Immune System Boosters

Immunity Crisis

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Immunity Crisis Summary


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Acquired Immune Response

The development of immunity to a particular pathogen occurs after initial exposure to the antigen. The immunity is due to the development of an acquired immune response to the pathogen. A baby is born virtually immunologically naive. Maternal antibodies that have crossed the placenta provide transient protection from infection until the newborn's own immune system has developed sufficiently to mount an immune response strong enough and fast enough to protect against initial infection. After a primary immune response to a pathogen, an acquired immunity is developed such that any further infection by that pathogen is immediately controlled. The secondary or acquired immune response to the pathogen is more rapid and of greater magnitude and thus provides elevated protection against infection. From birth throughout a person's life, the immune system is continually responding to new environmental challenges (e.g. bacteria and viruses), and developing immunity to those challenges. The study...

Medical indications of the acquired immune response

Acquired immune response is vaccination. The simple and elegant theory of vaccination is that induction of a primary immune response by a nonpathogenic form of an antigen leads to immunity of the infectious form. Common types of vaccines are attenuated pathogen, related noninfectious antigen, and purified proteins from the pathogen. Examples of all of these vaccines have been used to induce a primary immune response that confers acquired immunity. See also Affinity maturation Antigen-presenting cells Antigens, T dependent and independent Immune response Immunoglobulin class switching Maternal antibodies Memory, immunological Vaccines.

Activities outside the immune system

C5a also acts on liver cells and induces the expression of acute phase proteins. Furthermore, the mRNA for the receptors for C5a and C3a are widely expressed in a large number of tissues and organs, indicating that anaphylatoxins may have other, largely unexplored, functions outside the immune system. Particularly abundant transcripts for the C5a receptor are found in lung, spleen, heart, placenta, spinal cord and throughout the brain, and for the C3a receptor in lung, spleen, ovary, placenta, small intestine and less ubiquitously in the brain.

Immune response of the host

In ascariasis, as is thought to be the case in some other helminth infections. Experiments in mice have shown that the immune response in Ascaris infection is dominated by TH2 cells, which presumably explains the high IgE, mastocytosis and eosinophilia of the infections. In experimental infections in mice with other species of intestinal nematode, the TH2 response is crucial to the immune elimination of the parasites.

Overview Of The Immune System

Although a more detailed description of the immune system is provided in other articles of this encyclopedia, it is necessary to briefly review the basics of immunology. This is not meant to be a comprehensive review but, rather, is meant to provide the reader with sufficient background to interpret research in the field of behavioral neuroimmunology. The general purpose of the immune system is to defend the body against infection and disease by identifying and eliminating foreign nonself pathogens and mutated self cells. This is accomplished through the activity of two general categories of immunity innate (also called nonspecific or natural) and acquired (also called specific) immunity. Natural killer (NK) cells, macrophages, and neutrophils are agents of innate immunity. These cells serve a surveillance function and will attack pathogens or cancerous cells without specificity and without requiring prior exposure to the invader. In contrast, acquired immunity involves a specific...

Immune responses of the host

Bunyaviridae are highly immunogenic, inducing neutralizing antibodies which are type specific but show limited cross-reactivity within the genus. Recovery is normally followed by solid protection against reinfection. In some infections the immune response occurs too late to prevent invasion of the central nervous system or the liver. Thus animal infection with Rift Valley fever virus can produce overwhelming infection, with liver necrosis and high mortality. Some American hantaviruses target the lungs, rather than the liver, kidneys or central nervous system, resulting in hantavirus pulmonary syndrome. The intense inflammatory response in these infections leads to the release of mediators followed by increased vascular permeability throughout the lungs, and consequent clinical disease.

Immune response to carbohydrates

The length of an oligosaccharide, to be attached to proteins to form a suitable conjugate vaccine, must vary. In cases where there is a distinct tertiary structure (see above) of the saccharidic immunodeterminant in the natural, bacterial or viral product, that tertiary structure must undoubtedly be mimicked by the (synthetic or derived) saccharide to be conjugated. The resulting antibodies generated by the immune response would then be able to recognize readily the natural immunogen.

Colonic Immune Function and Colonic Bacterial Flora

The immune system of the gastrointestinal tract defends against infection (bacterial, viral, and parasitic) and luminal antigens ingested formed by bacteria. Nonspecific and specific mechanisms exist. The enteric immune system is vast and complex it interacts with the rest of the immune system as well as with luminal contents. Gut-associated lym-phoid tissue consists of both discretely organized tissue, such as Peyer's patches (lymphoid follicles with proliferative potential in response to antigen presentation) containing M cells, and the more diffuse lymphocytes and macrophages distributed among the submucosa, mucosa, and lamina propria (Figure 6). M cells function in antigen sampling of

Immunotherapy of EBVAssociated Malignancies

EBV-associated monoclonal tumors in otherwise immu-nocompetent individuals are known to be mostly invisible from an immunological point of view. In comparison, lymphoproliferative diseases after hematopoetic stem cell transplantation or solid-organ transplantation usually arise as polyclonal proliferations of EBV-infected immortalized cells that are subject to immune control. Immediate partial reconstitution of immune surveillance is the first action to take. Without treatment, benign polyclonal proliferations often progress to oligoclonality or monoclonality with greatly reduced chances for successful therapy.

Exercise And The Immune Response

Exercise induces a variety of coordinated physiological and biochemical responses which dramatically alter the distribution and function of immunocompetent cells. Exercise-associated changes in hormone release, blood flow distribution, cardiac performance and substrate utilization have significant implications for the functioning of the immune system. For example, short, vigorous bouts of exercise (e.g. sprinting), sustained, strenuous exercise (e.g. marathon running), or intermittent, vigorous exercise (e.g. soccer) induce an immediate leukocytosis with white blood cell counts increasing anywhere from two- to eightfold above pre-exercise levels. Immunological changes which accompany exercise are of both fundamental and applied interest. Physiologically, exercise-associated changes in the behavior of immune cells parallel changes induced by other physical stressors, such as thermal injury, hemorrhagic shock, and surgery. From a public health perspective, exercise-induced...

Helminth Survival Of The Immune Response

Of course, bacteria are not unique as invasive survivors of the immune response. Some of the most interesting examples are helminths, where survival, dependent on the nature of the immune response, can affect the ability to transfer disease. This is seen in Ascariasis, where in infected hosts the rise in IgE levels correlates inversely with the ability to excrete eggs. The lower the IgE, the more eggs excreted, and the worse the clinical disease. The consequence of this is that the lower the adaptive immune response, the greater the likelihood of transmission of the disease and hence survival of

Acquired immune deficiency syndrome

Infection with HIV, a retrovirus of the lentivirus subgroup is these days one of the most frequent causes of immune deficiency. This syndrome give rise to a diverse range of symptoms and the development of opportunistic infections and malignancies. Most infections in the West result from the B clade of HIV-1, but different clades (HIV families, that can be distinguished on the basis of viral sequence) predominate in other parts of the world. In South Asia the E clade predominate and in sub-Saharan Africa the A and C clades are the most common. Infection with the related retrovirus, HIV-2, which is found predominantly in West Africa. This infection gives rise to a more protracted disease course. Patients infected with this virus have fewer signs of immune deficiency.

Echinodermata Immune System

We now call an immune system, as a strong defence mechanism able to resist host attacks in an efficient way. The term immunis comes from the Latin meaning exempt , referring to protection against foreign agents. It is still believed that in all organisms of the animal kingdom the cells of self are virtually marked, so that they are not attacked by their own defence mechanism. Therefore, the immune system must have the capacity to discriminate between self and non-self, to transform itself to deal with future dangers, and, in addition, to change, since the self also evolves with time (e.g. during embryo development). However, the self non-self model of the immune system has recently been disproved because of many inconsistencies (1) not all foreign cells need to be destroyed, some in fact must be assimilated for nourishment (2) in mammals the growing embryo, in principle a host, is not destroyed by the immune system of the mother. This is just to quote two examples. To solve these...

The immune response to HIV and the correlates of protection

HIV induces neutralizing antibodies, antibody-dependent cellular cytotoxicity (ADCC), and cytotoxic T lymphocyte (CTL) activity in infected hosts. Unfortunately, it remains unclear as to whether any one, or all, of these activities can prevent infection and disease progression in the majority of individuals. It is important to appreciate that the quality of the immune response that protects against infection and the type of response required to contain infection may be different. This, of course, will have important implications for the development of preventative and therapeutic vaccines. This problem is further compounded by the fact that HIV-infected chimpanzees do not appear to develop an AIDs-like disease, and hence they may have a vital immunological difference that allows a vaccine to prevent HIV infection that will not extrapolate to protection of humans against the same infection.

Immune function under pressure

The scarce experimental results on immune function under hyperbaric conditions of about 10 atm indicate an overt immune suppression, most of which might be attributed to hyperbaric oxygenation. Practically, a full recovery in immune function has been observed shortly after return to the ambient pressure. effect of decrease in membrane fluidity by cholesterol, which markedly suppresses immune function.

