...

Breakdown of autotolerance

The ability to tolerate autologous antigens, a central feature of the adaptive immune system, is guaranteed in redundant ways at the level of both the B and T lymphocyte system. It is thought to be the result of negative selection within the central lymphoid organs, i.e. bone marrow and thymus, where sensitive stages of developing B (slgM1 slgD ) or T (CD44 CD 8' ) cell clones are eliminated by apoptosis due to high-affinity binding to autologous antigens. Autoreactive cell clones that escape these central selection processes for whatever reason are effectively controlled in their reactivity in the periphery, either passively by virtue of insufficient costimu-latory signals or by active suppressive immunoregulation. These peripheral mechanisms are not specific for autoantigens, but are identical to those that induce tolerance against any given foreign antigen. With regard to autoimmunity the interest has focused primarily on T lymphocytes, because of the central regulatory role of T...

Potential physiological roles of IL15

The presence of IL-15 mRNA in many normal tissues and the increased production of IL-15 by macrophages monocytes in response to bacterial or viral products suggests a role for IL-15 in protective immune responses, allograft rejection, and the pathogenesis of autoimmune diseases. Recently, a possible role for IL-15 in the pathogenesis of rheumatoid arthritis has been suggested. IL-15 is present in the synovial fluid of rheumatoid arthritis patients where it might contribute to recruitment of T cells and provide a means of stimulating T cells to produce macrophage-activating cytokines such as IFN-y. tumor necrosis factor a (TNFa) and granulocyte-macrophage colony-stimulating factor (GM-CSF). Studies of IL-2 and IL-2Ra knockout mice have revealed that IL-2 provides an immunoregulatory role in the immune system that cannot be compensated for by IL-15 or other cytokines. Comparative studies using the IL-2, IL-2Ra, and IL-2R 3 knockout mice are likely to reveal defects in the IL-2R 3...

Other laboratory and clinical features

The growth of LGLs appears to be under the regulation of various cytokines, in particular IL-2. Early studies demonstrated that high concentrations of IL-2, in the absence of other stimuli such as antigens or mitogens, can stimulate the proliferation of LGLs but not T lymphocytes. Moreover, LGLs propagated in the presence of IL-2 retain potent cytolytic activity. The capacity of LGLs to respond directly to IL-2 is probably due to the high level of expression of the II.-2 receptor (3 chain. In addition to IL-2, interferon y is also capable of stimulating the growth of LGLs. These observations, combined with the fact that LGLs themselves can secrete cytokines, suggest that LGLs are important players in the cytokine network of the immune system. killer (LAK) cells in vitro. LAK cells, propagated primarily from LGLs NK cells isolated from peripheral blood, contain more cytoplasmic granules and display a broader range of cytotoxicity against tumor cells than do their precursor LGLs....

Intervention by maternal antibodies

The maternal immune status deeply influences the immune capacity of the newborn, both by passive transfer of immunity and by priming of the developing immune system. The use of vaccination of pregnant women to protect the child is already much used and will be developed to encompass more pathogens in the future. A more specific approach to detection of disease and to specific therapy in antibody-mediated diseases of the newborn will follow the unraveling of the mysteries of self tolerance. Recognition of precipitating factors and manipulation of the immune system by See also Anemia, autoimmune hemolytic in human Idiopathic thrombocytopenic purpura Idiotype network IgG Insulin-dependent diabetes mellitus, human Neuromuscular junction autoimmunity Neonatal immune response Ontogeny of the immune response Rh antigens Rheumatoid arthritis, human Rheumatological disorders Sj grens syndrome Systemic lupus erythematosus (SLE), human Thyroid autoimmunity, human.

Hostpathogen interactions

As shown in animal models of mycoplasma infections, phagocytes which amass in infected tissue comprise the first line of defense against these organisms. However, in the absence of specific antibodies, mycoplasmas can survive neutrophil phagocytosis. This may be one of the mechanisms by which dissemination into unusual sites and persistence occurs in hypogammaglobulinemic patients. Interestingly, in vitro mycoplasmas can modulate class II major histocompatibility complex (MHC) expression by macrophages. Whether this influences the antigen-presenting function of these cells during an actual infection is still unclear. The fact that patients with hypogammaglobulinemia are more frequently colonized with mycoplasmas and ureaplasmas than persons with an intact immune system, and the finding that a significant fraction of those patients also suffer from mycoplasmal septic arthritis strongly suggest that antibodies protect the host from these bacteria. Secretory immunoglobulin A (IgA)...

Role of T cells in autoimmune disease

A further group of regulatory T cells (natural killer T cells - NKT) are a minor subpopulation which play a key role in regulating the immune response through the rapid production of IL-4 and IFNg. These cells have been shown to be deficient in persons with autoimmune, Type I diabetes. They are able to recognise lipid antigens in association with CD1 and respond by proliferation and the release of IL-4, IFNg and IL-10, promoting a Th2-type response and abrogating the autoreactive T cell response.

