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Alcohol And The Immune System

NK cells are important because they play a role in natural immunity against tumor and infected cells. In fact, advanced aging is associated with functional impairment ofNK cells and increased susceptibility to nutritional deficiencies. Studies from human and experimental animals have proven that EtOH acts as a co-carcinogen, and suppression of the immune system has been considered as one mechanism by which EtOH could increase the incidence or progression of cancers 3 , like Kaposi's sarcoma. A recent report regarding HIV-related cancers compared cancer incidences in Zimbabwe, Africa between 1990-1992 to those in 1993-1995. It showed an increase in the incidence ofKaposi's sarcoma with a doubling of the rates in both men and women. A significant increase in the incidence of squamous cell tumours, as well as non-Hodgkin's lymphoma in women was also observed 4 , Research shows a relationship between increased ethanol levels and a decrease in natural killer cells. Decreased natural killer...

Cellular immune response

The immune system is the recognition of pathogens and differentiation of nonself from self molecules. Once a microorganism is recognized as foreign, the immune system is activated to mount a defensive response to kill or eliminate the intruder. Insects lack immunoglobulin-based immune responses. The recognition of nonself is achieved by pattern recognition receptors (PRRs) that are germline-encoded immune proteins that recognize the pathogen-associated molecular patterns (PAMPs) presented on the surface of microorganisms. There are two families of PRRs the pepti-doglycan recognition proteins (PGRPs) and the Gram-negative binding proteins (GNBPs). The binding of PAMPs to PGRPs and GNBPs activates the proteolytic cascades involving serine protease and serpins. These cascades trigger an intracellular humoral pathway that controls antimicrobial peptide expression and a variety of unspecific cell defense reactions including phagocytosis, nodule formation, encapsulation and melanization,...

Humoral immune response

Insect humoral immune responses involve secretion of antimicrobial peptides by fat bodies that is functionally equivalent to the mammalian liver, into the hemolymph in response to challenges to the immune system. Most of our knowledge of the insect humoral immune response is derived from studies of Drosophila. To date, seven classes of antimicrobial peptides, including attacin, cecropin, defensin, diptericin, drosocin, dro-somycin, and metchnikowin, have been identified in Drosophila, and their expression has been found to be regulated by two NF-kB signaling pathways, Toll pathway and immune deficiency (Imd) pathway (reviewed by Bulet et al., 2004 Leclerc and Reichhart, 2004). The humoral signaling pathway is also triggered by the binding of PAMPs to PGRPs and GNBPs which is involved in the upstream infection recognition. The Toll pathway has long been recognized to be a critical signaling pathway during Grampositive bacterial and fungal infections. The Toll transduction cascade is...

Strategies to Overcome the Humoral Immune Response

The humoral and cellular immune response to recombinant adenoviral vectors, as described in several animal models, result in extinction of transgene expression, severe local inflammation, and production of neutralizing antibodies that prevent readministration 59, 63, 64 . A direct correlation between neutralizing antibody and the block to readministration of vector has been established by passive transfer of immunity by sera from treated to naive animals 59 , One approach to enhance adenoviral-mediated gene transfer is to modulate the host immune response by immunosuppression of the recipient organism. In contrast cyclosporin (CSA) alone failed to reduce the production of neutralizing antibodies to cFIX in hemophilia B dogs but was effective at prolonging gene expression of FIX 64, 65 . CSA reportedly inhibits early events in T-cell activation such as activation of interleukin-2 gene expression 69 , which may explain why CSA most likely affected the cellular rather than the humoral...

Specific immune responses to HIV

In spite of the fact that HIV-infected individuals show the gross abnormalities of immune function described above, they are able to mount a specific immune response to HIV itself. Although serum reactivity to all the viral proteins is detectable, virus neutralising titres are generally low and directed against the immunising virus strain (type specific immunity). Passive transfer of antibody from asymptomatic to symptomatic patients is claimed to be beneficial, but this requires confirmation. Antibodies to HIV may even facilitate infection of cells bearing immunoglobulin (Fc) receptors, such as monocytes. In AIDS a fall in the titre of antibodies to core protein (p24) is often associated with disease progression. p24 antigen, which is detectable in the serum of some patients, may show a rise at the same time and has been used as a marker of disease progression.

Ap immunotherapy prevents and Reverses Alzheimers disease neuropathology

Fortunately, through tenacity, a few extra animals were secured and the experiments were performed (Schenk et al. 1999). Specifically, PDAPP mice were immunized with Ap 42 plus adjuvant beginning at a very young age (6 weeks), prior to any plaque deposition, and were boosted monthly with immunogen until the mice were sacrificed at the age of 13 months. As a control, we immunized a group of mice with a fragment of serum amyloid protein (SAP). At the conclusion of the experiment, the brains of these mice were examined for plaque burden, astocytosis and microgliosis. Surprisingly, the mice that had been immunized with Ap peptide were essentially devoid of amyloid plaques. The result was so striking that our first reaction was to reconfirm the transgenic status of the Ap-immunized animals. We also examined alternative plaque detection methods, such as Congo red and thioflavin stains, which were also negative on the Ap-immunized brains. Remarkably, the simplest conclusion for this first...

Tumor Escape And Future Approaches To Cancer Immunotherapy

Recent progress in tumor immunology has led to novel insights regarding the functions and interactions of immune cells (T, B, NK, M and DC) and the molecules expressed on these cells, which are linked to the development and efficacy of TA-specific immune responses. In addition, a better understanding of the molecular signals and mechanisms involved in the generation of productive immune responses in general has focused attention on those molecular events that occur or do not occur in the tumor microenvironment. The realization that immune cells undergo apoptosis in tumors has led to a search for the mechanism(s) responsible for this death and was instrumental in identifying the TNF family of receptors and ligands as instrumental in mediating tumor-induced apoptosis (165-167). This realization was prefaced by the recognition of the Fas FasL pathway and its role in maintaining the immune privilege at sites such as the anterior chamber of the eye, the brain, the testis or the thyroid...

Cells involved in the immune response

The lymphocytes are a very heterogeneous group of cells, almost identical when studied using light microscopy methods and only showing slight differences by electron microscopy techniques and yet the group contains cells with many different roles. Although large numbers of lymphocytes can be detected in the circulating blood and body fluids, the majority of lymphocytes are to be found in the group of tissues known collectively as the reticulo-endothelial system. This includes such tissues as the liver, spleen, bone marrow, thymus and lymph nodes, all of which are important in the immune response. Experiments involving the removal of various tissues from experimental animals have indicated that there are two different features to the immune response. The removal of the thymus, a small gland located behind the sternum, impairs the ability of a young animal to reject skin transplants but does not affect to the same extent its ability to produce antibodies. This aspect of the immune...

General processes of the immune response

One very important group of cells known as the lymphocytes, which are widely distributed throughout the tissues, appear in increased numbers during an inflammatory response and are primarily responsible for the immune response. This is a specific response to the invading substance or agent by the animal and involves the production of cells and antibodies with the ability to recognize and bind the invading substance.

The Immune Responses Of The Primeboost Regimen With rBCGE12 AND rDISE12 Candidate Vaccine

Key words HIV, Vaccine, Immune response, CTL, BCG, Vaccinia. The development of an effective prophylactic vaccine for human immunodeficiency virus type 1 (HIV-1) is hindered by the lack of a known immunologic correlate of protection. However, until an efficacy trial is undertaken, those evaluating candidate vaccines must rely on criteria chosen from other clinical settings, such as the immune responses found in HIV-1 infected long-term nonprogressors and in HIV-1 exposed but uninfected, and primate vaccine studies. It is widely believed that two of more important responses for preventing or controlling HIV infection are a vigorous CD8+ cytotoxic T lymphocyte (CTL) response (CD8+ CTL) and the development of antibody that would neutralize primary transmitted viruses (1-4). Recombinant live attenuated Mycobacterium bovis BCG (BCG) vector-based vaccine targeted to HIV-1 and simian immunodeficiency virus were reported to induce both humoral and cellular immune responses in animal models...

Interactions Between the Lymphatic and Immune Systems and Other Organ Systems

Urinary System Interactions

Lymphatic system drains excess tissue fluid and removes cellular debris and pathogens. Immune system provides defense against pathogens and immune surveillance against cancer. Neuropeptides and emotional states affect immune function blood-brain barrier prevents antibodies and immune cells from entering brain tissue Alveolar macrophages remove debris from lungs Provides immune system with O2 disposes of CO2 thoracic pump aids lymph flow pharynx houses tonsils important to lymphatic and immune function urine flushes some pathogens from body acidic pH of urine protects against urinary tract infection Immune system requires that the testes have a blood-testis barrier to prevent autoimmune destruction of sperm Vaginal acidity inhibits growth of pathogens Physiology The Unity of Immune System Companies, 2003 Form and Function, Third Edition Chapter 21 The Lymphatic and Immune Systems 835

APCs In Initiation Of Mucosal Immune Responses

Antigens can be taken up across the epithelial linings of various mucosal tissues, and many of these tissues then generate robust sIgA responses. Most of our knowledge about this response has been gained from studies of gut-associated lymphoid tissue in rodents and of human tonsils. The major inductive sites of the mucosal immune system are follicles and organized aggregates of follicles, exemplified by Peyer's patches in the intestine and referred to generically as mucosa-associated lymphoid tissue (MALT). Antigens are often efficiently absorbed by specialized cells in the epithelium overlaying the MALT, the morphologically distinct M cells (37,38). In some cases dendritic cells extend processes between neighboring epithelial cells to sample antigens in the external milieu (39). Despite the well-developed conjunctival lymphoid follicles, however, most of the IgA+ plasma cells that populate the lacrimal glands appear to be generated in the gut or upper respiratory system, rather than...