Establishment of the immune response in vitro practical considerations

Sources of cells for immune responses in vitro The cellular component of an in vitro immune response (Table 1) must contain viable and potentially active leukocytes. Problems with respect to this essential requirement can arise due to differences between the in vitro and in vivo immune response systems. Within secondary lymphoid organs, in which immune responses are initiated, there is a high cell concentration and a cellular network permitting The loss of the in vivo intercellular interactions abrogates the delivery of signals required to control programmed cell death (also referred to under the morphologic term of apoptosis). This is particularly the case with T and B lymphocytes, but not with monocytic cells, endothelial cells or fibroblasts, which can be cultured without much problem. The majority of T and B lymphocytes may enter programmed cell death within the first 3 days of culture, in the absence of stimulation and cosignaling. Stimulation of the lymphocytes in vitro with...

Enrichment of cells for immune responses in vitro

Separation of mononuclear cell subpopulations has been successfully applied to increasing the efficacy of immune response systems in vitro. The simpler methods make use of the differential adherence of leukocyte populations. T lymphocytes can be separated by the preferential binding of B lymphocytes and monocytes to nylon wool, although some T lymphocytes may also display a degree of adherence. primary and secondary immune responses

Primary immune responses in vitro general considerations

Mononuclear cell cultures derived from secondary lymphoid organs are preferable, in general, to blood cell cultures. Within the former, the cell populations required for an immune response are correctly represented, whereas blood mononuclear cells have a greater dominance of T lymphocytes, and an important population of suppressor cells. The latter can be impaired, unless they are the subject of interest, using agents such as leucyl methyl esters, The expected concentration of antigen-reactive lymphocytes within a primary immune response in vitro will be not more than 1 in 10h. Considering the required cellular interactions, and that conventional cultures employ between 2 x 106 and 2 x 10 leukocytes ml 1, this low concentration of potentially reactive cells does not lend itself to success. Enrichment procedures have been particularly useful in circumventing this problem. The potential also exists to apply hollow fiber or similar capillary culture vessels, wherein cell concentrations...

Initiation of the primary immune response in vitro

With the immune response in vitro, B lymphocytes will be directly stimulated by antigen, whereas TH lymphocytes must await antigen processing. This can result in stimulated B lymphocytes requiring T lymphocyte help before it is available. A relatively simple solution is to apply, at the moment of immunization, the cytokines required by the B lymphocyte differentiation pathway (Figure 6 Table 2), the stimulated Th lymphocytes providing cytokines later in the response. Exogenous cytokines can be in two forms recombinant cytokines (Table 2), or a 'cytokine soup' derived from a mixed leukocyte reaction (MLR) or mononuclear cell cultures stimulated with mitogen. Not all cytokines are available in recombinant form, nor for all animal species. Furthermore, cytokine soups should provide all the required factors, not just some of them. The drawback with the cytokine soups is the variation between batches, due to variations in the responsiveness of different batches of mononuclear cells....

Initiation of the secondary immune response in vitro

Neither exogenous cytokines nor preprocessed antigen are obligatory for secondary immune responses in vitro (Figure 7). When applied, it is usually to study their influence on the immune response. These characteristics relate to the more efficient capacity of memory T lymphocytes to respond after antigenic stimulation, produce cytokines, and interact with B lymphocytes. The response is further assisted by the B lymphocytes presenting antigen to memory T lymphocytes.

Immune System Anatomy Of

Cells participating in the immune response are organized into discrete lymphoid tissues and organs and spread through the connective tissues of non-lymphoid organs. The cell type responsible for the specificity of the immune response is the lymphocyte. Approximately 2xl012 lymphocytes constitute the mature lymphoid system in humans together with a variety of 'accessory* cells which include epithelial cells, monocyte macrophages and other antigen-presenting cells. Accessory cells are required both for the maturation and for the effector functions of lymphocytes. The bone marrow, and earlier in fetal life, the liver, and the thymus provide the microenvironments for the differentiation of B and T lymphocytes respectively, and for the production of mature cells responsible for humoral or cellular immune responses. During B and T cell maturation, similar events occur in the bone marrow and in the thymus, namely the rearrangement of the genes encoding antigen receptors (immunoglobulin (Ig)...

Types of immunotherapy

A major goal of immunotherapy is to selectively reduce the unwanted immune response, but retain other protective immune responses. Existing anti-immune drugs are not clearly selective. Selectivity could be obtained in a variety of ways. One is by the induction of immunological tolerance. This comes in various forms, all defined as antigen-induced, antigen-specific immune suppression. Other approaches, less specific, would include inhibiting a portion of the HLA class I and II antigens or the HLA-peptide complex involved in presenting peptides to T cells. Alternatively, as some T cell responses to antigen use a narrow range of T cell receptors for antigen, targeting a subset of T cell receptors (TCRs) by using monoclonal antibodies or superantigens is being attempted. Targeting lymphocytes bearing markers of activation, such as interleukin 2 receptor (IL-2R, CD25), also offers a degree of selectivity.

Immunotherapy Of Tumors

The concept of the immune system being involved in the development of cancer and of manipulating it as a part of cancer therapy dates back almost 100 years to the experiments of William Coley with bacterial toxins ('Coley's toxin') used in the treatment of advanced breast cancer, apparently with some success. Ehrlich developed the concept of immune surveillance against the development of cancer, the immune system acting to detect and eliminate cancerous or precancerous cells. This hypothesis has received new impetus with the recent development of monoclonal antibodies and recombinant cytokines, particularly the interferons and more recently interleukin 2 (IL-2), thereby providing powerful tools for the manipulation of the immune response. For immune surveillance against cancer to be plausible theory, cancer cells must express antigens recognizable as foreign by and accessible to the immune system, which must in turn be able to mount a response against cells bearing such antigens. Such...

Mouse models for genetic defects of the immune system

The gene knockout technology has been particularly useful to study the function of the immune system. Numerous mouse strains with deficiencies in T cell and B cell function, in cytokines and their receptors or in the development of lymphoid organs have been developed. Analysis of these models not only gave new insights into mechanisms controlling the immune system but also provided valuable animal models of immunologically relevant diseases in

Approaches to immunotherapy with LAK or ANK cells

Adoptive transfers of LAK cells and IL-2 to tumor-bearing animals were effective in inducing the regression of established lung, liver and subcutaneous metastases of immunogenic and nonimmuno-genic sarcomas or adenocarcinomas. To achieve therapeutic effects with LAK cells plus IL-2, it was necessary to administer sufficient numbers of LAK cells and high enough concentrations of IL-2 and to reduce tumor burden by previous surgery or by-including chemotherapy. Therapy with LAK cells of IL-2 administered as single agents had little or no antimetastatic effects in animals bearing non-immunogenic tumors. On the other hand, high doses of IL-2 alone could induce appreciable tumor reduction in animals bearing immunogenic tumors. Basically, the experience with LAK cells plus IL-2 in animal models indicated that this form of therapy could be effective against a metastatic tumor if the tumor burden were first reduced by surgery or chemotherapy. Complete elimination of existing micrometastases...

Maturation Of Immune Responses

Maturation of adaptive immune responses involves a comprehensive system development of multiple components at both the protein and cellular levels in response to the introduction of foreign antigen (immunogen) into an immunocompetent host. Maturation of an immune response commences with recognition of a pathogen or foreign material, either particulate or soluble, and subsequently proceeds through a progressive manifestation of both specific humoral and cellular immune responses mounted to eliminate the material. Stimulation of humoral immune responses leads to production, secretion and circulation of soluble antibodies which react specifically with the antigen. Induction of cell-mediated immunity involves various immunological reactions mediated by stimulated T lymphocytes and can include direct interaction of the T cells with infected or transformed cells. Maturation events associated with cellular immune responses are in general less well defined than those related to humoral...

Examples of microenvironments in the immune system

Secondary lymphoid tissues and organs demonstrate increasing levels of complexity in organization. This results in increased compartmentalization of cells, each compartment typically containing cells of different types and assortment, and forming a distinct microenvironment. With the exception of diffuse lymphoid tissue composed of a random distribution of lymphoid cells in loose connective tissues, a common feature of the organization of secondary lymphoid tissues is the presence of lymphoid follicles (also called nodules). These structures represent the functional building blocks of the immune system responsible for the development and maintenance of humoral immunity. Lymphoid follicles are found as solitary nodules or as aggregates (e.g. Peyer's patches) associated primarily with the mucosa of respiratory and digestive tracts. In the lymph node, lymphoid follicles are located in the cortex and, in the spleen, in the splenic white pulp.

