Immune Response Ebook

How To Bolster Your Immune System

How To Bolster Your Immune System

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

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Immunity Crisis

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

Immunity Crisis Overview

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The Immune Response to Fungi From Microbe Sensing to Host Defensing

Most pathogenic fungi need a stable host-parasite interaction characterized by an immune response strong enough to allow host survival without elimination of the pathogen, thereby establishing commensalisms and latency. Therefore, the balance of pro-inflammatory and anti-inflammatory signaling is a prerequisite for successful host-fungus interaction. In light of these considerations, the responsibilities for virulence is shared by the host and the fungus at the pathogen-host interface, regardless the mode of its generation and maintenance. Studies with C. albicans have provided a paradigm that incorporates contributions from both the fungus and the host to explain the theme of the origin and maintenance of virulence for pathogens and commensals (Romani, 2004a). Through a high degree of flexibility, the model accommodates the concept of virulence as an important component of fungus fitness in vivo within the plasticity of immune responses orchestrated by dendritic cells (DC)....

Nervous System Communication to the Immune System

Immune system (Table 1.2 see also Blalock and Costa (1990), Carr (1991), Clarke and Bost (1989), DeSouza (1993), Gala and Shevach (1993), Harbour, Leon, Keating, and Hughes (1990), Harbour and Hughes (1991), Johnson, Downs, and Pontzer (1992), O'Neal, Schwarz, and Yu-Lee (1991), and Roupas and Herington (1989)). There are also data that support a role for the parasympathetic nervous system in influencing the immune system. Both muscarinic and nicotinic acetylcholine (Ach) receptors have been detected on T lymphocytes and macrophages (Tracey 2002). The cholinergic anti-inflammatory pathway, via the vagus nerve, may control the inflammatory response by inhibiting cytokine release from macrophages bearing nicotinic Ach receptors (Pavlov, Wang, Czura, Friedman, and Tracey 2003). Thus, since lymphoid tissues are innervated with sympathetic and parasympathetic fibers and contain specific receptors on their cell surfaces, it seems reasonable to perceive a mechanism by which the nervous...

The Natural Immune System

Natural killer (NK) cells are a major component of the immune system, which play important roles in host defences against cancer and microbial infections. NK cells are distinct from T or B lymphocytes, with a characteristic morphology of large granular cells, and can be readily identified by characteristic cell surface molecules. They have the ability to recognise and rapidly kill a wide array of tumour cells and also virus-infected normal cells. NK cytotoxic activity can be strongly augmented by interferon, interleukin-2, and other cytokines. NK cells are major producers of some cytokines, especially interferon gamma 41 they produce a neutrophil-activat-ing factor and upregulate polymorphonuclear leukocytes to kill Candida albicans 42 . eliminates the large Kupffer cells. Kupffer cell blockade modifies the immune response, exerts protective effects on anaphylactic and endotoxic septic shock, and decreases the liver-damaging effects of several hepatotoxins and ischaemic reperfusion....

Natural Immunity And The Natural Immune System

While the innate immune system has traditionally been considered by many to have evolved to defend against microbial pathogens 59,70-72 , others have proposed that the immune system did not evolve to fight infection 73,74 , Analysis of allorecognition challenged the paradigm that vertebrate immunity is pathogenetically focussed and directed support toward the idea that preserving individuality against the threat of invading conspecific cells (based on polymorphic compatibility molecules) was probably the driving force for all innate and adaptive immune systems and the defence function developed later 74 , Key molecules of the mammalian innate and adaptive immune systems were identified in sponges (Porifera) and some were considered likely to have acquired dual functions during evolution, acting first in adhesion and growth control and later in immune self self- and self non-self-recognition 75 , The bountiful evidence for the role of innate immunity in cell modulatory pathways of...

Immune System Communication with the Nervous System Hormones

There is now convincing evidence to show that the immune system can communicate with the central nervous system (CNS) (Wrona 2006). The invasion of the body by microorganisms activates cells of the immune system, which then releases a complex variety of soluble mediators called cytokines, which include interleukins, interferons, and tumor necrosis factors. These substances modulate the immune response but also influence the brain. This immune-to-brain pathway of communication triggers what we know as the sickness response. It is this effect which is discussed below and which constitutes the second arm of bidirectional communication.

Links Between Innate And Adaptive Immunity

There are many examples illustrating that the natural immune system serves as a foundation, on which the adaptive immune system has evolved. Briefly, the macrophage, which is a principal co-ordinator of natural immunity, is also fundamental to adaptive immunity as an antigen presenting cell. Moreover, macrophages initiate the acute phase response, which leads to the inactivation of the thymus and the inhibition of adaptive immunity. B lymphocytes secreting natural antibodies may have an effect on any lymphocyte of the adaptive system that expresses Fc-receptors. Natural killer cells produce IFN-gamma and other cytokones that affect cells of the adaptive system. Defensins also affect adaptive immunity. Complement has been established as a vital link between natural and acquired immunity, profoundly augmenting the antibody response to T-dependent antigens 79 . In turn, activated T cells produce INF-gamma, the major

Multiple Sclerosis As A Disease Of The Immune System

Normally, the immune system is able to distinguish between infectious organisms or foreign tissues (such as a transplanted organ), which are attacked or rejected, and the body's own organs or tissues, which are tolerated. How white blood cells perform these functions is a fascinating story. The process requires continual adaptation on the part of white blood cells to recognize through receptors on their surfaces and in proteins they make any disease-producing bacteria, virus, or fungus, and even the body's own cells that have become cancerous. Scientists have learned to activate the immune system through vaccination to defend the body against potentially infectious challengers. The other side of immunity, however, is that these white blood cells sometimes misrecognize and cause damage to the body's own cells and proteins. White blood cells that act in this way must be destroyed or held in check. If the system breaks down, autoimmune disease may occur. The immune system is then said to...

Influence of products of the immune system on the central nervous system

The immune system affects brain and behaviour, especially via the effects of immune cytokines on the central nervous system.(42) Although cytokines are relatively large molecules, some, particularly IL-1, can cross the blood-brain barrier via active transport. IL-1 is also produced in the brain by both microglia, which are macrophages resident in the central nervous system, and astrocytes. Peripheral IL-1 can affect the brain, including its production of cytokines, via stimulation of the vagus afferent fibres. There are cytokine receptors in the brain, including those for IL-1, IL-8, and interferon, on both glial cells and neurones. Cytokines play a role in the development and regeneration of myelin-producing oligodendrocytes. Brain cytokines play a role in immune effector mechanisms as regulated by the brain, including a role in brain infection and inflammation. Cytokines are relevant to the progression of multiple sclerosis, gliomas, HIV-associated dementia, brain injury, and...

The Role Of The Immune System In Type B Adverse Drug Reactions

On the basis of clinical criteria, it has been postulated that many idiosyncratic adverse drug reactions are immune-mediated (Park et al., 1998 Pirmohamed et al., 1998). Research into this area is now providing some direct evidence to support the clinical impression. The mechanism by which a drug leads to an immune-mediated adverse reaction is explained by the hapten hypothesis (Park et al., 1998) (Figure 6.2). Central to the hapten hypothesis is the assumption that small molecules such as drugs (< 1000 Da) can be recognized as immunogens (i.e. a substance capable of eliciting a specific immune response) only when they become covalently bound to an autologous high molecular weight (> 50 000 Da) macromolecular carrier such as a protein (Park et al., 1987). The term hapten has been coined to describe such substances that are not immunogenic per se but become immuno-genic when conjugated to a macromolecular carrier (this has been termed signal 1). The type of hypersensitive reaction...

The Immune System A Doubleedged Sword

The immune system evolved to protect the body from a variety of external (infectious agents or harmful molecules) and internal (malignant cells) threats. In this regard, the immune system provides the body with a means for minimizing or preventing disease. This is most clearly illustrated by individuals who have defects in immune function (immunodeficiency disease) resulting from genetic, developmental, infective, or therapeutic causes. Because of its destructive potential, however, the immune system is also capable of causing disease when confronted with inappropriate antigenic stimulation or loss of regulatory control ( 88).

Innate And Adaptive Immunity

Without an immune system we would quickly fall prey to the plethora of viruses, bacteria, and parasites that live within and around us. The immune system is a multi-layered defense system. In its broadest sense, it includes physical barriers, such as the skin and the lining of the gastrointestinal tract chemical barriers, such as stomach acid microbial barriers, such as beneficial intestinal microflora and the immune system proper (immune cells, antibodies, and so forth). This chapter focuses on the immune system proper. The cells of the immune system are called white blood cells (leukocytes) that, like red blood cells (erythrocytes), are derived from stem cells in the bone marrow. The production of the different types of cells from the bone marrow is shown in Figure 11.1 (adapted from reference 1). Other cells important in the immune response but not shown in the figure (e.g., natural killer cells and dendritic cells) are discussed below. As Figure 11.1 shows, leukocytes can be...

Role Of The Immune System In Cancer Prevention

Some researchers believe the immune system plays a critical role in preventing tumor development by searching out and destroying newly transformed cells. This process, known as immune surveillance, was first proposed by Ehrlich in 1909, and is supported by the following observations that associate immune depression with increased cancer risk 11,12 Approximately 40 percent of patients with immuno-suppression caused by the human immunodeficiency virus (HIV) are likely to develop cancer. Common cancers include Kaposi's sarcoma, non-Hodgkin's lymphoma, cervical cancer, and Hodgkin's disease. An alternate and more likely explanation for this disproportion is that cancers commonly associated with immunosuppressed states are virally induced, or they originate in the immune system itself. Accordingly, the problem is that the immune system fails to destroy viruses that cause or assist the development of cancer rather than that it fails to destroy tumor cells. In some cases, viruses can...

