Protection of rainbow trout against vibriosis and furunculosis by the use of attenuated strains of Vibrio anguillarum.

The fish pathogen Vibrio anguillarum causes a lethal infection in rainbow trout (Salmo gairdneri). Three different avirulent mutants, constructed by transposon insertion mutagenesis (VAN20 and VAN70) or as antibiotic-resistant mutants (VAN1000), were isolated by screening 200 individual isolated mutants for avirulence. When used as live vaccines, all three avirulent mutants were able to induce protective immunity against the homologous as well as a heterologous strain of V. anguillarum. When VAN1000 was used, protective immunity could be recorded 1 week after bath vaccination with 10(7) bacteria per ml of water for 30 min. A single-dose immunization was effective for at least 12 weeks. Western immunoblotting showed that strains of V. anguillarum have antigenic determinants in common with Aeromonas strains. Therefore, we tested and confirmed that VAN1000 also was able to induce protective immunity against challenge with Aeromonas salmonicida.     

Protection of rainbow trout against vibriosis and furunculosis by the use of attenuated strains of Vibrio anguillarum

The fish pathogen Vibrio anguillarum causes a lethal infection in rainbow trout (Salmo gairdneri). Three different avirulent mutants, constructed by transposon insertion mutagenesis (VAN20 and VAN70) or as antibiotic-resistant mutants (VAN1000), were isolated by screening 200 individual isolated mutants for avirulence. When used as live vaccines, all three avirulent mutants were able to induce protective immunity against the homologous as well as a heterologous strain of V. anguillarum. When VAN1000 was used, protective immunity could be recorded 1 week after bath vaccination with 10(7) bacteria per ml of water for 30 min. A single-dose immunization was effective for at least 12 weeks. Western immunoblotting showed that strains of V. anguillarum have antigenic determinants in common with Aeromonas strains. Therefore, we tested and confirmed that VAN1000 also was able to induce protective immunity against challenge with Aeromonas salmonicida.     

A test of life-history theories of immune defence in two ecotypes of the garter snake, Thamnophis elegans

1.  Life-history theorists have long observed that fast growth and high reproduction tend to be associated with short life span, suggesting that greater investment in such traits may trade off with self-maintenance. The immune system plays an integral role in self-maintenance and has been proposed as a mediator of life-history trade-offs.
2.  Ecoimmunologists have predicted that fast-living organisms should rely more heavily on constitutive innate immunity than slow-living organisms, as constitutive innate defences are thought to be relatively inexpensive to develop and can provide a rapid, general response to pathogens.
3.  We present the first study to examine this hypothesis in an ectothermic vertebrate, by testing for differences in three aspects of constitutive innate immunity in replicate populations of two life-history ecotypes of the garter snake Thamnophis elegans , one fast-living and one slow-living.
4.  As predicted, free-ranging snakes from the fast-living ecotype had higher levels of all three measures of constitutive innate immunity than the slow-living ecotype. These differences in immunity were not explained by parasite loads measured. Furthermore, both ecotypes exhibited a positive relationship between innate immunity and body size/age, which we discuss in the context of ectotherm physiology and ecotype differences in developmental rates.     

Plant pattern recognition receptor complexes at the plasma membrane

A key feature of innate immunity is the ability to recognize and respond to potential pathogens in a highly sensitive and specific manner. In plants, the activation of pattern recognition receptors (PRRs) by pathogen-associated molecular patterns (PAMPs) elicits a defense programme known as PAMP-triggered immunity (PTI). Although only a handful of PAMP-PRR pairs have been defined, all known PRRs are modular transmembrane proteins containing ligand-binding ectodomains. It is becoming clear that PRRs do not act alone but rather function as part of multi-protein complexes at the plasma membrane. Recent studies describing the molecular interactions and protein modifications that occur between PRRs and their regulatory proteins have provided important mechanistic insight into how plants avoid infection and achieve immunity.     