Mechanisms Underlying The Lack Of Correlation Between Clinical And Immune Responses

To date, a large number of TA-specific immunotherapy trials have been conducted in patients with malignant disease. It is clear from these studies that the various types of tumor vaccines i) have limited or no toxicity and ii) are able to induce TA-specific immune responses and or augment already established TA-specific immune responses in immunized patients. Nevertheless, the results of these studies have highlighted two challenges facing tumor immunologists and clinical oncologists. The first is the selection of the most effective immunotherapeutic strategy, since the various available strategies have not been systematically compared. Unfortunately, this information is not likely to become available in the near future given the prohibitive costs of clinical trials. The second is the understanding of why a TA-specific T cell-based immune response, which can be detected in a variable percentage of patients, is not paralleled by a clinical response in the majority of immunized...

Molecules Cells and Tissues of the Immune Response

The generation of an immune response of either the innate or acquired variety requires the interaction of specific molecules, cells, and tissues. This chapter provides an overview of these structures with brief descriptions, enhanced by schematic representations and light and electron micrographs of those elements whose interactions yield a highly tailored immune response that is critical to survival of the species. Many of the molecules of immunity are described in subsequent chapters. Adhesion molecules that are important in bringing cells together in the generation of immune responses, of directing cellular traffic through vessels or interaction of cells with matrix are presented here. All lymphocytes in the body are derived from stem cells in the bone marrow. Those cells destined to become T cells migrate to the thymus where they undergo maturation and education prior to their residence in the peripheral lymphoid tissues. B cells undergo maturation in the bone marrow following...

Humoral immune response to infectious haematopoietic necrosis virus

Amend and Smith (1974) showed that fish hyperimmunized with IHNV mounted a humoral immune response, with the production of neutralizing antibodies. It was later shown that viral neutralization by antibodies was complement-dependent (Hattenberger-Baudouy et al, 1989). The humoral immune responses to IHNV and other fish viruses are very similar. Young rainbow trout during an IHN epizootic did not have detectable neutralizing antibody titres, but by 4.5-6 months after infection, when the virus was no longer detectable, over half of the surviving fingerlings tested had a significant humoral immune response. By 8 months, the number of antibody-positive fish and the antibody titre had decreased (Hattenberger-Baudouy et al., 1989). Similar results were obtained by LaPatra et al. (1993b). Juvenile rainbow trout immersed in IHNV had a low prevalence and titre of serum anti-IHNV antibodies at 1 week postexposure, but by 6 weeks over 50 of the fish had high neutralizing antibody titres....

Dynamic Monitoring Of Anticancer Immune Responses

Determine the occurrence of immune-induced cancer regression in humans (56). The introduction of gene profiling arrays is particularly suited to circumstances when little is known about a biological event to conceive plausible hypotheses. This is clearly the case of immune-mediate cancer rejection. We tested whether global transcript analysis could segregate lesions likely to respond to immunotherapy by obtaining FNA from subcutaneous melanoma metastases prior to immunotherapy (49). This work was based on a previous observation suggesting that cutaneous melanomas can be segregated into two distinct taxonomies based on global transcript analysis (57). Such observation stimulated the question of whether two disease pathologically defined as melanomas had a different biology and consequently, perhaps, different predisposition to respond to immune therapy. However, the original observation was based on the analysis of cell lines or tissue preparations that has been collected a long time...

Essential Components Of An Effective Taspecific T Cellbased Immune Response

Tumor Microenvironment Immune Response

Although mechanisms of tumor-specific immunity and its role in the development and progression of cancer in man have been much debated, newer evidence suggest that the components necessary for mounting the anti-tumor immune response are present in cancer patients. Most of the immunization strategies, which have or are being tested in clinical trials today, share the common goal of inducing TA-specific CTL capable of lysing malignant cells. However, it should be stressed that TA-specific (CD8+) CTL and helper (CD4+) T cells as well as antibody-secreting B cells are essential for anti-tumor effector functions (5,7-10). Moreover, as in most chronic diseases, both non-specific and specific components of the host immune response play a role in the control of tumor growth and metastasis, with some components, e.g., natural killer (NK) cells, polymorphonuclear cells (PMN) and macrophages, thought to participate in the early phase of the response, prior to the appearance of T or B cells. It...

Effects of the Immune System

The majority of in vitro models commonly used are devoid of immune system factors that is, antimicrobial effects are studied in an environment that does not contain the host defense factors. The antimicrobial effect may thus be underestimated, because organisms are free from the inhibitory action of such immune system factors as leukocytosis, phagocytosis, and immunoglobulins. Shah 22 employed a model that incorporated fresh human blood from healthy volunteers in an effort to replicate in vivo immune system effects. The model consisted of a glass chamber (similar to the one-compartment model previously described) with an inner cell suspended within. The inner cell, composed of plexiglass, was enclosed at each end with membrane filters designed to allow diffusion of antibiotics. Heparinized human blood was incorporated into the inner chamber, and the outer chamber contained a nutrient medium. The bacterial inoculum was injected into the inner chamber, and antibiotics were administered...

Immune Response to Adenoviral Based Vectors in Humans

Host immune response can play a significant role in the outcome of in vivo gene therapy. Experiments with adenoviral vectors clearly demonstrate the development of neutralizing antibodies that block readministration and cellular responses that extinguish gene expression. However, most of the work described in this field relates to animal models that are naive to the virus. This will not be the case in humans, many of whom have been exposed to Ad due to a naturally acquired infection. A study performed by Chirmule et al. 147 surveyed normal subjects and cystic fibrosis patients to demonstrate the relevance of pre-existing immunity to Ad to the outcome of in vivo gene therapy. They found that antibodies reactive to Ad capsid proteins were present in 97 of individuals however, serum from only 55 of subjects actually neutralized Ad infection in vitro. Due to this discrepancy between seropositivity and neutralization of virus in vitro, the authors suggest that human trials should include...

Immune Surveillance

The hypothesis of immune surveillance was formulated by two prominent immunologists, Lewis Thomas in 1959 (Thomas, 1959) and Mac Farlane Burnet in 1964 (Burnet, 1971). In Burnet's words In large long lived animals inheritable genetic changes must be common in somatic cells and a proportion of these changes will represent steps toward malignancy. It is an evolutionary necessity that there should be some mechanism for elimination or inactivity of such potentially dangerous mutant cells and it is postulated that this mechanism is of immunological character. The evolutionary necessity of cancer protection is certainly true, but the unique role attributed to the immune system ignores two salient facts (1) tumor evolution involves the loss rather than the gain of many functions and (2) the cancer cell phenotype is easily malleable. This does not augur well for the immune recognition of tumors as nonself targets. Even if adventitious, immunologically recognizable mutations would occur, they...

Gut Immune System

The immune system in the GI tract, like in the rest of the body, can be subdivided into the following two categories (1) cellular and (2) humoral. T-lymphocytes generally regulate cellular immune functions, such as defense against viruses, intracellular bacteria, and proteins, whereas B-lymphocytes produce immunoglobulins (Ig) to fight bacteria. Primary immunodeficiencies are the result of inherited defects in either or both the cellular or humoral branches of the immune system. In the GI tract, the major Igs are the secretory forms of IgA and IgM. These antibodies bind luminal antigens and form immune complexes, thus restricting bacterial and viral attachment to epithelium and decreasing antigen burden on the mucosal immune cells. Antibody deficiency can lead to increased antigen uptake in the GI tract, as has been demonstrated with serum levels of dietary antigens following feeding (Cunningham-Rundles et al, 1979). However, it is interesting to note in the one disease exclusively...


Years, however, studies using specific immunotherapy with the humanized murine monoclonal antibody trastuzumab have yielded promising results. This antibody recognizes and binds to a transmembrane tyrosine kinase coded for by the c-erbB2 or HER2 gene, which is amplified and or overexpressed in up to one-third of all breast cancer specimens (Figure 17-2). When given to a heavily pretreated group of patients whose tumors overexpressed this gene product, trastuzumab produced a 16 percent objective response rate.81 Toxicity was minimal, consisting of fever and chills after the first weekly infusion, and mild pain, asthenia, nausea, diarrhea, and dyspnea. In addition, 5 percent of patients had evidence of cardiac dysfunction.

Immune Escape

Tumor induced immune suppression and immune escape Mechanisms and Possible Solutions Abstract It has been a general experience that results of immunomonitoring of patients with malignant disease treated with active specific immunotherapy have poor, if any, predictive value. Furthermore, lack of clinical response and or recurrence of disease in spite of induction and or persistence of tumor antigen (TA)-specific immune responses appears to be the rule more than the exception in clinical trials. These disappointing results are likely to be caused, at least in part, by tumor cells' ability to evade immune recognition and destruction. In this paper after a description of the essential components required to generate an effective TA-specific T cell-based immune response, we have reviewed the potential mechanisms underlying the lack of correlation between immunological and clinical response in immunized patients. They include qualitative and or quantitative defects in the generation and...