Pathogenesisinvolvement in disease

Whereas animal retroviruses have been known for a long time to cause a variety of diseases, including benign and malignant neoplasms, anemias, wasting syndromes, neurological disease and immunodeficiency states, the role of retroviruses as human pathogens has only been substantiated during the last 15 years. HTLV-I is etiologically associated with adult T cell leukemia (ATL) and tropical spastic paraparesis (see below). Although HTLV-II was originally isolated from patients with a T cell variant of hairy cell leukemia, its role in human disease has not been established. The two human lentiviruses HIV-1 and HIV-2 cause the acquired immune deficiency syndrome (AIDS). Foamy or spuma retroviruses are commonly found in several simian species, chimpanzees, cats, cattle and hamsters. There is no known association with disease in these animals. Infection of humans can occur through contact with animals Many other species also contain lentiviruses. A wasting disease in sheep with some features...

Immune abnormalities Autoantibodies

Reacting with self and exogenous antigens. On the contrary, rheumatoid factors isolated from rheumatoid arthritis patients are often of high affinity for their target. B cells that express high-affinity rheumatoid factors are very effective in presenting immune complexed antigens to T cells, contributing therefore to the generation of a specific secondary immune response that may be part of the etiopathogenesis of the disease. Proinflammatory cytokine family Interleukin 1 (IL-1) is mainly produced by activated macrophages in response to inflammatory stimuli. IL-1 has both systemic and localized effects on the immune system. For its role in septic shock and as a pyrogen, it is considered as the endogenous pyrogen. At inflammatory sites, it induces T and B cell activation and proliferation, and release of proteolytic and chemo-tactic substances from macrophages, and has a stimulatory effect on osteoclasts, with consequent cartilage reabsorption. Immunomodulatory cytokines TFNy is a...

Endothelial cells and the airway

See also Acquired immune deficiency syndrome (AIDS) Apoptosis Autoimmune diseases Autoimmunity Bacteria, immunity to Cytokine assays Cytokine genes, regulation of Cytokine receptors, soluble Cytokine receptors Cytotoxicity, mechanisms of Endotoxin (lipopolysaccharide (LPS)) Fas (CD95) and fas iigand Graft rejection Immunopathol-ogy insulin-dependent diabetes mellitus, animal models Insulin-dependent diabetes mellitus, human Macrophage activation Malaria Mixed lymphocyte reaction (MLR) Rheumatoid arthritis, animal models Rheumatoid arthritis, human Schistosomiasis Septic shock Superantigens Transplantation Lym-photoxin TNF receptors Tumors, immune response to.

Mechanisms controlling autoimmunity

Cell Bypass Theory

Because pathogenic autoimmunity is the exception rather than the rule, mechanisms must exist which normally prevent the development of autoimmune disease. In this respect the immune system is able to distinguish self from nonself and, ultimately, becomes 'tolerant' towards most self antigens. However, as alluded to above, many of the tolerance mechanisms controlling autoimmunity may be less concerned with repression of all self reactive lymphocytes than with preventing the development of pathogenic T cells and autoantibodies. Indeed, there is evidence from studies in transgenic mice to suggest that, in situations in which high-affinity antiself B cells are anergized, low-affinity antiself B cells escape this tolerization process. The danger model of immune responses proposes that, rather than discriminating self from nonself, the immune system primarily distinguishes between harmless and harmful. In this scenario, self would normally be considered harmless and would fail to Although...

Stress proteins as target antigens

Heat shock proteins have been shown to be among the dominant antigens recognized by both the regulatory (helper T lymphocytes) and effector (B lymphocytes and cytotoxic T cells (CTLs)) arms of the adaptive immune system for a variety of pathogenic infections and experimentally induced immune reactions.

Ankylosing spondylitis

If there is crossreactivity between HLA antigens and bacteria, then infection by such microorganisms will lead to the production of antibodies, which will have both antimicrobial as well as anti-self or autoimmune activity. Only a small proportion of the subset of the antimicrobial antibodies will also have anti-self or autoimmune activity. Those bacterial antigens carrying the shared sequences will be immunogenic, especially around the edges of the shared sequence, because it is at these sites that the immune system will not recognize that it is dealing with a self antigen. When present in sufficient quantities, such antibodies might activate the complement cascade and cause cytotoxic death with consequent stimulation of the inflammatory cascades, which will eventually result in localized tissue damage. There is thus no breakdown of tolerance and the evocation of bacterial antibodies having also anti-self or autoimmune activity is part of the normal immune response when encountering...

Probiotics and the control of immune dysfunctions

The immune system plays an essential role in the regulation of inflammatory-type diseases, and consequently a dysfunction of the immune system can lead to exacerbation of disease. Due to their potential for immune regulation, it has been suggested that probiotics offer potential for the alleviation of several immuno-inflammatory diseases. Perhaps most attention has been given to the ability of probiotics to regulate allergic atopic responses. In animal studies, L. casei Shirota has been shown to reduce cutaneous anaphylaxis in allergen-sensitized mice following dermal challenge (Yasui et al., 1999a). Both L. casei Shirota and L. plantarum L-137 have been shown to exhibit anti-allergy properties in mice, reportedly due to their ability to induce high-level systemic expression of IL-12 (Murosaki et al., 1998 Kato et al., 1999), which can down-regulate allergic responses. Indeed, some strains of lactobacilli have been shown to elevate systemic levels of IL-12 following oral delivery...

