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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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Interaction with the Immune System

PCV2 provides a valuable model for gaining insight into how ssDNA viruses interact with the host immune system and for understanding their pathogenesis. PCV2 is intriguing in its ability to persist in macrophages and dendritic cells without replication although its infectivity is retained. When natural interferon (IFN)-producing cells responded to an inducer of cytokine synthesis, their co-stimulatory function, which induces myeloid dendritic cell maturation, was clearly impaired in case of a concur rent PCV2 infection. Stimulation of the porcine immune system with IFN-a and IFN-g causes increased replication of PCV2 in vivo, while no changes were observed in IL-1-, IL-6-, tumor necrosis factor alpha (TNF-a)-, or IL-10-treated cells. With the circumstantial evidence compiled over the last years, one may assume that PMWS can be considered as an acquired immunodeficiency syndrome of pigs although direct evidence for this hypothesis is still missing.

Exercise and Immune Function

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

Apoptosis as an Antiviral Immune Response

Like all other living organisms, insects are constantly challenged by bacteria, fungi, and viruses. In vertebrate animals, immunity can be broken down into innate and adaptive immunity. Insects do not possess the adaptive immune response that is characteristic of vertebrates including antibodies and T cells. That does not mean, however, that insects are defenseless against invading microorganisms. Insects have robust innate immune systems that are in many ways similar to the innate immune mechanisms found in vertebrates. Over the past 10 15 years, enormous strides have been made in understanding the molecular basis for insect innate immunity against bacteria and fungi. Despite these advances, the understanding of how insects defend themselves against viruses has lagged behind. Work with baculoviruses has demonstrated that apoptosis can serve as an innate immune mechanism in insects. The importance of apoptosis in antiviral immunity in insects is only beginning to be understood, and...

Analyses of Immune Responses to Ontogeny Specific Antigens Using an Inbred Strain of Xenopus laevis J Strain

In this chapter, the procedures for specific detection of ontogenic emerging antigens during animal development are described. Anuran metamorphosis has provided us with a good experimental model for investigation of the mechanisms of tissue remodeling. The establishment of a syngeneic strain of Xenopus laevis described in this chapter has enabled us to perform a unique experiment to develop antibodies that specifically react to ontogenic antigens by immunizing syngeneic animals. This strategy was successful because the antibody repertoires produced in the adult frog serum were well subtracted by a number of common antigens expressed in syngeneic larvae. Here we show, using results of immuno-histochemical and T-cell proliferation analyses that adult frogs exhibit humoral and cellmediated immune responses to larva- or metamorphosis-specific antigen molecules in epidermal cells. Key Words Larval antigens epidermal cells skin metamorphosis tissue remodeling transformation antiserum...

Cell Mediated Adaptive Immune Responses to H pylori

The ability of the gastrointestinal tract to discern pathogenic bacteria from commensals is regulated through T-cell-dependent responses. CD4+ T-cells can be broadly divided into two functional subsets, type 1 (Th1) and type 2 (Th2) T-helper cells, each of which are defined by distinct patterns of cytokine secretion. Th1 cells produce IL-2 and IFN-y and promote cell-mediated immune responses whereas Th2 cells secrete IL-4, IL-5, IL-6, and IL-10 and induce B-cell activation and differentiation (82). The type of immune response to a particular microbial agent is governed by preferential expansion of one T-helper cell subset accompanied by a corresponding and relative down-regulation of the other (82). In general, most intracellular bacteria induce Th1 responses, whereas extracellular pathogens Although the acquired immune response to H. pylori is composed of both Th1- and Th2-type cells, cytokine profiles indicate a Th1 predominance, as the majority of H. pylori antigen-specific T-cell...

Immune Response Prevention and Control

Adult channel catfish produce peak neutralization titers on average 8 or 9 weeks after primary immunization with CCV, and a further moderate increase in titer of short duration is apparent after boosting. The importance of virus growth in eliciting the immune response is indicated by the observation that heat-inactivated virus is poorly immunogenic. Serum neutralization indices have been used to document a link between outbreaks of CCV disease and potential carriers of the virus. These studies, though not extensive, have given some indication that seroconverted adult fish are able to transmit CCV. Hopefully, other tools and techniques developed from genome studies will widen the scope and sensitivity of investigations into this aspect of pathogenesis. See also Antivirals Fish viruses Herpes simplex viruses (Herpesvirldae) General features, Molecular biology Latency Vaccines and immune response.

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.

Starvation And Immune Responses 41 Models of Starvation in Normal Mice

Animal models have been set up to investigate the effects of food restriction on immune responses. It is important to define the terms of reference carefully when assessing the literature. Starvation is defined as withholding all food for a short defined period and allowing the animal free access to water. Following this short period of starvation, the animal is then allowed free access to food. A period of 48 h of food withdrawal is usually used in mice, because 24 h produces mild immunosup-pression only and 72 h causes unacceptable mortality. Most studies using rat models have employed 72-h food deprivation for similar reasons (14,81,82). Food restriction generally means reducing the calorific intake to approx 30-50 of normal. Starvation causes significant immune impairment (83). It has been shown that acute starvation in mice reduces the number of CD4+ T-cells and suppresses the development of T-cell-mediated immunity (84). Furthermore, starvation causes delayed repopulation of the...

Immune Response to Infection

PPVs, in common with other poxviruses, stimulate a vigorous immune and inflammatory response in their hosts, and have evolved to replicate in the presence of this response. In sheep experimentally infected with ORFV, studies in the skin and lymph draining into (afferent lymph) and out of (efferent lymph) local lymph nodes have demonstrated that activated CD4+ (helper) and CD8+ (cytotoxic) T cells, B cells, and antibodies are generated as part of the sheep-acquired immune response to infection. The cytokines generated in lymph in response to virus reinfection are typical oftype 1 antiviral cell-mediated immune responses and include interleukin (IL)-1 p, IL-2, tumor necrosis factor (TNF)-a, granulocyte-macrophage colony-stimulating factor (GM-CSF), inter

The Cell Mediated Immune Response in Starvation

As mentioned earlier, the cellular immune system seems particularly sensitive to undernutrition and starvation. The reasons for this are unknown and it has been hypothesized that much immunosuppression is the result of specific micronutrient deficiency. However, these deficiencies occur relatively sporadically, yet the type of immune impairment seen is fairly consistent, casting some doubt on this hypothesis. The immune phenotype seen in SII includes reduced delayed-type hypersensitiv-ity responses (DTH), which is a sensitive measure of T-cell-dependent in vivo immune responses. Furthermore, circulating peripheral T-cells are reduced, particularly na ve (CD45RA+) T-Cells (91). T cell antigen-specific responses are severely impaired and vaccination efficacy is poor (92). Antibody responses are relatively preserved, but production of interferon (IFN)-y is markedly reduced both in vitro and in vivo (93). Children seem particularly affected by SII because of the immaturity of their immune...

The Effects Of Leptin On The Immune System 51 The Innate Immune Reponse

As mentioned earlier, the pattern of leptin release during an acute-phase response mirrors other cytokine gene expression, particularly IL-6 (11-13). It has been shown that LPS, IL-1, TNF-a, and other inflammatory stimuli increase gene expression and serum concentration of leptin as early as 6 h after the initial stimulus. The induction of gene expression makes leptin an ideal candidate to be a key player in an immune inflammatory response. It is of particular interest that LPS binds to a Toll-like receptor (TLR-4) on adipocytes and induces adipocyte expression of TLR-2 and secretion of leptin and other proinflammatory cytokines (102). TLR engagement provides an elegant mechanism whereby the production of leptin is induced at the start of an immune response before cognate recognition of a foreign antigen has occurred, which will, in turn, upregulate Th1 cognate immune responses if appropriate (see Section 5.2). This further illustrates the well-accepted concept of a critical interplay...

Evading the Immune Response

Viruses may use a number of strategies to evade the immune response. Evasion of cell-mediated immune responses Sanctuary sites Some sites are not easily accessible to the immune system for example, the brain and epididymis, which are separated from the blood by a barrier, and the kidney. HIV, for example, is present in the brain and semen. This may provide an explanation of why many HIV-infected individuals who generate strong cytotoxic T lymphocyte responses do not clear the virus. Herpes and measles viruses infect neurons and plasmodia infects red blood cells, neither of which express class I MHC. Even lymph nodes can act as a sanctuary. Infectious HIV has been found attached to FDCs in lymph nodes, even though neutralizing antibody was present.

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.

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...