The evolution of immune mechanisms

From early on in evolution, organisms have had to protect themselves from pathogens. Mechanisms for discriminating "self" from "non-self" evolved to accomplish this task, launching a long history of host-pathogen co-evolution. Evolution of mechanisms of immune defense has resulted in a variety of strategies. Even unicellular organisms have rich arsenals of mechanisms for protection, such as restriction endonucleases, antimicrobial peptides, and RNA interference.In multicellular organisms, specialized immune cells have evolved, capable of recognition, phagocytosis, and killing of foreign cells as well as removing their own cells changed by damage, senescence, infection, or cancer. Additional humoral factors, such as the complement cascade, have developed that co-operate with cellular immunity in fighting infection and maintaining homeostasis. Defensive mechanisms based on germline-encoded receptors constitute a system known as innate immunity. In jaw vertebrates, this system is supplemented with a second system, adaptive immunity, which in contrast to innate immunity is based on diversification of immune receptors and on immunological memory in each individual.Usually, each newly evolved defense mechanism did not replace the previous one, but supplemented it, resulting in a layered structure of the immune system. The immune system is not one system but rather a sophisticated network of various defensive mechanisms operating on different levels, ranging from mechanisms common for every cell in the body to specialized immune cells and responses at the level of the whole organism. Adaptive changes in pathogens have shaped the evolution of the immune system at all levels.     

Chromosomal changes in patients with acute dysentery and their relation to immunologic shifts

The correlation between the dynamics of the occurrence of the class of lymphocytes without chromosomal associations and with two associating acrocentric chromosomes (CL0 + 2) and the course of the disease, as well as the development of immunity in patients with acute dysentery, has been detected. The positive correlation between the occurrence of CL0 + 2 and cell-mediated immunity reactions presupposes the possibility of using this cytogenetic characteristic for evaluating the cell-mediated immunoreactivity of lymphocytes. No essential changes in the frequency of chromosomal aberrations in lymphocytes have been found to occur at all periods of observation.     

Immunogenicity of heterologous prime-boost regimens involving recombinant adenovirus serotype 11 (Ad11) and Ad35 vaccine vectors in the presence of anti-ad5 immunity

The high prevalence of preexisting immunity to adenovirus serotype 5 (Ad5) in human populations will likely limit the immunogenicity and clinical utility of recombinant Ad5 (rAd5) vector-based vaccines for human immunodeficiency virus type 1 and other pathogens. A potential solution to this problem is to utilize rAd vaccine vectors derived from rare Ad serotypes such as Ad35 and Ad11. We have previously reported that rAd35 vectors were immunogenic in the presence of anti-Ad5 immunity, but the immunogenicity of heterologous rAd prime-boost regimens and the extent that cross-reactive anti-vector immunity may limit this approach have not been fully explored. Here we assess the immunogenicity of heterologous vaccine regimens involving rAd5, rAd35, and novel rAd11 vectors expressing simian immunodeficiency virus Gag in mice both with and without anti-Ad5 immunity. Heterologous rAd prime-boost regimens proved significantly more immunogenic than homologous regimens, as expected. Importantly, all regimens that included rAd5 were markedly suppressed by anti-Ad5 immunity. In contrast, rAd35-rAd11 and rAd11-rAd35 regimens elicited high-frequency immune responses both in the presence and in the absence of anti-Ad5 immunity, although we also detected clear cross-reactive Ad35/Ad11-specific humoral and cellular immune responses. Nevertheless, these data suggest the potential utility of heterologous rAd prime-boost vaccine regimens using vectors derived from rare human Ad serotypes.     

Immunity status of Czech population with regard to poliomyelitis in 1970--1975

The results of examination of antibodies against all three types ofthe poliomyelitis virus from the period of systematically performed multipurpose immunological survey in the Czech Socialistic Republic (1970--1975) are presented and evaluated. The analysis of these results indicates that the status of immunity in the Czech population, systematically vaccinated against poliomyelitis, is good, as all requirements of collective protection against this disease have been met. At the same time, the results demonstrated that immunological surveys are at present the most suitable method of verifying the immunity of the vaccinated population and should be consistently performed.     

Innate immunity and adjuvants

Innate immunity was for a long time considered to be non-specific because the major function of this system is to digest pathogens and present antigens to the cells involved in acquired immunity. However, recent studies have shown that innate immunity is not non-specific, but is instead sufficiently specific to discriminate self from pathogens through evolutionarily conserved receptors, designated Toll-like receptors (TLRs). Indeed, innate immunity has a crucial role in early host defence against invading pathogens. Furthermore, TLRs were found to act as adjuvant receptors that create a bridge between innate and adaptive immunity, and to have important roles in the induction of adaptive immunity. This paradigm shift is now changing our thinking on the pathogenesis and treatment of infectious, immune and allergic diseases, as well as cancers. Besides TLRs, recent findings have revealed the presence of a cytosolic detector system for invading pathogens. I will review the mechanisms of pathogen recognition by TLRs and cytoplasmic receptors, and then discuss the roles of these receptors in the development of adaptive immunity in response to viral infection.     