Immune System In Cancer Treatment

The immune system's postulated role in preventing cancer by destroying cancer cells, along with other evidence, tells us it can also help destroy cells of established cancers. Its ability to do so, referred to as antitumor immunity, involves both the innate and adaptive immune systems. For example, recent evidence suggests the immune system may be capable of detecting the protein products of oncogenes on the cell surface immune responses to the HER-2 neu protein and mutated ras and p53 gene products have been re-ported.20,21 In addition, antibodies against the patient's own tumor have been identified in the sera of some patients with soft-tissue sarcoma, malignant melanoma, ovarian carcinoma, and lung cancer.22 The degree to which the immune system can destroy established cancers, however, has not been established. In general, the immune system may be more effective against small tumors and metastatic spread than against established solid tumors. What is clear is that the success of...

Altered Sleep and Concomitant Alterations in Immune Function

If sleep is indeed a restorative process that is important for the appropriate functioning of the immune system, it should come as no surprise that a number of researchers have attempted to investigate possible correlations between disordered sleep and disease, both incidence and or progression, particularly those diseases for which there is already evidence for an immunological component. This explains the interest in infectious disease (see above). In one study attempting to dissect the immune changes which might accompany sleep disruption, immune functioning between patients with chronic insomnia (17 adults meeting criteria for a chronic primary insomnia disorder) and good sleepers (19 adults with a regular sleep However, more subtle interactions have also been reported. Thus, the severity of disordered sleep in depressed and or alcoholic subjects also shows a correlation with altered innate and cellular immune functions, and furthermore may be related to changes in cytokines...

Perspectives On Origins Of Natural Immunity And Relation To The Neuroendocrine System

Interest in the dual functional and morphological division of the immune system is pervasive. Clearly access to the totality of immune capability is now balanced with all animals being considered. We now have innate, natural, non-specific, non-anticipatory, non-clonal responses of invertebrates in contrast to the adaptive, induced, specific, anticipatory, clonal responses typical of vertebrates. The innate is considered the most primitive and found in both animal groups invertebrates do not possess the adaptive system. This duality is expressed at every level of biological organization molecules, cells, tissues, organs, and organisms. Monolithic immunology, 19lh century preoccupation with humoral mechanisms was split when Metchnikoff discovered phagocytosis in invertebrates. This discovery changed the face of immunology, creating a permanent schism and according equal importance to cellular effectors (leukocytes) obviously the sources of the molecular products that they synthesize and...

Flavonoids and Immune Function

The effects of flavonoids on the immune system are complex and poorly understood. Depending on the conditions, flavonoids may inhibit, assist, or have no effect on immune function. Their effects on immune function are due to their ability to inhibit eicosanoid-mediated inflammation, histamine-induced inflammation, PTK or PKC activity, cell motility, or several of these. Clearly, additional work remains to understand the effects of flavonoids on immune function and to determine how these effects may influence tumor progression. It does seem, however, that at doses relevant to humans, immunostimulation or no effect on the immune system is more likely to occur than an immunosuppressive effect.

Signaling in Natural Immunity Natural Killer Cells

Natural killer (NK) cells are large granular lymphocytes noted both for their cytotoxic role in innate immunity and for their linking of the innate immune system to the adaptive immune system through cytokine secretion. In both of these roles, NK cells make use of their ability to recognize tumour- and virus-associated ligands. These cells are identified by their phenotype NK cells express CD 16, the low-affinity Fc receptor (FcR) for IgG, but NK cells do not express T cell antigen receptors or the B cell-associated surface immunoglobulin (slg).

Lymphocytes Participate in Both innate and Adaptive Immunity

At the mature stage, B cells possess a system that can sense the presence of microorganisms and contribute to their destruction. In addition to secreting Igs, B cells are able to present Ags (Roosnek and Lanzavecchia, 1991), upreg-ulate costimulatory molecules, express antimicrobial activity by producing reactive oxygen intermediates and other inflammatory cytokines, and secrete factors that can directly mediate microbial destruction (Yi et al., 1996 Lee and Koretzky, 1998). More recently, it was recognized that B cells can express toll-like receptors (TLRs) (Applequist et al., 2002 Bourke et al., 2003). This expression is augmented following engagement of the BcR or the costimulatory molecule CD40 or by stimulation with S. aureus Cowan I bacteria or unmethy-lated CpG DNA. Since TLR9 recognizes unmethylated CpG motifs characteristic of bacterial DNA and is involved in the immediate response to a wide range of microbes, B cells may, in addition to their role as Ab-producing cells...

Immune Response to Influenza Viral Infection

The influenza A virus enters the body through the respiratory tract. Although an infected individual can sneeze in your face to transfer the virus, inoculation is typically a bit more surreptitious. The virus can exist in nasal droplets on the doorknob that you will use to open the door to your office, on the handset to the phone you use to tell your kids you are coming home early from work, on the handle of the shopping cart at your local grocery store, or on the hand that you will shake to say hello or goodbye. In fact, most people infect themselves hand-to-nose. Once the virus obtains entry to the body, it has to gain entry into specific cell populations for its own survival as it is an obligate intracellular parasite requiring the host cell's machinery for replication. The typical influenza A virus productively infects respiratory epithelial cells (Matrosovich et al., 2004). Once the virus binds to the surface of the first respiratory epithelial cell, the race is on pitting...

Decreased Immune Response

A diet high in saturated and omega-6 fatty acids may promote cancer partly by decreasing immune function. In a study of 17 men who reduced their fat intake to less than 30 percent of calories, natural killer (NK) cell activity was markedly increased compared to baseline levels. In this study, the lower the fat content, the greater the NK cell activity.58 The exact mechanism of this inhibition was uncertain, but it may have been related to increased PGE2 production, which has an immuno-suppressive effect.

Immunotherapy Of Multiple Sclerosis Theoretical Basis And Practical Approach

This chapter covers the basics of immunology followed by the practical approach to immunotherapies in MS. We first review the basic immune mechanisms underlying the response to an antigen as the autoimmune theory holds that in MS, myelin proteins (or oligodendrocytes) are seen as foreign antigens by the immune system. We review experimental allergic encephalomyelitis (EAE), because many characterize it as the animal model of MS despite the fact that there exist many variations of this experimental disease that cannot qualify as a model of MS. We review the blood-brain barrier (BBB) and its disruption as the major biophysical obstacle that pathogenic immune system cells must traverse to reach their target. Finally, we describe the MS plaque in terms of immune content and what is known about the magnetic resonance imaging (MRI) correlations.

The Immune Response To Infection Injury And Inflammatory Agents

The immune system has a large capability for immobilizing invading microbes, creating a hostile environment for them, and bringing about their destruction (1). The immune system may also become activated, in a similar way to the response to microbial invasion, by a wide range of stimuli and conditions that do not directly involve pathogens these include burns, penetrating and blunt injury, the presence of tumor cells, environmental pollutants, radiation, exposure to allergens, and the presence of chronic inflammatory diseases. The response of the immune system to this diverse range of agents and conditions contains many common elements. These, however, vary in intensity according to their impact on the body. The elements of the response include the production of immunomodulatory proteins (cytokines), oxidant molecules (hydrogen peroxide, superoxide, hypochlorous acid, and nitric oxide), anti-inflammatory hormones (cortisol), natural antagonists (cytokine receptor antagonists), and...

The Immune Response To Antigens

Every protein or peptide from the environment can be considered an antigen. If an individual's immune system does not recognize a substance as foreign antigen, the individual is said to be tolerant-, if it does, he is said to be responsive or sensitized. The first step of the immune response consists of this recognition by macrophages and other antigen-presenting cells (APC), followed by phagocytosis. Phagocytosis is the digestion of peptides by enzymes in the endoplasmic reticulum and the presentation of these pep-tides back to the cell's surface through HLA class II (also called DR) antigen on APC and T-cell receptor on T cells together with accessory molecules. These accessory molecules, when present, amplify the immune response, when absent, they reduce it and limit its intensity. If the antigen is presented in the context of class II molecules and T-cell receptors, but without accessory molecules, the stimulated cells undergo apoptosis (cell death). However, if accessory...

Trypanosomes Vary Surface Proteins to Outwit the Immune System

Parasitic eukaryotes live in hostile environments and must elude the defenses of their host. Many adaptations have occurred in parasitic eukaryotes to overcome host defense systems and allow the parasite to thrive in these one-sided relationships. Many parasitic microorganisms attempt to elude the immune system of their host by changing their surface proteins (Fig. 19.12). The idea behind this strategy is straightforward. The immune memory cells recognize the proteins on the surface of the original generation of invading germs. However, if each successive wave of invaders changes its

Glutamine and the Immune System

Improve both natural killer cell and T-cell activity in vitro and in vivo.46,105 Glutamine may also reduce immuno-suppression caused by tumors. Because some enzymes involved in PGE2 production are inhibited by glutathione, and because PGE2 is an immunosup-pressive compound, glutamine, as an inducer of glutathione synthesis, can reduce immunosuppression.106 The ability of cancer cells to evade immune destruction is one of the main reasons conventional immunostimulant drugs have had only limited success (see Chapters 11 and 12). The potential anticancer effects of glutamine are summarized in Table 18.1. Chapters 11 and 12 Immune System Stimulate support the immune system

The Case for Immunotherapy

Although proposed as a potential therapy for cancer over a century ago, immunological-based strategies have only become a reality in the past two decades. Both the innate and adaptive immune responses are believed to play key roles in tumor surveillance (Diefenbach and Raulet 2002). While innate immunity relies on phagocytes, natural killer (NK) cells, natural antibodies, and complement proteins, adaptive immunity recruits antigen-presenting cells (APC), T cells and B cells (Janeway et al. 2001). As a primeval system of defense, innate immunity depends on invariant receptors recognizing common features of tumor cells, although it has no immunological memory and can often be evaded. The ability to recognize tumors specifically and to prevent their regrowth becomes more efficient with the emergence of adaptive immunity. This property of specificity is based on clonal selection of lymphocytes bearing antigen receptors. A broad range of effector cells, cytokines, chemokines, antibodies,...