Immune Response and Persistence

SIV-infected macaques typically produce high levels of antiviral antibodies and high-frequency cytotoxic T-lymphocyte (CTL) responses to the infecting virus. These immune responses persist for the lifetime of the infected host in both natural and experimental infection. SIV deletion mutants that are progressively more attenuated based on viral load measurements generate progressively weaker anti-SIV antibody responses. Anti-SIV CTL responses have been demonstrated as being major histocompatibility complex (MHC) restricted. Detailed investigation of CTL responses has been impeded by a lack of information regarding MHC types in different monkey species. However, a considerable amount of new information regarding MHC alleles and their cognate peptides is emerging for rhesus macaques. The importance of CD8+ lymphocytes in limiting the extent of SIV or SHIV replication has been definitively shown using CD8+ T-cell depletion. Extensive depletion of CD8+ cells was accomplished by intravenous...

Immune Response to SIV Infection

As SIV infection is lifelong, the host immune response cannot clear the infection but, in some cases, it can exert considerable control on the level to which SIV replicates. Before day 5 after mucosal SIV inoculation, there is little evidence of innate immune responses with only modest increases in type 1 interferon levels and interferon-stimu-lated gene levels at the site of inoculation. At days 6-7 PI, there is a dramatic and simultaneous increase in innate antiviral immune responses in all lymphoid tissues that coincides with the dramatic explosion of viral replication in these tissues. By days 10-14 PI, SIV-specific CD8+ T-cell responses are present in blood and in the mucosal sites of inoculation, with strong antiviral T-cell responses widespread by day 28 PI. This rapid increase in antiviral effector T cells occurs as viral replication and plasma vRNA levels decline from a peak at 14 days PI. The temporal relationship between the decline in plasma viremia and the appearance of...

Evasion of Host Immune Responses

Given the complexity of an antiviral immune response, there are many ways in which a virus can subvert this defense and persist in the host. Table 3 provides an outline of these strategies. As described above in EBV group I latency, HSV latency and HIV-1 Table 3 Viral strategies for evading the immune system3 Infection of sites not readily accessible to the Immune system latency, viruses can restrict the repertoire of genes they express or even become transcriptionally quiescent. This strategy renders the pathogen effectively invisible to the immune system. Lastly, cytokines and chemokines are important messengers for the coordination and orchestration of the immune response. TNF is targeted for example by poxvirus T2 protein that acts as a TNF receptor homologue. Secretion of this protein from infected cells results in the quenching of free TNF from the bloodstream. EBV BCRF-1, a homologue of IL-10, can block the synthesis of IFN-y and IL-2. Adenovirus VA RNA, HIV TAR RNA, and EBV...

The Adaptive Immune System

We find it useful to think of the immune system as a chemical sense organ, similar to the more familiar senses of taste and smell. They all function to identify novel materials, in a sense, which we then arrange to remove or inactivate. The immune system comes into play once foreign materials have achieved access to the interior. It is our cellular and molecular surveillance organ, and must not only distinguish between self and non-self, but also arrange for the inactivation, destruction, and removal of cells or molecules that it determines to be foreign. Foreign molecules are potential pathogens. The immune system makes no value judgments harmful or inert, if it is foreign, it should be removed.

Cytokines That Direct Immune Responses In The

Antigen-presenting cells (APCs) direct the quality of the emergent T cell response and have the capacity to subvert CNS immune responses toward inflammatory or noninflammatory outcomes, including whether CD4+ T cell activation generates a Th1 or a Th2 response. Although cell-surface interactions e.g., involving B7 family members or CD40, are known to play a role, the major influence on quality of T cell response is through release of specific regulatory cytokines by APCs. Macrophages that are induced with different colony-stimulating factors produce distinct cytokines and differentially elicit Th1 (APC1) vs. Th2 (APC2) responses 39 . Prominent among these are IL-12, IL-18, and IL-23, all of which are implicated in induction of Th1 immune responses and specifically interferon-gamma (IFNy) production, and IL-10, which directs Th2 responses. These cytokines are discussed in more detail below. A question that arises is how are these APCs directed to induce Th1 or Th2 It has been proposed...

Overview of the Immune System

The immune system includes several interacting components. Nonspecific immunity (protection against any invasion) is provided by the barriers of the skin and mucous membranes lining the lungs and gut. Additional nonspecific defenses are provided by the inflammatory response and the complement proteins in the bloodstream. We shall not deal further with these defenses.

The Role of Membrane Complement Regulatory Proteins in Cancer Immunotherapy

Anti-tumor monoclonal antibody therapy represents one of the earliest targeted therapies in clinical cancer care and has achieved great clinical promise. Complement activation mediated by anti-tumor mAbs can result in direct tumor lysis or enhancement of antibody-dependent cellular cytotoxicy. Chemotaxis of phagocytic cells by complement activation products C5a is also required for certain cancer immunotherapy such as combined P-glucan with anti-tumor mAb therapy. However, high expression levels of membrane-bound complement regulatory proteins (mCRPs) such as CD46, CD55 and CD59 on tumors significantly limit the anti-tumor mAb therapeutic efficacy. In addition, mCRPs have been shown to directly or indirectly down-regulate adaptive T cell responses. Therefore, it is desirable to combine anti-tumor mAb therapy or tumor vaccines with the blockade of mCRPs. Such strategies so far include the utilization of neutralizing mAbs for mCRPs, small interfering RNAs or anti-sense oligos...

Interaction of the Microbiome with the Innate Immune Response in Chronic Wounds

Abstract Microbes colonizing and or infecting chronic wounds undoubtedly play a major and interactive role in impaired healing, especially in amplifying and perpetuating the host innate immune response. The development of molecular techniques to identify and quantify microbial organisms has revolutionized our view of the microbial world. These less-biased, high throughput methods greatly enable investigations regarding host-microbe interactions in the chronic wound environment. This review focuses on the mounting evidence implicating microbes and excessive inflammation in chronic wounds, as well as the challenges associated with understanding how microbes modulate wound healing and the innate immune response. Our bodies are colonized inside and out by microbes, estimated to exceed the number of eukaryotic cells of our bodies 10-fold. In most cases, these microbes are harmless and provide functions that we as humans have not had to evolve on our own (Gill et al. 2006). Despite constant...

Adaptive Immune Responses

Induction of Th2 Immune Responses and or Suppression of Th1 Responses In certain protozoan infections, cysteine proteases are critical for the induction of Th2 type immune responses. Leishmania are obligate intracellular parasites that live as nonmotile amastigotes within cells of the mononuclear phagocyte lineage of their mammalian hosts. The outcome of infection in leishmaniasis is determined by the Th1 versus Th2 nature ofthe effector response with parasites successfully establishing infection by driving a Th2 immune response.11 Inhibition of Leishmania mexicana cathepsin B, with a specific inhibitor, caused a switch in the polarisation of T-cell differentiation from a Th2 to a protective Th1 phenotype in mice.12,13 In addition, mutants of L. mexicana lacking cysteine protease activity induced less IL-4 and IgE in BALB c mice compared to wild type parasites.14 Finally, the delivery of recombinant cysteine proteases derived from either L. mexicana, or Trypanosoma cruzi, elicited...

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...

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

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...

Host Immune Responses

An early nonspecific containment phase (innate immunity) and a later HSV-specific effector phase (adaptive immunity) contribute to protection. Natural killer (NK) cells and rapid production of IFN type I provide a threshold of resistance to HSV-1 infection and were associated with the natural resistance of certain mouse strains. In mice, IFNa p inhibit the onset of IE gene expression, limit virus spread into the nervous system, and activate NK cells. Dendritic cells (DCs) are required for activation of NK cells and CD4+ and CD8+ T cells in response to HSV-1. Conventional CD11c+CD8a+ DCs are the principal antigen-presenting cells during acute HSV-1 infection. The plasmocytoid CD11c+B220+ DCs secrete large amounts of type I IFN in vitro after exposure to HSV-1 and help lymph node DCs to induce HSV-specific cytotoxic T cells (CTLs) optimally during a primary immune response. Various reports have incriminated or refuted the association of HLA with HSV infections.

Innate Immune Responses

Substantial evidence supports the view that cysteine proteases secreted by a range of pathogens specifically prevent cells of the innate immune response promoting Th1-adaptive immune responses.10,25-27 The mechanisms are varied and depend on the substrate specificity ofthe protease and ofthe location ofthe pathogen within the host. The innate immune system constitutes the first line ofhost defence during infection and plays a crucial role in the early recognition ofinvading pathogens. Unlike the adaptive immune response, the innate immune response is relatively nonspecific, relying on the recognition ofevolutionarily conserved structures on pathogens, termed pathogen-associated molecular patterns (PAMPs), through a limited number of pattern recognition receptors (PRRs).28 A number of different PRR families have been described but the best characterised is the family of TLRs. To date, 13 TLRs have been identified in humans and are distinguished by their recognition of distinct PAMPs...