Immune System Development

As it matures, the fetus develops its immune organs. Lymphocytes are generated in the primary lymphoid organs the bone marrow, thymus, and intestinal Peyer's patches. 2'3 T and B lymphocytes from these tissues then start circulating and eventually localize in peripheral or secondary immune tissues, where adaptive, or acquired, immune responses take place. Effective immune responses require immune cells to be localized in secondary lymphoid organs. The neonate requires time for its immune tissues to become mature. Because of their lack of immune system development, neonates are typically more susceptible than older animals to respiratory or intestinal infections. Probiotics have been developed to assist in maturing the intestinal immune tissues. Cytokines and chemokines serve as lymphoid tissue hormones and help to regulate immune system development and differentiation. 5 organ, the lymph node, spleen, or specialized lymphoid tissues in the gut or respiratory sites. In these secondary...

Neuroimmune interactions with the mucosal immune system

There is substantial evidence indicating that the nervous system and immune system can interact in a variety of ways that modifies the function of each. Anatomically, the gut has a rich plexus of nerves that play a critical role in organization of gut motility, and are likely to be important in other functions such as regulation of epithelial cell function. Nerve fibers can be observed in close proximity of lymphoid cells in Peyer's patches and in the lamina propria. The major neuropeptide mediators of the enteric nervous system are substance P, vasoactive intestinal peptide (VIP) and somatostatin, and lymphoid cells have receptors for each of these transmitters. In vitro, each of these neurotransmitters has been shown to have the potential for modifying the response of lymphoid cells. The effects of these transmitters are complex, but in general, somatostatin and VIP inhibit proliferation and differentiation of lymphoid cells, whereas substance P is stimulatory. In addition, VIP has...

Alterations of immune responses by UV radiation

One of the most intriguing questions raised by studies of the immunology of photocarcinogenesis is how UVB irradiation brings about systemic alterations of immune function. It is not at all obvious how exposing the skin to UV rays brings about activation of the suppressor cell pathway in response to tumor-associated antigens. Clues for answering this question have come mainly from studies of the effect of UV irradiation on other immune reactions, particularly on the suppression of delayed and contact hypersensitivity reactions. Cytokines produced by UV-irradiated kera-tinocytes can also affect antigen presentation by Langerhans cells. Following UV irradiation, kera-tinocytes are activated to produce and secrete a wide variety of immunoregulatory cytokines. Among these, tumor necrosis factor a (TNFa) appears to contribute to the downregulation of contact hypersensitivity responses initiated within UV-irradiated skin. In addition, dendritic cells with altered antigen-presenting activity...

Late Gestation Glucocorticoids and Programming of Immune Function

Function of the immune system is influenced by basal glucocorticoid levels and by HPA axis responsiveness,48 raising the possibility that alterations in postnatal HPA axis function induced by exposure to excess glucocorticoids in late gestation might alter susceptibility to postnatal inflammatory immune disease. Investigations in rats and pigs have demonstrated that prenatal stress results in postnatal immunosuppression.49 51 These effects are likely mediated by prenatal exposure to glucocorticoids but alterations in postnatal HPA axis function do not necessarily account for altered postnatal immune function in these studies,50'51 suggesting that prenatal stress has direct programming effects on development of the immune system. Only a few experimental studies have examined effects on postnatal immune function, beyond the immediate neonatal period, of glucocorticoid exposure in late gestation. Mice aged 5 months, born after prolonged maternal dexamethasone treatment during the final...

Cells Of The Immune System And Their Specific Receptors And Products

The immune system consists of a wide range of distinct cell types, each with important roles. The lymphocytes occupy central stage because they are the cells that determine the specificity of immunity. It is their response that orchestrates the effector limbs of the immune system. Cells that interact with lymphocytes play critical parts both in the presentation of antigen and in the mediation of immunologic functions. These cells include dendritic cells, and the closely related Langerhans cells, monocyte macrophages, natural killer (NK) cells, neutrophils, mast cells, basophils, and eosinophils. In addition, a series of specialized epithelial and stromal cells provide the anatomic environment in which immunity occurs, often by secreting critical factors that regulate migration, growth, and or gene activation in cells of the immune system. Such cells also play direct roles in the induction and effector phases of the response. The cells of the immune system are found in peripheral...

Immunogenicity and immunotherapy

All of the antigens listed in Table 1 have been shown to elicit antibodies in animal models, cystic fibrosis patients with P. aeruginosa-'miectcd lungs, and or humans with burn wound infections. This has provided the rationale for pursuit of vaccine and passive immunotherapy studies (Table 2). In many cases. Holder IA (1988) Pseudomonas immunotherapy. Sero-diagnosis and Immunotherapy 2 7-16. Pier GB, Desjardin D, Grout M et al (1994) Human immune response to Pseudomonas aeruginosa mucoid exopolysaccharide (alginate) vaccine. Infection and Immunity 62 3972-3979.

Ontogeny And Phylogeny Of The Immune Response

Many invertebrates exhibit cellular recognition and aggressive reaction against foreign cells and antigenic structures. Such organisms also exhibit innate constitutive mechanisms, such as cellular engulfment or phagocytosis of foreign materials and the formation of bactericidal substances. Some relatively primitive vertebrates such as sharks have circulating serum immunoglobulins that have considerable structural similarity to the same types of molecules in mammals (March-alonis and Schluter, 1994). The evolution of the vertebrate immune system has been in the direction of greater diversity and complexity in relation to the recognition of non-self, the specificity of the immune response, and the structures of the molecules involved (Du Pasquier, 1992). The immune response of vertebrates exhibits the highest degree of specificity in that all vertebrates are capable of generating an immunological response upon stimulation by an antigen (cf. Roitt, 1977). The immune response in...

Regulation Of The Immune Response

As noted in Figure 19.12, the development of the immune response is extremely complex but also must be highly regulated if the host is to mount an appropriate response to one or more specific antigens. The mechanisms of the regulation of the immune response involve the presence of specific surface gene products as well as the production of stimulatory and inhibitory signals both within the immunocyte and via signals secreted and received by cells in the immune Genetics in the Regulation of the Immune Response f While it is obvious that specific genes control the amino acid sequence of the immunoglobulins 8 and T cell-receptor components involved in the immune response, the elucidation of the genetics involved in cellular interactions that mediate the immune response has also been a major g topic of immunobiology. Many of the genes coding for products involved in the regulation of the H immune response of the organism are located in regions of the genome designated as the major...

Selenium Deficiency Viral Disease and Mutation and Immune Function

Human selenium supplementation (e.g., 200 mg day), even in apparently selenium-replete individuals receiving a diet providing 120 mg Se day, was able to stimulate the proliferation of activated T cells of the immune system. It elicited an enhanced response to antigen stimulation, an enhanced ability to generate cytotoxic lymphocytes, an enhanced ability to destroy tumor cells, and increased natural killer cell activity. Growth-regulatory interleukin-2 receptors on the surface of activated lymphocytes and natural killer cells became upregulated. In a study in Liverpool, UK, healthy adult subjects with initial plasma selenium concentrations below 1.2 mmol l were given placebo or 50 or 100 mg daily supplements of selenium as selenite for 15 weeks. After 6 weeks, they were given oral live attenuated polivirus vaccine, and after 9 weeks, 74Se stable isotope was given intravenously to measure their body Se pool size. The Se supplements significantly increased the Se pool size, and the...

Immune responses of host

The course of the disease in human beings and other animals, the possibility of persistent sequelae and the relative high mortality rate before the antibiotic era all suggest that the immune response to infection with S. moniliformis is imperfect. Humans and other animals obviously mount an immune response to the infection but which components are important in its curtailment is uncertain and whether the resolution of an established infection depends upon antibody production alone is untested. Experimentally, antibody (passive or active) also incompletely diminishes the consequences of challenge with the organism in the mouse.

Autonomic pathways to the immune system

The limbic system of the brain, which is pivotal in aspects of affective and cognitive behavior, directly regulates the neurohormonal and autonomic outflow of the nervous system. As the hypothalamus is central to this process, it is pertinent that perturbations of the hypothalamus also affect immune responses. For example, experimentally introducing lesions into the anterior lobe of the hypothalamus of rats depresses antibody responses, while electrically stimulating the hypothalamus at the time of immunization enhances antibody responses. Lesions in hypothalamus and hippocampus have also been found to alter such immune responses as NK activity and T cell functions. Focusing further down the autonomic nervous system, we find that the ultra-structural features of the contacts made between the sympathetic nerve termini in lymphoid tissues and lymphocytes are similar to nerve synapses, indicating the likelihood of some sort of intimate control or regulatory function. So it is no surprise...

Cellular immune responses

In published reports of patients with disseminated strongyloidiasis, some unspecified impairment of the cell-mediated immunity is often cited as the cause of the dissemination of the parasite. Though plausible, this concept is not supported by experimental or clinical data. In canine and primate models no correlation has been demonstrated between decreased lymphocyte responsiveness to S. stercoralis antigens in vitro and behavior of the infection. Human studies have been few and inconclusive, in part because immunocompromised patients with disseminated infection are frequently on drug regimens that greatly and nonspecifically depress their cellular immune response. An argument against a central regulatory function of cellular immunity in the protection against disseminated strongyloidiasis is provided by the fact that disseminated S. stercoralis infection has not emerged as an opportunistic infection in patients with the acquired immune deficiency syndrome (AIDS), even in areas such...