HIV and the immune system

Human immunodeficiency virus (HIV) is a retrovirus that gradually destroys the immune system's function. When the retrovirus becomes active, the patient develops acquired immunodeficiency syndrome (AIDS), which is characterized by profound immunological deficits, opportunistic infection, secondary infections, and malignant neoplasms. HIV disables and kills CD4+ T cells, which lowers the immune system's capability to fight infection. The number of CD4+ T cells triggers other cells in the immune system to attack invading organisms. HIV lowers the CD4+ T cell count and thereby inhibits other immune system cells to go on the attack. In addition to the T-cell count, the viral load (VL) is a test used to evaluate the status of the patient's immune system. The higher the number, the higher the viral load. Maintenance of the normal immune system Reconstruction of the normal immune system

The Host Immune Response

Recently, there have been important advances in our understanding of the host response to A. fumigatus infection (Figure 8.1 A). (i) Several of the receptors (Toll-like receptors TLR-2, TLR-4, and dectin-1 receptor) and pathways (ERK, NFkB) used by the cells of the innate immune system to recognize and respond to A. fumigatus infection have been identified (ii) macrophage-mediated phagocytosis of conidia has been delineated in greater detail (iii) the role of dendritic cells (DCs) in activating the T cell response through antigen presentation has also been examined. These exciting and evolving fields will be discussed. Readers interested in comprehensive summaries describing the host immune response to A. fumigatus infection are directed to several excellent recent reviews (Roeder et al., 2004 Walsh et al., 2005 Brown 2006 Rivera et al., 2006).

Effects Of Antioxidants On Immune Function Effects of Vitamin E

A number of studies in which anti-oxidant status has been raised by dietary supplementation indicate that improvement of anti-oxidant status is associated with an increase in cellular aspects of immune function. Vitamin E exerts modulatory effects on both inflammatory and immune components of immune function. In general, vitamin E deficiency and low tissue vitamin E content enhance components of the inflammatory response and suppress components of the immune response. Dietary vitamin E supplementation brings about the opposite effect. Studies in animals have demonstrated that vitamin E deficiency impairs cellular and humoral immunity and is associated with an increased incidence of disease. Supplementation of the diet with vitamin E, at levels that are several fold greater than requirements, increases resistance to a number of pathogens. Resistance of chickens and turkeys to Escherichia coli and of mice to pneumococci, was enhanced by vitamin E supplementation. A similar phenomenon...

Ascorbic Acid and Immune Function

The observation that high concentrations of vitamin C are found in phagocytic cells has underpinned the concept that ascorbic acid is an important nutrient for optimal immune function. However, although the role of vitamin C as a key component of antioxidant defense is well established, most studies have shown only minor effects on a range of immune functions, except in cases where the vitamin may be acting by interacting with GSH metabolism. Unlike deficiencies in vitamins B6, E, and riboflavin, deficiency of vitamin C does not cause atrophy of lymphoid tissue. In a study of ultra marathon runners, dietary supplementation with 600mg day of ascorbic acid reduced the incidence of upper respiratory tract infections after a race by 50 (62). It is interesting to note that strenuous exercise has been shown to deplete tissue glutathione content. The interrelationship between gluta-thione and ascorbic acid may therefore play a role in the effect of exercise on immune function. When...

Glutathione and Immune Function

One of the first indications that glutathione influences aspects of immune function, which are related to T lymphocytes, came from a study in which the GSH content of these cells was measured in a group of healthy volunteers (65). The numbers of helper (CD4+) and cytotoxic (CD8+) T cells increased in parallel with intracellular GSH concentrations up to 30 nmol mg of protein. However, the relationship between cellular glutathione concentrations and cell numbers was complex, with numbers of both subsets declining at intracellular glutathione concentrations between 30 and 50 nmol mg of protein. The study also revealed that cell numbers were responsive to long-term changes in GSH content. When the subjects engaged in a program of intensive physical exercise daily for 4 weeks, a fall in glutathione concentrations occurred. Individuals with gluta-thione concentrations in the optimal range before exercise, who experienced a fall in concentration after exercise, showed a 30 fall in CD4+ T...

The Immune Response in TMEV Infection

As discussed in the preceding chapter, TMEV induces a biphasic disease. The acute phase of disease (first month) is primarily a gray matter disease similar to poliomyelitis. The later chronic disease occurs several months postinfection and is characterized by primary inflammatory demyelination. Immunosuppressive regimens during the acute disease are detrimental because an intact immune system is required to control infection. In contrast, immunosuppression during chronic disease is beneficial because it ameliorates inflammation as the immune response becomes pathogenic (Welsh et al., 1987). responses (Biron, 1998). For example, the cytokine IFN- plays a pivotal role in the early immune response to TMEV (Fiette et al., 1995). Natural killer (NK) cells and CD8+ and CD4+ T cells are also activated early in infection and play an important role in viral clearance (Kaminsky et al., 1987 Welsh et al., 1987 Borrow et al., 1992 Dethlefs et al., 1997 Murray et al., 1998). However, during...

Effects of Folic Acid on Immune Function

As the vitamin is also intimately involved in sulfur amino acid metabolism, it might be expected that the vitamin would modulate anti-oxidant status and immune function. However, there is evidence that only the second of these two effects occurs. Indeed, oxidative stress may impair folate metabolism. In a double-blind, placebo-controlled crossover intervention in healthy subjects, it was found that although a folate rich diet and folate supplements caused a fall in plasma homocysteine concentrations, there was no change in anti-oxidant activity (plasma and red blood cell glutathione peroxidase activity and red cell superoxide dismutase activity) or oxidant damage (plasma malonaldehyde) (85). Infection and inflammation are often associated with hyperhomocysteine-mia, an indicator of folate insufficiency (86). It has been hypothesized that the underlying cause of this effect is that the active form of folate (tetrahydrofolate) is susceptible to oxidation during the oxidative stress...

TBI and Immune Surveillance

In addition to central neuropathological consequences, TBI has humoral neural signs, such as elevated circulating levels of catecholamines, which contribute to the immunosuppression observed in patients with TBI by inducing the release of the immunosuppressive cytokine, IL-10. Therefore, the central insult provoked by TBI has clinically significant sequelae in that it puts the patients at increased risk for depressed immune surveillance, infection and sepsis (Plata-Salaman 1998 Woiciechowsky et al. 1998). In point of fact, inflammation is a critical aspect of the central and peripheral response to TBI. The process by which the central and the peripheral responses interact constitutes an important part of the pathophysiology of TBI, and is regulated in large part by the blood-brain barrier. Numerous immune mediators released within minutes of the primary injury determine and guide the neuroimmune sequence of events that follows, and its protraction in time (Morganti-Kossmann, Rancan,...

Natural Immunity And Aging

Human aging can be considered as a dynamic process that leads to a continuous adaptation of the body to the deteriorative changes occurring lifelong. This picture is conceptualised in the remodelling theory of aging 29,30 , based on experimental evidence obtained from studies on human immunosenescence and on healthy very old people (centenarians) as a model of successful aging. Specifically, these results show that the aging process affects immune responses differently some of them decline while others remain unchanged or increase 31-33 , Accordingly, a variety of immune responses and parameters are well conserved in centenarians 34 10 , Data from the literature seem to indicate that natural immunity remains preserved or less affected by aging than clonotypic and adaptive immunity. Indeed, the absolute number of cells belonging to the natural immunity compartment, such as dendritic cells (DCs), monocytes macrophages and granulocytes is not affected by age, while their ability to...

The Neural Immune System in CFS

If persistent infection is not the cause, another hypothesis is that it is infection triggers abnormal processes in the immune system. A number of papers have reported immune activation in CFS (for review, see Strober (1994)) but it is not clear whether these change are the cause or the result of changes brought about by the CFS such as inactivity, disturbed sleep and chronic stress. Some data do support some underlying immunological problem first, some CFS patients appear to have an antibody against a specific nuclear antigen (Von Mikecz, Konstantinov, Buchwald, Gerace, and Tan 1997) second, patients have a dysregulated 2,5 RNase L antiviral defense pathway (Suhadolnik et al. 1999) and third, treatment with an immune active agent, mismatched RNA, may reduce disability (Strayer et al. 1994) (a study to replicate this outcome has recently been completed). The immune dysregulation hypothesis was further supported by reports from two prominent groups that found evidence for immunological...

Strategy of the Adaptive Immune Response

On first exposure to a given microbe or any other antigen, systemic evidence of the adaptive immune response takes a week or more to develop during this delay the host depends on the protection provided by innate immunity, which may not be sufficient to prevent disease. This first response to a particular antigen is called the primary response. As a result of that initial encounter, the adaptive immune system is able to remember the mechanism that proved effective against that specific antigen. As a result, when the same antigen is encountered later in life, there is an enhanced antigen-specific immune response called the secondary or anamnestic response. The efficiency of the secondary response reflects the memory of the immune system. antigen, p. 372 The adaptive immune response uses two basic strategies for countering foreign material. One response, humoral immunity, works to eliminate antigens that are extracellular, for example, bacteria, toxins, or viruses in the bloodstream or...