Complementderived Dangertransmitters Shape Innate And Adaptive Immune Responses Following Physiological And

The immune system needs to distinguish between physiologic changes in the environment, e.g., physiologic cell death and the necessity to clear these cells without substantial inflammation and pathological changes that demand inflammation. In short, danger-sensing needs to translate into adequate dangertransmission that tailors the immune response. The complement system is well suited for this task as it releases a panel of bioactive cleavage fragments, the function of which is regulated by interaction with soluble and cell-bound proteins. Cleavage fragments of C3 (e.g., C3a, C3b, iC3b, C3dg) have the ability to act as danger-transmitters that instruct cells of the innate and adaptive immune systems through interaction with specific receptors (C3aR, CR1 CD35 , CR2 CD21 , CR3 CD11b CD18 , and CR4 CD11c CD18 , Likewise, cleavage products of C5 i.e., C5a as well as the membrane attack complex (C5b-9 MAC) can transmit humoral inflammation and translate humoral into cellular inflammatory...

The Secondary Immune Response and Duration of Immunity

One of the more striking variations in the immune response to FMD vaccines is the extent to which it is boosted by subsequent vaccinations. The increase in neutralising antibody titre may often exceed 1.5 log10 (Pay 1984) whereas little or no boosting of the immune response is apparent in the data from some other reports (Francis et al. 1983 Rocha et al. 1983), suggesting that the initial and subsequent vaccinations did not stimulate the development of immunological memory. This prompts the question of what variables impact on the secondary response and, by extrapolation, on the duration of protective antibody titres. Antigen pay-load has been studied by Rweyemamu and colleagues (Rweyemamu et al. 1984) using Al(OH)3 saponin FMD vaccines in cattle containing between 7 and 329,760 ng of 146S per dose. These authors concluded that the primary response was dose dependent but that there was no evidence of low dose tolerance or high dose immunological paralysis. Whereas the highest primary...

The Cognate Immune Response

As mentioned earlier, the innate and cognate immune systems are interlinked, so that many of the effects of leptin discussed in Section 4 will have implications for the behavior of responding lymphocytes. It is also clear that an organism mounts a coordinated immune response to an infectious pathogen that initially comprises innate immunity and then evolves, if appropriate to involve the cognate immune system. An important point of communication between the innate and cognate arms of the immune systems lies with macrophages and dendritic cells. These cells produce cytokines that polarize and activate T-cell responses and act as professional antigen-presenting cells by presenting peptide bound to major histocompatibility complex (MHC) molecules to T-cells along with high levels of costimulation. As leptin can effect the production of proinflammatory cytokines from macrophages (56) and dendritic cells (GM Lord, unpublished data) and also increase expression of MHC molecules and...

Inflammatory And Immune Responses

Innate Immune Response Adaptive Immune Response In contrast, the molecules introduced into the body by acarine parasites may induce an adaptive immune response that is highly specific for a particular epitope (sequential or structural) on an immunogenic molecule (antigen) from the parasite. An epitope is the part of the antigen that receptors on B and T lymphocytes recognize. The adaptive immune response is stronger and quicker with successive exposures and involves T and B lymphocytes and memory cells of each type. It may be accompanied by an inflammatory reaction too that can be delayed. With the help of type 2 T-helper cells (Th2) B cells become plasma cells that produce antibody directed at the offending molecules from the mite. Activated Th1-type helper cells activate cytotoxic T cells (Tc) that perform functions that kill the parasite directly or damage it. Helper T cells release specific cytokines such as Interleukin 2 (IL-2), interferon Y (IFN-y), and other interleukins (IL-4,...

Brain Autoantigens in the Immune System

However, quite unexpectedly, several observations showed that CNS-specific autoantigens were also produced within the immune system, most prominently by thymus cells, mainly stroma, and that these ectopic autoantigens actively influenced the generation of the autoimmune T cell repertoire. At about the same time, two laboratories described a whole family of MBP and MBP-related genes in the immune cells (Pribyl et al. 1993 Grima et al. 1992). Both groups described MBP-like sequences in the thymus as well as in lymph nodes and the spleen. In particular, MBP expression by thymus stroma cells was unexpected. Then Kojima et al. showed directly for the first time the co-existence of CNS autoantigen and specific autoreactive T cells in the same rodent thymus. The autoantigen was the calcium binding protein S-1000, which is expressed in astrocytes, rather than in myelin

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-

Immune Response

In infected birds, the only significant immune response is the appearance of type-specific neutralizing antibodies which apparently recognize the regions of Env involved in receptor recognition. Group specific responses against Env or other proteins are not usually observed in infected chickens, although inoculation of virus into mammals induces antibodies capable of recognizing all virion proteins in the absence of subgroup-specific reactivity. The limited immune response observed in infected chickens has been attributed to the presence of endogenous pro-viruses whose expression (even at a low level) can induce tolerance to antigens in common with infect ing virus. Indeed, it has been suggested that induction of tolerance might be a desirable feature for the animal, since it could prevent or limit immunopatho-logical sequelae of infection. Postinfection immune response seems to be of little consequence in preventing subsequent malignant disease, since the cells which will eventually...

Immune Responses

Infection of respiratory or enteric tracts of adults results in antiviral antibodies in the serum, secretory antibody in the respiratory and enteric tracts, colostrum and milk, and development of virus-specific T cells. These immune responses are useful for diagnostic purposes, terminate infection, and probably ameliorate subsequent infections, but they do not necessarily prevent reinfection. In newborns, passive oral immunization with neutralizing antibody can sometimes prevent fatal coronavirus enteritis. Because coronavirus diseases are generally most severe in newborns that do not respond well to active immunization, an attractive strategy to protect these newborn animals that is being explored is to vaccinate pregnant dams in order to maximize antiviral antibodies in the colostrum and milk. Coronaviruses can sometimes infect cells of the immune system and may modulate cytokines and immune responses to unrelated immunogens. Infected macrophages can spread infection to distant...

Immunotherapy

Immune responses to infection are vital as evidenced by the fact that healthy, immunocompetent individuals resolve infection. An interesting correlation between administration of highly active antiretroviral therapy (HAART) and a decrease in cryptosporidiosis in AIDS patients has been observed. HAART does not directly affect the parasite but exerts its effects through enhancing the immune system of these patients. A picture is slowly emerging of the immune responses during infection. CD4+ T cells play an important role as well as CD8+ (a p and y 8) intraepithelial T cells. Cytokines involved in clearance include INFg, IL-12, and IL-15. 12,13

Host Immune Response

Very little is known about immunological defense by cellular immunity against HHV-6. The presence of HHV-6-specific T cell clones in seropositive individuals has been reported. Natural killer (NK) cells, a key component of the innate immune system, are known to play an important role against viral infections. Infections of PBMCs with HHV-6 and HHV-7 lead to upregulation of their NK cell cytotoxicity by inducing IL-15, which is one of the NK activity-enhancing cytokines. The cell type in PBMCs that has been identified as the source of IL-15 is the monocyte macrophage. In fact, it has been reported that HHV-6 interacts directly with monocytes and induces IL-15 in them. This enhancement of NK cell cytotoxicity following infection is consistent with the previous observation that NK activity increased during the acute phase of exanthem subitum. IL-15 production following viral infections may therefore represent a powerful host defense mechanism involved in restricting viral growth and in...

Discharge And Home Healthcare Guidelines

This name was more appropriate in the early years of the AIDS epidemic, when healthcare providers were aware only of the late stages of the disease and did not fully understand its mechanisms. The more current name for the condition is HIV disease, which refers to the pathogen that causes AIDS and encompasses all the phases of the disease, from infection to the deterioration of the immune system. AIDS is still the name that most people use to refer to the immune deficiency caused by HIV.

Exotic Viruses and Unmet Needs

Viruses and hantaviruses have made it clear that, with world travel requiring less time than many virus disease incubation periods, disease might spring up at any locale, and geographic containment alone is not realistic. There have been 15 outbreaks of Ebola virus infections reported since 1967, and the horrors of these infections have received considerable publicity. Hantaviruses have long been known to cause Korean hemorrhagic fever (KHF). More recently hantavirus pulmonary syndrome (HPS), with rapid disease course and mortality as high as 50 in less than a week, has occurred in regions of the USA. These examples have been part of the stimulus for investigations of immunotherapy, extended evaluation of available antiviral drugs, and new drug discovery to define effective strategies to treat and contain exotic virus outbreaks. Hyperimmune polyclonal equine antibody and MAb are being developed and tested to prevent acute Ebola disease and death in non-human primates. Furthermore,...

Viruses and Apoptosis

Induction of apoptosis later in the virus life cycle could assist the release of the newly produced virus particles, especially nonenveloped nonlytic viruses, from the cell. The presence of virus in apoptotic bodies, which are phagocytosed by other cells, helps the virus evade the host immune surveillance system and spread. Virus-induced apoptosis also contributes to the clinical manifestations and cytotoxicity associated with virus infections. The viral gene products involved in activating PCD and their targets in the cell are only starting to be identified (Table 2).

