Immune Response Ebook

How To Bolster Your Immune System

How To Bolster Your Immune System

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

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Immunity Crisis

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

Immunity Crisis Overview


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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.

Aging And The Immune System

Aging of the immune system involves changes in the capacity for self-renewal, in the relative preponderance of cell populations and in the quantity of immunoglobulin molecules of different isotypes and of different interleukins. We have relatively little definitive information on the exact nature of changes in the capacity for self-renewal of stem cells and of precursor cells. There appears to be an age-related decrease in the number of cells which synthesize terminal deoxynucleotidyl transferase (TdT) and are precursors of both T and B cells. However, it remains possible that the observed decrease does not depend on changes in the precursor cells themselves but is due to regulator cells feeder cells from old mice cannot support the in vitro growth of TdT4 cells, while feeder layers from young animals can do so. In short it is possible that self-renewal decreases with age as a function of regulator cells rather than of precursor cells themselves. In the immune system the most striking...

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.

Understanding your immune systems role in endometriosis

The answer may lie in the immune system. The study of the immune system and its relation to endometriosis and other immune-related diseases (such as lupus, fibromyalgia, and chronic fatigue syndrome) has rapidly progressed in the last decade. The immune system does seem to play a role in endometriosis. New research sheds more and more light onto the inner workings of the immune system, but at the same time that research makes the waters murky. Endometriosis isn't immune (forgive the play on words) to this confusion. In the next sections, we highlight and try to simplify the immune system's involvement in endometriosis.

Immune responses of the host

Ever since the 1960s, LCMV was used to study virus-induced cell-mediated immunity. There are two types of murine infection an acute infection that correlates with vigorous cell-mediated immunity (as measured by CTL assay) or a persistent infection that correlates with little cell-mediated immunity (Figure 2). The immune response to the acute infection either kills the mouse by engendering meningitis, or subsides and leaves the mouse LCMV-immune. Adoptive transfer of splenocytes from an LCMV-immune mouse can clear infection in a persistently infected mouse. Clearance is mediated by CDS and not LCMV infection induces inflammatory intermediates such as interferon y (IFNy) and tumor necrosis factor a (TNFa), both of which influence the host's immune response to other pathogens. IFNy stimulates the proliferation of natural killer (NK) cells that serve to eliminate certain pathogen-infected cells and some tumors. TNFa produced in the liver as a result of LCMV infection can clear hepatitis B...

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...

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.

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.

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.

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

Immune function and regulation

Although Fas is expressed by many tissues and cell types, the expression of FasL is relatively restricted. Both CD8+ and CD4+ T cells, natural killer (NK) cells and lymphokine-activated killer (LAK) cells all express functional FasL and are capable of inducing apoptosis in Fas-expressing target cells. However, in spite of its expression by cytotoxic effector cells, in most instances FasL does not appear to play a critical role in CTL killing. Analysis of perforin gene deficient mice and mice mutated in the Fas pathway (lpr lpr mice) has indicated that CTL killing of target cells is mediated primarily via the perforin granzyme pathway. In accordance, mice that are perforin deficient are susceptible to many viral infections, whereas Fas-deficient mice mount a normal immune response to most pathogens.

Propionibacteria and the immune system

The impact of propionibacteria on the immune system was mainly studied regarding the cutaneous species, which display marked immunomodulatory properties (Roszkowski et al., 1990). Indeed, P. avidum KP-40, administered parenterally to mice, increase significantly mice thymocyte proliferation and peripheral blood lymphocytes and monocytes counts (Isenberg et al., 1995). Oral supplementation by the same strain furthermore counteracts the drop in lymphocytes counts triggered by anaerobic exercise in young male healthy sportives (Pottkamper et al., 1996). Such properties were thus sought in the dairy group of propionibacteria. A pioneer study in this field was undertaken with the species P. acidipropionici, orally administered to mice. The treatment resulted in an enhanced phagocytic activity of peritoneal macrophages activity, assessed using killed salmonella in a phagocytosis assay (Perez Chaia et al.,

Immune function and cancer

The diet is believed to play an important role in the onset of carcinogenesis, and there are a number of carcinogens present in food, including mycotoxins, polycyclic hydrocarbons, and pesticides. Associations have been made between dietary fat intake and morbidity and mortality from breast and colon cancer. Another possible mechanism for the proposed protective effects against cancer of olive oil compared with sunflower oil involves diet-induced alterations in host immune responses. Both the type and concentration of dietary fats have been reported to influence immune status in several animal models. The PUFA C18 2 is necessary for T-cell-mediated immunity, but high intakes will suppress immune function and may therefore increase the risk of cancer. Furthermore, comparisons between the effects of diets rich in C18 2 and those rich in C18 1 on varying indicators of immune function in mice have shown that, while dietary C18 2 predisposed animals to suppression of certain...