The Immune System Shows Circadian Organization

Light and daily rhythms have a profound influence on immune function. Many studies have described circadian variations of different immune parameters such as lymphocyte proliferation, antigen presentation, and cytokine gene expression. The number of lymphocytes and monocytes in the human blood reach maximal values during the night and are lowest after waking. Natural killer (NK) cells, by contrast, reach their highest level in the afternoon, with a normal decrease in number and activity around midnight. granzyme B, perforin, interferon (IFN)-y, and tumor necrosis factor (TNF)-a found in NK cells underlines the circadian nature of NK cell function (Arjona and Sarkar 2005). Thus, the existence of molecular clock machinery may be conserved across different lymphocyte subsets and peripheral blood cells. Moreover, they may share common entrainment signals. Emerging data in the human and animal literature suggest that circadian regulation may be crucial for the host defenses against cancer....

Mechanisms Of The Effects Of Oxidants And Antioxidants On Inflammation And Immune Function

The oxidant molecules produced by the immune system to kill invading organisms may activate at least two important families of proteins that are sensitive to changes in cellular redox state. The families are nuclear transcription factor kappa B (NFkB) and activator protein 1 (API). These transcription factors act as control switches for biological processes, not all of which, as illustrated earlier, are of advantage to the individual. NFkB is present in the cytosol in an inactive form, by virtue of being bound to IkB. Phosphorylation and dissociation of IkB renders the remaining NFkB dimer active. Activation of NFkB can be brought about by a wide-range of stimuli including pro-inflammatory cytokines, hydrogen peroxide, mitogens, bacteria and viruses and their related products, and UV and ionizing radiations. The dissociated IkB is degraded and the active NFkB is translocated to the nucleus where it binds to response elements in the enhancer and promoter regions of genes. A similar...

Immune System Evolution

Because invertebrates lack an adaptive immune system, to survive they evolved effective intrinsic defence strategies against a variety of microbial pathogens. This ancient form of host defence, innate immunity, is present in all multicellular organisms including humans. The Japanese horseshoe crab Tachypleus tridentatus, is a model protostome organism. Its innate immune system includes a hemolymph coagulation system that participates both in immunity against microbes and in hemostasis. Early work on the evolution of vertebrate fibrinogen suggests a common origin of the arthropod hemolymph coagulation and the vertebrate blood coagulation systems. This assumption could not be verified by comparing the structures of coagulogen, the clotting protein of the horseshoe crab, and of mammalian fibrinogen. However, the crystal structure of tachylectin 5A (TL5A), a nonself-recognizing lectin from the hemolymph plasma of Tachypleus tridentatus provides new insights. TL5A shares not only a common...

Natural Immunity And The Neuroendocrine System

What are some of the general features of the neuroendocrineimmune system The immune system has been referred to as the mobile brain because of shared molecules between the nervous, endocrine and immune systems, the three regulators that govern and control homeostasis a balanced milieu. Opinions concerning the significance of these interrelations are divided. There are those who view the whole organism and therefore favor a unifying theme with respect to the three systems central nervous system (CNS), endocrine system (ES), and immune system, (IS). Still others, the reductionists, prefer to retain a strict separation despite substantial evidence indicating enormous overlap. Within the CNS, neuropeptides are small molecules responsible for transmitting certain signals. In vertebrates the hypothalamus produces several of these transmitters, that cause pain (e.g., substance P) or suppress it (e.g., endorphins, enkephalins). In the ES the inner portion of the adrenal medulla, when...

Neurotransmitter Release by Cells of the Immune System

Ricci, and Amenta 2002 Warthan et al. 2002). The synthesis of catecholamines was shown to increase after mitogen treatment of rat lymphocytes obtained from spleen, thymus, and mesenteric lymph nodes (Qiu, Peng, Jiang, and Wang 2004). The ability to express tyrosine hydroxylase was greatest in mesenteric lymph node cells compared to the spleen and thymus. Although more work needs to be done, the available data suggest that endogenous catecholamines may suppress IL-2 production and thereby modulate T cell expansion (Tsao, Lin, and Cheng 1998). It has been suggested that in the dual regulation of immune function by endogenous and exogenous catecholamines, endogenous catecholamines may be more important since the lymphocytes are responding to antigen and performing an immune response (Qiu et al. 2004). Similar to catecholamines, stimulating lymphocytes with mitogens enhances the synthesis and release of acetylcholine (Kawashima and Fujii 2003). Both muscarinic and or nicotinic...

Proteins that are Very Similar to Self Immune Response Genes

Similar to self reveals another level of control, the histocompatibility-linked immune response genes (Ir genes Benacerraf and McDevitt, 1972). For example, when mice are immunized with the B subunit of lactate dehydrogenase from pig hearts, some strains respond well while others respond very poorly. The genes that control responsiveness map to the class II region of the mouse MHC (Melchers et al., 1973). It is now clear that Ir genes often reflect the ability of individual peptides to bind to MHC molecules and thus initiate immune responses (Rammensee et al., 1993 Engelhard, 1994a, b). The genetic factors that govern immune responsiveness are particularly well seen when inbred mice are immunized with proteins from different mouse strains where there are slight allelic differences in the sequence of that protein. Allelic differences between proteins of different individuals within a species are known as allotypes. In many cases, allotypic differences were first detected serologically...

Individual Drugs Used To Stimulate The Immune System

A number of disorders can be treated with immuno-stimulating agents (also known as biological response modifiers or immunomodulating agents) these drugs enhance the body's immune response. These conditions include immunodeficiency diseases, cancer, some types of viral and fungal infections, and certain autoimmune disorders. The drugs may work on cellular or humoral immune systems or both. Immunostimulating agents are nonspecific they cause general stimulation of the immune system. Among the agents capable of general potentiation of the immune system are extracts and derivatives from bacteria, yeast, and fungi. They also include a variety of peptides, cytokines, and synthetic compounds. In most cases, the pharmacology of these agents has not been well described. The most commonly used agents are discussed next.

Innate Immune Responses to Influenza Virus Inflammation

Whereas TLRs can mediate pathogen recognition and initiate an antiviral response in the tissue parenchyma, recruitment of cells (i.e., inflammation) is necessary for the development of effective innate host defenses and the subsequent development of adaptive immunity. In addition to driving the transcription of the type I interferons, ligation of the Toll-like receptors also stimulates an inflammatory response (Diebold et al., 2004 Pasare and Medzhitov, 2004).The inflammatory response is initiated to recruit a variety of leukocytes (e.g., macrophages, NK cells, and B and T lymphocytes) from the blood to further control virus replication and to begin initiation of the adaptive immune response that will be considered later. Again, almost coincident with infection of the first cell, Toll-like receptor activation results in the transcription of inflammatory cytokine genes. These include IL-1 and TNF-a (Julkunen et al., 2001 Conn et al., 1995). In turn, these proinflam-matory cytokines...

Natural Compounds That Suppress The Immune System

Many natural compounds I discuss have the potential to inhibit aspects of the immune system. Although none of these is generally considered a primary immunosup-pressive agent, each can produce immunosuppression as a secondary effect, at least under some circumstances. Natural compounds can induce immunosuppression in many ways, such as by reducing signal transduction (immune cells need signal transduction to function), reducing NF-xB activity, histamine release, vascular permeability, and immune cell migration, as well as by causing anti-inflammatory effects. The most potent anti-inflammatory compounds tend to be those that reduce production of PGE2 or other inflammatory pros-taglandins or leukotrienes. Taking all of these actions into account, we can see that most compounds included in this book have the potential to contribute to an immu-nosuppressive effect however, earlier in this chapter we also saw that most could also contribute to a stimulatory effect. What is the overall...

Neuroendocrine Hormone Influence on the Immune System

The immune system, in addition to autonomic nervous activity, is influenced by hormones released by the neuroendocrine system (Table 1.3 see also Brooks (1990), Carr (1992), Clevenger, Sillman, and Prystowsky (1990), Clevenger, Sillman, Hanley-Hyde, and Prystowsky (1992), Foster, Mandak, Kromer, and Rot (1992), Jain et al. (1991), Johnson, Farrar, and Torres (1982a), Johnson, Smith, Torres, and Blalock (1982b), Johnson, Torres, Smith, Dion, and Blalock (1984), Kelley (1989), Kruger, Smith, Harbour, and Blalock (1989), Matera, Cesano, Bellone, and Oberholtzer (1992), Mathew, Cook, Blum, Metwali, Felman, and Weinstock (1992), McGillis, Humphreys, and Reid (1991), Ottaway, Bernaerts, Chang, and Greenberg (1983), Pascual, Xu-Amano, Kiyono, McGhee, and Bost (1991), Provinciali, Di Stefano, and Fabris (1992), Rouabhia, Chakir, and Deschaux (1991), Smith, Hughes, Hashemi, and Stefano (1992), Stanisz, Befus, and Bienenstock (1986), and Zelazowski, Dohler, Stepien, and Pawlikowski (1989)). A...

The Cells of the Immune System

The cells of the immune system can move from one part of the body to another, traveling through the body's circulatory systems like vehicles on an extensive interstate highway system. They are always found in normal blood, but their numbers usually increase during infections, recruited from reserves of immature cells that develop in the bone marrow. Some cells play dual functions, having crucial roles in both innate and adaptive immunity. The formation and development of blood cells is called hematopoiesis (Greek for blood and to make). All blood cells, including those important in the body's defenses, originate from the same type of cell, the hematopoietic stem cell, found in the bone marrow (figure 15.4). Stem cells are induced to develop into the various types of blood cells by a group of cytokines called colony-stimulating factors. Some of the cells of the immune system are already mature as they circulate in the bloodstream, but others differentiate, developing functional...