Type III hypersensitivity

Antibodies binding to equivalent amounts of soluble antigens give rise to immune complex formation. The antigens involved in inducing the pathogenic immune response can be either foreign or self, and the antibodies either IgG or IgM. When complexes are formed, they usually activate complement and then bind to C3b receptors on erythrocytes. The erythrocytes are then responsible for removing complexes from the plasma and transporting them to the sinusoids of the liver and spleen, where they are removed by macrophages. However, if immune complexes are formed in great excess of antigen, or if the complex is very small and soluble, the reticuloendothelial system will not be able to degrade them efficiently. These complexes will circulate in the blood and subsequently deposit in various tissues of the body, inducing local inflammation. The resulting pathogenic features depend on the sites of immune complex deposition.

Perinatal Estrogen Exposure Diethylstilbestrol

Estrogenic steroids exert regulatory actions on immune function in adult animals that are well documented but not well understood mechanistically. Autoimmune disease may be caused, at least in part, by endogenous estrogen, as has been observed with increased serum estradiol levels (e.g., during pregnancy) and infections resulting from depression of cell-mediated immunity (Hamilton and Hellstrom 1977 Mathur et al. 1979). Pharmacologic or suprapharmacologic levels of steroidal and nonsteroidal estrogenic compounds have been shown to further result in numerous alterations of immune function, particularly when administered perinatally during lym-phoid organ organogenesis. Effects of such administration in rodents include myelotoxicity (Fried et al. 1974 Boorman et al. 1980), suppression of cell-mediated immunity (Kalland et al. 1978 Ways and Bern 1979), significant thymic atrophy (Greenman et al. 1977 Aboussaouira et al. 1991), suppression of natural killer (NK) cell activity (Seaman et...

Immunodeficiency and radiation sensitivity

Certain types of severe combined immune deficiency (SCID) are characterized by an inability of lymphocytes to rearrange TCR and Ig genes due to a functional loss of a recombinase. There is an increased sensitivity of these lymphocytes to the killing effects of radiation. Two protein subunits, called Ku proteins (originally identified as a nuclear antigen in certain autoimmune diseases) mediate the rearrangement of Ig and TCR genes by binding to a 350 kDa protein (catalytic subunit) which functions as a DNA-protein kinase. This DNA-protein kinase activity is absent in SCID mice and in some forms of human SCID. The radiation sensitivity of SCID cells is corrected by transfecting the DNA-protein kinase catalytic subunit, thus implicating this pathway in both Ig TCR rearrangement and radiation sensitivity. Additional immunodeficient states such as Wegener's syndrome in humans, and the syndrome of 'wasted' mice are associated with radiation sensitivity. Studies of these abnormalities are...

Selective immunosuppression

Tolerance in its classical definition depends on knowing the antigenic epitopes to be recognized, and hence a major drawback of studies in human and experimental autoimmunity is our lack of understanding of the important epitopes. Nevertheless there are a variety of experimental approaches which are finding their way into human application, at least to the clinical trial stage. A major objective is to ensure that in established disease, with an ongoing immune response, the therapeutic strategy does not potentiate rather than suppress the immune response. Peptides given systematically, without adjuvant, are of low immunogenicity and are being developed for therapy. Trials of myelin basic protein (MBP) peptides, based on the 89-102 immunodominant region, are in progress, with different variants being run by Neurocrine Inc. and Immunologic. Neurocrinc's trial involves using peptide derivatives known as 'altered peptide ligands', which upon binding to TCR do not elicit a complete immune...

Consequences of autoimmunity

Autoimmunity is defined as an immune response leading to reaction with self antigen, i.e. any molecule that is a normal body constituent of the animal mounting the response. Self reactivity can arise either through the triggering of receptors directly by autoantigen or by virtue of cross-reaction between foreign and self antigens. Topographic similarity of B cell epitopes or sequence homologies of linear T cell epitopes may lead to such cross-reactions and it is highly unlikely that the immune system is able to recognize all foreign antigens specifically without some recognition of self epitopes also occurring. Techniques such as polyclonal activation of cells with mitogens, and the establishment of lymphocyte clones and hybridomas, have established that self reactive T and B lymphocytes are frequently found in individuals who lack readily detectable autoantibodies in their serum. Indeed, at least some degree of self reactivity appears to be a normal physiological phenomenon during...

Superantigens in disease

The potent immunostimulating properties of SAgs have recently been exploited for immunotherapy of cancer. Recombinant fusion proteins between tumor reactive monoclonal antibody fragments and SAgs mutated to reduce MHC class II binding have been used successfully to treat experimental tumors. Such

Group A streptococcus

Several immunologic diseases result from infection with S. pyogenes, the group A streptococcus. Acute glomerulonephritis, characterized by hematuria, proteinuria, hypertension and edema, may appear 6-14 days after infection caused by a limited number of group A streptococcal serotypes. Attack rates are related to the magnitude of the immune response, with high levels of antibodies to streptococcal cell membrane antigens being found in the serum of affected patients. Electron microscopic demon

Diagnosis and clinical characteristics

Gene confirms the diagnosis of X-linked hyper- gM. Patients with X-linked hyper-IgM have been found to produce specific antibodies in response to vaccination, but the antibodies are restricted to the IgM isotype. Patients lack germinal centers in their lymph nodes and do not exhibit memory responses to repeated immunizations. Because the genetic defect is not lethal to T cells, carriers have random inacti-vation of the X chromosome in their T cells. As few as 30 of the carriers' CD4 T cells may express normal CD40L with no apparent effect on immune function (Figure 1).