Immune Responsevaccinations Parasite Control

Veterinary health care provider who is familiar with the conditions prevalent in the area. Timing of administration should be coordinated with the desired timing of peak immune response. For maximum response, the sheep must be in good health and nutrition with minimal stress.

From an artificial experimental system to normal immune systems

These observations provided the basis for a strategy followed by the immune system to deal with potentially aggressive tissue-specific T cells produced throughout life, which is not based on their elimination or inactivation, but on their recruitment into the regulatory pool, thus progressively reinforcing peripheral tolerance. This strategy appears fully adapted to the T cell population dynamics in development. The finding that functional recruitment of RTEs requires antigen recognition also explains why newly formed T cells with specificities towards nonself antigens differentiate as naive resting cells to recruit-ment-resistant PRMs. It follows that antigens introduced in adult life will induce conventional immune responses that are no longer submitted to regulation, providing the basis for the developmental shift from tolerance to immunity.

Studies on the immune response

It is generally assumed that the extremely diverse HLA system evolved in response to the increasing variety of microorganisms against which an immune response is required. Extensive studies are underway to define the peptides which 'fit' into the groove of the HLA molecule. Certain peptides are shown to fit into the groove of certain HLA alleles but not others. This contact is thought to be a critical step in the immune response, accounting for the fact that some individuals in one species are resistant to a microbe while others are not. Even the response to cancer antigens is thought to be controlled by the HLA specificity present in the patient.

PUFA and the Immune System

Repeated demonstrations that PUFA can modify the production and activity of various components of the immune system have left unexplained the mode of action by which it exerts its effects. Several mechanisms had been proposed, including the following membrane fluidity changes that might effect the capability of cytokines to bind to their respective receptors on the cell membrane lipid peroxidation decrease in free-radical-induced tissue damage prostaglandin production an indirect mechanism whereby prostaglandins that are derivatives of PUFA modify cytokine activity regulation of gene expression PUFA influences on the signal transduction pathways and on mRNA activity. The role of PUFA in immune function is complicated by the fact that n-3 and n-6 have differential effects on various immune components. A recent review (Zimmer et al., 2000) indicated that n-3 fatty acids induce a decrease in lymphocyte proliferation in humans and rats, a decrease in interleukin-1 (IL-1) production and a...

The Immune System and Stress

The immune system is the collection of organs, tissues, and cells responsible for the organism to resist attack by antigens or invasive foreign bodies, particularly microbes. In light of the research of the past few decades, the classic definition and conceptualization of the immune system has changed. The immune system, once considered a closed system (i.e., it reacts only to internal body events), is now recognized to be open and subject to activation by the nervous system. There are established strong relationships between the components of the immune system and behavior with reciprocal influences on each other. The recognition of these interactions gave rise to the label psychoneuro-immunology (PNI), a term probably first introduced by (Solomon, 1989). The popularity of PNI is easily attributable to the classic studies and writings of Ader and his associates (Ader et al., 1987) which have provided an impressive body of evidence that the nervous system is capable of modulating the...

Psychological Stress and the Immune System

Early studies in the field examined the effects of stress on general components of the immune system, such as T-cells and natural-killer (NK) cells. More recent studies chose to measure another component of the immune system the cytokines, a system that is composed of molecules called interleukin. They are a group of naturally occurring proteins that are important in the activation of lymphocytes of the immune system. They were discovered in the 1970s, and several known types of interleukin (IL) are recognized as crucial constituents of the body's immune system. The most studied interleukins are interleukin-1 (IL-1) and interleukin-2 (IL-2). IL-1 is considered a proinflammatory and a pyrogenic agent, whereas IL-2 is considered an anti-inflammatory agent. The EFA has a differential effect on the production and the activity of ILs. For example, a diet based on n-3 PUFA abolishes the anorexia response to IL-1 (Endres, 1997, Calder, 1997, DePablo et al., 2000). DHA (n-3) administration...

The immune response to viruses

Studies of patients with isolated immunodeficiencies give an insight into the relative importance of the different components of the immune response, lndi viduals with isolated defects of cell-mediated immunity develop severe, sometimes fatal viral infections such as measles and chickenpox. A single case of natural killer (NK) cell deficiency has been reported, with increased susceptibility to severe primary herpesvirus infections. Those subjects with isolated immunoglobulin deficiency recover normally from most viral infections, except enteroviruses (which may cause chronic central nervous system infection). Such 'experiments of nature' coupled with an extensive body of experimental work in animal models permit the following generalizations. The immune response may be divided into three phases (see Table 1) and into humoral and cell-mediated components, which include specific and nonspecific mechanisms.

Vitamin D And The Immune System

Vitamin D, is hydroxylated in the kidney to its physiologically active form, la,25-dihydroxyvitamin D, (loi,25(OH)2D3), known as calcitriol. Substantial evidence is accumulating that the hormonal form of vitamin D, calcitriol, can regulate the differentiation, growth and function of a broad range of cells or organs that are not directly involved in calcium homeostasis. In particular, calcitriol plays an important regulatory role in cell differentiation and proliferation of the immune system. It mediates its effects via specific intracellular vitamin D3 receptors (VDRs). Malignant cell lines of the myelomonocytic and lymphocytic cell lineage, as well as normal peri

Complementary Interactions between Proteins and Ligands The Immune System and Immunoglobulins

All vertebrates have an immune system capable of distinguishing molecular self' from nonself and then destroying those entities identified as nonself. In this way, the immune system eliminates viruses, bacteria, and other pathogens and molecules that may pose a threat to the organism. On a physiological level, the response of the immune system to an invader is an intricate and coordinated set of interactions among many classes of proteins, molecules, and cell types. However, at the level of individual proteins, the immune response demonstrates how an acutely sensitive and specific biochemical system is built upon the reversible binding of ligands to proteins.

The adult immune response Lymphoid organs

There is evidence to support retardation in the initial phases of the humoral response. This is based on observations where the response to an inoculated bacteriophage by a rabbit produced more antibody, more rapidly than Didelpbis. Similar observations have been made in koalas (Phascolarctos spp.), where it is thought to be due to a delay in B cell activation because B cell numbers are present in similar proportion to those in placental mammals. In Monodelphis it has been shown that the primary immune response consists almost equally of IgM and IgG. However, in general, the humoral response in marsupials has the primary features that typify an immune response in placental mammals, including the ability to mount antibody-based or immediate hypersensitivity responses.

Therapeutic modification of the immune response

Immune response modifiers A considerable literature now exists on the use of genetically engineered cytokines in the treatment of cancer. Initial enthusiasm has now abated with the realization that the immune system can not easily be turned on to tumor targets by the indiscriminate activation of the immune system by cytokines such as IL-2 and interferon a. However, interferons do have a defined role and proven efficacy in the management of certain conditions, particularly melanoma, renal cell carcinoma and hairy cell leukemia and as adjuvant therapy in certain hematological malignancies such as low-grade lymphoma and myeloma. Both IL-2 and interferon a, used as sole therapy for metastatic melanoma or renal cell carcinoma, produce response rates of 5-40 . depending on patient selection criteria. In essence, fit patients with a low disease burden (and prior nephrectomy in the case of renal cell carcinoma) are most likely to respond to either agent. Some metastatic sites (e.g. lung)...

Immuno Grid The Virtual Human Immune System Project

ImmunoGrid is a 3 year project funded by the European Union which began in February 2006 and establishes an infrastructure for the simulation of the immune system that integrates processes at molecular, cellular and organ levels. It is designed for applications that support clinical outcomes such as the design of vaccines, immunotherapies and optimization of immunization protocols. The first phase of the project concentrated on improving and extending current models of the immune system. We are now entering the second phase which will design and implement a human immune system simulator. Since the new models are orders of magnitude more complex than the previous ones, grid technologies will be essential in providing the necessary computer infrastructure. The final phase of the project will validate the simulator with pre-clinical trials using mouse models. The immune system is a complex and adaptive learning system which has evolved to defend the individual against foreign...

Considering Immunotherapy

Many doctors already use immune therapy in cancer patients as well as patients with autoimmune disease, a category it seems endometriosis may fall into. (See Chapter 4 for more on the immune system and endometriosis.) The link between the immune system and endometriosis I Research may link the female sex hormones (estrogen and progesterone), testosterone, follicle-stimulating hormone, and luteinizing hormone to the immune system. Hormonal and menstrual cycle irregularities are common with endometriosis. A normal immune system checks the growth of endometrial tissue outside the endometrial cavity, just like it would check the growth of any neoplastic (new or tumor) cells found where they don't belong. However, most women with endometriosis may have malfunctioning immune systems that don't destroy stray endometrial cells before they have a chance to take up residence. Most immune therapy involves intravenous infusions or injections of medications that stimulate the immune system to...