Vaccination and immunotherapy

The defects in host immunity associated with serious fungal infections are being defined and some progress has been made in attempts to boost or reconstitute the immune response. Examples include IFN7 in patients with chronic granulomatous disease and granulocyte colony-stimulating factor and GM-CSF in neutropenic patients. In the case of cryptococcosis, monoclonal antibodies to capsular glucuronoxylomannan have been shown to confer protection when passively administered to mice infected with C. neoformans. This, despite the fact that specific antibodies appear to play a limited role in normal host defense against C. neoformans. Increased understanding of the complex network of cytokines regulating the cellular immune response has raised additional therapeutic possibilities. Soluble I1.-4 receptor and antibody against IL-10 have been shown to be beneficial in murine candidiasis and II.-12 has been shown to be beneficial in animals models of cryptococcosis and histoplasmosis....

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...

Immune response to a cancer

There is some evidence that cancer cells have surface membrane antigens called tumour-specific antigens (TSA) or tumour-associated antigens (TAA) that are recognized by the immune system as non-self, and can elicit an immune response. Antibodies secreted by B-lymphocytes will coat tumour cells and with the help of complement and phagocytic cells can cause tumour cell destruction. CD8+ T-lymphocytes and NK cells can cause direct tumour cell killing, whereas CD4+ T-cells release cytokines to augment tumour cell killing by macrophages. The concept of immune surveillance as protection against cancer, whereby lymphocytes continuously check dividing cells for mutations and destroy unacceptable cells, has not been proved (Fig. 11.15).

Immunotherapy of cancer

Numerous attempts have been made to employ immuno-logical methods to treat cancer, but none have been very successful. The different techniques can be grouped together as active, passive and adoptive immunotherapy. Active immunotherapy refers to those techniques designed to enhance components of the immune system most likely responsible for antitumour activity. Bacillus Calmette-Guerin (BCG) has been used to enhance cellular immunity, particularly macrophage function, and various cytokines such as IFN, IL-1, IL-2, IL-4, IL-12 and TNF are being tested to enhance immune function. Passive immunotherapy usually refers to the use of monoclonal antibodies directed against TSA in an attempt to destroy the tumour cell. Adoptive immunotherapy refers to the transfer of immune components such as macrophages and NK cells from one individual to another. The most extensively studied in this group are known as lymphokine-activated killer (LAK) cells.

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.

Specific immunotherapy

Immunotherapy (desensitisation) has been used in the treatment of allergic diseases since 1911. Extracts of allergen to which the patient is sensitised are given in increasing concentration, starting with a very dilute solution, until tolerance is achieved. Allergen immunotherapy is specific to the allergen being Several studies evaluating the effectiveness of specific immunotherapy in food allergic diseases such as peanut and fish allergy produced conflicting results. The majority of the studies did not find evidence of protection in peanut allergic patients, and severe reactions during the treatment were common. However, some studies have supported the use of immunotherapy in the treatment of fish and egg allergy. The overall consensus is that specific immunotherapy has no place in the treatment of food allergy.

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 ml1, 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....

Secondary immune responses in vitro general considerations

Both secondary lymphoid organs and blood can be sources of mononuclear cells for secondary immune responses (Figure 7). The suppressor cell problem within blood mononuclear cells is less apparent, or critical, with secondary responses, and may not require prior inhibition. Nevertheless, lymphoid organ cells have been the more widely applied in secondary immune responses in vitro. Table 3 Advantages of employing secondary compared to primary immune responses immunological help Reduced obligation for preprocessing of antigen Reduced obligation for exogenous cytokine addition Requirements for 'enhancement factors' less likely Absence of accessory cell function less of a problem In vitro immune response system can be simple - mononuclear cells plus antigen Increased manipulability of the immune response system facilitating studies on accessory cell and cytokine involvement in the immune response systems. Secondary response systems have a number of advantages (Table 3) relating to memory...

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)...

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)

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.

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...

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....

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

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.

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...

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...

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...

Acquired immune deficiency syndrome AIDS

See also Acquired immune deficiency syndrome (AIDS) Bone marrow and hematopoiesis Candida, infection and immunity Cryptosporidiosis Cytomegalovirus, infection and immunity Epstein-Barr virus, infection and immunity Graft-versus-host reaction Haemophilus, infection and immunity Herpes simplex virus, infection and immunity Immunodeficiency, primary Immunodeficiency, secondary Immunosuppression Legionella, infection and immunity Listeria, infection and immunity Lymphoma Mycobacteria, infection and immunity Nocardia, infection and immunity Pneumocystis car-inil, infection and immunity Pseudomonas aeruginosa, infection and immunity Staphylococcus, infection and immunity Streptococcus, infection and immunity Toxoplasmosis Transplantation Var-icella-Zoster virus, infection and immunity.