Preface to the First Edition

Part IV deals with the role of fats and oils in overall nutrition. The importance of antioxidants in nutrition and food preservation is presented. Excess fat intake is associated with many disease conditions. This section describes various omega fatty acids and their sources, the role of dietary fats in atherosclerosis, eicosanoids production, immune system, coronary heart disease and obesity. The various types of lipid-based synthetic fat substitutes are discussed.

Serologic Relationships and Variability

All attempts to demonstrate antigenic crossreactivity between EAV, LDV, PRRSV and SHFV have been unsuccessful. Even though antiviral antibodies are detected in infected animals by a week after infection, all four viruses can cause persistent infections. The mechanism by which these viruses evade clearance by the immune system is not known. Neutralization escape virus variants have been reported to arise during persistent LDV infections. Antiserum obtained from animals chronically infected with LDV and PRRSV contains infectious viral immune complexes. Plasma from LDV-infected mice has a higher nonspecific binding activity than plasma from uninfected mice virus-specific binding measured by an ELISA usually cannot be detected until the plasma has been diluted at least 1 400.

Pathogenicity and Clinical Features of Infection

Phosphoglucose isomerase (2-3-fold), glutathione reductase (2-3-fold), aspartate transaminase (2-3-fold) and glutamate-oxaloacetate transaminase (2-3-fold). The elevated LDH levels result primarily from a decreased rate of clearance of normal turnover enzyme from the blood. A permanent reduction in the population of Kupffer cells involved in receptor-mediated endocytosis of LDH has been shown to occur soon after infection of mice with LDV. A decrease in the humoral and cellular immune response to non-LDV antigens is observed during the first 2 weeks after LDV infection. Thereafter, the immune response to other antigens is normal. In immunosup-pressed C58 and AKR mice, one isolate of LDV, LDV-C, can induce a sometimes fatal poliomyelitis. Immunosuppression is required to delay antibody production so that virus can reach the central neurons system (CNS) and infect the susceptible ventral motor neurons. LDV-infected neurons become the targets of an inflammatory response. In mice 6 months...

Physiological Signals

Soluble signals have been categorized according to the cell of origin or the mode of delivery to the recipient, or target, cells. Generic terms for signal molecules are agonists, because they produce an effect, or ligands, because, in producing their effect, they bind to target cells. Secretions that are released from one cell and reach nearby target cells by diffusion through the extracellular space are called paracrine. Some secretory products may also act on the cells that produced them, in which case they are called autocrine secretions. Communication that depends purely on diffusion is highly efficient when the distances between communicating cells are short, but it becomes increasingly inefficient when distances exceed a few cell diameters. Nerve cells are specialized to conduct electrical impulses with great speed (as high as 120 m sec) over the long distances they span and to release neurotransmitters from their terminals. Neuro-transmitters diffuse across the synaptic spaces...

Models of Autoimmunity

Diabetes, particularly type I (insulin-dependent diabetes mellitus, IDDM) has been associated with viral infections. A potential mechanism described above is molecular mimicry. The principle here is that a virus encoding a crossreacting epitope is also present in the pancreas of the genetically susceptible individual. Infection with a virus having the crossreacting protein and or epitope could initiate a crossreacting immune response. Here, the cell in the pancreas that contains the peptide in association with MHC molecules would be recognized by T cells and attacked. Two laboratories, those of Oldstone and Zinkernagle, have constructed transgenic mice to test this hypothesis. Lymphocytic choriomeningitis virus (LCMV) glycoprotein (GP) or nucleocapsid protein (NP) genes controlled by the insulin promoter were inserted into the germ line. Such transgenic mice expressed the viral GP or NP protein in the islet cells of the pancreas. These mice therefore consider the viral protein as...

Future Perspectives

Some of the initial studies on molecular mimicry and virus-induced autoimmunity indicated that viruses share common sequences with host components. It has been demonstrated that some viruses have acquired host genes and modified these to subvert the immune system. Herpesviruses encode MHC-like molecules, Fc receptors, IL-10-like factor and complement regulatory proteins, and poxviruses have incorporated into their genome, IL-1 receptor, tumor necrosis factor (TNF) receptor, IFN-y receptors and complement control proteins. In addition, viral proteins need to perform specific functions in the cell to replicate its genome and assemble new virions. These functions use the existing cellular machinery and therefore mimic many of the host cells, which also perform similar tasks. The key question is still how are these infections which are associated with autoimmune disease able to initiate the pathway leading to self-reactive immune responses

Proteins Involved in Evading Host Defenses

A number of conserved ORFs encode proteins involved in evading host defense systems. The virus replicates in macrophages, which have important roles in activating and orchestrating the innate and adaptive immune responses. By interfering with macrophage function the virus can thus disrupt both of these types of host response. One protein, A238L, inhibits activation of the host transcription factor nuclear factor kappa B (NF-kB) and also inhibits calcineurin phosphatase activity. Calcineurin-dependent pathways, such as activation of NFAT transcription factor, are therefore inhibited. This single protein may prevent transcriptional activation of the wide spectrum of immunomodulatory genes whose expression depends on these transcription factors. So far, A238L has been shown to inhibit transcription of cyclooxygenase 2 (COX2) mRNA, thus inhibiting production of prostaglandins, which have a pro-inflammatory role. A238L has also been shown to inhibit transcription from the tumor necrosis...

Opportunistic Infections and Malignancies Associated with HIV Infection

OIs and malignancies in patients with HIV infection emerge as a consequence of immune deficiency related to CD4+ T-lymphocyte depletion. A CD4+ T-lymphocyte count below 200 cells per mm3 is defined as AIDS even in the absence of other diseases or symptoms since this represents such an increase in risk for OI and malignancy. An important phenomenon to recognize is 'immune reconstitution inflammatory syndrome' (IRIS). Following initiation of HAART, recovery of the immune system can be associated with an apparent worsening of an

Brief History of Hivaids

Although the first cases of acquired immune deficiency syndrome (AIDS) were recognized in the United States in 1981, phylogenetic analysis of human immunodeficiency virus (HIV) sequences suggest that HIV may have been initially transmitted to humans around 1930. By 1985, HIV had been identified in every region of the world and an estimated 1.5 million people were infected globally. Since then, unprecedented scientific advances have been made in the epidemiology, basic science, and treatment of this newly identified virus. Despite these advances, the global HIV pandemic has expanded rapidly. By 2007, an estimated 33.2 million people were living with HIV and greater than 20 million people had died of AIDS. AIDS is now the leading cause of death among people 15 59 years old and the world's most urgent public health challenge. The implementation of effective prevention strategies has proven challenging but there have been notable successes. In the US and Western Europe, extensive...

HIV Care and Treatment

The HIV epidemic intersects with other important diseases. By weakening the immune system, HIV predisposes to opportunistic infections such as tuberculosis (TB). Globally, more than 21 million people are co-infected with TB and HIV. Although TB infection remains latent (neither contagious nor symptomatic) in most people without HIV, with TB HIV co-infection the risk of progression to active, contagious disease increases 100-fold. TB and HIV synergistically worsen the burden of both diseases. The global TB incidence has increased, fueled by a rapid increase in HIV-associated TB in Africa. TB is also a leading cause of death among people living with HIV. Increased collaboration between TB-elimination and HIV-treatment programs is necessary to control both of these diseases.

Lessons from Successful Vaccines against Other Pathogens

Although there are now successful vaccines against persistent viral infections (HBV and HPV) and even one against a virus capable of latency (VZV), retroviruses such as HIV-1 present new challenges. Probably the most challenging is the unparalleled mutation rate of HIV-1. The enormous genetic diversity of this virus means that if the first rounds of replication are not aborted by vaccine-induced immune responses, the virus will escape the immune response and establish long-term reservoirs of latent infection refractory to immune clearance. If HIV-1 infection cannot be prevented by vaccination, then reducing the rapid diversification of HIV-1 in a new host by controlling replication to the lowest possible levels is a second major challenge.

Gender Ethnicracial And Life Span Considerations

Anaphylactic shock can occur at any age and in both men and women, but women seem a little more susceptible than men. Individuals with food allergies (particularly shellfish, peanuts, and tree nuts) and asthma may be at increased risk for having a life-threatening anaphylactic reaction. People at the ends of the lifespan are most at risk. To prevent infants and children from experiencing severe allergic reactions, pediatricians carefully plan vaccines and diet to limit the risk of allergic reaction until a child's immune system is more mature. Severe food allergy is more common in children than in adults, but diagnostic contrast, insect stings, and anesthetics are more common in adults than in children. Teenagers with food allergies and asthma may be at high risk for an allergic reaction because they are more likely to eat outside the home and less likely to carry their medications. Older people also have a great risk of anaphylaxis, and their risk of death is high owing to the...