History of Immunology

Edward Donall Thomas Joseph Murray

In 1948, Astrid Elsa Fagraeus established the role of the plasma cell in antibody formation. The fluorescence antibody technique developed by Albert Coons was a major breakthrough for the identification of antigen in tissues and subsequently demonstrated antibody synthesis by individual cells. While attempting to immunize chickens in which the bursa of Fabricius had been removed, Bruce Glick et al. noted that antibody production did not take place. This was the first evidence of bursa-dependent antibody formation. Robert A. Good immediately realized the significance of this finding for immunodeficiencies of childhood. He and his associates in Minneapolis and J.F.A.P. Miller in England went on to show the role of the thymus in the immune response, and various investigators began to search for bursa equivalence in man and other animals. Thus, the immune system of many species was found to have distinct bursa-dependent, antibody-synthesizing, and thymus-dependent cell-mediated limbs. In...

Preface to the First Edition

The recognition of different central and peripheral immune mechanisms leading to immunological tolerance are all based on Ehrlich's concept of horror autotoxicus , i.e. acquired or active immune regulation of unwanted immune responses against self. The finding that B lymphocytes generally require the help of T lymphocytes in their antibody response to a defined antigenic stimulus led to the discovery of distinct immune cell subsets including helper cells, cytotoxic cells and regulatory cells. The identification of the idiotype-anti idiotype network was born out of the discovery that the antigen binding site of the antibody itsself can act as an antigen for anti-idiotypic antibodies. Anti-idiotypic immune responses are part of the physiological immune surveillance aimed at limiting the extent of an immune response. The identification of different lineages of antigen presenting cells has taken away much attention from T lymphocytes as the exclusive regulators of immune and autoimmune...

Acquired immunodeficiency syndrome

(AIDS) A disease of humans caused by Human immunodeficiency viruses (HIV) 1 and 2. Globally, more than 36 million people were infected by the year 2000. The incubation time from infection to development of AIDS appears to range from 6 to 13 years (median 10 years). AIDS is primarily a disease of the immune system so the infection usually results in a wide range of adverse immunological and clinical conditions. The extent of the disease is generally measured by the CD4+ lymphocyte count, and as the count declines to below 200 per microliter there is serious risk of AIDS-related complex (ARC), a syndrome involving opportunistic infections, such as recurrent bacterial infections, candidiasis, pulmonary tuberculosis, Pneumocystis carinii pneumonia, EBV-associated lymphoma, and Kaposi's sarcoma. The opportunistic infections (i.e. those caused by microorganisms that seldom cause disease in persons with normal defense mechanisms) and cancers resulting from immune deficiency are

Living Parts Tissues Cells Compartments and Organelles

In people (and most other multicellular animals) there are fourteen major tissue types. There are many texts with illustrations and descriptions of the various cell types and tissue, e.g. Kessel and Kardon (1979) which is full of beautiful electron micrographs. Some of these tissue types are familiar bones, muscles, cardiovascular tissue, nerves, and connective tissue (like tendons and ligaments). Other tissues are the constituents of the digestive, respiratory, urinary and reproductive systems. Skin and blood are both distinctive tissue types, made of highly specialized cells. Lymphatic tissue, such as the spleen and the lymph nodes make up the immune system. Endocrine tissue comprises a network of hormone-producing glands (for example, the adrenal gland, source of adrenaline) that exert global control over various aspects of the body as a whole. Finally, epithelium, the most basic tissue type, lines all of the body's cavities, secreting materials such as mucus, and, in the in-

Development of the epidemic

The first recognised cases of the acquired immune deficiency syndrome (AIDS) occurred in the summer of 1981 in America. Reports began to appear of Pneumocystis carinii pneumonia and Kaposi's sarcoma in young men, who it was subsequently realised were both homosexual and immunocompromised. Even though the condition became known early on as AIDS, its cause and modes of transmission were not immediately obvious. The virus now known to cause AIDS in a proportion of those infected was discovered in 1983 and given various names. The internationally accepted term is now the human immunodeficiency virus (HIV). Subsequently a new variant has been isolated in patients with West African connections The definition of AIDS has changed over the years as a result of an increasing appreciation of the wide spectrum of clinical manifestations of infection with HIV. Currently, AIDS is defined as an illness characterised by one or more indicator diseases. In the absence of another cause of immune...

The Composition of Cells

Proteins are the molecules that accomplish most of the functions of the living cell. The number of different structures and functions that proteins take on in a single organism is staggering. They make possible all of the chemical reactions in the cell by acting as enzymes that promote specific chemical reactions, which would otherwise occur only so slowly as to be otherwise negligible. The action of promoting chemical reactions is called catalysis, and enzymes are sometimes refered to as catalysts, which is a more general term. Proteins also provide structural support, and are the keys to how the immune system distinguishes self from invaders. They provide the mechanism for acquiring and transforming energy, as well as translating it into physical work in the muscles. They underlie sensors and the transmission of information as well.

Identification Of The Ara H 2 Tcell Epitopes

To understand food hypersensitivity reactions it is important to identify and characterize the protein allergens that are responsible for the immunologic disorder as well as the immunological responses. What is so different about the protein allergens that causes them to be recognized as pathogenic moieties by the immune system Why do peanut allergies persist throughout the life of an individual while allergies to similar proteins in other legumes such as soy are outgrown early in life Various proteins involved in hypersensitivity reactions to peanut have been identified (8, 9, 10, 11, 12), three of which have been cloned and characterized (Ara h 1, Ara h 2 and Ara h 3, 10, 11, and 12 respectively). Identification, isolation of the native Ara h 2 and characterization

Virulence of Anaerobic Bacteria and the Role of Capsule

Anaerobic Organisms

The immune system is active in protection against anaerobic infection. Anaerobes activate complement directly, thus attracting polymorphonuclear leukocytes. Anaerobes are susceptible to killing by macrophages and are killed by oxidative and monoxidative mechanisms intracellularly. Both humoral and cell-mediated immune mechanisms actively protect the host from anaerobes. These include circulating antibodies and complement that have been shown to protect from experimental bacteremia, and T-lymphocytes that resist abscess formation (8).

Anterior poliomyelitis virus Synonym for

Antigenic drift The appearance of a virus with slightly changed antigenicity after frequent passage in the natural host. This is presumably due to selection of mutants under pressure of the immune response. Commonly described in influenza virus infections, but also observed with many other viruses. apoptosis Mechanism by which many viruses induce cell death transforming viruses encode proteins that inhibit cellular apoptotic pathways. Plays a major role in viral infections and in the host response to them. CTLs, NK cells, and cytotoxic cytokines all kill virus-infected target cells through apoptotic pathways. In the infected host, T-lym-phocyte apoptosis plays a role in the natural history of the T cell responses to viral infection. The immune response is silenced by the physiological elimination of lymphocytes by apoptosis, and an overzealous elimination can lead to viral persistence.

What causes the inflammation in the plaque

Macrophages monocytes from the blood stream that have been turned on by interacting with lymphocytes. Monocytes part of the human immune system that protects against infections and moves quickly to sites of infection. Monocytes are responsible for phagocytosis, or digestion, of foreign substances in the body. proteins made by the immune system to defend against infectious agents. At times, antibody may be directed against our own tissues, resulting in autoimmune disease. Antibody is produced when B-cells are stimulated by antigen.

Adaptation to Cancer

Interesting and controversial intervention studies have examined the effect of positive attitude and social support in reducing the physical effects of cancer. According to some psychoneuroimmunology studies, depressed mood may reduce immune functioning. ''Wellness communities, startled by Harold Benjamin in Santa Monica, California, promote the idea that depression weakens immune response. They suggest that a positive attitude may likewise enhance it. Stronger immunity, it is argued, will lead to reduced physical manifestations of the disease. Women assigned to the support groups survived an average of 36.6 months, while those in the control group survived an average of only 18.9 months. Support group members also experienced less anxiety, depression, and pain. This study's impressive results have sparked further research into the role of social support and immune functioning, as well as the role of psychotherapy in reducing the psychosocial difficulties of the cancer experience. The...

Microvilli Cilia and Flagella

Moving Mucus

Immunity to Infection Enables the immune system to recognize and selectively attack foreign organisms Changes in the glycocalyx of cancerous cells enable the immune system to recognize and destroy them Forms the basis for compatibility of blood transfusions, tissue grafts, and organ transplants Binds cells together so that tissues do

Future Avenues Of Investigation

Understanding the relationship of the immune system and autoimmune diseases to androgens. Although not discussed in the text, an important aspect of sexual dimorphism is that females are much more likely to develop autoimmune diseases than men. Further investigation is required to understand the role of physiological concentrations of androgens in the normal function of the immune system and possible protection against the development of autoimmune disorders (see ref. 71).

Causes Of Death In Childhood

The causes of death vary with age as shown in Table 1.2. In the newborn period the most common causes are congenital abnormalities and factors associated with prematurity, such as respiratory immaturity, cerebral haemorrhage, and infection due to immaturity of the immune response.