Two Arms Of The Immune System Affected By Stress

Immune System Arms

Molecules such as cytokines, chemokines, adhesion molecules, major histocompatability complexes (MHC), and antibodies link the innate and adaptive arms of the immune system (Fig. 2). The innate immune system provides the first line of immune defense and is composed primarily of neutrophils, macrophages, and dendritic cells. Under nonstress conditions, these professional phagocytes gain rapid entry into infected tissues to clear pathogens by receptor-mediated phagocytosis, leading to the production of free radicals and the release of enzymes that kill the ingested microorganisms. The adaptive immune system is primarily composed of B and T Two Arms of The Immune System Adaptive Immunity Fig. 2 Two arms of the immune system are affected by stress. Fig. 2 Two arms of the immune system are affected by stress. similar increases in blood neutrophil lymphocyte ratios. Variable decreases in blood TH TC cell ratios are also observed in stressed animals, but these ratios may be more responsive...

Mechanisms of the skin immune response

A first line of skin immune defense follows from the induction of the expression of a large series of soluble and membrane-bound molecules by epidermal as well as dermal skin cells. These factors contribute to vasodilatation and the attraction, homing and activation of immune cells. A typical example of this nonspecific immune reaction is irritation reaction induced by small chemicals acting as haptens. Much information on the mechanisms in the antigen-specific skin immune response is obtained from animal model experiments with contact allergens that are able to bind protein, thus providing carrier (T cell) epitopes for the haptenic allergen. The contact allergic response is considered to be a classical example of delayed-type hypersensitivity.

Marsupial Immune System

Studies of the immune system, both anatomically and physiologically, have been limited to only a few of the more than 100 known species. Much of the work has been on four species the Virginian opossum (Didelphis virginiana), the South American short-tailed opossum (Monodelphis domestica) and two Australian species, the brush-tail possum (Trichosurus vulp cula) and the quokka (Setonix brachyurus). These are considered typical of marsupials it is assumed, as in placental mammals, that the structure and function of the immune system are similar regardless of the species. What differences are present probably reflect different dietary habits and different evolutionary pressures within their respective environments. The ability to develop and maintain an immune response is dependent on thymic maturation. The Marsupialia include species with thymic tissue in both intrathoracic and superficial ventral cervical locations. The cervical thymus has its origin in the cervical sinus, whereas the...

The common mucosal immune system

In summary, mammals possess a common mucosal immune system, in which antigen stimulation of MALT induces an exodus of specific lymphocytes which home to the various mucosal effector sites (Figures 1 and 2). These responses are finely regulated and T cells and cytokines are of central importance for ultimate plasma cell differentiation and production of S-IgA antibodies in external secretions. The current need for vaccines, including the universal efforts to develop immunity to human immunodeficiency virus (HIV), compels us to increase our understanding of how we can use the common mucosal immune system to advantage for the ultimate prevention of infectious diseases at mucosal sites.

Bivalency in the Immune System

Immunology Drugs

IgG and IgE antibodies, prime components of the immune system, are bivalent proteins containing two identical receptors (Fab sites Fig. 2.12) 21 . When binding bivalently to a surface (Fig. 2.12a) or to a soluble bivalent ligand (Fig. 2.12b), we postulate that the enhancement (P) for a given antibody is inversely proportional to the monovalent dissociation constant (K fflnlty) and directly proportional to the effective concentration (Ceff) of ligand near an available receptor (Fig. 2.12). If we assume Ceff to be constant for all antibodies (that is, that they have the same average distance between Fab sites), then greater enhancements will result from higher affinity (lower K fEnity) ligands. At cell surfaces, the enhancement for the binding of a polyclonal mixture of IgG with high monovalent affinity (average K ffinity 1 nM) to the surface of Bacillus sp. was 100 143 . Cremer and co-workers examined the binding of a polyclonal mixture of IgG to phospholipid mem-

Natural infection and immune response to parvovirus B19

VP2 is the primary target of antibodies induced by first exposure to the virus. As the antibody response matures, specificity against VP1 epitopes develops. Linear epitopes, clustered in the VP 1-unique region, are essential for an effective, neutralizing immune response. Using standard dot blot analysis, virus is rarely detected in sera beyond day 15 after inoculation, but when evaluated by polymerase chain reaction, low level viremia can still be demonstrated in some patients for more than 2 months after natural infection.

Influence of the nervous system on the immune system

Immune system is essentially autonomous - a closed system driven by challenges from foreign antigens and self-regulating, predominantly through the actions of cytokines. Yet the striking similarities in overall behavior between the immune system and the nervous system were also appreciated. For example, both are involved in the receipt and processing of information. In the case of the nervous system this is sensory information, while for the immune system it is molecular topological information. Both systems respond to a diverse range of stimuli and in each case the response is specific for stimulus. In each, there are a range of available responses and the system adapts its resources to provide what is appropriate in any situation. Neither the immune system nor the nervous system can know in advance exactly what stimuli are likely to occur and so each system has the capacity to respond to unexpected stimuli. Both systems have the ability to remember specific stimuli and to modify and...

Immune System Defense Mechanisms

The lung is similar to all other organs by containing lymphocytes (T and B cells) in the interstitium. These defense cells originate from the bone marrow and lymph nodes and respond to foreign invaders with cellular (acquired antibody) mechanisms. Dendritic cells present antigens to the lymphocytes. Considering that up to 1010 antigenic particles may reach the alveoli every day, the challenge for the pulmonary immune system is to process this foreign material and not overamplify an inflammatory response. Basic immune mechanisms in the lungs are similar to the rest of the body and are not covered here. Lymphatics are the main pathway for removal of immune cells that have already responded to foreign substances or cells in the lungs. The lymphatic drainage also removes excess fluid filtration from the pulmonary capillaries as described earlier. Pulmonary lymphatics start as blind end vessels in the acini, where they collect fluid and lymphocytes through a leaky endothelium. Lymphatics...

Experimental and clinical observations supporting the immune surveillance theory

In all species cancer is mainly associated with old age, being from about 2 years in mice to about 70 years in humans. Older mice have been found to be less resistant to xenogeneic, allogeneic and syngeneic tumor cells than younger mice. These observations may indicate involvement of the immune system in prevention of tumor development, as the immune system becomes less effective with increasing age. Immunodeficient animals show a higher frequency of virus-induced and chemically-induced tumors. Natural killer (NK) cells, part of the first line of defense as they are able to kill cells without prior sensitization, are presumed to play an important role in immune surveillance. Mice with genetically determined low levels of NK cells, beige mice, display an increased incidence of spontaneous tumors and a lower natural resistance to syngeneic leuke-mias. Furthermore, nude mice which have no functional T cells but normal NK cells do not show an increased incidence of tumors in general, but...

Invertebrate Immune Systems

Invertebrates, despite their lack of lymphoid immune systems, recognize and respond to nonself substances at least as efficiently as do vertebrates. Invertebrates rely on a diversity of mechanisms, some of which are inducible however, the responses are in most cases short-lived and do not discriminate between individual pathogens. Therefore, responses mounted by invertebrates to potentially infectious agents are mediated by immune systems only in the sense that they resemble qualitatively the 'innate' or 'natural' immune responses of vertebrate myeloid cells and nonimmunoglobulin, humoral components. As invertebrates include about 95 of the extant animal spccies, and represent a vast diversity of organisms, from unicellular protozoans to the more complex echinoderms and protochordates, it is not surprising that a considerable range of strategies for recognition and defense against potential pathogens and parasites are to be found in these taxa.

Neuroendocrine pathways to the immune system

In addition to corticosteroid effects, a number of the nonsteroidal hormones, produced by other neuroendocrine organs in response to hypothalamic-pituitary messages, also influence immune responses for example, sex hormones diminish in vivo responses, while growth hormone, thyroxine and insulin elevate responses under certain conditions. Numerous neuropeptides and neurotransmitters, which exert multiple functions as intercellular messengers within the nervous system, may also modify functional properties of cells of the immune system (Figure 2). For example, in addition to the elevation of CRH, corticosteroids and the catecholamines with stress, levels of 3-endorphin, which is derived along with ACTH from cleavage of the pro-opiomelano-cortin polyprotein, are also elevated, as are levels of several other opiates. Opiates function to alleviate pain during a fight-or-flight encounter but also inhibit immune responsiveness. In contrast, two anterior pituitary hormones, growth hormone and...

Immune responses to antigenic material in immune privileged sites

The manner in which these features create immune privilege and the associated 'deviant' systemic immune response (to privileged antigens) is the subject of intense investigation at the present. Current evidence indicates that privilege may result from an actively acquired, dynamically regulated, antigen-specific immune response that is able to express itself within the privileged site while avoiding nonspecific, tissue-destructive inflammation. Since this 'deviant' immune response is systemic in nature, the selective deficiencies (delayed hypersensitivity and production of complement fixing antibodies) are evident when the same antigens are encountered at other, nonpriv-ileged sites of the body. The unique features of immune responses to antigens expressed on grafts placed in privileged sites are also elicited when other types of nongraft antigens are inoculated into the privileged site, including antigens associated with tumors, haptens, virally encoded antigens, soluble heterologous...