Taurine and Immune Function

Taurine, together with sulfate, can be regarded as biochemical end products of cysteine metabolism. However, it is apparent that taurine also plays a role in immune function. It is the most abundant free nitrogenous compound (often incorrectly classified as an amino acid) in cells. It is a membrane stabilizer and regulates calcium flux thereby controlling cell stability. It has been shown to possess anti-oxidant properties and to regulate the release of pro-inflammatory cytokines in hamsters, rats, and humans (87-89). deprived of taurine, substantial impairment of immune function occurs (88). A large decline in lymphocytes, an increase in mononuclear cells, and a decrease in the ability of these cells to produce a respiratory burst and to phagocytose bacteria, occurs. There was a rise in y-globulin concentrations in deficient animals. Spleen and lymph nodes showed regression of follicular centers and depletion of mature and immature B lymphocyte numbers. The changes were reversed by...

Mechanisms of Estrogen Effects on the Immune System

A concise description of ERs and their interactions with DNA is helpful to appreciate the molecular mode of action of estrogens and to understand the diversity of potential effects of estrogens on the immune system. Estrogen exerts its biological functions on target tissues by both ER-dependent and ER-independent mechanisms. Estrogen binds to two specific, but distinct receptors, ERa and ERP, which belong to the nuclear hormone receptor family. ERs are ligand-activated transcription factors and are located both intracellularly and presumably on the cell surface. Heat shock proteins, such as hsp90, bind to unliganded ERs to maintain the receptors in an inactive but functionally prepared state for ligand binding (Pratt and Toft, 1997). Each type of ER appears to be differentially expressed in various tissues. It is conceivable that the differences in the relative expression of ERs in different tissues may result in the selective actions of estrogen in the immune system. ERa and ERP...

Regulation Of Natural Immunity

Leukocyte migration is essential for reactions to inflammatory stimuli at various locations in the body. However, leukocyte movement is also crucial during non-inflammatory processes such as haematopoietic development and routine passage through secondary lymphoid organs, which is also required for effective antigen presentation. Immune defects occur in chemokine receptor deficient mice. Chemokines, their receptors and adhesion molecules play a key role in the regulation of the immune response during inflammatory and under homeostatic conditions. Leukocyte trafficking plays a role during developmental processes, for example in haematopoiesis and thymic maturation of T cells and in regulatory circuits that ensure immune surveillance and communication between the innate and adaptive components of immunity 47 . 5.2. Neuroendocrine regulation of natural immunity Natural killer (NK) cells, y8 T lymphocytes and CD5+ B lymphocytes are key effector cells in the natural immune system. These...

Stress and the Immune Response to Influenza Virus

The idea that psychological stress may cause measurable changes in an individual's susceptibility to infectious disease is not new. One of the earliest proposals was put forth by Ishigami (1919) in which he described the influence of psychic acts on the progress of pulmonary tuberculosis. Now, it is generally acknowledged that humans and animals exposed to chronic psychological or physical stressors have decreased resistance to microbial pathogens. The consequences of stress-induced modulation of the immune system include increased susceptibility and frequency of disease, prolonged healing times, and a greater incidence of secondary health complications associated with infection (Bailey et al., 2003). However, knowledge about how the perception of stress is processed in the central nervous system and then transmitted to peripheral physiological systems is incomplete. Therefore, information about the mechanism(s) by which a stressor, through its effects on the immune system, might...

Use of Immunotherapy in Conventional Cancer Medicine

We now look at how immunotherapy has been used in conventional cancer medicine. From this discussion, we obtain ideas on how natural compounds might be used to produce some of the same effects on the immune system, and we also see how the use of natural compounds differs from that of most conventional immunotherapy agents. The primary distinction between conventional immunotherapy agents and natural immunostimulant The majority of human cancers exhibit low immuno-genicity, probably due to one or more of the immune-evading mechanisms described earlier. This does not mean, however, that immunotherapy is necessarily ineffective against them. Conventional immunotherapy can be divided into two categories, active and passive, each discussed below. In general, conventional immunother-apy in humans is most effective in patients with a relatively healthy immune system and a low tumor burden (i.e., at an early stage of malignancy). Active Immunotherapy The term active immunotherapy refers to...

Cumulative Immune System Suppression

Although the concept of cumulative toxicity on immune system function has already been addressed, it must also be emphasized that the immune system will often only demonstrate the effects of the cumulative toxicity in a sudden, dramatic fashion clinically. Furthermore, the many different insults that finally caused the immune system to collapse may have been present for months, years, or even decades prior to the loss of health. This is probably the primary reason why long-term toxin exposure still gets so little blame for the devastating damage that it causes. Other biological systems will typically demonstrate a gradual erosion of function over time. Not the immune system, however. Even if certain aspects of the immune system do gradually become compromised from prolonged toxic exposure, the intact organism, in this case the human, will usually compensate in a variety of different ways. This gives the distinct impression that good health is very suddenly and dramatically replaced...

Immune Function in Sleep Disorders

Insomnia and obstructive sleep apnea are the most prevalent sleep disorders in the general population (Ancoli-Israel 1993). Such disturbances result in major alterations in the immune system and may be mediated by the augmented activity of the HPA axis and or sympathetic nervous system, as we will soon describe. Convincing evidence confirm the correlation between immune alterations and insomnia, as, for instance, is shown in chronic insomnia patients, whose CD3+, CD4+, and CD8+ cells are reduced (Savard, Laroche, Simard, Ivers, and Morin 2003). Moreover, a decrease in the number of natural killer (NK) cells is also associated with augmented sympathetic tonus (Irwin, Clark, Kennedy, Christian Gillin, and Ziegler 2003), and the balance between Th1 and Th2 response is impaired in these patients with predominance of the Th2 response (Sakami et al. 2002). Th2-type cytokines enhance the humoral immune response. In addition, alterations in Th1 Th2 balance are characteristic of autoimmune...

Restraint Stress Suppresses the Immune Response to Infection with Influenza Virus

Stress-induced Effects on Innate Immune Responses to Infection with Influenza Virus In the initial studies of stress and the immune response, a murine model of influenza viral infection was initiated by intranasal challenge of C57BL 6 male mice physical restraint (RST) was selected as the stressor (Sheridan et al., 1991). Our first observations showed that RST reduced the accumulation of cells in the lungs of influenza-infected mice (Hunzeker et al., 2004). In addition to having effects in the lungs, RST was also responsible for a reduction in lymphadenopathy in the draining lymph nodes (Hermann et al., 1995). The cells whose numbers were suppressed by RST included macrophages, NK cells, and T and B lymphocytes. During the past 15 years or so, our studies have revealed that this effect of RST has a substantial impact on both the innate and adaptive immune response to influenza virus infection. Natural killer cells play an important role in the early innate defenses to influenza...

Neuroendocrine Hormone Release by Cells of the Immune System

There is now substantial evidence that cells of the immune system produce neuroendocrine hormones. This was first established for ACTH and subsequently for TSH, GH, PRL, LH, FSH and the hypothalamic hormones SOM, CRH, GHRH, and LHRH (Weigent and Blalock 1995). The evidence supports the idea that neuroendocrine peptides and neurotransmitters, endogenous to the immune system, are used for both intraimmune system regulation, as well as for bidirectional communication between the immune and neuroendocrine systems. Although the structures of these immune-cell-derived peptides are, for the most part, identical to those identified in the neuroendocrine system, both similarities and differences exist in the mechanism of synthesis to the patterns previously described in the neuroendocrine system. At least two possibilities exist concerning the potential function of these peptide hormones produced by the immune system. First they act on their classic neuroendocrine target tissues. Second, they...

C albicans and the Host Immune System

When C. albicans infects a host it enters into a battle with the host immune system, particularly cells of the innate immune system. Neutrophils and macrophages are involved in mopping up fungal cells found in the bloodstream, and it is important to know how both host and fungus respond during these interactions. The adaptive immune response is involved in determining the outcome of systemic infection, so interactions of C. albicans with the major antigen processing and presenting cells, dendritic cells, are also important. One of the major areas of recent improved understanding is the identification of host receptors and their corresponding fungal ligands. C. albi-cans-host cell receptor interactions have been recently reviewed by Filler (2006). The MyD88-dependent signalling pathway is essential for resistance to C. albi cans infection (Bellocchio et al., 2004 Villamon et al., 2004a). MyD88-deficient mice infected with C. albicans had significantly reduced survival and higher organ...

How Neuroblastoma Escapes the Innate and Adaptive Immune Systems

Neuroblastoma employs a variety of tactics to evade the immune system (Table 14.2). It downregulates immune-activating while overexpressing immune-inhibitory receptors. By repressing the expression of class-I and class-II MHC (Lampson et al. 1983) as well as CD1d (Metelitsa et al. 2001), they interfere with both the afferent and efferent arms of adaptive immune response. In addition, NB cells can avoid immune recognition and destruction by releas Table 14.2. Neuroblastoma can evade the immune system Table 14.2. Neuroblastoma can evade the immune system Immune function Adaptive immunity T cells

Natural Compounds That Stimulate Andor Support The Immune System

A large number of natural compounds can stimulate or support the immune system or do both. A selected list of some of the major compounds is provided in Table 12.1. Note that many other natural compounds discussed in this book (and many not included) could act as immunostimulants or supportive agents. For example, CAPE has been reported to increase the susceptibility of tumor cells to NK cell attack and induce expression of tumor-associated antigens on human melanoma and brain cancer cells lines in vitro.1,2 As another example, oral administration of proanthocyanidins to mice has increased NK cell cytotoxicity and enhanced ex-vivo IL-2 production by immune cells.3 Even though not comprehensive, Table 12.1 does include many of the well-known natural immunostimulants and supportive compounds. Reference books that discuss additional natural compounds with these effects are cited in Chapter 16. In addition to stimulating the immune system, we must also inhibit immune evasion. One primary...