Cis Regulatory Elements that Target AID to Immunoglobulin Loci

Somatic hypermutation (SHM) is a mutagenic process that randomly alters the DNA sequence of the immunoglobulin (Ig) genes by introducing point mutations and single nucleotide deletions and insertions. The mutagenic activity is focused on the variable (V) regions (referred to in this context as the rearranged VJ or VDJ exon) of the Ig gene loci that encode the antigen-binding sites of the Ig. This allows for the generation of Ig molecules with slightly altered affinity for the cognate antigen, and ultimately, in the context of a germinal center immune response, for the emergence of B cells with higher affinity for the antigen. Class switch recombination (CSR) is a somatic DNA recombination in the Ig heavy chain (IgH) locus that leaves the antigen-binding site intact, but replaces the initial C constant (C) region with another chosen from a set of distinct C regions residing in this locus. As the C regions encode the effector function of the Ig molecule, CSR allows for an optimal immune...

Mechanisms of oral tolerance

T-helper cells are differentiated into two subsets, known as Th1 cells and Th2 cells. Th1 cells produce cytokines such as gamma-interferon and induce macrophage activation. In the absence of gamma-interferon, the antigen-presenting cells express another cytokine, IL-10, and induce Th2 cells to produce IL-4 cytokines. The latter cytokines will instruct naive B-cells to produce IgE. The balance between gamma-interferon and IL-4 at the time of the immune reaction will govern the immune outcome. High interferon IL-4 production facilitates the induction of a Thl-type immune response, whereas high IL-4 production induces a Th2 pathway. In oral tolerance, it is suggested that T-helper cells known as Th3 type are involved. These cells, which produce TGF- 31, may be responsible for oral tolerance, since TGF- 1 downregulate inflammatory cytokines and promote IgA production.24

Immunological Mechanism

Classical IgE-dependent anaphylaxis is a type I immunologic reaction, which can happen when a sensitized person is re-exposed to an allergen, usually at least a few weeks after the first exposure. Allergens are usually bivalent proteins with a molecular weight between 10,000 and 70,000 D. Allergen-specific IgE antibodies -synthesized by plasma cells after the first allergen contact - reversibly bind with the Fc portion to receptors on mast cells and basophils. The antigen-binding part of the IgE antibodies (the Fab portion) extends into the extracellular space. During a subsequent antigen contact, the bivalent antigen can then build a bridge between two cell-attached IgE antibodies, which will cause a release of preformed mediators, mainly hista-mine, from intracellular granules. It also causes the quick synthesis of other mediators such as leukotrienes C4, D4, and E4, triggered from membrane-attached phospholipids. These primary mediators cause the clinical appearance of anaphylaxis....

Factors contributing to development of tolerance

What happens when we encounter an antigen for the very first time has an important impact on what the outcome may be, i.e. whether we are sensitised or tolerised. We encounter most antigens early in life, during infancy, and as it happens this is the period when tolerance development is impaired. In fact, this delayed post-natal maturation of tolerance has been suggested as the reason for the increased frequency of allergic symptoms in infancy.26 So it appears that there is an immunological vulnerable period, perhaps due to the inability of the immature immune system to induce tolerance. Clearly, this is an exciting area and only further research will elucidate the current ambiguity.

Rescue of Autoreactive B Cells by T Cell Independent Antigens of Type I TLRLigand AntigenComplexes

In the other way, autoantigen-TLR-ligand complexes might activate immature B cells to proliferation, rather than to apoptosis of the autoantigen-specific B cells, as, for example, LPS has been seen to induce such responses on a polyclonal level with immature B cells. Thereby, autoantigen-TLR-ligand complexes could compete with autoantigen-natural IgM-complement complexes for reactions leading either to survival and proliferation or to apoptosis of the autoantigen-reactive cells. This may well occur during the peak of a bacterial infection and might become chronic if the infection is chronic. A real danger of autoimmune disease (in the case of dsDNA IgG or chromatin to SLE) should only arise if the response of the rescued, matured, activated au-toreactive B cells is taken over by a helper T cell-dependent, or otherwise AiD-inducing action of the immune system.

Role of Inflammation in Neurodegenerative Disorders

Two types of glial cells, namely microglia and astrocytes, are the primary players of the inflammatory process in the brain (35,36). Under normal conditions, microglia serve a function of immune surveillance. Astrocytes, on the other hand, act to maintain ionic homeostasis, buffer the action of neurotransmitters, and secrete nerve growth factors. In response to immunological stimuli or injuries in the brain, glia, especially microglia, readily become activated. Traditionally, injury- and or neuronal death-induced glial activation have been called reactive gliosis with the term reactive microgliosis specifically referring to the activation of microglia. Perhaps in analogy to certain components of the immune response observed in the peripheral system, activated astrocytes and microglia which are either resident or, as some have speculated, recruited to the injury site play a key role in tissue repair through phagocytosis and secretion of various trophic factors. However, activated glia,...

Biology Of Microglia

Determining the relative contribution of monocyte-derived macrophages and intrinsic microglia to the disease process, although conceptually important, is hampered by the fact that no single surface marker reliably differentiates intrinsic microglia from blood-borne monocytes 2 (see also below). There are several animal models that have contributed significantly to an understanding of micro-glial cell biology. The bone marrow chimera studies by Hickey and colleagues provided the first evidence that perivascular microglia (macrophages) in normal brain are a distinct population of CNS macrophages, different from parenchymal ramified microglia. Perivascular macrophages turn over more rapidly, and they are capable of presenting antigen in immune response reactions although intrinsic microglia represent a stable population with limited antigen presenting potential 9,10 . The early phase of an effective immune response to invading pathogens is essential for the survival of organisms and is...

Autoantibodies in diabetes complications

The lack of an immune response to self when responses to environmental antigens are retained is due to immunological tolerance. The role of tolerance, or lack of tolerance, is important to the understanding of autoimmune diseases and transplantation immunobiology (Mackay 2000). A loss of natural tolerance (to self) underlies all autoimmune diseases. Many more individuals develop autoimmune phenomena than autoimmune disease. Immune-mediated (Type I) diabetes results from an organ-specific autoimmune-mediated loss of insulin-secreting P cells. This chronic destruction process involves both cellular and hormonal components detectable in the peripheral blood, months or even years, before the onset of clinical diabetes (Kukreja & Maclaren 1999). In order to elicit an immune response, a molecule must be recognized as non-self by the biological system.

Bromoviruses Bromoviridae

To investigations of the role of co-infections in development of disease and of host genetic factors affecting infection and development of disease. Approaches to vaccination can be tested. The role of the cell-mediated immune response in protection from infection or from development of tumors remains a challenging area for investigation. See also Bovine immunodeficiency virus (Retroviridae) Human T-cell leukemia viruses (,Retroviridae)-. HTLV-1, HTLV-2 Immune response Cell mediated immune response, General features Immune escape mechanisms Latency Persistent viral infection.

Release of First MLV Followed by Reports of pvMD

Further investigation revealed that the vaccinated animals that succumbed to pvMD responded with serum antibodies to the other components of the vaccine but did not respond to the BVDV component. This suggested that the susceptibility to pvMD might be correlated with failure of the immune system to recognize BVDV. Questions raised by pvMD lead to the elucidation of the etiology of MD.

Analysis of Cre Activity and Gene Deletion in Conditionally Targeted Mice

Advances in conditional gene targeting have facilitated temporal control of gene inactivation, allowing for the first time comparison of gene requirements in embryonic and postnatal hematopoiesis in vivo. The interferon inducible MxCre mouse is particularly effective in inducing conditional gene deletion in the hematopoietic and immune systems in the adult mouse. Hence, it is widely used to study the role of conditionally targeted genes in the adult. The Mx promoter is silent unless activated by interferon, or the interferon inducer poly(I) poly(C) pIpC . Some leakiness of Cre expression may be detected, presumably owing to endogenous interferon expression. The inducer is administered intraperitoneally in neonates or adult mice allowing control of timing of the deletion by the investigator. Although protocols to induce the Mx promoter vary between studies, three injections of 250 g of pIpC to seven injections of 450 g every other day have been used successfully in adult mice. This...

Common Types Of Childhood Cancer Leukemia

Leukemia is identified as being either acute (growing quickly) or chronic (growing slowly). Children with leukemia are typically diagnosed with an acute form of the disease. Acute leukemia is divided into two types, (1) acute lymphocytic leukemia (ALL), also known as acute lymphoblastic leukemia (2) and acute myelogenous leukemia (AML), also known as acute myeloid leukemia, acute myelocytic leukemia, and acute nonlymphocytic leukemia. ALL is a cancer of the lymphoblasts (cells that help form an individual's immune system). AML is a cancer type that affects immature bone marrow cells (American Cancer Society, 2004).