Aberrant humoral responses

The immediate-type reaction, in contrast to delayed-type hypersensitivity, is always a humoral immune response. In an organism sensitized by a given allergen, a new contact with the allergen will lead to an immediate reaction. The localization of the allergen by specific antibodies of the IgE class (reagin) on to mast cells leads to the activation of the mast cells. The resulting degranulation of the mast cells releases mediators such as histamine, serotonin, heparin and proteolytic enzymes. The result is an immediate inflammation reaction which may range from a local skin reaction to a potentially lethal anaphylactic shock.

Acute parvovirus B19 infection in humans

Parvovirus B19 diseases arise either from direct viral toxicity for specific target cells or as a result of the host immune response (Table 1). Direct viral infection leads to destruction of marrow erythroid cells in normal individuals, but cessation of red cell production is short-lived due to rapid immune clearance of virus, and the long lifespan of erythrocytes precludes the development of anemia.

Dysregulation of the Fas FasL apoptotic pathway and pathological consequences

Natural mutations in the Fas and Fas ligand genes have provided insight into the role of these molecules in the immune system. As noted earlier, the autosomal recessive genes lpr (lymphoproliferation) and gld (generalized lymphoproliferative disease) are spontaneously derived mutations in mice that result in the development of progressive lymphadenopathy and splenomegaly. Mice homozygous for the lpr gene express very little Fas due to a mutation that interferes with expression of the full-length Fas protein. The phenotype of gld gld mice results from a point mutation in the FasL gene that alters the ability of the translated protein to bind to its cognate receptor. Fas. Both mutant mouse strains have a phenotype characterized by hypergammaglobulinemia, autoantibody production, glomerulonephritis, arthritis and vasculitis. Significantly, a functional human equivalent of the lpr lpr mouse exists. Children with autoimmune lymphoproliferative syndrome (ALPS) have a phenotype that is very...

Free radicals and immune cell function

In addition to DTH responses, an index of oxidative damage to sperm DNA was also measured these levels were significantly increased when vitamin C intakes were low. This carefully controlled study clearly demonstrated the importance of the balance between anti-oxidant status, oxidant levels and immune response. The study is especially noteworthy since all other dietary anti-oxidants, such as vitamin E and 3-carotene, were provided throughout the study at recommended daily allowance (RDA) levels.

Nonhuman primates as animal models for human disease

Primates arc widely used as models for studying HIV infection of humans. Although HIV does not infect all of the different species of nonhuman primates, it does infect chimpanzees. Thus far, however, there are few documented cases of chimpanzees succumbing to HIV-induced pathogenesis despite several chimpanzees having been infected for over 10 years with the virus. Therefore, combined with their endangered status, the use of chimpanzees is hardly practical for the study of HIV infection in humans. SIV infection of the rhesus macaque (Macaca mulatto), however, has proved to be a very effective animal model for studying HIV pathogenesis in humans. Due to the nucleotide sequence similarity between HIV and SIV and the similar course of disease progression between humans and rhesus macaques, SIV infection in rhesus macaques is widely-used as an animal model of HIV infection in humans. More importantly, the immune systems of humans and rhesus monkeys have been found to bind and present...

Historical and physiological background

Thomas Addison reported in the mid-1800s on a series of patients who had succumbed to a disease -later named after him - associated with degeneration of the adrenal glands. Foreshadowing a relation between the adrenal cortex and the immune system, he noted that the blood of one patient 'had a considerable excess of white corpuscles'. By the early 1900s patients with Addisons disease, as well as adrenalectomized animals, were known to suffer from low blood glucose and salt loss. These effects were traced in the 1930s to two distinct hormones from the adrenal cortex, each essential for life glucocorticoids, which influenced blood glucose and mineralocorticoids, which regulated salt balance. The vital role of mineralocorticoids was well explained by their effects on salt balance, but that of glucocorticoids could not be accounted for by effects on glucose, and remained obscure for many years. By 1940 it was known that glucocorticoids exert numerous other actions, in particular on lymphoid

Adjuvant Arthritis

Adjuvant arthritis (AA) is a disease induced in rats by immunization with killed Mycobacterium tuberculosis (MT) organisms in oil, a substance known as complete Freund's adjuvant. The work of C.M. Pearson and his colleagues in the 1950s and 1960s helped establish AA as a standard model of chronic inflammation produced by immunological processes. Two opposing theories were put forth to explain the pathogenesis of AA the first proposed that the joints were damaged as bystanders to an immune response directed to MT antigens disseminated to the sites of inflammation the second proposed that AA was caused by an autoimmune attack against a cross-reactive self antigen. Despite the uncertainty of its pathogenesis, AA has served for many years as a reliable and convenient model for testing treatments for inflammation.