Pathway of Adenovirus Cell Entry

Adenoviruses cause a significant number of acute respiratory, gastrointestinal, and ocular infections in man. While these infections are usually self-limiting they can result in significant morbidity and in immunocompromised individuals are capable of causing fatal disseminated infections 1 . Among the 50 different adenovirus (Ad) serotypes, representing six different subgroups (A-F) 2, 3 , the majority of information on the molecular basis of host cell interactions is derived from studies on the closely related types 2 and 5 (subgroup C) 4 . It is, therefore, not surprising that replication-defective forms of Ad5 are currently being used for most in vitro and in vivo gene delivery applications 5, 6 . Despite some reported successes, adenovirus-mediated gene delivery remains hampered due in large part to the host immune response to viral proteins 7, 8 . Increased knowledge of Ad structure 9, 10 and host cell interactions 11 may allow redesigning of viral vectors in order to avoid some...

Antibodies as Specificity Elements

The immune system of higher eukaryotes produces antibody molecules that recognize a broad range of small molecules. By immunizing animals with specific antigens, produced by conjugating organic compounds to carrier proteins, antibodies that specifically recognize the original small molecule can be generated. This allows protein scaf-

Host response to infection

Efforts over the last 10 years to improve the effectiveness of vaccines against furunculosis have led to a much improved understanding of the salmonid immune system, and a number of comprehensive reviews have been published (Warr and Cohen, 1991 Secombes, 1994a Secombes and Olivier, 1997). In general, most components of the fish immune system are analogous to those of higher vertebrates. These include physical barriers and chemical barriers to prevent infection, inducible but non-specific humoral factors, phagocytes and non-specific cytotoxic cells, which mediate an inflammatory response, and, finally, specific immunity, effected by lymphocytes. It is this last type that is responsible for 'immunological memory', ensuring that responses to a second exposure are faster and stronger than the initial response, thus conferring immunity (Secombes and Olivier, 1997). Specific immune responses include both humoral immunity, based on the production of antibodies by B cells, and cellular...

What is the vaccine for MS

There seems to be a great deal of confusion in the minds of many MS patients and their families about a vaccine for MS. Some seem to think of any injectable drug as a vaccine, but this is not a correct concept. All of the medications currently approved by the FDA for chronic (long-term) use in MS are drugs but are not considered to be vaccines, although their use is to prevent periods of ill health. Interferon-beta-lb (Betaseron) and interferon-beta-la (Avonex and Rebif) and glatiramer acetate (Copaxone) are injectable drugs but are not vaccines. In contrast, a vaccine, which is generally injected, stimulates the immune system, resulting in antibody formation or a direct effect of lymphocytes against proteins or cells that have specific proteins on their surface. Several vaccines against cells in the immune system have been used in research trials.

What is the importance ofHSV6 in MS

Both HSV-6 and HSV-7, as well as EBV, can infect the cells of the immune system (lymphocytes) and stimulate them to uncontrolled reproduction (immortalize them). Although all three viruses can infect the immune system and immortalize them, only HSV-6 and HSV-7 can infect cells in the nervous system. The HSV-6 virus has been found in the cells that make myelin, the oligodendrocytes, of MS patients. Research into a possible role for EBV, HSV-6, and other related viruses continues. No convincing relationship of HSV-6 or HSV-7 to MS has, as yet, been firmly established. However, this remains an active and important area of research.

Pemphigus Vulgaris An Autoimmune Disease

The immune system normally produces defensive antibodies that selectively attack foreign substances and leave the normal tissues of our bodies alone. But in a family of disorders called autoimmune diseases, antibodies fail to distinguish our own cells and tissues from foreign ones. Such misguided antibodies, called autoantibodies, thus launch destructive attacks on our own bodies. (Autoimmune diseases are discussed in more detail in chapter 21.) One such disease is pemphigus vulgaris28 (PEM-fih-gus vul-GAIR-iss), a disorder in which autoantibodies attack the proteins of the desmosomes in the skin and mucous membranes. This breaks down the attachments between epithelial cells and causes widespread blistering of the skin and oral mucosa, loss of tissue fluid, and sometimes death. The condition can be controlled with drugs that suppress the immune system, but such drugs reduce the patient's immune defenses against other diseases.

Betaestradiol Regulates Immunoglobulin M Production Through Interaction With Estrogen Receptors

Abstract Estrogens have diverse effects on cell growth, differentiation and homeostatic functions, and have been shown to play an important role in regulating immune system. Most of these E2 functions are mediated by estrogen receptors (ERs). Recently, it was reported that ERs were expressed immunocompetent cells, such as B cell, T cell, Natural killer cell and macrophage. In this study, it was examined that effect of 17 -Estradiol (E2) on antibody production by splenocytes isolated from C57BL 6N mice. E2 regulates immunoglobulin M (IgM) production by mouse splenocytes. IgM production was enhanced 2.0-fold at 10-10 M E2. This enhancing effect of E2 was canceled by ER antagonist ICI 182780. Previously, it was reported that two subtypes of ERs, such as ERa and ER . Both ERa selective agonist, 4,4',4 -(4-propyl- 1H -prazole-1, 3, 5-triyl)trisphenol and ER selective agonist, 2,3-bis-(4-hydroxyphenyl)-propionitrile enhanced the production of IgM as well as E2. Recently, ERs are expressed...

Peptidehlagfp Complexes

Abstract Antigen-specific T cell responses are essential in host immune defense in health and disease. For many years, it was believed that the immune system was effective only in combating infectious diseases caused by invading agents such as bacteria and viruses. More recently, however, the immune system has been shown to play a central role in protection and recovery against cancer. This latter role is not well understood, but there are numerous reports that the immune system slows down the growth and spread of tumors in cancer patients. Many clinical trials for cancer immunotherapy are in progress and use anti-tumor vaccinations that have been designed to elicit antigen-specific T cell responses. Therefore, in defining anti-tumor immune responses that may be used for immunotherapy trials, the detection and quantitative analysis of antigen-specific T cell populations has been an important step toward understanding the cellular immune response in patients. In this chapter, we...

Lymphatic Cells and Tissues

Lymphatic tissues are composed of a variety of lymphocytes and other cells whose roles in the immune system will be examined in this chapter. These include 3. Macrophages. These cells, derived from monocytes of the blood, phagocytize foreign matter (antigens) and display fragments of it to certain T cells, thus alerting the immune system to the presence of an enemy. Macrophages and other cells that do this are collectively called antigen-presenting cells (APCs). In some places, lymphocytes and other cells congregate in dense masses called lymphatic nodules (follicles), which come and go as pathogens invade the tissues and the immune system answers the challenge. Lymphatic nodules are, however, a relatively constant feature of the lymph nodes and tonsils. They also form clusters called Peyer2 patches in the ileum, the last segment of the small intestine.

Skewed Differentiation Lineages with

Perhaps owing to the overall decline of the immune system during aging briefly discussed above in the Introduction, stem cell transplantation studies have repeatedly shown that engraftment of the immune system is diminished and or delayed in the face of the enhanced production of myeloid cells, particularly granulocytes and monocytes macrophages (33, 54, 55). It is worth repeating that during the engraftment process, stem cell function is the net result of intrinsic and extrinsic influences. Cell-autonomous influences, discussed above, include genetic and epigenetic alterations as a function of age, whereas extrinsic influences are manifested via cytokines and other humoral influences but perhaps most importantly through incompletely understood close-range interactions with cells comprising the stem cell niche (56) in which stem cells reside. An example of a stem cell-intrinsic change affecting lymphopoiesis is the finding that human CD34+ cells show impaired ability to generate...

Thymus and Reproduction

The thymus plays an important role in the immune system, and it has been suggested that thymic cells and peptides play a role in determining reproductive lifespan in females (Bukovsky and Presl 1979 Rebar 1982 Suh et al. 1985). The relationship of age-associated thymic involution with diminution of ovarian function is supported by the alteration of ovarian function in neonatally thymectomized mice (Nishizuka and Sakakura 1969). In addition, in congenitally athymic (nude) mice, follicular loss is first evident at two months of age and this is specifically due to a reduction in the numbers of primary follicles. The first ovulation is delayed until two and half months of age, compared to the first ovulation in the one and half month old normal mouse females. By four months, an overall reduction in all fractions of the follicle population occurs in nude mice, and ovulation ceases (Lintern Moore and Pantelouris 1975). Interestingly, the absence of the thymus might also be responsible for...

Are There Apcs In The Retina

Stream into the neural parenchymal tissue (79) it was believed for many years that these barriers naturally extend to blood-borne cells. However, inflammatory processes do occur in the brain and retina and there is evidence that the normal central nervous system (CNS) is subject to regular patrol by lymphocytes, most likely of the activated or blast form since resting T cells do not normally enter the CNS parenchyma (80). This is supported by evidence that in autoimmune conditions, such as multiple sclerosis or uveitis, autoreactive T cells do indeed enter the CNS or eye, respectively. A paradigm has emerged that low numbers of lymphocytes, albeit activated, access and patrol the CNS parenchyma for potential pathogens (81). If, as evidence to date would indicate, DCs are excluded from the normal neural retina (and brain parenchyma), which cell type within the neural retina acts to present Ag to patrolling activated T cells If, as outlined earlier, it is accepted that DCs act as the...

Current research and the future

To improve existing treatments the effects on the underlying HIV infection and the impact on the immune system of anti-tumour therapy need to be identified. As anti-HIV therapies have a clinical effect on tumour incidence, complex issues of drug drug interactions and overlapping toxicities must be considered.