Role of Fas FasL in immune privilege and immune escape

A similar mechanism of elimination of activated T cells by constitutive expression of FasL may provide a means of escape from the immune system by tumor cells. Certain tumors, including a proportion of melanomas, colon cancer cells and hepatocellular carcinomas, have been demonstrated to constitutively express FasL and appear to use this as a means of evading the T cell immune response by eliminating tumor-reactive T cells as they become activated. It has become clear in recent years that tight regulation of the Fas FasL apoptotic pathway is critical not only in maintaining immune system homeostasis but also in modulating host responses to pathogens and tumor cells. Disruption of this pathway by cytokines, pathogens and carcinogens can clearly result in disease progression. Understanding of these processes presents the opportunity for the development of novel therapies for certain diseases and manipulation of the immune response for induction of tolerance or immunity. Enari M,...

Basic biology of the rabbit immune system

The rabbit immune system is comparatively similar to the human system with only minor differences in tissue and cellular organization. The rabbit gut-as-sociated lymphoid tissue (GALT) is organized into a prominent appendix, obvious Peyer's patches and some diffuse lymphatic nodules. The human appendix is vestigial and has more diffuse lymphatic nodules. The GALT, as well as other peripheral tissues of the rabbit and human, are innervated with a well-developed lymphatic system of nodes and ducts. Also, similar to human, the rabbit has a prominent spleen and a thymus which atrophies in adulthood. Lymphopoiesis begins in the rabbit's bone marrow, and as the cells mature they populate the appropriate tissues and organs. Rabbit leukocytes are categorically similar to those in other mammalian reticuloendothelial systems. The composition of lymphoid cell populations and circulation pathways in the normal dynamic nature of the immune system are also similar, an observation which accents the...

Alternative explanations for the phenomena assigned to the immune surveillance theory

Those being skeptical with regard to the immune surveillance theory refer to the alternative explanations for phenomena such as increased tumor incidence in immunodeficiency, spontaneous regression of tumors, and the association of tumor cells with cells from the immune system. tumor incidence in immunodeficiency are also entirely plausible. The increased tumor incidence in immunodeficient renal transplant patients is primarily due to an increase in skin cancer (squamous cell carcinoma) and non-Hodgkin lymphoma (the majority being of B cell origin), whereas a substantial increase in the more common cancer types, such as breast cancer, cancer involving the respiratory system, and gastrointestinal cancer, is not observed in these patients. Non-Hodgkin lymphoma and skin cancer in immunodeficiency are associated with a viral etiology (Epstein-Barr virus (EBV) and human papillomavirus (HPV), respectively). It is therefore conceivable either that these viruses are carcinogenic themselves or...

The Immune Response Features a Specialized Array of Cells and Proteins

The immune response consists of two complementary systems, the humoral and cellular immune systems. The humoral immune system (Latin humor, fluid ) is directed at bacterial infections and extracellular viruses (those found in the body fluids), but can also respond to individual proteins introduced into the organism. The cellular immune system destroys host cells infected by viruses and also destroys some parasites and foreign tissues. The proteins at the heart of the humoral immune response are soluble proteins called antibodies or im-munoglobulins, often abbreviated Ig. Immunoglobu-lins bind bacteria, viruses, or large molecules identified as foreign and target them for destruction. Making up 20 of blood protein, the immunoglobulins are produced by B lymphocytes, or B cells, so named because they complete their development in the bone marrow. The agents at the heart of the cellular immune response are a class of T lymphocytes, or T cells (so called because the latter stages of their...

Hyper and hyporesponsiveness examples of dysfunctional immune responses

Ciency virus (HIV) in targeting CD4-bearing cells of the immune system is well known. When the loss of CD4 cells becomes acute, most immune responsiveness fails, as these cells are crucial for the induction of other activities in the system. One additional example of an inadequate immune response may be the outgrowth of malignant tumors in otherwise healthy individuals. Many experimentally induced tumors are quite immunogenic, e.g. immunization with a small or attenuated tumor dose protects from further challenges with the same tumor, indicating that the immune system is capable of recognizing and killing the tumor cells. Unfortunately, this is not the case for most spontaneous tumors which are non-immunogenic (hence their spontaneous appearance). They are, however, antigenic - capable of inducing a specific immune response if appropriate costimu-latory signals are provided. Nonimmunogenic tumors transfected with mixtures of cytokines (e.g. IFNy) and or with costimulatory molecules...

Role of CD1 in the immune system

The initial reports implicating CD1 in T cell function demonstrated that human T cell clones expressing either a (3 or y 8 T cell receptors (TCRs) recognized tumor cells expressing specific isoforms of human CD1. These CD 1-restricted T cells were pheno-typically CD4CD8 or double negative (DN) T cells. CD lb-restricted proliferative and cytotoxic responses of human DN-ct p+ and DN-y 8+ lymphocytes specific for M. tuberculosis and M. leprae were seen in cells isolated from blood of normal humans. Also, CD 1-restricted T cells specific for mycobacterial antigens have been found among CD8+ TCR-a 3+ T cells. In addition, mouse NK1+ TCR-c*P+ T cells, which appear to be entirely CD1 restricted, were isolated recently. These T cells were either DN or CD4+. Thus, it is now accepted that CD1 recognition is broadly distributed among T cell subsets. The different biochemical features of the various members of the CD1 family and the wide spectrum of recognition by T cell subsets indicate that CD1...

Cellular and molecular basis of the humoral immune response

In an immune response which is independent of T cells, the antibodies produced are mainly of the IgM class. Even in a T-dependent response, B cells first develop into plasma cells which secrete IgM antibodies. However, in a T-dependent response, factors secreted by the T cells (cytokines) will direct B cells to switch to other Ig classes IgG, IgA or IgE. Consequently the B cell product (antibody) will acquire the biological properties characteristic of each Ig class. Maturation of the immune response In a T-dependent response, the affinity of the secreted antibody for the antigen increases. This is referred to as affinity maturation of the immune response. Analysis of the primary structure of antibody molecules has shown that the increase in antibody affinity correlates with an accumulation of somatic mutations in the variable region of the antibody molecule. Antigen-activated B cells migrate into the primary follicles of the lymphoid organs. There, proliferation of B cells leads to...

Consequences of Immune System Cells Stimulation by Superantigens

The arachidonic acid lipid pathways. ,,, This SAgmediated hyperstimulation of the immune system of the host can overwhelm the host regulatory network and thereby assist pathogen evasion of the adaptive immune response. 18 Moreover, the excessive and aberrant activation of T cells causes damage to tissues and organs and cell apoptosis which may result in disease and even death. 13,22 Superantigen activity, particularly SPE A, has been found in acute-phase serum samples from strepto-coccal disease patients. 4

History of the immune surveillance theory

By Jensen and Ehrlich on tumor rejection tempted Ehrlich to suggest a role for the immune system in the control of tumor growth. However, attention for this idea soon faded as it became known that transplant rejection or acceptance was merely a consequence of genotypic variation between host and donor rather than of a specific antitumor response. The interest in tumor immunology revived around 1950 with the introduction of inbred animal strains creating a tool to study tumor rejection in genetically identical animals. From then on proof accumulated for a role of the immune system in the eradication of tumors. In 1959, stimulated by the ideas of Thomas and others, Burnet postulated the immune surveillance theory. At present, malignant tumors are believed to arise as a result of a series of specific genetic events which include the activation of oncogenes and the loss of function of tumor suppressor genes. A large array of control mechanisms are operative within a cell to prevent...

Immune responses to parasites

Because of the long-lasting nature of parasitic infections it was widely believed until comparatively recently that there were very few effective immune responses against most parasites. However, it is now clear that immunity is the rule. The evidence for this comes from a number of sources. First, there is the epidemiological evidence in endemic areas rhe majority of people develop clinical immunity to parasitic infections, the prevalence of infection falls with age while immunological parameters increase and some immunity to reinfection occurs. Second, there is the experimental evidence in every animal model investigated some degree of immunity can be demonstrated and it can be argued that there is no reason why humans should be any different. However, immunity is seldom complete and tends to be unstable and individuals suffering from concurrent infections or undergoing immunosuppressive therapy often suffer recrudescences of their dormant infections. The immune response to any...