Tuning the Adaptive Immune Responses The Instructive Role of DC

As DC are equipped with several TLR, they are the main connectors of the innate and adaptive immune systems. DC are bone marrow-derived cells of both lym-phoid and myeloid stem cell origins that populate all lymphoid organs, as well as nearly all nonlymphoid tissues and organs. The dual activation tolerization function of DC is mediated by their capacity to change the context of antigen presentation and to communicate to T cells the nature of the antigens they are presenting. This process exemplifies the importance of TLR not only in direct early immune responses, but also in activation of adaptive immunity. The DC system consists of a network of different subpopulations (Romani & Puccetti, 2006a). The ability of a given DC subset to respond with flexible activating programs to the different stimuli, as well as the ability of different subsets to convert into each others confers unexpected plasticity to the DC system. DC are uniquely adept at decoding the fungus-associated...

Effects of Vitamin B6 on Immune Function

Vitamin B6, although having no anti-oxidant properties, plays an important part in anti-oxidant defenses because of its action in the metabolic pathway for the formation of cysteine, which, as indicated earlier, is the rate limiting precursor in glutathione synthesis. Vitamin B6 status has widespread effects on immune function (79). Vitamin B6 deficiency causes thymic atrophy and lymphocyte depletion in lymph nodes and spleen. Antigen processing is unaffected. However, the ability to make antibodies to sheep red blood cells is depressed. In human studies, the ability to make antibodies to tetanus and typhoid antigens is not seriously affected. Various aspects of cell-mediated immunity are also influenced by vitamin B6 deficiency. Skin grafts in rats and mice survive longer during deficiency, and guinea-pigs exhibit decreased delayed hypersensitivity reactions to bacille Calmete-Guerin (BCG) administration. Deficiency of vitamin B6 is rare in humans but can be precipitated with the...

Insect Immune System and Parallels with the Innate Immune Response of Mammals

Melanisation Insect

Insects have maintained a parallel immune response to the innate immune response of vertebrates, despite their divergence approximately 500 million years ago. The preservation of this immune response highlights its success and efficacy in combating microbial infection (Kavanagh & Reeves, 2004 Salzet, 2001 Leclerc & Reichhart, 2004 Kanost et al., 2004). It was initially thought that the innate immune response was inferior to the adaptive immune response, as the adaptive immune system has the ability to 'remember' pathogenic encounters. However, it is now generally agreed that the innate immune response is a very important arm of the immune system, being the first line of defence encountered by invading microbes. The importance of the innate immune response in fighting infection has been highlighted by disorders in which aspects of this immune system are not functioning, such as neutropenia and CGD (Segal, 1996 Meyer & Atkinson, 1983 Gerson & Talbot, 1984 Latge, 1999)....

Immune function

The small intestine and its mesentery contain a very high proportion of the body's lymphocytes and also a very large number of macrophages. Normal function of these cells is essential for the defense mechanisms against intraluminal bacteria and bacterial products as well as other non-self agents that could be introduced by the alimentary route. The intestinal T lymphocytes are important antibody producers, while the macrophages are essential for initiating and regulating defense reactions in different pathological conditions through their secretion of cytokines, mainly tumor necrosis factor and interleukins such as IL-1, IL-2, IL-6, etc. Activation of macrophages to secrete cytokines may initiate all aspects of an inflammatory response reaction. Intestinal ischemia may, on the one hand, activate this high number of intestinal macrophages, but on the other hand hypoxia is likely to impair the immune cell function of the gut. However, the detailed mechanisms of activation, the different...

Active immunotherapy

Active immunotherapy is the immunization of the patient with materials that elicit an immune reaction capable of eliminating delaying tumour growth. It includes the administration of non-specific stimulators of the immune system, such as the bacillus Calmette-Gu rin (BCG) and cytokines. Unfortunately, cancer usually grows in an immunosuppressed environment and, therefore, non-specific cancer vaccines, with the identification of tumour-associated antigens and the ability to genetically modify tumour cells, offers the promise of a specific, active immunotherapy. Passive immunotherapy of cancer includes the administration of materials that have the ability to mediate anti-tumour response directly or indirectly. This material could be antibodies, used either native or conjugated to a toxic agent, or cells (lymphocytes or macrophages).

Adaptive immunity

Humoral immunity provides specific adaptive immunity. Antigen-presenting cells, mainly dendritic cells and macrophages, recognize, ingest, and process foreign antigen. These antigens are presented to B cells in conjunction with class II and class I major histocompatability complex (MHC) molecules on the antigen-presenting cells. This process, which usually requires T cells, activates B cells to produce a specific immunoglobulin which opsonizes micro-organisms and activates complement, hence promoting their removal. Cellular immunity also provides an adaptive immune response in which cytotoxic T cells are generated against target cells, usually virally infected cells, tumor cells, or allogenic graft cells. This requires helper T cells and appropriate interleukin 2 (IL-2) secretion, and allows distinction of self from non-self. Activated T cells also influence other immune cells, including macrophages, increasing their phagocytic and bacterial killing capacity.

The Immune Response

The immune system typically recognizes the invading pathogen at the site of entry, where it launches a generalized innate immune response. Signal molecules recruit inflammatory cells to the area which engulf cell debris and released virions. Virus proteins are presented to the adaptive immune system in local lymph nodes, allowing the host to create a directed defense against the virus. Effector T cells specific for virus antigen stimulate B cells to secrete virus-specific antibodies. There are two predominate types of antibodies produced in response to virus infection, IgM and IgG. The first antibody produced is the IgM isotype and is present in the blood within days and remains in circulation for several months. As the adaptive response develops, B cells switch antibody isotypes to secrete the IgG form. Investigators use the detection of antibodies as indicators of virus exposure, and can utilize knowledge of the presence of specific isotypes to discern acute infection from past or...

The Immune System

The immune system, the cells and tissues that recognize and attack foreign substances in the body, provides the body's specific defenses. The immune system fights pathogens and helps to stop the growth and spread of cancers. The immune system is made up of several tissues and white blood cells. The components of the immune system, shown in Figure 47-5, are found throughout the body. The tissues include the bone marrow, thymus, lymph nodes, spleen, tonsils, and adenoids. The white blood cells of the immune system are called lymphocytes (LIM-foh-sietz). Each part of the immune system plays a special role in defending the body against pathogens. Bone marrow, the soft material found inside long bones, such as the femur, makes the billions of new lymphocytes needed by the body every day. The thymus, a gland located above the heart, helps produce a special kind of lymphocyte.

Whats New in This Edition

We have again updated coverage throughout the text to reflect the rapid and sometimes surprising growth in the field of microbiology. This effort is particularly evident in Chapter 15 (The Innate Immune Response) and Chapter 16 (The Adaptive Immune Response) reflecting the latest thoughts on how the immune system protects us from infectious disease. The Innate Immune Response New coverage of toll-like receptors in the immune system The Adaptive Immune Response New discussion on damaging effects of infection and of the immune response

Current Clinical Oncology

Kai-Uwe Lewandrowski, Maurie Markman, Ronald M. Bukowski, Roger Macklis, and Edward C. Benzel, 2006 High-Grade Gliomas Diagnosis and Treatment, edited by Gene H. Barnett, 2006 Squamous Cell Head and Neck Cancer, edited by David J. Adelstein, 2005 Hepatocellular Cancer Diagnosis and Treatment, edited by Brian I. Carr, 2005 Biology and Management of Multiple Myeloma, edited by James R. Berenson, 2004 Cancer Immunotherapy at the Crossroads How Tumors Evade Immunity and What Can

In Memoriam Martha A Shaughnessy BS December 3 1943September 9 1997

Coauthored 71 peer-reviewed papers, 66 of which were in collaboration with other members of the Allergy-Immunology Division. She also coauthored ten book chapters, primarily in areas of allergen immunotherapy and occupational immunologic lung disease, her two major research interests. She was admired and respected

Bacterial and Mitochondrial Replication

Another unique feature of prokaryotic chromosomal replication is the mechanism bacteria have evolved to protect their chromosomes. The lack of a protective nuclear membrane in bacteria makes the chromosome susceptible to attack by viruses (bacteriophages). As a result, many bacteria produce restriction enzymes that degrade foreign nucleic acids. These restriction enzymes recognize specific short sequences and cleave the DNA at those sites. However, methylation of the recognition sequences in the bacterial chromosomal DNA prevents most restriction enzymes from digesting the chromosomal DNA of the bacteria. In this way, methylating enzymes add methyl groups to the replicated bacterial chromosome, preventing chromosomal degradation by its own restriction enzymes. This methylation and restriction process functions as a primitive immune system by destroying foreign bacteriophage DNA before it can usurp the bacteria's replication system. Bacterial restriction enzymes are used to...