The future

Although AA has been a familiar laboratory model for decades, we are only now appreciating the charm of its complexity and the value of the secrets it can reveal about health, autoimmunity and the immunology of the host-parasite interaction. As we might have guessed from the constellation of elements affecting its induction, the development of AA is an outward expression of the subleties of immune regulation. Health or disease is not the mere outcome of response or nonresponse. The immune system can respond to MT and to the hsp65 hsp60 molecules in many ways and it is the nature of this response that determines health or disease. 'The nature of this response' is a conceptual handle of the black box of immunological regulation. Present research is attempting to open the box to reveal the clockwork of the system.


In terms of the immune response of the host, it is becoming increasingly apparent that the cellular response to cross-reactive antigens may play a more significant role in the observed pathological damage Finally, the specific mechanisms operating in the interaction between host genetic factors and environment resulting in the induction of autoimmune disease of the heart is still not clear. In rheumatic fever there appears to be a marker called D8 17 which is inherited in an autosomal fashion and is preferentially increased in the B cells of rheumatic fever patients. However it is well-known that not all strains of group A streptococci cause rheumatic fever, even in the genetically susceptible individual. The most plausible explanation for this discrepancy is that only certain strains exhibit the epitopes that activate the immune system to produce tissue cross-reactive antibodies and activated T cells. Then, only in the context of the immune response (a heightened response, break in...

Rantes 103

Specific immune response 1, 2 cells involved in 13-18 in infection 223-36 phagocytes 178-9 tumours 292-3 sperm antigens 259, 265, 266 spleen 24, 130, 131 macrophages 11 SR-A 88, 276 SR-AI 88 SR-AII 88 SR-B 88 Src family 54 Staphylococcus spp. 216 Staphylococcus aureus 87, 235 stem cell factor 7 stem cells 2-3 Streptococcus spp. 227, 228


Immunological tolerance is a state of unresponsiveness to a challenge, which would have been expected to elicit measurable immunity. Self tolerance refers to immunological unresponsiveness towards one's own self antigens. Deletion or inactivation of T- or B-cell clones whose antigen receptors recognize self-antigen (tolerance induction) often occurs during lymphocyte maturation in primary lymphoid tissues. Some self-reactive clones exist in the periphery, implying that tolerance to self-antigens can be induced by peripheral mechanisms. Operational tolerance can merely reflect sequestration of self-antigens, such that they are not accessible to the immune system (e.g., lens crystallin in the eye). Tolerance is broken (more appropriately, immune responses develop) when the sequestered antigens are exposed to the immune system. Loss of self-tolerance leads to autoimmunity. The spectrum of autoimmune diseases range from organ specific (e.g., Hashimoto's thyroiditis) through diseases...

Clinical aspects

IL-2 has been used in AIDS (acquired immune deficiency syndrome) patients as an immunostimula-tory agent able to limit the effects of CD4 depletion. After IL-2 injection and under some clinical conditions, IL-2 treatment is followed by an increase of the CD4 count without affecting the viral load. See also Interleukin 2 receptor Interleukin 4 Interleukin 7 and its receptor Interleukin 9 and its receptor Interleukin 15 and its receptor Tumors, immune response to.

Human Ir genes

A number of studies have demonstrated HLA associations with the immune response to different antigens. While it is more difficult to formally demonstrate Ir genes in humans, it is clear that the human MHC gene products function in an analogous manner to the mouse. One example where Ir gene effects in humans most likely play a role is the association of HLA alleles with autoimmune diseases such as Perhaps the most striking and relevant example of Ir gene effects in humans is the demonstration by Hill and colleagues that the HLA-B*530I allele controls the binding of a particular peptide from the liver stage-specific antigen of the malarial parasite, Plasmodium falciparum, thus making B*53()l an immune response gene for this peptide antigen. Most importantly, this peptide represents a critical cytotoxic T lymphocyte epitope and the B'53()l allele (which is present at greatly increased frequencies in West African populations) confers a high degree of resistance to malaria. Thus, immune...

The hsp65 connection

The immune response to hsp65 is not exclusive to arthritis. It appears that inflammatory exudates outside of the joints, pleural effusions for example, are also rich in T cells responsive to hsp65. Moreover, immunization of some strains of mice with hsp65 or hsp60 has been found to induce diabetes mellitus. The epitope of hsp60 associated with diabetes differs from the 180-188 epitope associated with arthritis. Nevertheless, it is clear that hsp65 immunity is not limited to the inflammation of immunological arthritis. In fact, immunity to hsp65 is not necessarily associated with immunopathology the T cells of healthy humans respond very well to hsp65 and even to self hsp 60. Moreover, hsp65 is a dominant antigen in the immune response to infection or vaccination with Mycobacteria or other bacteria.

Should We Worry About Selenium Deficiency

The body's immune system naturally makes free radicals that can help destroy invading organisms and damaged tissue, but that can also harm healthy tissue. Selenium, as an antioxidant, may help control levels of free radicals and help to relieve symptoms of arthritis. Selenium deficiency is commonly associated with HIV or AIDS, and has been associated with a high risk of death from this disease. Researchers believe that selenium may be important in HIV disease because of its role in the immune system and as an antioxidant. Today scientists are actively investigating the role of selenium in HIV or AIDS, and see a need for clinical trials that evaluate the effect of selenium supplementation on HIV disease progression.