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...

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.4951 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...

Mediation Of The Immune Response

Differentiation of the lymphocyte population also results in the differentiation of function. T cells generally are involved in the mediation of responses that directly involve the interaction of the T cell with cells bearing antigenic components. B cells, in contrast, when activated directly or indirectly by a specific antigen, produce antibodies, which in turn circulate in the organism, reacting with antigen occurring at a distance from the cell and producing the antibody. This latter response, characteristic of B cells, is termed the humoral immune response. Each is considered separately below. The Humoral Immune Response Humoral immunity is the result of the formation of specific antibodies reactive with specific antigens and the ultimate consequences of such a reaction either by eliminating foreign antigens or in producing abnormal reactions within the host itself (autoantibodies). In order to consider the humoral immune response, however, it becomes necessary to understand the...

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...

Immune system pathways to the nervous system

If the immune system is also able to influence the nervous system then effects should be evident during times of immune activity. The fact that when we have a cold or 'flu' we feel drowsy, feverish and unsociable alerts us to the possibility of immune activity affecting the nervous system and behavioral and cognitive patterns as a consequence. Indeed, hypothalamic electrical activity has been observed to increase at the time of peak B cell responsiveness to administered antigen, and neurotransmitters such as norepinephrine in the hypothalamus also show profound changes at this time. Potentially there are at least two ways in which this could occur. Lymphocytes themselves have only limited access to the brain and so responding lymphocytes could secrete neurological mediators or, alternatively, cytokines produced during the course of the immune response could directly affect neural tissues. In practice, both these pathways probably operate (Figure 3). A variety of neuroendocrine...

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...

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...

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 system and scrapie pharmacological strategies for control

A functional immune system is required for efficient experimental transmission of scrapie and for TSE agents to cross the 'species barrier'. Outram and Dickinson have shown that immunologically immature, perinatal mice are less susceptible to scrapie infection than their 3-week-old littermates, and SCID mice are relatively refractory to infection by peripheral, natural, routes of infection. Various immuno-modulators can affect the incubation period of peripherally-routed scrapie if administered at the time of infection. Phytohemagglutinin and methanol-ex-tracted BCG increase susceptibility to infection, while prednisone acetate, dexamethazone, arachis oil and the antiviral agent HPA-23 have the opposite effect. However, interferon, antilymphocyte serum, cyclophosphamide, neonatal thymectomy or whole body irradiation fail to alter incubation period. The polyanions, dextran sulfate and pentosan polysulf-ate, increase survival time considerably, even when administered weeks after...

Immune responses to human neoplasms

The first evidence for immune responses to human cancers was published in the late 1960s. However, this area remained controversial until technical advances made it possible to characterize the antigenic targets of the immune responses observed. Antigens recognized by patients' antibodies were identified first. While antibodies have been detected to a few antigens which were individually unique for each patient's tumor, most antibodies have defined antigens that are shared by many tumors, generally irrespective of their histological type. Cell-mediated immune reactions are demonstrated in assays of either CTL activity or T helper cell responses, with most work nowadays concentrating on antigens recognized by CTLs. Since tumor cell killing by CTL is restricted by the ability of a given patient's MHC class I molecules to present target peptides, an antigen targeted by CTLs will appear as unique to each neoplasm, even if it is shared by many tumors, unless the tumor cells and the CTLs...

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

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

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

Immune response in syphilis

T. pallidum infection evokes cellular and humoral immune responses. The humoral response manifested by production of phospholipid and treponemal antibodies is the basis for serodiagnosis of syphilis. The phospholipid or cardiolipin antibodies are detected by a variety of flocculation tests using a defined mixture of cardiolipin-lecithin-cholesterol as antigen (Venereal Disease Research Laboratory, VDRL antigen or VDRL test). A second type of antibody, known as cardiolipin F (detected by immunofluorescence) and directed against host-cell mitochondrial cardiolipin (autoantibody), is also associated with syphilis, but is not used for serodiagnosis. Treponemal antibodies, once detected by the cumbersome T. pallidum immobilization test (TPI) are now identified by immunofluorescence (FTA-ABS) or microhemagglutination test (MHA-TP). Treponemal antibodies appear after infection almost simultaneously with the cardiolipin antibodies. The treponemal antibodies persist in the host for many years...

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...