Regulation of immunity in Trypanosoma cruzi infection

Immunity to T. cruzi is complex, involving among other components, antibody production, CD4+ helper cells, CD8+ T cells as both regulators and effectors of immunity, and possibly, double-negative T cells. In addition, several of these components have been implicated in pathogenesis in the chronic infection. Although the immunosuppression observed in the infection seems quite severe, it also appears to provide for a sufficient level of immune responsiveness to control the infection in most hosts. At the same time, immunosuppression may provide the regulatory control necessary to prevent massive chronic pathogenesis in all hosts. Continued study of the relative roles of lymphocyte populations and the products they secrete in immunity and pathogenesis may provide the understanding necessary to enhance immunity to T. cruzi without the feared consequence of increased pathogenesis.     

热休克蛋白gp96作为抗原载体的研究进展

gp96是存在于真核生物细胞内质网中的分子量约为96kD的热休克蛋白(又称GRP94)。它属于HSP90家族,是胞质HSP90的旁系同源蛋白。研究证实从小鼠肿瘤组织中分离的gp96注射小鼠后,可使小鼠获得针对该肿瘤细胞的特异细胞免疫力。随后发现这种特异性免疫不是由gp96引起,而是由其结合的小肽诱发。gp96受体的发现给这种现象的解释提供了线索。人们提出了多种假说来解释这种现象,其中一些得到了广泛的支持。另外,gp96还参与免疫调节过程。完全了解gp96在免疫系统中的作用机制对开发新型药物如肿瘤和病毒感染治疗性疫苗具有重要意义 。     

An evolutionary perspective on the systems of adaptive immunity

We propose an evolutionary perspective to classify and characterize the diverse systems of adaptive immunity that have been discovered across all major domains of life. We put forward a new function‐based classification according to the way information is acquired by the immune systems: Darwinian immunity (currently known from, but not necessarily limited to, vertebrates) relies on the Darwinian process of clonal selection to ‘learn’ by cumulative trial‐and‐error feedback; Lamarckian immunity uses templated targeting (guided adaptation) to internalize heritable information on potential threats; finally, shotgun immunity operates through somatic mechanisms of variable targeting without feedback. We argue that the origin of Darwinian (but not Lamarckian or shotgun) immunity represents a radical innovation in the evolution of individuality and complexity, and propose to add it to the list of major evolutionary transitions. While transitions to higher‐level units entail the suppression of selection at lower levels, Darwinian immunity re‐opens cell‐level selection within the multicellular organism, under the control of mechanisms that direct, rather than suppress, cell‐level evolution for the benefit of the individual. From a conceptual point of view, the origin of Darwinian immunity can be regarded as the most radical transition in the history of life, in which evolution by natural selection has literally re‐invented itself. Furthermore, the combination of clonal selection and somatic receptor diversity enabled a transition from limited to practically unlimited capacity to store information about the antigenic environment. The origin of Darwinian immunity therefore comprises both a transition in individuality and the emergence of a new information system – the two hallmarks of major evolutionary transitions. Finally, we present an evolutionary scenario for the origin of Darwinian immunity in vertebrates. We propose a revival of the concept of the ‘Big Bang’ of vertebrate immunity, arguing that its origin involved a ‘difficult’ (i.e. low‐probability) evolutionary transition that might have occurred only once, in a common ancestor of all vertebrates. In contrast to the original concept, we argue that the limiting innovation was not the generation of somatic diversity, but the regulatory circuitry needed for the safe operation of amplifiable immune responses with somatically acquired targeting. Regulatory complexity increased abruptly by genomic duplications at the root of the vertebrate lineage, creating a rare opportunity to establish such circuitry. We discuss the selection forces that might have acted at the origin of the transition, and in the subsequent stepwise evolution leading to the modern immune systems of extant vertebrates.     

Are zinc-bound metallothionein isoforms (I+II and III) involved in impaired thymulin production and thymic involution during ageing?

In the elderly, many alterations of both innate and clonotypic immunity have been described. Alterations to the immune system in the elderly are generally viewed as a deterioration of immunity, leading to the use of the term immunosenescence. However, although many immunological parameters are often notably reduced in the elderly, retained function of both innate and clonotypic immunity in the elderly is tightly correlated to health status. Recognising the important role of the immune system in ageing, over the last few years, journals oriented towards gerontology and geriatric sciences have increasingly published articles dealing with the immunology of ageing, but a specialised journal in this area does not exist. Immunity & Ageing is a new Open Access, peer reviewed journal that aims to cover all the topics dealing with innate and clonotypic immunity which are relevant to ageing. The journal will provide an opportunity to focus on this topic, which is emerging as one of the critical mechanisms of ageing. Furthermore, as an online, Open Access journal, Immunity & Ageing will promote immediate accessibility to research, which is generally not possible for articles published in printed journals. We hope this forum, concentrating on the themes of ageing and immunology with a strong focus on human studies, will create a new perspective for viewing a world that is inevitably becoming older.     