Exercise and Immune Function

Aging leads to a diminution of resting immune function, increasing the risk of infection, tumor development, and autoimmune diseases (Shephard and Shek, 1995). The production of IL-2 is decreased, sometimes with a decrease of total T-cell count, and often with changes in T-cell subsets and proliferative responses to mitogens. However, NK cell activity remains unchanged. In theory, moderate exercise training should help to reverse the adverse effects of aging upon the immune system. However, there have been relatively few studies comparing the immune responses of young and older individuals to acute exercise and to training. A single bout of moderate exercise seems to be well tolerated by the elderly. The NK cell response is as much as in younger individuals, but perhaps because of a low initial proliferative capacity, older subjects show less stimulation of lymphocyte proliferation by moderate activity and less suppression with exhausting exercise. Perhaps because resting immune...

Innate Immune Response

Many of the studies on gut responses to gluten have been performed in the established chronic lesion. Little is known of innate responses that can elicit effects within minutes to hours of exposure to gluten. In vitro studies demonstrated an increase in the expression of HLA antigen on the cells in the surface layers of the intestinal mucosa occurring within 2-4 h after exposure to gluten. Gluten also causes the production of the proinflammatory cytokine IL-15 at the surface epithelium. IL-15 expressed by the surface enterocytes activates NK-like T cells to recognize gluten presented by MHC class 1a molecules in the context of the NKG-2D receptor. The NK-like T cell may be a key player in both the damage to the surface epithelium and be a proin-flammatory influence on adaptive response that occurs in the underlying lamina propria. This induction of innate immune responses by gluten may have important consequences. Since the gluten peptides enter into the epithelial compartment and...

Virus evasion of host immune responses

The ability of arenaviruses to persist in their long-term carriers is facilitated by antigenic variation that allows evasion of host immune responses. Neutraliz-ation-resistant variants of Junin and Tacaribe viruses escape the humoral immune response, and certain epitope variants of LCMV escape the CTL response. In addition to viral variants that can escape host immune surveillance, variants have been described that suppress the immune response and thereby persist. Docile is a variant of the Aggressive isolate of LCMV (UBC), and Clone 13 is a variant of the LCMV (Armstrong strain). Both Docile and Clone 13 replicate very well in the spleen and poorly in the brain in contrast to their parental viruses. Both Docile and Clone 13 elicit poor CTL responses when tested 7 days after infection, and consequently, both persist in the mouse longer than their parental viruses. Docile and Clone 13 isolates actually do elicit CTL by day 3 after infection, but these viruses replicate so vigorously...

Immune responses of the host to chickenpox

In order to properly understand the immune response of the host, it is first necessary to visualize the pathogenesis of primary VZV infection. A schema is shown in Figure 2. This model includes two viremic stages, with the characteristic chicken pox exanthem appearing after the second viremia. Chickenpox is acquired from small virus-laden droplets which are carried by air currents from an infected child to a nonimmune (susceptible) individual. The site of infection is probably the conjunctivae or the

Effects of mercury on the immune system

Little is known about the principal mechanism by which mercury affects the immune system. An effect on the selection mechanisms in the thymus has been suggested, allowing potentially autoreactive cells to escape into the periphery. A direct mitogenic action on lymphocytes seems to be well established and could result from the chemical effects of this heavy metal on some cell membrane components, such as calcium channels, or direct action on nuclear proteins. Other possible mechanisms would be increased expression of major histocompatibility complex (MHC) class II molecules on cell surfaces, with consequences for antigen presentation, or alterations As shown in BN rat spleen cells, the effects of mercuric chloride are associated with increased production of interleukin 2 (IL-2). In accordance with in vitro results, individuals occupationally exposed to mercury have an increased absolute number of T lymphocytes which correlated with the time of exposure. Of particular interest are the...

Structural organization of the mucosal immune system

Lymphocytes associated with mucosal sites arc located in three major compartments 1) organized tissue such as the Peyer's patches, BALT, tonsils, mesenteric lymph nodes and appendix 2) the nonorganized lymphoid cells present diffusely throughout the lamina propria and 3) the lymphocytes present within the mucosal epithelium, the intraepithelial lymphocytes (IELs). Lymphoid cells in organized structures such as the Peyer's patches are thought to be primarily less mature cells that play an important role in initiation of immune responses, i.e. they carry out functions of the 'afferent' limb of the immune response due to their interaction with antigens traversing the specialized M cell epithelium of these sites. On the other hand, lymphocytes in the diffuse lamina propria compartment are more mature cells, many of which are activated, that are thought to carry out effector functions, such as IgA production. The function of intraepithelial lymphocytes in vivo is uncertain, although their...

Immune Response Ir GENES

Immune response (Ir) genes can be defined as any gene locus at which different alleles affect the magnitude of an immune response. Thus, Ir genes were identified on the basis of a complex phenotype and, not surprisingly, comprise a heterogeneous group of structural genes. Nevertheless, genes encoded within the major histocompatibility complex (MHC) clearly have the most dramatic effect on the immune response to a variety of antigens, and thus became the first well-characterized Ir genes.

Reptilian Immune System

Reptiles evolved from primitive amphibians nearly 300 million years ago during the Carboniferous period. They sprang from a basic stock, the long-extinct order Cotylosauria or 'stem reptiles'. A side-branch of stem reptiles led to the turtles and tortoises order Testudines Chelonia. The closest surviving descendants of the cotylosaurs are the tuatara that live on a few islands off New Zealand. Descended from ancient forms related to the tuatara is the much more successful order of the Squamata comprising the lizards (suborder Lacertilia) and snakes (suborder Ophidia Serpentes). Stem reptiles also gave rise to other lines. One of these lines led to the crocodilians and modern birds another led to the mammals. Reptiles are not only the closest ancestors of the birds and mammals, but are also the first vertebrates to exhibit the change from free-living larvae, as in fish and amphibians, to an embryo completely protected by an amnion similar to that found in avian and mammalian embryos....

The immune response to infections

The development of vaccines has been based on two requirements safety - the product should not induce undue morbidity and efficacy - immunization should prevent clinical disease on subsequent exposure to the wild-type agent. Other than measurement in relatively recent times of specific antibody levels and particularly a functional test such as neutralization of infectivity, generally no other parameters of the immunogenicity of the product were considered. Most current vaccines are to 'acute' infections, i.e. those in which the agent replicates for a few days, replication is halted and then cleared without persistence of the infectious agent. Diseases caused by agents which cause chronic infections, i.e. the immune response is subverted in some way, pose a greater challenge to vaccine development. Many of the diseases for which vaccines are now needed are in this category. Our knowledge of the different responses generated and their role during infection has come from the study of...

Radiosensitivity of cellular components of the immune system

The type and magnitude of specific immune responses is determined by the interaction of antigen-presenting cells such as dendritic cells and macrophages with T and B lymphocytes. However, the effector arms of the immune system depend on interactions of numerous leukocyte subsets. In addition to lymphocytes and macrophages, natural killer Table 1 Radiosensitivity of cellular components of the immune system

Characteristics of the acquired immune response

The first time an antigen enters the body a wide spectrum of events occurs. The antigen is usually contained at the site of entry and in nearby lymph nodes by various phagocytic cells such as macrophages and dendritic cells. These cells process the antigen and present pathogen-derived peptides to CD4+ and CD8+ T cells in association with major histocompatibility complex (MHC)-encoded molecules. Antigen binding by surface immunoglobulin and cognate help by CD4+ T cells induce B cells to differentiate to antibody-secreting plasma cells. During a primary immune response there is a lag time of approximately 3-4 days before antigen-specific antibody is evident in serum, and the levels do not peak until approximately day 7. The antibodies produced are primarily immunoglobulin M (IgM), which are characteristically very heterogeneous in their affinity for the antigen. IgG antibodies do not appear in the serum until approximately day 7 and do not peak until day 14. Thus the primary humoral...

Conclusion Utility Of Acquired Immune Responses

Acquired immune responses ultimately determine whether an infectious organism will be controlled and disease prevented.1-3'6-1 Vaccines enhance immunity by altering the acquired immune response. Much research is now aimed at biotherapeutics that alter the balance between Th1 and Th2 cytokine responses. Because cytokines set the direction and amplify the intensity of specific antipath-ogen and vaccine immune responses' setting the direction of the early specific acquired immune response will help

Vitamin C And The Immune System

Ascorbic acid (vitamin C) is required for the optimal functioning of all cells, tissues, and organs. It is the most important water soluble antioxidant and is a cofactor in many hydroxylating reactions. Man, primates, guinea pigs and a few other species lack the capability to synthesize ascorbic acid, for them ascorbic acid is an essential nutrient. There is abundant evidence from animal and human studies that the immune system is sensitive to the level of intake of vitamin C.

Mechanisms of changes in reptilian immune system

Body temperature is a salient factor regulating the performance of reptilian immunological functions. It must be noted in this regard that reptiles, in contrast to fish and amphibians, have become restricted in the temperature range over which physiological activities, including immune responses, can occur. Photo-periods, humidity and nutrition are also critical modulators of reptilian immune processes. Endogenous rhythmic factors that are not as yet characterized appear also to control immune reactivity independently of external conditions. Thus, it was not possible to induce thymus regeneration in winter reptiles even if they were maintained in optimal environmental conditions, including the species-specific preferred temperature. Studies in lizards and turtles have documented that the impact of seasonal and other environmental factors on the immune system is mediated by fluctuations in levels of circulating corticosteroids and sex hormones. Therefore, reptiles represent unique...