Dietary Changes and Nutrients That Can Help

It is best to avoid foods that trigger allergic reactions. In addition, a rotation diet, in which the same food families are eaten only once every four days, may reduce the chances of future allergies developing. Avoiding an allergenic food for six months to a year sometimes allows the immune system to recover and not react to the problem food, as long as it is not consumed too often.

Use in Prevention and Therapy

Selenium has anticancer properties, possibly through its effects on the immune system or its antioxidant actions (Fig. 3.16). Regions of the USA with the highest intakes of selenium tend to have lower rates of cancer,8,9 and higher blood levels of selenium are associated with lower risk of cancer.8,9 Supplementation in older men can reduce risk of lung, colon, and prostate cancer by nearly 50 .9

Avoiding mineral deficiency

1 Zinc An adequate supply of zinc is vital for making testosterone and healthy sperm. Men who don't get enough zinc may be temporarily infertile. Zinc deprivation can make you lose your appetite and your ability to taste food. It may also weaken your immune system, increasing your risk of infections. Wounds heal more slowly when you don't get enough zinc. That includes the tissue damage caused by working out. In plain language If you don't get the zinc you need, your charley horse may linger longer. And, yes, zinc may fight the symptoms of the common cold. To date, several studies have confirmed that sucking on lozenges containing one form of zinc (zinc gluconate) shortens a cold by a day or two. Others show no differences. Your choice. l Zinc Moderately high doses of zinc (up to 25 milligrams a day) may slow your body's absorption of copper. Doses 27 to 37 times the RDA (11 mg males 8 mg females) may interfere with your immune function and make you more susceptible to infection, the...

Etiology and pathogenesis

The pathogenesis of ulcerative colitis is unknown. A widely accepted hypothesis suggests that, in the genetically susceptible individual, a combination of host and environmental factors leads to the initiation and perpetuation of an abnormal intestinal immune response, resulting in ulcerative colitis.16 In support of this theory, colitis in animals occurs in a wide variety of genetically altered rodents, including knockout mice for interleukin (IL)-2, IL-10 and T-cell receptor and HLA-B27 transgenic rats.17 Interestingly, most of these animal models do not develop colitis in Current evidence suggests that colitis results when the intestinal mucosal immune system in patients with inflammatory bowel disease reacts inappropriately to intestinal bacteria. Evidence supporting this hypothesis includes the fact that most animal models of colitis do not develop disease in germ-free environments, the reports of efficacy of antibiotics in the treatment of colitis and pouchitis, and the seasonal...

Fatvital Yes But Less Is Enough

Triglycerides can be made of saturated or unsaturated fat in fact more than ninety-five percent of the fat we take in is in the form of triglycerides. That is also the body's stored form of fat and is composed primarily of fatty acids. It gets its name because it is made up of three (tri) fatty acids attached to a glycerol backbone (a small compound related to carbohydrates). Fatty acids have important roles to perform in terms of fat transport and metabolism, immune function, and maintaining the function and integrity of cell membranes. *21 Adipose (fat) tissue helps to hold the body organs and nerves in position and protects against traumatic injury and shock. The layer of fat beneath the skin serves to maintain body temperature. Fats aid in the absorption and transport of the fat-soluble vitamins, A, D, E, and K, as well.*22

Fifteen Steps to Fight the Inflammation Syndrome

Effect of Dietary Supplementation with Black Currant Seed Oil on the Immune Response of Healthy Elderly Subjects. American Journal of Clinical Nutrition 70 (1999) 536-543. Yaqoob, P., et al. Effect of Olive Oil on Immune Function in Middle-Aged Men. American Journal of Clinical Nutrition 67 (1998) 129-135.

Medical Physical and Functional Problems

Many chronic medical conditions, such as osteoporosis, arthritis, depression, and diabetes have nutritional consequences. Loss of body water, lean body mass, and bone mass decline of the immune response over- and underweight malnutrition and declining taste, smell, and thirst are among the problems that affect physical strength, functional ability, and vitality. At times, specialized diets or medical nutrition therapy are needed these are

Food Allergies and Sensitivities

Food sensitivities occur when a component of the diet triggers an allergic reaction or an abnormal, overzealous immune response.1415 Food sensitivities can cause histamine-medi-ated allergic reactions resulting in itching, swelling, and hives. They can also trigger autoimmune reactions, where immune cells activated by exposure to the food component cross-react with and harm the body's own tissues. Sensitivity can develop to foods or food additives and can produce a wide variety of symptoms. Symptoms can be confined to the digestive tract, such as bloating, cramping, diarrhea, or irritable bowel syndrome.1,15 They can also occur in parts of the body far away from the digestive tract, such as the joints (arthritis), skin (swelling and hives) and brain (headache).1,4,15 Symptoms can occur immediately after eating the food, or may be delayed for hours.

Lupus Erythematosus What Is Lupus Erythematosus

No one really understands the cause or causes of lupus. Fever is common at its onset, suggesting that a bacterial or viral infection initiates the immune response (although inadequate vitamin B1 also may cause fever). The hormone estrogen may influence lupus because it is most often diagnosed in women between their late teens and thirties. However, a hormonal link is tempered by the fact that estrogen therapies have not been useful as a treatment. It is conceivable that a woman's immune systems is simply biologically different in some ways from that of a man.