Antigen Presenting Cells

For initiation of an immune response, naive T cells need to be activated or 'primed'. For that, they require both the recognition ofthe specific MHC peptide complex (signal 1) and simultaneous co-stimulation (signal 2). Although all nucleated cells express MHC-I and can potentially display MHC-I microbial peptide complexes after infection, only a specialized group of leukocytes, named APCs, expresses both MHC-I and MHC-II as well as co-stimulatory molecules. The best-characterized co-stimulatory molecules are B7-1 and B7-2, which bind to the CD28 molecule on the T-cell surface. In addition, T cells express CD40 ligand, which interacts with CD40 on APC further enhancing co-stimulation and enabling T-cell response. Finally, there is another group of adhesion molecules such as lymphocyte function-associated antigen-1 (LFA-1) on APCs which Figure 1 Interactions between virus-specific T cells and APCs. Three-color confocal microscopy was used to demonstrate immunological synapse formation...

Viral Subversion of Antigen Presentation

Considering the crucial role of antigen presentation for host defense, it is not surprising that many viruses have evolved maneuvers to evade or divert this process. Particularly, the essential role played by APCs in host defense to pathogens makes them an ideal target for viruses to suppress the immune response, thereby maximizing their chances of survival, replication, and transmission. Indeed, many viruses that cause major health problems are able to interfere with the ability of APCs to prime an efficient and effective antiviral immune response. In fact, many viruses have developed different mechanisms to subvert each stage of APC biology. Furthermore, with the greater understanding of antigen presentation pathways comes the discovery of An interesting example of virus blockade of antigen presentation from very initial steps is the ability of the prototypic arenavirus lymphocytic choriomeningitis virus (LCMV), to dramatically block DC development from early hematopoietic...

The Role Of Complement In Liver Regeneration

The complement system plays a crucial role in the early innate immune response, and we have thus far postulated several potential links between this system and regeneration of the liver based on factors common to both. However, recent studies have provided evidence for a definitive role for complement in the regenerative response. C3 appears to be activated early after the initiation of liver regeneration, as cleavage products are observed in the serum 2-3 hours after CCl4 injection107 and PHx (personal observation). Exemplifying the reciprocal nature of complement proteins and cytokines, C3 and C5 have been shown to be involved in cytokine production during early liver regeneration. Following PHx, increases in TNF-a and IL-6 mRNA are observed108. In mice lacking C3 (C3-'-) and in mice treated with an inhibitory antagonist for the C5a receptor (C5aR), there is a reduction in TNF-a and IL-6 mRNA levels. Further, both of these cohorts also show impaired activation of NF-kB and STAT3108....

Manifestations of Antigenic Variation

Immune response to viruses is generally thought of as negative selection that is, elimination of the pathogen. There are a few examples where immune recognition has a positive influence on the continued proliferation of the recognized pathogen, due to viral mechanisms to exploit immune elimination. Some viruses can use Fc receptors or mannose receptors to internalize antibody-bound virus into a replication mode instead of a destructive one. Alternatively, the virus may sabotage the immune response by changing antigenicity. A primary basis of antigenic variation is selection of virus mutants by antibodies. These are known as escape mutants, and since the escaped virus is resistant to antibody neutralization it possesses a fitness advantage in the presence of antibody. Escape mutants may also be selected by CD4+ or CD8+ T cells. There is certainly variation in the T-cell epitopes, but a lack of definitive examples that these have been selected by T cells as an immune evasion mechanism...

Biology Of Astrocytes

We have used a transcriptional gene-profiling technique to define the role of cytokines in regulating astrocytic cell function and interactions in human fetal astrocytes. Because IL-1 has been shown to be a critical initiating cytokine in the early stages of astrocyte activation both in vivo and in vitro 82,83 , we have focused on the IL-1-induced gene activation program in astrocytes. The results are similar to those obtained in adult astrocytes 84,85 and suggest that IL-1 is a potent modulator of human fetal astrocyte gene expression resulting in activation repression of a large number of factors involved in inflammation, development and growth, cell-matrix interactions, and the maintenance of the BBB. For example, application of exogenous IL-1 to such cultures induces the expression of multiple acute phase genes involved in the early stages of an immune response, including chemokines, cytokines, and adhesion molecules, the majority of which are known to be strongly proinflammatory...

Breaking Ignorance The Case of the Brain

2 Brain Autoantigens in the Immune Abstract Immunological self-tolerance is maintained through diverse mechanisms, including deletion of autoreactive immune cells following confrontation with autoantigen in the thymus or in the periphery and active suppression by regulatory cells. A third way to prevent autoimmunity is by hiding self tissues behind a tissue barrier impermeable for circulating immune cells. The latter mechanism has been held responsible for self-tolerance within the nervous tissue. Indeed, the nervous tissues enjoy a conditionally privileged immune status they are normally unreachable for self-reactive T and B cells, they lack lymphatic drainage, and they are deficient in local antigen-presenting cells. Yet the immune system is by no means fully ignorant of the nervous structures. An ever-growing number of brain specific autoantigens is expressed within the thymus, which ensures an early confrontation with the unfolding T cell repertoire, and there is evidence that B...

The Proteolytic Enzymes Of S Aureus

Amongst the proteins secreted by S. aureus are proteolytic enzymes belonging to three distinct catalytic classes, namely metallo- (aureolysin), serine (V8, Spl proteases, epidermiolytic toxins) and cysteine (staphopain A, StpA and staphopain B, StpB) proteases.20-24 Based on in vitro studies, staphylococcal proteases are considered potentially important virulence factors. They possess the ability to degrade critical components of the host defence system, such as elements of the complement system, cytokines and receptors on host immune cells 25-29 thus providing defence against the host immune response.17,30 They can also contribute to virulence directly, or indirectly, by interception of host enzymes and degrading endogenous proteinase inhibitors, resulting in tissue damage.25,31 Besides host-derived proteins, S. aureus proteases cleave a score of self-derived surface proteins, affecting its adhesive phenotype, thus contributing to bacterial detachment.9-11 Taken together, this...

Pentraxins in Humoral Innate Immunity

Abstract Innate immunity represents the first line of defence against pathogens and plays key roles in activation and orientation of the adaptive immune response. The innate immune system comprises both a cellular and a humoral arm. Components of the humoral arm include soluble pattern recognition molecules (PRMs) that recognise pathogens associated molecular patterns (PAMPs) and initiate the immune response in coordination with the cellular arm, therefore acting as functional ancestors of antibodies. The long pentraxin PTX3 is a prototypic soluble PRM that is produced at sites of infection and inflammation by both somatic and immune cells. Gene targeting of this evolutionarily conserved protein has revealed a non-redundant role in resistance to selected pathogens. Moreover, PTX3 exerts important functions at the crossroad between innate immunity, inflammation and female fertility. Here we review the studies on PTX3, with emphasis on pathogen recognition and crosstalk with other...

Circoviruses and Gyroviruses Induce Diseases

PCV1 and PCV2 seem to be restricted to pigs. PCV2 is the etiological agent of a new disease in swine, the so-called post-weaning multisystemic wasting syndrome (PMWS), and may be involved in several other porcine circoviral diseases (PCVDs) like porcine dermatitis and nephropathy syndrome (PDNS) or porcine respiratory disease complex. PMWS was first recognized in Canada in 1991. Since then it has been described as a major economic concern in virtually all pig-producing areas of the world. PMWS primarily occurs in pigs between 60 and 80 days old. Maternal antibodies confer titer-dependent protection against PCV2 infection - higher titers are generally protective, but low titers are not. PMWS is characterized by wasting, respiratory signs, enlargement of superficial inguinal lymph nodes, diarrhea, paleness of the skin or icterus, but the clinical signs are often variable. The most consistent feature of PMWS is a generalized depletion of lymphocytes. Secondary infections with...

Important Classes of Antiviral Targets and Compounds

As yet, there are no FDA-approved drugs targeting virus assembly but ST-246 is progressing through development. It was discovered as part of the program to prepare for bioterrorism, pox viruses being one of the perceived threats. Investigations with ST-246 resistant virus indicated that the mechanism involves the F13L gene which codes for a major virus envelope protein, p37. Intracellular enveloped viruses (IEVs) are formed from intracellular mature viruses (IMVs) and p37 participates in this wrapping process. ST-246 inhibits this stage and so IEVs are not available to be transported to the cell surface to produce extracellular virus. Exactly how ST-246 acts is being elucidated. Deleting F13L from vaccinia resulted in a virus (delta F13L-Vac) which replicates in cell culture although producing smaller plaques than wild-type (wt) virus. In mice infected with delta F13L-Vac, no lesions were produced but there was a good immune response which protected mice from subsequent challenge with...