Breast Cancer Metastasis Controlling Genes

Cancer cells can grow by escaping from the attack of immune cells, thus disrupting the host immune system, which is progressively suppressed as a result of tumor progression and metastasis. The molecular mechanisms by which cancer cells evade the host immune system have been investigated in mouse models and clinical samples. Tumor cells employ several mechanisms to evade immune response including loss of tumor antigen, alteration of HLA class I antigen, defective death receptor signaling, lack of costimulation, immunosuppressive cytokines, and immunosuppressive T cells (9). Gutierrez et al. showed that FasL expression by breast tumor plays a central role in the induction

The Antibody Response

In the first year of life, a child will develop many infections, particularly of the respiratory tract, middle ear or gastrointestinal system. A baby unfortunate enough to have been born without a functioning immune system is unlikely to survive the first year because of the inability to fight these infections. The importance of the immune system is also vividly illustrated by the almost invariably fatal acquired immune deficiency syndrome (AIDS), in which the human immunodeficiency virus (HIV) destroys the immune system. The purpose of this chapter is to provide a brief outline of the basics of the immune response, and to set the stage for the more detailed chapters to follow. One of the easiest ways to understand the concepts and nomenclature of a complex system is to look at how the relevant concepts developed. This chapter therefore begins with a brief account of the history of antibody research, and then moves on to look at a typical antibody response.

The Innate Immunity The Art of Microbe Sensing and Shaping of Specific Immunity

The innate immune system distinguishes self from nonself and activates adaptive immune mechanisms by provision of specific signals. The constitutive mechanisms of defense are present at sites of continuous interaction with fungi and include the barrier function of body surfaces and the mucosal epithelial surfaces of the respiratory, gastrointestinal, and genitourinary tracts. Microbial antagonism (lactobacilli and bifidobacteria have shown efficacy in the biotherapy of candidiasis, Antigen-independent recognition of fungi by the innate immune system leads to the immediate mobilization of immune effector and regulatory mechanisms that provide the host with three crucial survival advantages (i) rapid initiation of the immune response and creation of the inflammatory and co-stimulatory environment for antigen recognition (ii) establishment of a first line of defense, which holds the pathogen in check during the maturation of the adaptive immune response and (iii) steering of the adaptive...

Development Of Cancer And Characteristics Of Cancer Cells

This original cancer cell divides to produce daughter cells, these cells also divide, and soon there is a population of cancer cells. As they divide, they develop malignant characteristics, such as the ability to invade and metastasize. They also develop other characteristics that help assure survival, for example, the ability to evade the immune system, to mutate when faced with adverse conditions, and to induce the growth of new blood vessels through the process called angiogenesis. The development of these characteristics marks the third stage in carcinogenesis, the first two stages being initiation and promotion, respectively. In this book, I use the term

What Else May Be Important In Causing Multiple Sclerosis

The combination of unidentified genes, geographic location, and an abnormal immune response to myelin has led scientists to consider that MS may be caused by a virus. Some viruses can infect the CNS, including, in rare instances, viruses that cause common childhood diseases. Polio, a once-common scourge that has been virtually eradicated in industrialized nations, was, like MS, more common in temperate climates than in the tropics. One hypothesis is that paralytic polio does not develop in the less stringent sanitary conditions and close living arrangements that are common in warmer climates and favor the occurrence of infections earlier in childhood, when maternal antibodies are still present and paralysis is much less likely. Scientists have also speculated that MS results from altered immune response to Other pieces of the puzzle remain unsolved as well. During their reproductive years, women are more susceptible to MS than men. Female hormones, such as estrogen and progesterone,...

Actions of Hypothalamic Releasing Hormones

In addition to pituitary hormones, hypothalamic-releasing hormone receptors and their effects have been documented on cells of the immune system (Tables 1.2 and 1.3). Corticotropin-releasing hormone (CRH) inhibits lymphocyte proliferation and NK cell activity (Jain et al. 1991 Smith et al. 1992). The GH-releasing hormone (GHRH) receptor has also been identified on cells of the immune system. The GHRH receptor binding sites are saturable and are found on both thymocytes and splenic lymphocytes (Guarcello, Weigent, and Blalock 1991). Other in vitro findings suggest GHRH may inhibit NK cell activity and chemotaxis and increase IFN-y secretion (Guarcello et al. 1991 Zelazowski et al. 1989). Recently, GHRH was shown to modulate IL-6 secretion from human peripheral blood mononuclear cells without any significant effect on IL-8 secretion (Siejka, Stepien, Lawnicka, Krupinski, Komorowski, and Stepien 2005). In addition, leukocytes have been shown to respond to thyrotropin-releasing hormone...

Apoptotic Cells And Their Phagocytosis

Our increasing understanding of cellular corpse generation and elimination 64 has contributed immensely to our appreciation of the scope of innate immune function. The concept of physiological cell death emerged from studies of animal development during the latter half of the 19lh century 65 . However, the idea that a cell can activate a suicidal program of self-destruction (programmed cell death), which can be modified by external signals has only been developed during the last half of the 20lh century, and this was considered essential for the development, homeostasis and integrity of multicellular organisms 65 , The description of cell death by apoptosis in the early 1970's provided a phenotype which became a focus for the investigation of homeostatic, 'physiological' cell death (cellular homeostasis) in normal and pathological tissues (e.g. cancer regression) 66 , Apoptosis was viewed as a prelude to the orderly removal of the non-viable cells by phagocytosis in the absence of...

Typical Antibody Response

The most fundamental property of the immune system is the ability to distinguish self from nonself. An incoming substance will be regarded as antigenic if it differs from self. We will explore the question of what is self in Section 2.4, but for now, let us consider the case of the first encounter of a bacterial infection, where the bacterium may be safely assumed to be nonself. Three or four days after the primary antigenic challenge, the immune response starts to switch to IgG, a process which requires T cells (Fig. 2.5). Like IgM, IgG antibodies interact with complement and kill bacteria. In addition, IgG greatly facilitates phagocytosis of any remaining bacteria by binding

Fifty Years of Revolution

French Anderson explored a more direct approach to controlling genetic problems repairing or replacing the defective genes themselves. In 1991, Anderson and his coworkers inserted normal genes for producing a key immune system chemical into blood cells of a child who suffered a rare inherited illness caused by lack of this chemical. This treatment, the first gene therapy given to a human, restored the young girl to health. Meanwhile, Nancy Wexler and others tried to identify the mutated genes that produced inherited diseases such as Huntington's disease, a brain-destroying ailment that afflicted Wexler's family. Cooperative effort among several research groups led to identification of the Huntington's gene in 1993. In that same year, Cynthia Kenyon identified genes in worms that lengthened the worms' lifespan, hinting that genetic changes underlay not only inherited illnesses but the much more common diseases associated with aging.

What Distinguishes Self from Nonself

As a general rule, the immune system does not respond to self, a concept that Ehrlich called 'horror autotoxicus' (reviewed by Silverstein, 1989). What, then, is self Chemical differences between self and nonself are often extremely subtle. Even though the DNA sequences of different humans are typically 99 identical, grafts between unrelated humans are virtually always rejected by the immune system, because they are recognized as nonself. A single amino acid substitution can often be detected by the immune system. How can the immune system make such fine discrimina- A moment's reflection can tell us that the ability to distinguish between self and nonself is unlikely to be encoded in the germline, but must be learned by the immune system during development. A child inherits half its genes (haplotype) from the mother and half from the father, and is tolerant to the products of both sets of received genes. However, the genes that the child inherits from the father cannot have been...

Current Applications And Challenges

The scope of natural immunity is vast and complicated by extraordinary diversity, redundancy, cooperation and amplification. Research to date has established the legitimacy of the field but the surge in exploration must continue if we harbour any desire to live in harmony with our immune system. Nevertheless, our increasing understanding of the mechanisms of the natural immune system and its importance for the development of a strong adaptive response has provided a strong incentive to better understand the dynamic interplay between infectious agents and host defence in man 34 and to develop new adjuvants as a component of improved vaccines. Current approaches to immune potentiation and adjuvant design combined with vaccine delivery are rapidly moving the field forward 81 . Toll-like receptors, in particular, are being targeted in vaccine development and in cancer therapy 82 . The use of the innate immune system by itself has been proposed as a biodefence strategy for protection...

Cytokine Influences on the Nervous System

The evidence suggests that both IL-1 and CRH activate corticotrophs, but they elicit different patterns in the regulation of POMC (Ruzicka and Huda 1995). Thus, IL-1 evoked an early release of P-lipotropin and an intermediate release of Pendorphin while CRH caused an early P-endorphin secretory response. Such a distinct pattern allows the pituitary to be specifically activated and therefore determine the interaction with the immune system. In addition to its effects on the hypothalamic-thyroid axis and the hypothalamic-gonadal axis. Thus, IL-1 inhibits the ovarian steroid-induced LH surge and release of hypothalamic luteinizing hormone releasing hormone (LHRH) in rats (Kalra, Sahu, and Kalra 1990). It also decreases plasma thyroid hormone and TSH levels in rats, probably by suppressing hypothalamic TRH secretion (Dubuis, Dayer, Siegrist-Kaiser, and Burger 1988).

Host Defense Mechanisms

To understand how autoimmunity occurs, one first needs to review the basic processes of immune response and immune regulation. Host defense mechanisms can be broadly defined as 2 types innate and adaptive (or antigen-specific) immunity.1'2 Although adaptive immunity is usually the most effective mechanism for eliminating invading organisms, this response is relatively slow, taking up to 7 to 10 days for effective primary immune responses and 2 to 3 days for anamnestic or memory responses. During this time, rapidly proliferating infectious agents could produce significant tissue injury and possibly death of the organism if left uncontrolled. For this reason, broadly reactive host responses, which are constantly maintained or can be rapidly induced, are essential in containing infections until the adaptive immune response kicks in.