Karoly Toth Jacqueline F Spencer and William S M Wold Summary

Oncolytic adenovirus (Ad) vectors belong to a new class of cancer therapy agents that destroy cancer cells as part of the virus's lytic infectious cycle. In this chapter we describe an immunocompetent, semi-permissive cotton rat tumor model to evaluate the safety and efficacy of oncolytic Ad vectors. With this model one can investigate the effect of the host immune system on the vector-tumor interaction as well as the vector's effect on normal host cells in vivo. This chapter describes procedures for analyzing the growth and cytolytic properties of oncolytic Ad vectors in cotton rat cells in vitro. We discuss handling and husbandry issues and techniques for subcutaneous, intratumoral, and intravenous injection of cotton rats. We present methods for generating subcutaneous tumors in cotton rats and assessing the efficacy of Ad vectors upon intratumoral injection. Also, we discuss procedures for determining the biodistribution of a replicating Ad in cotton rats.

Anti Lselectin antibody did not overcome unresponsive state of T cells induced by superantigen

It is essential for homeostasis of the immune system to maintain the peripheral tolerance. T cell inactivation, in which T cells exhibit only weak responses on antigenic stimulation as to impaired IL-2-production and proliferation, is called anergy and recognized as one of the mechanisms to downregulate immune responses.15 We used SEB-induced anergy as a model system of unresponsiveness induced in vivo. Although MEL14 significantly enhanced the proliferation of responding T cells obtained from PBS-injected mice, the proliferation of unresponsive T cells from SEB-injected mice was not induced by the in vitro stimulation of SEB even in the presence of MEL14 (Fig. 2). This result indicates that signaling via L-selectin does not rescue the unresponsiveness of T cells.

Peripheral Tcell Tolerance

It is generally believed that many T cells escape central tolerance, especially those with the capacity to react with self-antigens not expressed in the thymus. This view is consistent with the relative ease of inducing organ-specific autoimmunity by deliberate immunization with peripheral antigens. While tissue-specific, self-reactive T cells generally ignore their target antigen because it is inaccessible or not presented in an immunogenic form, organ-specific autoimmune diseases are common 49 . In order to minimize autoimmunity mediated by self-reactive T cells in the periphery, the immune system has apparently developed various peripheral tolerance mechanisms that can restrain, quell, or kill such cells. Peripheral tolerance is much more than a backup mechanism to prevent autoimmunity - it is an active process that is probably invoked to limit T-cell response to all antigens.

Assessment And Outlook

TCR CDR 3 analysis is a descriptive method to visualize the composition of the entire T-cell repertoire, which can be combined with other, functional readout assays of the cellular immune system. At this point, it represents a highly reproducible and high-throughput approach to gauge the T-cell repertoire in any tissue. Comparative analysis aids to compare the TCR diversity over time or in different anatomic compartments and aids to establish novel markers in the context of immunotherapy or disorders of the immune system. TCR analysis has been predominantly employed in human diseases. TCR CDR3 analysis can also be performed in murine disease models, or in non-human primates (49). The determination of the TCR repertoire may also be helpful in pre-clinical settings, i.e. in testing differences in protein or peptide composition, or vaccine formulations which affect the cellular immune response. Since T-cells are able to sense a single amino acid residue difference in antigenic peptides,...

Mmtv And The Rise Of Tumor Immunology

However, the results could not be replicated by other investigators (Shimkin, 1977a). Many of the early negative observations could be written off by the newly described transplantation histocompatibility antigens. The subject was more or less dropped in the 1950s and some authorities came to the conclusion that the virus was not immunogenic, echoing Woglom's conclusion in 1929 that tumor immunology was not a promising field (Shimkin, 1977a Woglom, 1929, 1947). However, Prehn and Morton are credited with reviving the field of tumor immunology. Prehn used carcinogen-induced sarcomas and Morton used MMTV-infected C3H mice for his experiments (Shimkin, 1979b). However, it has been difficult to determine whether the immune system suppresses or stimulates tumorigenesis, or does both (Heppner, 1972 Prehn, 2006). The MMTV-LTR also became noteworthy because it contained the MMTV-related superantigen (Acha-Orbea et al., 1999 Marrack et al., 1991 Pullen et...

Nonspecific cellular factors

Should A. saJmonicida successfully breach the non-specific immune defences of fish, it will encounter specialized cells of the host immune system, namely the phagocytic cells. These include monocytes, or macrophages, and granulocytes (neutrophils, eosinophils and basophils). The macrophages of fish are similar to those of higher animals in both morphology and function and they act as antigen-presenting cells, cytokine-secreting cells and effector cells, with the ability to actively phagocytose bacterial cells (Secombes and Fletcher, 1992 Secombes and Olivier, 1997). Less is known about the function of neutrophils in the immune reaction of salmonids. Lamas and Ellis (1994a) demonstrated that neutrophils isolated from Atlantic salmon migrated in fish serum in response to the presence of A. saJmonicida, although, strangely, A-layer-deficient strains acted as stronger chemoattractants. Neutrophils were also found to be phagocytic, but phagocytosis was low compared with macrophages (Lamas...

Innate Immunity and in Vivo Gene Therapy

Recent progress in our understanding of the significance of innate immune responses to adenovirus infection in vivo have important implications for strategies of in vivo gene therapy using adenovirus. First, the phagocyte-based immune system is present and active prior to vector administration in contrast to adaptive immune responses. Therefore, any strategy designed to deliver large amounts of vector to tissues must take into account the loss of vector due to phagocyte-mediated clearance. Second, clearance of adenovirus by macrophages results in potent inflammatory signals which profoundly influence both molecular and cellular inflammation and likely determine the extent of tissue damage and systemic effects due to adenoviral infection of the

Anatomy And Function Of The Lymph System

The lymphatic system is a network of vessels throughout the body. It is part of the body's immune system and is involved in the removal of foreign matter and cell debris. Lymph vessels are usually associated with the circulatory system, and lymph originates from lost blood plasma or interstitial fluid from the capillary beds. The lymph system serves to filter and return this fluid to the circulatory system.

Conclusions and Perspective

Lates, and will help in designing new approaches to treatment. Progress in Whipple's bacteriology has overshadowed the likely role of the immune system in the pathogenesis, which needs to be clarified. The author's Web site is Whipple's Disease online at . He can be reached at .

Primary Sclerosing Cholangitis

The etiology of PSC has remained poorly understood since the earliest description of the disease. The current thinking is that PSC occurs as a consequence of a genetically determined dysregulated immune system, resulting in an uncontrolled inflammatory response in the bile ducts with destruction and fibrosis and, ultimately, biliary cirrhosis. The allo- and or autoantigen(s) that trigger this restricted inflammatory response in the bile ducts are unknown. Putative agents include bacterial antigens absorbed through a diseased bowel mucosa, particularly in patients with underlying IBD, as well as cytotoxic bile acids, viral infections, and ischemic injury.

Uva Uvb and Sunscreens

Some people distinguish between two forms of ultraviolet radiation and argue, fallaciously, that one is less harmful than the other. UVA has wavelengths ranging from 320 to 400 nm and UVB has wavelengths from 290 to 320 nm. (Visible light starts at about 400 nm, the deepest violet we can see.) UVA and UVB are sometimes called tanning rays and burning rays, respectively. Tanning salons often advertise that the UVA rays they use are safe, but public health authorities know better. UVA can burn as well as tan, and it inhibits the immune system, while both UVA and UVB are now thought to initiate skin cancer. As dermatologists say, there is no such thing as a healthy suntan.

Mouse Model Exhibiting the Phenomenon of Inhibition of Tumor Growth by Tumor Mass

An animal model that exhibited the phenomenon of the inhibition of tumor growth by tumor mass was developed (5,6). Several passages of the Lewis lung carcinoma (LLC) in C57B6 mice, with constant selection for the occurrence of low numbers of metastases in the lungs, resulted in an LLC-low metastatic (LLC-LM) phenotype. This LLC-LM tumor typically grew from an inoculum of 1 x 106 cells in the subcutaneous dorsum of mice, to a 1500-mm3 primary tumor in 2 wk. Within 13-21 d after resection of the primary LLC-LM tumors, the lungs of resected mice filled with neovascularized metastases. Lung weights, which correlated with tumor burden, were increased by 400 , compared with mice with intact primary tumors. L ungs of mice with unresected primary tumors were free of metastases (6). Thus, in this model, the presence of the primary tumor is associated with suppression of the growth of its remote metastases. Comparable results were seen with SCID mice lacking both T- and B-cell populations,...

Host Defense Mechanisms

A virus causes infection by invading host cells, multiplying new virions, and exiting the host cell to attack others. As part of their survival strategies, hosts have evolved effective mechanisms to defend against viral invaders by employing multifaceted immune responses. Virulence and pathogenesis are the consequences of the complex interactions between the infecting virus and host immunity. Vertebrates deal with viral infections by two types of immune responses, innate nonspecific and adaptive specific responses. The innate immune response is a rapid response to prevent the spread of viruses during the early phase of the invasion. The innate immune response includes synthesis of interferons to inhibit virus replication and the induction of natural killer (NK) cells to lyse virus infected cells. The adaptive immune response has two components, the humoral and cell-mediated responses. The humoral response attacks viruses when they are present in the host's circulation by...