Consumer groups at risk of foodborne illness 221 Infants and children

Certain consumer groups are at high risk for acquiring foodborne illnesses. For example, infants and children are more highly susceptible to infections because of their immunological naivety. Repeated exposure to pathogens or immunizations creates antigenic memory as adaptive immunity matures. Therefore, the

John M Walker Series Editor

Chemosensitivity Volume 2, In Vivo Models, Imaging, and Molecular Regulators, edited by Rosalyn D. Blumethal, 2005 110. Chemosensitivity Volume 1, In Vitro Assays, edited by Rosalyn D. Blumethal, 2005 109. Adoptive Immunotherapy Methods and Protocols, edited by Burkhard Ludewig and Matthias W. Hoffman, 2005 108. Hypertension Methods and Protocols, edited by J r me P. Fennell and Andrew H. Baker, 2005 107. Human Cell Culture Protocols, Second

Antiviral Combination Therapy

Virus latency remains an obstacle to successful antiviral chemotherapy for which no solution appears to be in sight. Members of the Herpesviridae are notable for being able to establish latent infections with HSV and VZV, latency is established in neuronal cells. During latent HSV-1 infection, the latency-associated transcript (LAT) of HSV-1 is the only known viral gene expressed. A micro-RNA (miR-LAT), which is generated from the exon 1 region of the LAT gene, reduces the induction of apoptosis and so contributes to the survival of that latently infected neuron. Few, if any, HSV proteins are expressed, so affording little chance for either the immune system or antiviral drugs to control the infection. Latency can be established despite ongoing antiviral chemotherapy although there is some evidence from animal models that famciclovir may be more effective than valaciclovir in reducing the load of latent virus when given very early during experimental infections. It still remains to be...

Genome Organization and Protein Expression

CSF virus (CSFV) is an enveloped virus with a diameter of c. 40-60 nm. The single-stranded RNA genome has a size of 12.3 kb. It has positive polarity with one open reading frame (ORF) flanked by two nontranslated regions (NTRs). The 5' NTR functions as an internal ribosomal entry site (IRES) for cap-independent translation initiation of the large ORF that codes for a polyprotein of about 3900 amino acids. The polyprotein is co- and post-translationally processed by viral and cellular proteases. From 11 viral proteins, four constitute the structure of the particle, namely three envelope glycoproteins (Erns, E1, and E2) and one core (C) protein. The remaining seven non-structural proteins are Npro, p7, NS2-3, NS4A, NS4B, NS5A, and NS5B. The main target for neutralizing antibodies is the viral envelope glycoprotein E2. To a lesser extent, the host's immune system produces neutralizing antibodies to Erns. This viral envelope glycoprotein occurs as a disulfide-bonded homodimer in the virus...

Death Receptor Signaling

Viruses encode a plethora of molecules that interfere with signaling by extracellular ligands and their respective receptors. In some cases, these viral factors mimic TNFR1, such as the cytokine response modifier (CRM) proteins of cowpox virus, M-T2 protein of myxoma virus, and S-T2 orthologs encoded by several poxviruses. These soluble or membrane-bound receptor mimics act as TNFa-sinks, thereby diminishing the frequency of the interaction between TNFa and the host receptor. Similarly, the viral TNF-binding protein (vTNF-BP) 2L from tanapox (and several other poxviruses) sequesters TNF directly, but bears amino acid similarity to MHC class I rather than TNFR. Another TNFR-superfamily receptor mimic found in cowpox and mousepox viruses is vCD30, which diminishes signaling to the host cell and the proliferation of B and T cells via CD30L, dampening the immune response to infection (Table 1).

Regulatory Viral RNAs and RNABinding Proteins

Micro-RNAs (miRNAs) are small hairpin-forming RNAs that are processed to mature forms both in the nucleus by the nuclease Drosha and in the cytoplasm by Dicer. Just as endogenous cellular miRNAs regulate cellular protein expression, the number of known virus-encoded miRNAs is growing rapidly. HIV miR-N 367 targets and suppresses the translation of Nef and negatively regulates virus replication. The polyomavirus simian virus 40 (SV40) produces an miRNA that suppresses the T-antigen (TAg), effectively evading immune surveillance. The Bcl-2 homolog BHRF-1of EBV is regulated by three distinct miRNAs that are encoded in the 3'-UTR of BHRF1 on the opposite strand. The HSV latency-associated transcript (LAT) also encodes an miRNA, whose targets were recently identified as components of the TGF- signaling pathway, including TGF- itself and the downstream adapter SMAD3, the regulation of which results in the suppression of cellular stress responses.

Host Response to Infection

There are no detailed studies of the immune response of finfish to infection by aquareoviruses but, from observations that have been reported, it is clear that cellular and humoral immune reactions are stimulated. While not consistent, local infiltration of host inflammatory cells, particularly in the liver of infected fish, has been observed during aquareovirus infections. Moreover, in studies in which sera have been collected from infected fish, specific neutralization titers of > 1 4000 have been obtained in neutralization tests. Further evidence of an immune response comes from studies with a vaccine produced in China for use against GCRV. A crude inactivated GCRV vaccine was produced in the late 1970s and was reported to provide good protection (70 survival of fingerlings).

Pathology and Histopathology

After infection, the tonsils are the location of primary virus replication. Thereafter, the agent progresses to neighboring lymphoreticular tissues. Through lymph channels the virus reaches regional lymph nodes, from where it spreads to the blood vascular system. Massive secondary virus replication takes place in spleen, bone marrow, and visceral lymph nodes. Major targets for the virus are cells of the immune system. In the peripheral blood, main target cells for the virus appear to be mono-cytes. In later stages of the disease, infected lymphocytes as well as granulocytes are found. Early events that are not completely understood play a significant role in the pathogenesis and manifestation of CSF. As early as 24 h post infection with virulent virus, that is, when animals are still asymptomatic and 2-4 days before virus can be detected in the peripheral blood, a progressive lympho-penia is observed resulting in severe immunosuppression. The reason for the massive cell death is not...

Properties of Proteins

Interest has recently focused on (1) proteins concerned with attributes possessed by cowpox but not vaccinia virus, such as the ability to grow on Chinese hamster ovary (CHO) cells, to produce A type inclusions (ATI) and in analysis of white pock mutation, and (2) proteins involved in evasion of the host's immune response. pock character is associated with loss of a gene (CmrA), homologous to the B13R of vaccinia virus, which encodes a 38 kDa protein, one of the most abundant early gene products. The CmrA predicted amino acid sequence is similar to that of inhibitors of serine proteases (SERPIN) which are involved in blood clotting, and has in vitro serine protease inhibitor activity causing inhibition of both apoptosis and production of interleukin 1 J (through inhibition of caspase 1) and inhibition of granzyme B, a serine protease released by cytotoxic T lymphocytes. Other cowpox proteins which may be involved in inhibition of aspects of the host's immune response include soluble...

Activation of Ignorant Autoreactive T Cells The Transition from Autoreactive to Autoaggressive

Traditional concepts list four activation mechanisms that may break tissue-specific autoimmunity, most of these related to concurrent microbial immune responses. These are Bacteria and viruses can be spotted by the innate and adaptive immune systems, either via pattern receptors or specific T and B cell receptors. But some of the organisms can fight back. One way is via superantigens, secreted proteins that activate large groups of T cells and thus make them produce pro-inflammatory cytokines in amounts big enough to flood a patient's body and cause severe disease. Toxic shock syndrome was widely publicized some years ago as an example ofsuperantigen-mediated pathogenesis. One version is caused in people by the toxic shock syndrome toxin-1 (TSST-1), a superantigen released from Staphylococcus aureus (Llewelyn and Cohen 2003). Apart from producing acute disease, superantigens were credited with shaping the immune repertoire, and, most important in our context, with triggering...

Why Cells Commit Suicide

Cells may also commit suicide in times of distress, for the good of the organism as a whole. For example, in the case of a viral infection, certain cells of the immune system, called cytotoxic T lymphocytes, bind to infected cells and trigger them to undergo apoptosis. Also, cells that have suffered damage to their DNA, which can make them prone to becoming cancerous, are induced to commit apoptosis.

Polymicrobial Sepsis As A Model

In addition to suppressing TNF-a and IL-1, IL-10 can be immunosuppressive, in part through its ability to block Th1 and promote Th2-mediated immune response. This has been most evident in models where an endogenous IL-10 response to injury may contribute to the immunosuppression leading to secondary infections. For example, following a burn injury, mice are more susceptible to lethal cecal ligation and puncture. However, this increased susceptibility could be prevented by treating the mice with a monoclonal antibody against IL-10 in the interim between the burn injury and the cecal ligation and puncture. Similarly, an endogenous IL-10 response following cecal ligation and puncture was responsible for the decreased antimicrobial response and increased mortality resulting from lung exposure to Pseudomonas aeruginosa.

Individuals with chronic disease

Transplant surgery, like all major surgeries, leads to short periods of immune suppression during which the patient may be at increased risk for infection (Cryer, 2000). Graft survival rate has greatly improved since the introduction of cyclosporine. However, pharmacological suppression of the immune system can lead to infection, a leading cause of mortality in kidney transplant patients HIV infection is characterized by gradual loss of immune function because of destruction of CD4 T lymphocytes. The onset of symptomatic AIDS results in increased risk of opportunistic infections that may be life-threatening (Sneller and Lane, 2001). Patients who are successfully receiving highly active antiretroviral therapy (HAART) may not be at increased risk for foodborne illnesses since severe immune suppression is not typical until the symptomatic phase of HIV infection is marked by low T cell counts (Crowe and Mills, 2001).