Preface to the First Edition

The recognition that defenses are mediated via mucosal barriers dates back several thousand years. Ingestion of Rhus leaves to modify the severity of reactions to poison ivy is a centuries old practice among native North Americans. The modern concepts of local immunity, however, were developed by Besredka in the early 1900s, followed by the discovery of IgA in 1953 and its isolation and characterization in 1959. Studies in the early 1960s demonstrated the presence of IgA in a unique form in milk and, shortly thereafter, in other external secretions. These studies were followed by the discovery of the secretory component and the identification of the J chain. These remarkable observations were soon complemented by the characterization of the bronchus-associated lymphoid tissue (BALT) and the gut-associated lymphoid tissue (GALT), the observation of circulation of antigen-sensitized or reactive IgA B cells from BALT and GALT to other mucosal surfaces such as the genital tract and the...

The Fight Against Resistance

Good new approaches are available to prevent resistance. In particular, calculated enzyme flexibility is very seldom so high that a simultaneous attack on several pathways does not have a good chance of success 44, 45 . The evolutionary flexibility of pathogens can be estimated by considering genetic mechanisms for immune escape and new mutations available Are there specific antigen-shifting mechanisms What about recombination, resistance plasmids, genome instability, transposons - to name just some of the more common mechanisms. Interestingly, this list shows that meticulous genome annotation (see above) is in fact

Introduction To Free Radicals And Antioxidants

Free radicals, such as the toxic oxyradical species hydroxyl radical (*OH) or the less reactive superoxide radical (O2* ), arise normally during mitochondrial oxidative metabolism. Also, the body's immune system cells purposefully generate free radicals to neutralize viruses and bacteria. Environmental factors such as pollution, radiation, cigarette smoke, and herbicides can also generate free radicals. Therefore, biological systems are continuously interacting with free radicals arising either from metabolism or from environmental sources, i.e., leading to a process called oxidation.

The Clonal Selection Theory

The immune system is amazingly versatile. It can respond to almost any substance by making specific antibodies, provided that the substance is seen as nonself. How is this achieved The mechanisms by which this specificity and diversity is produced has fascinated generations of immunologists.

Bidirectional Communication and Sleep

Neuroendocrine hormones produced by the hypothalamus influence sleep. Thus, CRH is a potent inducer of waking while GHRH promotes SWS (Obal, Fang, Payne, and Krueger 1995 Opp and Imeri 2001). These same hormones are produced by cells of the immune system (Weigent and Blalock 1995) and thus the immune and nervous system share regulatory molecules which supports their ability to interact. There are some data to suggest that chronic sleep loss might be detrimental to the immune system. Thus, sleep deprivation in nonimmune mice appeared to impede the clearance of influenza virus along the respiratory tract (Renegar, Crouse, Floyd, and Krueger 2000). Also, sleep-deprived humans immunized against infection with influenza virus had lower virus-specific antibody titers compared to non-sleep-deprived individuals (Spiegel, Sheridan, and Van Cauter 2002). Despite the evidence that sleep loss has effects on immune function and secretion of cytokines, the significance of these changes on the...

Autoreactive Repertoire

Self-reactive T-cell clones should be deleted in the thymus during ontogeny (central tolerance) or inactivated peripherally through anergy by inappropriate antigen presentation (peripheral tolerance). High-affinity interactions of self-reactive T cells in the thymus with self-epitope-loaded MHC molecules on thymic epithelium or medullary dendritic cells result in clonal deletion of the autoreactive clones (negative selection). Interactions between T cells and self-MHC with nonspecific epitopes are not of high enough avidity to cause apoptosis of the developing T cell but provide sufficient signal to retain the lymphocyte in the thymus (positive selection) for further differentiation. The problem with this form of tolerance is that it depends on self-antigens being present in the thymus during T-cell ontogeny. This could be true for common cellular molecules present in all cells, but would not necessarily be true for specialized or sequestered antigens, such as thyroglobulin, cardiac...

Lymphocyte Development General Aspects

Prior to the pioneering work of Gowans, it had been felt that lymphocytes had something to do with the immune system. Gowans showed that lymphocytes were the immune system (Gowans et al., 1962 Gowans and McGregor, 1965). There is now a large body of evidence that during their development both T and B lymphocytes undergo both positive and negative selection by antigen (von Boehmer, 1994 Nossal, 1994). Negative selection is concerned with the deletion of auto-reactive cells or cells which have receptors that are unable to function. Positive selection selects for functional receptors early in development, and for activation and survival during immune responses.

Dual focus driving intentionality down and defining the biological contrasted with the physical

The same physical events, will lead that system to respond as if the state of affairs A exists. This echoes definitions proposed earlier of correctness and error in terms of functional activity. For example if the nerves leading from the baroreceptors are stimulated electrically over the range of frequencies that convey information about blood pressure changes the system will respond as if those changes had occurred. This principle is exploited in the production of some vaccines. The immune system normally responds to infectious agents, however molecules that resemble sufficiently the key features of those agents that trigger the immune response can also trigger that response.

Brief Evolutionary Perspectives

Experience in antimicrobial drug therapy has taught us that multi-drug treatment is the most effective approach to minimising the selection of resistant organisms. Apparently, through expression of large families of active peptides at each site of pathogen exposure, nature has been following this approach for thousands of years in optimising the innate immune response. From a broad perspective, genes of the adaptive immune system encoding immunoglobulins and T cell receptors are known to undergo a series of genetic amplifications, rearrangements and mutations that generate a protective diversity promoting survival of the individual. Homologous events involving genes of the innate immune system can be seen as generating a protective diversity promoting survival of a population or species. Specific examples are presented below. The mechanisms for this genome instability in innate immunity genes remain to be elucidated, but may represent a precursor for the more familiar examples...

Summary and Conclusions

It is now well established that the nervous system and immune system speak a common biochemical language and communicate via a complete bidirectional circuit involving shared ligands such as neurotransmitters, neuroendocrine hormones, cytokines, and the respective receptors. Thus, neurotransmitters, neuropeptides, and cytokines represent the signaling molecules relaying chemical information and depending on the stimulus either neurons or immune cells can be the initial source. The chemical information in turn can be received by both neurons and immune cells since they share receptor repertoires. This complete biochemical information circuit between neurons and immune cells allows the immune system to function as a sensory organ (Blalock 1994). A sixth sense, if you will, that completes our ability to be cognizant not only of the universe of things we can see, hear, taste, touch, and smell but also the other universe of things we cannot. These would include bacteria, viruses, antigens,...

Hope through Research

Progress in multiple sclerosis (MS) research is being made at a remarkable rate. Twenty years ago, very little was known about the regulation of the immune system, and before the approval of Betaseron in 1993, no therapy had ever proved capable of changing the underlying course of MS. Now five approved, disease-modifying drugs are available to treat individuals with Ms. But the work in Ms research is not over. scientists are closer than ever to understanding the underlying cause of Ms, and finding additional treatments for all forms of Ms. Research efforts sponsored by the National Multiple Sclerosis Society (NMSS), the National Institutes of Health (NIH), private drug and biotechnology companies, and other Ms agencies around the world are contributing to this progress.

Host Cells in Conjunction Epithelial and Endothelial Models

Figure 2.2 Host-pathogen interaction - players and processes. During the course of infection fungi interact with different host cells such as epithelial, endothelial, and immune system cells. This interaction is characterized by successive events at the cellular level. They include adhesion (1), entrance (2), persistence or even proliferation inside (3), and finally exit from host cells (4). Pathogens contrive these steps by using and manipulating host cell structures and functions. Each of the processes can be crucial for the overall outcome of the interaction Figure 2.2 Host-pathogen interaction - players and processes. During the course of infection fungi interact with different host cells such as epithelial, endothelial, and immune system cells. This interaction is characterized by successive events at the cellular level. They include adhesion (1), entrance (2), persistence or even proliferation inside (3), and finally exit from host cells (4). Pathogens contrive these steps by...

Summary Cellular Mechanisms in Antibody Production

In this Chapter, we have reviewed the complex web of cellular interactions that lead to the immune response. We have seen that the immune response represents the outcome of interactions between antigen-presenting cells, T cells and B cells. For most antigens, there is an obligatory requirement for T cell help, which in turn requires processing of antigen and presentation of peptides in the groove of MHC molecules. Activation of lymphocytes also In the following chapter, we will explore the features of antigen that determine the outcome of encounters with the immune system.

Mycoplasma pneumoniae pneumonia

Many findings suggest that immune mechanisms, rather than actual direct infection, may play a role in the development of clinically apparent M. pneumoniae pneumonia as well as some of the extrapulmonary complications. First, M. pneumoniae is able to cause a wide variety of extrapulmonary symptoms but is never isolated from clinical material except sputum or nasopharyngeal secretions. Second, M. pneumoniae or its antigen have seldom been demonstrated in the lungs of patients with fatal pulmonary infection. Evidence has been reported to support the notion that repeated subclinical M. pneumoniae infections with consequent sensitization of T lymphocytes, and probably other components of the immune system (autoantibodies), may be necessary before manifestations such as pneumonitis occur. Third, antithymocyte globulin abrogates or diminishes the severity of experimental M. pneumoniae infection in animals, and corticosteroids have been used with some beneficial clinical effects in patients...

Oral and Oesophageal Epithelium Model

A further improvement of the RHOE model in order to mimic the in vivo situation more closely is the supplement with polymorphonuclear leukocytes (PMNs), which generates simple aspects of the immune system (Schaller et al., 2004). Epithelial cells in contact with C. albicans induce a strong immune response that attracts PMNs to the infection site. Q-RT-PCR was employed to measure the immune response generated concluding that the extension of the system provides a useful tool for studying the immunological interaction between keratinocytes and C. albicans, as well as the role of PMNs in C. albicans pathogenesis.