Examples and Potential of Gene Therapy

Some gene therapy successes have, however, been noted. Children born with severe combined immune deficiency, X-SCID, have a poor prognosis using traditional medicines. The disease is caused by a mutation on the X chromosome in the gene encoding the gamma chain (yc) of the interleukin-2 receptor. Mutations in this gene prevent two types of white blood cell, the T-cells and natural killer cells, from developing normally (Sugamura et al., 1996). With little or no defence against infection, sufferers usually die within the first year of life unless a bone marrow donor can be found. Stem cells were collected from the bone marrow of an affected infant and treated with a retrovirus carrying a wild-type copy of the yc gene (Cavazzana-Calvo et al., 2000). When the transgenic stem cells were returned to the infant they were capable of generating all of the cells required for a fully functional immune system for at least 10 months (Fischer, Hacein-Bey and Cavazzana-Calvo, 2002). Removing the...

Suggestions For Further Study

Factors and tolerance thresholds that precipitate susceptibility to specific pathogens are not known, and development of optimal husbandry techniques for different shellfish species, age classes and environmental holding conditions should be a priority. Alternative treatments to broad-spectrum antibiotics are required, and this may be achieved by more research into vaccines and or mechanisms to stimulate the immune system in shellfish.

Effects Of Neoplasms On Captive And Wild Fish

Because of concern about adverse effects on humans, considerable emphasis has been placed on the use of fish neoplasms as sentinels for the presence of chemical carcinogens (Sonstegard and Leatherland, 1980 Dawe, 1990 Grizzle, 1990). However, a fish population exposed to chemical carcinogens could also be adversely affected by the toxicity of environmental pollutants therefore, neoplasms can also be considered as sentinels for less conspicuous impacts of pollutants on the fish themselves. Effects on behaviour (Ostrander et al., 1988) and the immune system (Faisal et al., 1991 Seeley and Weeks-Perkins, 1991 Weeks et al., 1992) of fish have been documented. Because of complex effects of pollutants on food chains, growth rates of fish in polluted environments can increase or may not change, but reduced growth rates of fish have occurred in some polluted environments (Grizzle et al., 1988a). Decreased reproduction could be caused by several mechanisms, including toxicity to fish larvae...

Structure of the outer membrane

The B. burgdorferi outer membrane contains a relatively low density of transmembrane-spanning proteins as determined by freeze-fracture electron microscopy studies (Walker et al., 1991 Radolf et al., 1994 Jones et al., 1995). This may explain why B. burgdorferi is more susceptible to disruption by routine physical manipulations such as centrifugation and resuspension and is more susceptible to detergents compared with Gram-negative bacteria. It is very likely that the unusual surface of this bacterium contributes to the unique properties that B. burgdorferi s.l. possesses, e.g. the ability to survive in both the mammalian host and the tick and to evade the mammalian immune system. Thus, a comprehensive analysis of the membrane architecture and constituents would yield insight into the unique physiological mechanisms by which the bacterium survives in diverse environments and may also elucidate pathogenic mechanisms operative during LB.

How do approved drugs used in MS prevent attacks

Glatiramer acetate (Copaxone), although not an interferon, appears to behave as theorized. As designed, it seems to function as a decoy for the immune system. It prevents myelin-like proteins from activating mechanisms causing additional myelin damage. Extrapolating from animal studies, there appear to be a number of beneficial effects on immune function when using Copaxone. There is recent evidence that Copaxone plays an important role in MS by switching off cyto-toxic lymphocytes (CD8+ cells) and turning on immunosuppressive activity.

Phase 2 uncompensated shock

Numerous chemical mediators have been identified in shocked patients, but the roles of each have not been clearly identified. They include histamine, serotonin, cytokines (especially tumour necrosis factor and interleukin 1), xanthine oxidase (which generates oxygen radicals), platelet-aggregating factor, and bacterial toxins. They are largely produced by cells of the immune system, especially monocytic macrophages. It has been suggested that these mediators, which developed as initial adaptive responses to severe injury and illness, may have deleterious consequences in the unnatural setting of the resuscitated patient.When the role of these chemical mediators is more fully understood, blocking agents may be produced which will improve the treatment in phase 2 shock.


Gene expression profiling approaches for the monitoring of anticancer immune responses Abstract Modulation of cancer growth by the immune system is a natural phenomenon that can be enhanced by immune manipulation. The complexity of this biological event has only partially explored. Conventional monitoring of immune responses has extensively focused on specific interactions between immune and cancer cells based on limited number of well defined molecules. The discovery of additional co-factors and multiple components involved in a variety of signal transduction and other regulatory pathways of immune recognition has broadened the horizons of conventional immunology studies. As the understanding of the network of interactions between individual molecules associated with immune function increases, it is becoming apparent that no single mechanism or hypothesis can in itself explain complex phenomena such as immunologically-mediated tumor rejection. As described in depth in previous...

Primary Low Grade BCell Lymphoma of the MALT Type and Immune Deviation

Within the scope of this chapter it is impossible to review special immunological features of the eye however, it should be mentioned that the anterior eye chamber (comparable to brain, placenta, testicle) has a special immunological state of reduced activation of the specific and non-specific immune system. This condition of local immune suppression, termed the immune privilege, is expressed in delayed or totally suppressed rejection of allogenic transplantations in these organs. This is illustrated in the survival of corneal and lens transplants in the anterior eye chamber and is called immune tolerance. It is known that such tolerance is transferable by injection into a second animal of splenocytes from an animal that was primed by inoculation of an antigen, demonstrating that antigens from the anterior eye chamber receive a signal that produces immune deviation and that regulatory T-cells have developed.

Risk of progression and the value of surrogate markers

Variables associated with rapid disease progression include a symptomatic PHI, older age at diagnosis and receiving a large inoculum of virus, for example via a contaminated transfusion from a donor with a high viral load. The effect of prophylaxis against opportunistic infections (for example cotrimoxazole for pneumocystis and toxoplasmosis) has been to delay the onset of AIDS and to change the pattern of disease represented by the first AIDS-defining illness. Antiretroviral treatment has independently been shown to increase survival before and after AIDS. Some infected individuals do not progress for many years and work is in progress to determine whether this is due to their genetic makeup, amount of viral inoculum, characteristics of the infective virus or their immune system.

Innate Immunity and Programming of Adaptive Responses

Phagocyte-based mechanisms of innate immunity are primarily responsible for clearing the bulk of adenovirus administered to the lungs during massive infections. However, clearance of adenovirus-infected cells is due to both NK and CTL-based mechanisms belonging to innate and adaptive cellular immunity, respectively. Further, successful reinfection by adenovirus is inversely proportional to the presence of neutralizing antibodies produced by the humoral adaptive immune system 19, 69 . While these topics are covered in detail in other chapters of this book, it is worth noting how innate immune responses to adenovirus infection in vivo regulate these adaptive immune responses. Cytokines, produced by cells of both innate and adaptive immunity have a profound effect on the nature and magnitude of specific adaptive immune responses. TNFa, the principal mediator of the acute inflammatory response adenoviral infection of the lung, also has been shown to profoundly affect both cellular and...

Conclusion on the Role of Ovarian Surface Epithelium in Adult Human Ovaries

Formation of new germ cells and primary follicles may require not only involvement of immune system related cells, but also certain hormonal milieu, namely high levels of LH hCG and estrogens (Table 1). The fetal primary follicles may be able to persist for up to 12-15 years, until replaced by follicular renewal prior to or at menarche.

Persistence in the host

Once a B. burgdorferi s.l. strain has disseminated from the site of inoculation, infections tend to persist in most animals and in humans lifelong if untreated (Gern et al., 1994 Kurtenbach et al., 1994 Zhong et al., 1997). The lack of self-limitation of B. burgdorferi s.l. infections is remarkable as B. burgdorferi s.l. induces strong cellular and humoral immune responses that target a variety of Osps expressed in the host (Roehrig et al., 1992 Golde et al., 1993 Schaible et al., 1993). Both the quality and the quantity of antibodies produced in response to B. burgdorferi s.l. are dependent on the mode of infection. A large number of studies have been conducted that have analysed this phenomenon using laboratory animals as well as natural vertebrate hosts (Roehrig et al., 1992 Gern et al., 1993 Kurtenbach et al., 1994). It was found that infections with B. burgdor-feri s.l. induced by tick bites are normally characterized by a lack of antibodies to OspA and B. However, strong and...

Host Response to Gene Therapy Vectors

Three phases have been described in the elimination of adenovirus after intravenous delivery 57 . Phase one involves innate immune mechanisms, which occurs within 24 h postinfection and accounts for the elimination of 90 of the adenoviral DNA. Phase two is mediated by the adaptive immune system and consists of a cytotoxic T lymphocyte (CTL) and or antibody response to the transgene and or to the viral proteins. Phase three is characterized by a slow and constant decrease of the transgene expression even in the absence of an immune response to the transgene and is thought to be the result of leaky expression of viral gene products which leads eventually to clearance of the transduced cells. A. Innate Immune Response Although immune-related mechanisms play a significant role in eliminating the recombinant Ad genome following in vivo administration of Ad vectors, it is not clear how the immune response to Ad vectors is initiated, i.e., for the immune system to be sensitized to Ad...