Cytokines a bridge between the nervous system and the immune system

Cytokines are cell-derived peptides that may modify the functions of the cells that secrete them, as well as the functions of other cells that have receptors for them. Table 2 lists a number of cytokines that are produced and act in both the nervous system and the immune system. which exogenously-produced cytokines could be transported into the CNS. Although such pathways have now been identified and the circumstances under which the blood-brain barrier is sufficiently compromised to allow cytokines to pass from the blood into the CNS are known, it has also been shown that these pathways are not the only means by which these mediators come to be present in the brain. A number of years ago, it was demonstrated that IL-1 and IL-6 are produced by cells in the pituitary gland and that IL-1 may be the regulator of IL-6 production by these cells. Given the knowledge that these two cytokines are mediators of inflammatory reactions and that one or both can stimulate the production of...

Phylogeny Of The Immune Response

In comparison with vertebrates, the immune response of invertebrates is extremely limited. Specific antibody produced by interactive lymphocyte subpopulations together with extremely finely tuned discrimination of self from nonself and a high degree of memory are confined to the vertebrates, and yet, invertebrates comprise over 95 of all known species of animals. Clearly, the invertebrate immune system is not defective in any way so why have the vertebrates developed such sophisticated immune processes Examination of the phylogeny of immunity and consideration of possible evolutionary and environmental pressures favoring its development may help to answer this question. As a preliminary, however, it is essential for a brief consideration to be made of the phylogeny of the main animal groups together with a basic description of the invertebrate and vertebrate immune systems.

Host Immune Response

Another potentially serious limiting factor in graft survival, despite optimal in vitro tissue processing and efficient implantation protocol, is host rejection of the graft. Whereas the brain is still considered to be an organ with a limited immue response (historically called immunoprivileged ), rejections of grafted tissues can occur through the classic cell-mediated immune response. The immune reactions to neural grafts have been studied for a long time, but the necessity of immune suppression is still debated. A review by Widner emphasizes the complexity of the immune response in the brain and also questions the impact of immunosupressive therapies on allo- or even xenograft survival. Furthermore, it should be noted that another host reaction, the degeneration of the graft mediated by brain macrophages that does not involve the presence of lymphocytes, can also be considered a form of rejection. The role played by reactive microglia in graft survival is the object of intense...

The Immune System as a Sensory Organ

The phenomenon of sickness behavior illustrates that the immune system may be considered as another sensory organ of the body. Following this definition, the immune system's function is to detect noncogni-tive stimuli,'' such as bacteria, viruses, and tumors, and to alert the CNS of their presence. The immune system has particular receptors (or, in this case, different types of cells) that detect specific stimuli, produce signals that can be understood by the CNS, and transmit messages to the brain. As a result of receiving this specific sensory input, the CNS is able to respond by inducing physiological and psychological changes in behavior designed to combat infection.

Features of the immune response to specific types of pathogens within the CNS

Viruses invade the CNS through hematogenous dissemination or by retrograde transport up neurons that have processes extending into sites of infection in the periphery. As intracellular pathogens, their tropism for different neural cells and effect on host cell function determine the severity of disease. The paucity of MHC antigen expression within the CNS can make the cytotoxic T lymphocyte (CTL)-mediated clearance of viruses difficult and may predispose to chronic or relapsing infections. Their capacity to establish latency also allows viruses to avoid detection by the immune system. In other circumstances, antiviral antibodies can shut off virus production by infected neurons in a noncytolytic manner and promote recovery from disease. During chronic CNS infection caused by human immunodeficiency virus (HIV), the long-term production of Fungi are generally avirulent pathogens most individuals with fungal infections of the CNS have some underlying immune deficiency. The greater...

Roles outside the immune system

Aside from its role as a secreted factor in the immune system, there is evidence for an intracellular mode of action for MIF in many cell types. MIF is widely expressed in many tissues regardless ot immune status, including immunologically privileged sites such as the lens and brain. MIF was identified as a highly abundant protein associated with cell differentiation in the acapsular, immune-privileged eye lens in the embryonic chick. It was also cloned from human and mouse lens, confirming its identify with MIF from other sources. Northern blots for human and mouse showed that MIF mRNA is highly abun dant in many tissues, including lens and brain and MIF protein was also isolated from bovine brain cytosol.

Immunotherapy Of Autoimmune Diseases

The term 'immunotherapy' is used in two somewhat different senses. One is 'therapy of the immune system', aimed at targets ranging from antigen-presenting cells to activated T cells, macrophages and B cells. Another context is the use of immunological reagents, such as antibodies, T cells or their modifi cations in therapy. Immunotherapy in both senses has been applied vigorously in animal models of autoimmune diseases, and increasingly attempts are being made to apply immunotherapy to a wide range of human diseases.

Adaptive Immune Response to Gluten

Celiac disease is characterized by an immune response to the storage proteins of wheat, rye, and barley, with wheat as the most immunogenic. Wheat gluten is composed of glutenin and gliadin, and evidence suggests that the gliadin fraction induces disease. Information gathered from T cell clones derived from chronic lesions of the small intestines of celiac patients with established disease demonstrate that gliadin peptides are presented by HLA class II molecules to CD4+ T cells. Several studies have suggested that unaltered native gliadin peptides were antigenic but lacked the negatively charged amino acids needed to bind to the recognition sites of the DQ2 or DQ8 molecules. It has since been recognized that the gliadin peptides are made more antigenic by tissue transglutaminase, and it is these altered (deamidated) peptides that either perpetuate or cause gluten sensitivity in celiac disease.

Nutritional regulation of immune function in low birth weight infants and in the elderly

There are many striking similarities between the two ends of the age spectrum. Both neonates and the elderly have suboptimal immune responses and are susceptible to infection. When nutritional deficiency complicates the picture, impairment of immuno-competence is more marked and longer-lasting. The immune system develops during fetal life and the first few months after birth. If an infant is born preterm or if he or she exhibits growth retardation as a result of a number of environmental factors, including maternal malnutrition or infection, im-munocompetence is reduced. The impact on T lymphocyte numbers and cell-mediated immunity is most discernible. The preterm infant of low birth weight generally recovers its ability to mount immune responses by the age of 3 months. However, the small-for-gestational-age (SGA) infant may continue to show reduced cell-mediated immunity for several months and years. There is a significant difference in the immunocompetence of SGA infants who exhibit...

Immunotherapy Of Allergic Diseases

Allergen immunotherapy represents the dominant immunologic, as opposed to environmental or pharmacologic, approach to management of allergic diseases such as allergic rhinitis, conjunctivitis and asthma. It was developed empirically, coincident with the modern-day discovery of allergy by Portier, Richer and von Pirquet. In essence, it involves identification of the allergen(s) to which a patient exhibits immunoglobulin E (IgE)-dependent sensitivity followed by subcutaneous administration of minute amounts of natural extracts containing these allergens. The goal is lasting modification of immune processes responsible for the maintenance of atopic symptoms. Other, infrequently used, forms of desensitization (i.e. IgE-mediated drug reactions)

Hematopoietic and Immune System

More profound changes occur in the adaptive immune functions, which rely on the memory (T cell) lymphocytic cell line. Life-long antigen exposure induces increases in the number of memory T cells, but with enhanced reactivity against self-antigens, priming the individual for autoimmune disease. In healthy adults, IgA concentration increases by 0.2 gl-1 per decade throughout life. The T lymphocytes, however, respond more poorly to ongoing antigen assault in later life. Thymic involution associated with neural and hormonal changes of aging is an impediment to T-cell maturation in older persons. The basis of intrinsic function deficits of memory cells, on the other hand, has been ascribed to defective signaling and includes hyporesponsive-ness to mitogen-stimulated proliferation and decrease in genetic suppression, allowing increased stimulation of inflammatory cytokines the balance between pro-and anti-inflammatory cytokines shifts with aging, favoring the inflammatory pole, especially...

Breast feeding and Immunity to Infection

Mucosal immune system and produce antibodies against mucosal pathogens that the mother is exposed to and which the infant is most likely to encounter. Breast milk contains several factors that protect against infections in the breast-fed infant either through passive immunity or by activating the infant's immune system. These include secretory IgA and IgM antibodies specific to maternal pathogenic encounters, short-chain fatty acids (SCFA), which can inhibit bacterial growth, block bacterial toxins and activate eosinophils, bactericidal lactofer-rin, lysozymes, and mucins, as well as lymphocytes (both T cells and B cells), which may transfer primed immunity to the infant. Additionally, cytokines and other growth factors in human milk contribute to the activation of the lactating infant's immune system, rendering breastfed infants less susceptible to diarrheal diseases, respiratory infections, otitis media, and other infections and may impart long-term protection against diarrhea....

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