Link Between Genetics And Immunology

To better understand the association between HLA genes and autoimmune diabetes, and specifically the IDDM1 locus, it is important to realize that approximately 40 of the functional genes that have been identified in the class II section of the HLA locus encode for proteins that are involved in the immune response. The MHC is classified into three major sections termed class I, II, and III. Class I and II genes encode for an alpha (a) and beta (p) heterodimers that form the cleft or pocket on antigen-presenting cells (APC), where antigen is bound and presented to T lymphocytes. The amino acid sequences in these pockets are variable (polymorphic), especially for class II molecules, giving them the ability to bind to a wide variety of different peptide antigens. APCs such as macrophages, dendritic cells, activated T cells and B cells, use HLA class II molecules to bind peptides derived from extracellular proteins and specifically present them to T-helper lymphocytes (also termed CD4+ T...

The Anti Inflammation Syndrome Step Avoid or Limit Refined Grains

Some people might argue that whole-wheat bread is far superior to refined white bread. While whole-wheat bread does contain more fiber and a few more vitamins and minerals, it also contains more antinutrients, such as lectins. Lectins, a family of proteins, interfere with the absorption of vitamins and minerals and, in some people, stimulate unneeded immune cell activity. According to Loren Cordain, Ph.D., of Colorado State University at Fort Collins and author of The Paleo Diet, lectins may exacerbate the abnormal immune response at the heart of rheumatoid arthritis.

What Else Might Help

According to Loren Cordain, Ph.D., a researcher at Colorado State University, lectins also might trigger symptoms of rheumatoid arthritis in some people. Lectins are a family of plant proteins found primarily in legumes, but also in wheat and rice. Like gluten, lectins may cause an inflammation of the gut, leading to a more generalized immune response. Temporarily avoiding lectin-containing foods may confirm a sensitivity to them.

Functions and probable functions

One of the most characterized physiological functions of these polyunsaturated fatty acids is the role of eicosanoids. Eicosanoids work as autocrine paracrine hormones and mediate a variety of functions, such as immune response, blood pressure regulation, blood coagulation,33 movement of calcium and other substances into and out of cells, relaxation and contraction of muscles, and cell division and growth.34 The eicosanoids include substances such as prostaglandins and leukotrienes. Arachi-donic acid is the precursor for a group of eicosanoids that include series-2 prostaglandins and series-4 leukotrienes, while EPA is the precursor for a group of eicosanoids that include series-3 prostaglandins and series-5 leukotrienes.28 Eicosanoids derived from ro-6 fatty acids are pro-inflammatory and pro-aggregatory agonists, while those derived from ro-3 fatty acids tend to inhibit platelet aggregation and be anti-inflammatory.3536 Adequate production of the series-3 prostaglandins is thought...

Series Editor Introduction

Age-related blindness is another serious disability that affects millions of seniors globally and the numbers affected will increase as populations age. Both cataract and age-related macular degeneration (AMD) risks have been reduced in individuals whose diets are rich in antioxidants such as vitamins C and E, zinc and carotenoids including beta-carotene, lutein, and zeaxanthin. The development of these diseases, the role of nutrients, including carbohydrates, in prevention of progression, and the lifestyle factors that can increase as well as decrease risk are examined in depth in the next chapter. The elderly are also at risk for loss of certain immune functions such as those linked to fighting infections and responding to vaccinations. The importance of essential micronutrients in maintaining and even enhancing immune responses in the elderly is outlined in the following chapter. The three chapters contain well-organized reviews of the functions of the immune system, the organs and...

Lyme Disease and Rickettsia

It is much more difficult to cure the disease once it has burrowed into tissues and organs. One reason is the phenomenon of stealth bacterial conversion (L-form bacteria), where the bacteria becomes invisible to the body's immune system, as well as to antibiotics. When this occurs, the only way to combat the organism is to give antibiotics over a long period of time, usually more than three months. Even then, some cases remain uncured. As we have seen, elevated glutamate levels in the nervous system can result in widespread damage to neurons and other normal cells. The more intense the immune response, the greater the damage. Yet something worse can occur if the immune system is impaired. While a normal response will end an infection quickly, a prolonged response which is the result of an impaired or unbalanced immune system can produce long-term damage, leading eventually to neurodegeneration.536 This happens because glutamate levels that remain elevated for long periods of time will...

Dynamic Preservation Of Immunologic Tolerance

And subsequently to the 'positive selection' destiny terminating in its differentiation into a mature T cell. The immunoregulatory properties of the peptide are expressed by its ability to influence (by the mechanism previously described) the population of helper and cytotoxic T cells, thereby defining the nature and aim of the immune response. One of the key questions regarding the developmental aspects of the immune system relates to the signaling events which determine the fate of selection of its inherent constituents (positive versus negative selection). Moreover, it is clear that in comparison to an adult animal, the fetus and newborn are highly susceptible to the induction of immunological tolerance.