Personality and health

Although, as was seen in previous chapters, personality is reasonably settled, it is not set in stone. To some extent personality is modifiable and so it is with Type A behaviours. Generally, we can alter our perceptions and emotional reactions by working on our cognitions. So, someone who recognises Type A tendencies in himself or herself might set various life-style changes in place, ranging from taking more exercise and learning relaxation techniques to broadly changing typical reactions to stressful situations. An example might be learning to be relaxed when standing in a supermarket checkout queue behind someone who cannot find the correct money or who seems to have forgotten the pin number on their card. In this situation, the Type A person would be tense with frustration and impatience and even potentially hostile. The control of any such way of reacting can only be good for the immune system. Linked to attitude or approach to life and the proneness to disease is what is...

Asymmetric Division in Stem Cells

Classically, stem cells are defined as cells that 1) are pluripotential or multi-potential (i.e., able to generate different cell types, 2) have the ability to self-renew and at the same time generate progeny that are committed to a differentiation pathway, and 3) divide throughout the life span. Some of the most common stem cell lineages include cells in the immune system, germline, skin, intestinal epithelia and brain (reviewed in Hall and Watt 1989). Embryonic cells are also considered stem cells although they do not The other argument would be that RA is activating neuron-specific genes and DMSO is activating muscle-specific genes, thus forcing these cells to differentiate, and into specific lineages. However, several additional studies lend support to the scenario where activities of certain genes maintain an undifferentiated multi-potential state and inactivation of those genes is necessary for the cells to differentiate (Littlefield and Felix, 1982 Bhat et al. 1988 Williams et...

Material to be transferred between the cells

In a multicellular organism there are not just two cells, or two kinds of cells, but many. They talk to one another and direct each other's activities. Details of these cell-cell interactions are being uncovered in many areas of research, including embryo development and immunology. Embryo development and the immune system provide dramatic illustrations of the complexity of cell-cell interactions. The three-way dialogue we have outlined in this chapter is manifested less dramatically elsewhere, but it is fundamental to multicellular life. At the whole-body level, homeostasis (chapter 6) depends on cell-cell communications of the sort we have touched on here. Cells respond to signals from one another. Thus, homeostasis is extended from the single cell, as described in chapters 6 and 8, to the vast multicellular assemblies that constitute organisms such as ourselves.

Overview Components of Innate Immunity

Innate immunity is the first line of defense against infections. The phylo-genetically ancient, phagocyte-based effector mechanisms of innate immunity exist in their mature state prior to microbial exposure and infection does not alter the intrinsic specificity of the system components. This is in sharp contrast to the more recently evolved mechanisms of adaptive immunity in which the microbial encounter leads to gene rearrangements that alter the intrinsic properties of the system components, e.g., following infection, microbe-stimulated antibody gene rearrangements lead to production of antibodies of greater affinity for the microbe. Mechanisms of innate immunity are either constitutively active or are activated very rapidly after infection (prior to development of adaptive immune responses) and serve three very important functions. First, as the initial host response, innate defenses limit or prevent infection by rapidly eliminating microbes (clearance). Second, the effector...

Contributions Of Virus And Host To Disease Severity

Effective forms of prophylaxis and therapy are needed for diseases caused by biothreat agents, not only to treat persons exposed in an attack but also to reduce the psychological impact of terrorism by reassuring the public that protective measures are available. Responding to the threat of highly pathogenic viruses will require an understanding of three factors that combine to produce severe illness (1) viral cytopathic effects, (2) virus-induced suppression or evasion of innate and adaptive immune responses, and (3) intense host inflammatory responses that produce many signs and symptoms of disease and contribute to a fatal outcome. The other two factors that contribute to the severity of illness result from interactions between viruses and the human immune system. The virulence of these agents appears to be based in large part on the fact that they have never adapted to humans but instead have coevolved with various animal species, in which they are maintained through natural...

Mechanism Of Action Studies

There are several reports that indicate that TNP can also affect nonendothelial cells. As mentioned in Section 2., TNP enhances the proliferation of normal human, but not tumor-derived, B-lymphocytes in vitro, this phenomenon requires the presence of normal T-cells (9). Also in vitro, TNP stimulates the proliferation of murine B T-lympho-cytes in the presence of phytohemagglutinin (13). Follow-up in vivo experiments showed an increase in the size of axillary or mesenteric nodes in a murine model following treatment with TNP this increase was not apparent in T-cell-deficient mice (9). The mechanism by which TNP modulates the immune system warrants further investigation.

Altered Bacterial Growth Characteristics

Microorganisms are known to rapidly develop adaptively to a variety of environments, possibly as a result of metabolic changes. In an in vitro environment, bacteria differ from those cultivated in vivo in terms of amino acid composition, the synthesis of toxic metabolites, and metabolic rate 24 . Overall, bacteria are more metabolically active in vivo than in vitro. However, replication generally occurs more rapidly in an in vitro environment, possibly due to the lack of immune system effects. For example, it has been shown that the typical growth rate of microorganisms in an in vivo animal model of infection may be on the order of 0.02-0.05 h-1, wheras the growth rate in an in vitro batch culture may approach 2-3 h-1 25 . Continuous culture of microorganisms, which allows precise control of growth rate, may allow maintenance of microorganisms in a state of growth more closely approximating that of organisms in the natural state 25 .

Molecular Regulation in Mesenchymal Stromal and Hematopoietic Cells during Tumor Neovascularization

Growth factors produced by the tumors act as potent chemoattractants for hematopoietic cells VEGF, SDF-1, Ang-1, PlGF, and BDNF 66,98 . The recruitment of hematopoietic BMDCs and the infiltration of these cells into diseased tissue are often massive in scale, particularly in tumors. The predominant populations are myeloid cells (macrophages, neutro-phils, etc.), and they also produce chemokines, angiogenic growth factors, and MMPs, thus promoting tumor angiogenesis and progression 10,11 . However, T and B cells may also play important roles at certain stages of carcinogenesis 99,100 . But if the presence of these cells is indicative of a response of the immune system directed against the cancer cells or of a nonspecific inflammatory response that favors tumor growth remains to be determined. Alternatively, if the immune cell infiltrate in tumors is the result of the exponential expansion of precursors (i.e., stem or progenitor cells), the function of BMDCs in the tumor might be...

Tolerance Due to Negative Tcell Selection

Numerous laboratories (e.g., 10, 11 ) have demonstrated deletion of potentially autoreactive T cells by active killing when ap TCRs on immature CD4+CD8+ thymocytes or semi-mature CD4+ or CD8+ (single-positive thymocytes characterized by elevated CD24) are engaged by MHC and peptide ligands of high affinity for the TCR. cTECs do not have the capacity to initiate this process of negative selection, probably because they lack costimulatory molecules such as B7-1, B7-2, and CD40L. Immature thymocytes must encounter other antigen-presenting cells, particularly those of hematopoietic origin such as dendritic cells or macrophages 12 , or epithelial cells in the thymic medullary region 13, 14 to result in elimination. Estimates of the proportion of T cells that are deleted by high-affinity interactions with thymic antigen-presenting cells range from 5 15 to over 50 16 of T cells that had undergone positive selection in the thymic cortex. The process of clonal deletion of strongly...

Selftolerance Due to Thymusderived Regulatory T Cells Natural Regulatory T Cells

The past half-decade has seen a large upsurge of information on T cells that suppress the function of effector T cells. While such regulatory T cells (TR) have come to be identified in different ways, a population of CD4+ T cells that consti-tutively express CD25 (interleukin-2 receptor) initially described by Sakaguchi and coworkers (reviewed in 37, 38 ) remains the most thoroughly studied. In a lymphopenic host these cells are necessary to prevent spontaneous autoimmunity to certain organs including testis, prostrate, ovaries, thyroid, pancreas, and stomach, depending on the mouse strain. CD4+CD25+ TR comprise 5-10 of the peripheral T-cell pool and suppress the activation of CD4+ and CD8+ effector T cells by a process that requires cell-to-cell contact at a suppressor effector cell ratio of 1 1 39 . It is also possible that CD4+CD25+ TR act on APCs to suppress T-cell activation, but inhibitory cytokines do not seem to be involved 37, 38 . Of particular relevance to central T-cell...

Alcohol dehydrogenase ADH

AIDS the acquired immunodeficiency syndrome, a disease caused by the human immunodeficiency virus (HIV). This virus attacks lymphocytes of helper T subclass and macrophages. The depletion of these cells makes the patient susceptible to pathogens that would easily be controlled by a healthy immune system. The infection is transmitted by sexual intercourse, by direct contamination of the blood (as when virus-contaminated drug paraphernalia is shared), or by passage of the virus from an infected mother to her fetus or to a suckling baby. AIDS was first identified as a new infectious disease by the U.S. Centers for Disease Control and Prevention in 1981. See Appendix C, 1983, Montagnier and Gallo. HIV, lymphocyte, retroviruses.

Brain to blood blood to brain

Were derived from ROSA26 animals, that are transgenic for lacZ. Contribution of the donor NSCs to the recipient blood was determined using H-2kb, which is expressed by hematopoietic cells of donor origin (ROSA26), but not of recipient (BALB c) origin. Donor-derived engraftment was observed in 100 of bone marrow recipients, 100 of embryonic NSC recipients, 70 of adult NSC recipients, and 63 of the clonal adult NSC recipients. Between 35 and 65 of CD45-positive hematopoietic cells were donor derived, regardless of whether initial tissue came from adult brain or embryonic brain. Donor-derived hematopoietic cells were present in the blood 5 to 12 mo posttransplant. Repopulation of the immune system after neural cell transplant took an average of 3 wk longer than after bone marrow transplant.