Bone Marrow Transplantation

The success of allogeneic transplantation in dealing with acute leukemia resistant to standard chemotherapy led investigators to use autologous transplantation against other cancers responsive to chemotherapy and radiation. Canellos (1985) compared the relative merits of allogeneic versus autologous BMT for treating non-Hodgkin's lymphoma. The former was limited by the few donors, patients in a gross state of relapse, infections from suppressed immune systems, the limiting effect of prior chemotherapy on whole-body irradiation, and graft-versus-host disease, a severe complication of allogeneic transplantation in which the donor cells attack the transplant recipient. Autologous BMT was more practical it not only obviated dependence on a limited number of donors and eliminated graft-versus-host disease GVHD, but also involved compromised stem-cell reserve and marrow contamination by malignant cells (p. 1452). Canellos emphasized that the use of ABMT with combination chemotherapy against...

Evolution Of The Cytokine Field

Although he term cytokine was first used only in the 1970s 8 , the origins of cytokine research can be traced to the middle of the 20th century (reviewed by Oppenheim and Feldmann 9 Vilcek 10 ). Among the earliest described factors are endogenous pyrogen 11 (which is probably identical to the cytokine later termed IL-1), nerve growth factor (NGF) 12 , and interferon 13 . The present field of cytokine research is the result of a fusion of several separate areas of investigation. The arguably most important foundation for the cytokine field was research in cellular immunology. In the 1960s, several groups investigating lymphocyte interactions in cultures reported that soluble factors produced by activated lymphocytes affected various functions of white blood cells 14-18 . Several other fields of investigation contributed to the development of cytokine research. Interferons were originally described in the 1950s as selective antiviral agents 13 , but it gradually became apparent that...

Overview of Cytokine Networks

Cytokines associated with the innate immune response are those induced early after infection by virus replication per se. One of the most important of these early components of the immunologically nonspecific response are type 1 (a and J) interferons (IFNs) which are generally synthesized and released by infected cells. IFN-a f can induce an antiviral state in surrounding cells and can also influence the characteristics of the subsequent immune response. In addition, phagocytic cells, responsible for processing and presentation of viral antigens to initiate the antigen-specific immune response, produce a variety of cytokines, including IFN-a ft. These antigen-presenting cells, generally dendritic cells and monocyte macrophages, may or may not be infected or produce infectious virus. Important cytokines and chemokines produced by antigen-presenting cells in the initial phases of the response to many viral infections are tumor necrosis factor (TNF), monocyte chemotatic proteins (MCP),...

Overview of Cytokine Networks Fig 1

Cytokines associated with the innate immune response are those induced early after infection by virus replication per se. One of the most important of these early components of the immunologically nonspecific response are type 1 (a and J) interferons (IFNs) which are generally synthesized and released by infected cells. IFN-a f can induce an antiviral state in surrounding cells and can also influence the characteristics of the subsequent immune response. In addition, phagocytic cells, responsible for processing and presentation of viral antigens to initiate the antigen-specific immune response, produce a variety of cytokines, including IFN-a . These antigen-presenting cells, generally dendritic cells and monocyte macrophages, may or may not be infected or produce infectious virus. Important cytokines and chemokines produced by antigen-presenting cells in the initial phases of the response to many viral infections are tumor necrosis factor (TNF), monocyte chemotatic proteins (MCP),...

Biological Function and Historical Background

Restriction enzymes apparently evolved as a primitive immune system in bacteria. If viruses enter a bacterial cell containing restriction enzymes, the viral DNA is fragmented. Destruction of the viral DNA prevents destruction of the bacterial cell by the virus. The term restriction derives from the phenomenon in which bacterial viruses are restricted from replicating in certain strains of bacteria by enzymes that cleave the viral DNA, but leave the bacterial DNA untouched. In bacteria, restriction enzymes form a system with modification enzymes that methylate the bacterial DNA. Methy-lation of DNA at the recognition sequence typically protects the microbe from cleaving its own DNA.

Host Receptor Recognition Site

Animal viruses have to recognize a specific host cellular receptor for entry during infection. Host receptor binding is the initial step of virus life cycle and could be an effective target for preventing virus infection. Based on the atomic structure of animal viruses, it was found that the receptor recognition site is located in an area surrounded by hyper-variable regions of the antigenic sites. Usually, the area is in a depression (called the 'canyon') on the viral surface that may be protected from recognition by host antibodies. This structural feature is, for instance, present in human rhinovirus (also known as the common cold virus), and the active site of influenza virus hemag-glutinin (HA). The receptor-binding site on influenza virus HA does not have a deep depression, but it is surrounded by antigenic sites. The receptor-binding area on the surface of the viral capsid is conserved for recognition by the receptor, whereas the sites recognized by antibodies are distinct from...

Transmission and Tissue Tropism

Human CMV may be transmitted by direct person-to-person contact at any time shedding is occurring, but immune status dictates the likelihood of disease following transmission. There is no seasonal variation in infection rates. Primary infection of an immunocompetent host results in a viremia which disseminates virus to organs, including the salivary glands and kidneys. The more immunocompromised a host, the greater the likelihood of spread to additional organs, with or without disease. Congenital transmission may occur throughout gestation following primary maternal infection, although some believe disease risk is greatest during the first half of pregnancy. Seropositive mothers who reactivate virus during pregnancy are less likely to transmit virus because their own adaptive immune response probably reduces the virus load. Congenital infection is a consequence of CMV crossing the placenta, possibly via carriage in maternal leukocytes or replication in trophoblasts. Virus is also shed...

Clinical Features of Infection

Congenital CMV disease typically follows a subclinical primary infection of an expectant mother. Disease is much less likely to follow reactivated maternal infection, although virus transmission occurs. Perinatal infection can result in a similar disease pattern, but at a much lower frequency. While 0.5-1 of infants are infected in utero, fewer than 10 suffer disease. Cytomegalic inclusion disease is the worst manifestation of congenital CMV, representing an extremely broad spectrum of different syndromes, including petechia, hepatosplenomegaly, jaundice, microencephaly and other serious neurological damage. A majority of symptomatic infants suffer subclinical disease with slowly developing hearing loss and mental retardation. Cytomegalic inclusion disease is the most significant disease caused by CMV, and seems to be a manifestation of widespread viral growth before the immune system has had a chance to develop. Congenitally infected neonates may present with rashes, hepatitis,...

Complement And Ocular Tolerance

The eye is an immune-privileged site. One of the characteristic features of the immune-privileged sites is that if an antigen is introduced to these sites a systemic tolerance can be induced. Introduction of an antigen into the anterior chamber (AC) leads to a deviant systemic immune response, known as anterior chamber-associated immune deviation (ACAID)51-52. ACAID involves the gen- The complement system has been reported to be essential for the development of suppressed DTH after AC injection of antigen and hence plays an important role in the development of tolerance53. In this report Sohn et al. proposed that binding of iC3b to CR3 present on APC induces production of TGF-P2, followed by upregulation of IL-10 and downregulation of IL-12. Under the influence of TGF-P2 there is increased production of IL-1054 and downregulation of IL-12 production by APC, which directs the immune response away from the Th1 pathway and toward a Th2-like response, which in turn leads to suppression of...

The Biological Functions Of

Kgp-null P. gingivalis strains lacked the black pigment characteristic for this species and were less virulent.46,53 In concert with the two Rgp members, Kgp also directly binds and cleaves fibrinogen and indirectly breaks down collagens via the activation of the matrix metalloproteinase system, resulting in an increased bleeding tendency and tissue damage at the infected periodontal site.54-57 Whilst the proteolytic activity of Kgp is important for generating peptides amino acids as the energy and carbon source suitable for the asaccharolytic nature of P. gingivalis, it is also utilized by P. gingivalis to manipulate and evade the host immune response via complex mechanisms,58-62 mainly involving the degradation of surface molecules of immune cells 63-66 and interference with the cytokine system of the host.61,67 In addition, Kgp can also bind host epithelial cells and other bacteria, providing a biological basis for the attachment and colonization of P. gingivalis.49,68...

Brief Survey Of Major Cytokine Families

One way to classify cytokines is to divide them on the basis of their principal functions into mediators of innate immunity, mediators of adaptive immunity, proin-flammatory cytokines, regulators of hematopoiesis, etc. The difficulty with this approach is that most cytokines are pleiotropic, i.e., they generally mediate more than one important function. A more rational and practical basis for the grouping of cytokines is based on their molecular structure and the nature of interacting receptors (Table 2.2).