Scientific Foundations

Arthritis drugs work in different ways. Some drugs target a molecule of the immune system called a cytokine that directly triggers inflammation. These drugs are designed to attach to the molecule. This stops the molecule from stimulating inflammation. One type of arthritis that has benefited from the use of arthritis drugs is rheumatoid arthritis. This form of arthritis occurs when the body's immune system somehow recognizes components of the body as being foreign, and so attempts to dispose of the invader. The body attacks itself. Over time, this increasingly destroys joints.

Cytokines and Obesity

Antibody A molecule created by the immune system in response to the presence of an antigen (a foreign substance or particle). It marks foreign microorganisms in the body for destruction by other immune cells. Antigen A molecule, usually a protein, that the body identifies as foreign and toward which it directs an immune response. Immune system A system in the human body that fights off foreign substances, cells, and tissues in an effort to protect a person from disease. Lymphocyte A cell that functions as part of the lymphatic and immune systems by attacking specific invading substances.

Immune Mediated Diseases Correlations

Immune-mediated inflammatory diseases, or IMIDs, is another term, which is used to describe immune-mediated diseases associated with inflammatory pathogenesis mechanisms. IMIDs are characterized by immune dysregulation that results in acute or chronic inflammation, causing organ or tissue damage. One causal manifestation of immune deregulation is the inappropriate expression of proinflammatory cyto-kines, such as IL-1, IL-6 and TNF-a as well as Th1 Th2 cytokine disbalance leading to pathological consequences. This is in agreement with the cytokine theory of disease, which states that an overproduction of cytokines can cause the clinical manifestations of disease (Nathan 2002 Frieri 2003 Elenkov et al. 2005 Tracey 2005). For instance, Th1-associated IMIDs include rheumatoid arthritis, Crohn's disease, multiple sclerosis, SLE, type I diabetes mellitus, psoriasis, sarcoidosis, an-kylosing spondylitis, uveitis, and pathologic conditions associated with lung transplantation. Th2-associated...

Antiinflammatory mediators

Antibodies to the core region of the endotoxin molecule can be detected and have been measured as an indicator of circulating endotoxin. A decrease in the concentration of these antibodies is proposed to reflect their consumption from current or recurrent exposure to endotoxin. In a study of patients undergoing major vascular surgery, a fall in antibody titres mirrored the elevation of TNF receptor status but only in those whose recovery was uncomplicated. The lack of correlation between endotoxin antibodies and TNF receptors in non-survivors may indicate an imbalance or inappropriate anti-inflammatory response leading to an overwhelming suppression of the immune system and patient demise, which supports the anti- and pro-inflammatory paradigm. Attempts have been made to correlate the levels of various pro and anti-inflammatory mediators with the final outcome with varying success. There is evidence to suggest that baseline serum IL-10 and TNF-a levels, together with IL-10 TNF-a ratio...

Definitions and Etiology

In contrast, in an inflammatory arthritis such as RA there is a systemic illness with inflammation of many joints, usually the small joints of the hands, wrists and feet, often spreading to include the knees and hips. There is evidence of a systemic immune response, with activation of clones of autoreactive T cells and increased production of many cytokines, including interleukin (IL)-1 , tumor necrosis factor (TNF)-a, IL-6, and others. There is also activation of the acute-phase response, with reduced albumin synthesis and increased production of fibrinogen, C reactive protein, and other acute-phase reactants. The systemic inflammation leads to altered energy and protein metabolism and wasting of body cell mass and muscle mass, described as 'rheumatoid cachexia.'

Immunological and Hormonal Aspects of Normal Pregnancy

Pregnancy has a significant effect on the immune system, in order to maintain the fetal-maternal allograft, which is not rejected despite displaying paternal histocompatability antigens 12 . While there is no overall immunosuppression during pregnancy, control or tolerization of anti-fetal T cells is critical 13 . Clinical improvement usually occurs in patients with immunological disorders such as rheumatoid arthritis RA when they become pregnant 14 . Clinical improvement occurs as well in psoriatic arthritis and Graves' disease. On the other hand, systemic lupus erythematosus (SLE) may flare during pregnancy. T cell subset studies in pregnancy are discrepant, as peripheral blood CD4+ and CD8+ cell levels have been variously reported to decline, remain unchanged and increase during pregnancy. Although, the distinction between Th1 (T cell helper 1) and Th2 (T cell helper 2) immune responses in humans remains less clear than in the mouse the general agreement is that in pregnancy there...

The Good the Bad and the Promising

In evolving mechanisms to evade these defenses. The HCV-encoded NS3 4A protease is an effective antagonist of both the RIG-I and TLR3 signaling pathways that are induced by dsRNA regions of secondary structure in the ssRNA HCV genome. Not only does NS3 4A inhibit direct signaling for IFN secretion, but it also prevents IFN amplification via the autocrine and paracrine loops (Foy et al. 2003). HCV core protein induces in vitro expression of suppressor of cytokine signaling (SOC) proteins, which downregulate the JAK-STAT pathway (Bode et al. 2003). Lastly, because the HCV polymerase lacks a proofreading function, a number of viral variants can be generated during the course of a persistent infection, thus affording a great deal of viral complexity and variable sensitivity to IFN (Gale and Foy 2005). The understanding of the molecular strategies employed by the virus to evade immune surveillance will provide novel targets for therapeutic control of HCV (see the chapter by Loo and Gale,...

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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