Reasons for some Parasites Causing Detrimental Effects

Secondly, parasites inhabiting tissues of organ systems other than the gut tend to be more pathogenic than gut-inhabiting forms because they directly utilise and damage host tissue thus generating a stronger immune response. It is not surprising therefore that it is parasites living on the eye (Diplostomum), in the blood system (Sanguinicola), the body cavity and viscera (tapeworm larvae such as Ligula, Schistocephalus and Diphyllobothrium), the swim bladder (Anguillicola crassus) and gills (Gyrodactylus salaris and sea lice) which occupied pride of place in a recent symposium dealing with parasitic diseases of fish (Pike and Lewis, 1994). Fifthly, parasites can become more harmful to the host as a result of damage to the innate and adaptive arm of the immune system caused by detrimental changes in the environment. Examples are provided by low water temperature (Chubb, 1982 Hardie et al., 1994 LeMorvan et al., 1998 Bernstein et al., 1998), specific pollutants including heavy metals...

Cancer Vaccines That Elicit

Dendritic cells are key to induction of CD8 T-cell responses to tumors. DC are attracted to tumor sites by cytokines released either by the tumor itself, or nearby DC, NK cells or other elements of the innate immune system. After ingestion of potentially antigenic material, the DC migrate to nearby lymph nodes where they in turn activate CD4 and CD8 T cells to peptides displayed on their MHC molecules (94, 95). Peptide-presenting DC can be prepared in the laboratory either by peptide pulsing or by transfection with cDNA encoding key peptides. It is also possible to present larger antigenic protein structures to DC, and allow them to process these naturally into peptides for MHC loading. A promising recent approach involves introducing tumor antigen genes into hematopoietic stem cells, and then infusing these back into mice where they travel to bone marrow and produce antigen-laden DC. The advantage is better homing of such cells to lymph tissues where they can interact with T cells...

Extracellular Sequestration and Release of FGF2

The involvement of sulfate groups in FGF-2 sequestration by the subendothelial ECM was studied by growing the ECM-producing cells in the presence of chlorate, a potent inhibitor of sulfation (61). Both the FGF-2 content and growth-promoting activity of sulfate depleted ECM were less than 10 of native ECM, indicating that sulfate moieties of HS are involved in FGF-2 sequestration and growth promoting activity of the ECM. FGF-2 is also sequestered by HS on cell surfaces, as revealed by immunohistochemistry (137), release by glycosyl phosphatidylinositol specific phospholipase C (PI-PLC) (142,143), and displacement by heparin from the luminal surface of blood vessels (144). Heparanase, an endoglycosidase that specifically degrades HS, was found to be a most efficient specific releaser of active FGF-2 from ECM (145). The authors' studies suggest that heparanase activity expressed by metastatic tumor cells and activated cells of the immune system may not only function in cell migration and...

Maintenance therapy after combination therapy

The National Institutes of Health has defined general principles for the therapy of HIV (34). Both plasma HIV RNA levels (viral load) and CD4+ T cell counts should be followed for monitoring of response to treatment. The combination of these values has been determined to be a more accurate assessment of prognosis (35). In addition, they are a useful tool in determining the efficacy of antiretro-viral treatment while the patient is awaiting clinical response. CD4+ counts indicate the extent of immune system damage and the risk for opportunistic infections. Although HIV RNA levels are more predictive of the risk for disease progression, CD4+ counts are a more accurate measurement of the effect of antiretroviral therapy.

Signaling Milieus At The Effector Sites

Once plasmablasts have extravasated into the effector sites, various signals promote their final maturation to plasma cells and support plasma cell survival and ongoing dIgA secretion. Many of the same signals support expression of pIgR by the overlying epithelium. VIP increases SC secretion by primary cultured lacrimal acinar cells (61). Some signals, e.g., a-MSH, VIP (62-65), and nitric oxide, are released from nerve endings (66). The epithelial cells themselves provide additional critical signals, including IL-6 (67-69), which is an important survival factor for plasma cells, and TGF- , which supports epithelial function in the mucosal immune system in autocrine fashion, by enhancing epithelial expression of pIgR (70) and IL-6 (71), and in paracrine fashion, by supporting dIgA production (72,73). Systemic hormones support mucosal immune functions at several different effector sites. Ventral prostate and urethral gland epithelial cells express pIgR, and IgA+ cells populate the...

Proteolytic Cleavage of Autoantigens During Apoptosis

A role of apoptotic cells in the establishment and maintenance of tolerance to peripheral tissues has also been established 55-60 , providing the immune system with the appropriate forms of autoantigens that will likely be encountered during homeostatic cell death of self-tissues.

How adult salmonid fish are becoming infected

What has intrigued biologists most about the life cycle of IHNV is that virus typically can not be reisolated from adult fish until they approach sexual maturity. There are two hypotheses to explain this phenomenon. The first is that fish may become reinfected by a new exposure to IHNV during the spawning migration. This implies that the virus is present in the environment or in another host. The second hypothesis is that fish surviving IHNV as fry may develop a latent infection, which is reactivated when the fish reach sexual maturity. Fish returning to fresh water to spawn are undergoing stress, which may weaken the immune system so that the fish cannot control the virus (Mulcahy et al, 1984b). Hormonal changes may play a role, but injection of sex hormones did not induce

The Dream and the Reality

Severe combined immune deficiency (SCID) is a term used to describe several exceedingly rare, but cruel, genetic diseases that mimic AIDS. Affected children are normal at birth, but within months, as the protective antibodies that their mothers provided to them disappear, they are plagued by repeated bouts of unusual infections. They fail to grow well and are often hospitalized for pneumonia. Because of a single small genetic error, their immune systems cannot properly make the T cells and B cells that normally patrol the human perimeter and quickly kill foreign bacteria, fungi, and viruses that are incessantly trying to invade. When he was 12, David told his parents and his doctors that he wanted to take the risk. Unfortunately, heroic efforts to find a bone marrow donor who would be a perfect immunological match were unsuccessful. There was one other choice. Scientists at the Dana Farber Cancer Institute in Boston had developed a technique to help imperfectly matched bone marrow...

How Many Genes

Each human unfertilised egg contains one complete human DNA genome in its 23 chromosomes, and each human sperm cell contains a human genome, with an equal chance it will have an X sex chromosome or a Y sex chromosome. On fertilisation there are two genomes, one from each parent, but the females have two X chromsomes and the male has an X and a Y. When the embryo develops, each cell has these two DNA genomes, and this is true of every cell in our body, except for red blood cells. Some cells of the immune system have a slightly altered genome. Also, there is a small amount of DNA in the respiratory mirochondria, which are inherited from the mother. they could last much longer than a lifetime. The whole architecture of the body is determined by genes, but this design, as we have seen, is fundamentally incompatible with indefinite survival. Also, the major maintenance mechanisms are all specified by genes. For example, the efficiency of DNA repair depends on the success of enzymes, whose...

Selected Examples Of Ageassociated Susceptibility To Bacterial Infections

Research concerned with TB was at a low ebb during much of the 20th century. In the 1980s there was a resurgence of research prompted by the recognition that (a) TB was a prominent opportunistic infection among AIDS victims and (b) many cases of TB were caused by antibiotic-resistant organisms. Much has been learned in the last decade. There has been some debate concerning which experimental animal serves as a suitable model of human TB and, further, as to whether or not aging experimental animals are more susceptible to Mycobacterium infections than young adults. It was reported that old mice were no more susceptible than young adults to M. tuberculosis (16). The levels of bacteria in target organs and the frequency of death from infection were reported to be essentially the same in young and aged mice. Systematic studies by Orme and associates have shown that there is a difference in the way mice (young and old) cope with M. tuberculosis infection depending on the route of infection...

Natural Killerlymphokineactivated Killer Cells

Among the former were genes encoding IFNy, MIP 1a, MIP ip, and lymphotactin. Among the latter were caspase II, apoptosis receptor TDAG 8, and metallothionein I. Also, some genes were suppressed such as mouse TCRy chain, mouse MEL 91, mouse diacylglycerol acyltransferase, and several others. Overall, it could be concluded that substances directly involved in regulating immune responses are produced at the site of receptor activation and that NK cells and their activating Ly 49 receptors are important initiators of microbial immunity and key elements of the innate immune system (263). NK-T cells, like NK cells, are enlisted early in the course of many infections. Cytokines such as IL-2 and IL-12 stimulate both types of cells to produce IFNy and display cytotoxicity. Activators such as a-galactosylceramide stimulate rapid activation of NK-T cells. Evidence has been provided that NK-T activation leads quickly to NK activation and IFNy secretion (268). Those activated NK-T cells...

Why arent drugs used together to get a better effect

In a form of shorthand that immunologists use, helper T-cell immune function is referred to as CD4 Th1 function, and suppressor inducer T-cell (immunoreg-ulatory) is referred to as a type of CD4 Th2 function. The net result of both the interferons and glatimer acetate is to shift immune function away from Th1 activity toward Th2 function. It would seem that the drugs used in combination might be more effective in altering immune function to increase CD4 Th2 func

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