Innate immunity to Paracoccidioides brasiliensis infection

Innate immunity is based in pre-existing elements of the immune system that directly interact with all types of microbes leading to their destruction or growth inhibition. Several elements of this early defense mechanism act in concert to control initial pathogen growth and have profound effect on the adaptative immune response that further develops. Although most studies in paracoccidioidomycosis have been dedicated to understand cellular and humoral immune responses, innate immunity remains poorly defined. Hence, the main purpose of this review is to present and discuss some mechanisms of innate immunity developed by resistant and susceptible mice to Paracoccidioides brasiliensis infection, trying to understand how this initial host-pathogen interface interferes with the protective or deleterious adaptative immune response that will dictate disease outcome. An analysis of some mechanisms and mediators of innate immunity such as the activation of complement proteins, the microbicidal activity of natural killer cells and phagocytes, the production of inflammatory eicosanoids, cytokines, and chemokines among others, is presented trying to show the important role played by innate immunity in the host response to P. brasiliensis infection.     

Effect of dietary beta-1,3 glucan on immune responses and disease resistance of healthy and aflatoxin B1-induced immunocompromised rohu (Labeo rohita Hamilton).

The immunostimulant beta-1,3 glucan was fed at 0.1% in feed for 7 days to healthy and aflatoxin B1 (AFB1)-induced immunocompromised fish, Labeo rohita (one of the major tropical carp species), in a 60 day trial. The effects of AFB1, glucan and their interactions on non-specific and specific immunity levels and disease resistance of fish were studied. A single intraperitoneal injection of AFB1 at 1.25 mg kg(-1) body weight) caused a significant (P < 0.05) reduction in non-specific immunity as measured through neutrophil phagocytic indices, serum bactericidal activity, and specific immunity as measured through bacterial agglutination titre against Edwardsiella tarda, as well as reduced protection against Aeromonas hydrophila challenge in comparison to control fish which were exposed neither to aflatoxin nor to glucan. Feeding of glucan to healthy fish raised the non-specific and specific immunity level and protection against bacterial infection compared with the control. Feeding of glucan to AFB1-induced immunocompromised fish for 7 days significantly raised the degree of resistance against A. hydrophila challenge and the non-specific immunity level in comparison to non-treated AFB1 exposed fish. Although feeding of glucan was able to increase specific immunity, all measured through haemagglutination titre against sheep red blood cells, and bacterial (E. tarda) agglutination titre in healthy fish in comparison to all other groups, no significant increase in specific immunity to the aflatoxin-exposed group was seen.     

Pre-erythrocytic-stage immune effector mechanisms in Plasmodium spp. infections.

The potent protective immunity against malaria induced by immunization of mice and humans with radiation-attenuated Plasmodium spp. sporozoites is thought to be mediated primarily by T-cell responses directed against infected hepatocytes. This has led to considerable efforts to develop subunit vaccines that duplicate this protective immunity, but a universally effective vaccine is still not available and in vitro correlates of protective immunity have not been established. Contributing to this delay has been a lack of understanding of the mechanisms responsible for the protection. There are now data indicating that CD8+ T cells, CD4+ T cells, cytokines, and nitric oxide can all mediate the elimination of infected hepatocytes in vitro and in vivo. By dissecting the protection induced by immunization with irradiated sporozoite, DNA and synthetic peptide-adjuvant vaccines, we have demonstrated that different T-cell-dependent immune responses mediate protective immunity in the same inbred strain of mouse, depending on the method of immunization. Furthermore, the mechanism of protection induced by a single method of immunization may vary among different strains of mice. These data have important implications for the development of pre-erythrocytic-stage vaccines designed to protect a heterogeneous human population, and of assays that predict protective immunity.     

Cloning and mapping of the genetic determinants for microcin C7 production and immunity.

Microcin C7, a peptide antibiotic inhibitor of protein synthesis, is produced by Escherichia coli K-12 strains that carry the 43-kilobase low-copy-number plasmid pMccC7. Microcin C7 production and immunity determinants of this plasmid have been cloned into the vectors pBR322 and pACYC184. The resulting plasmids overproduce microcin C7 and express immunity against the microcin. Mcc- and Mcc- Imm- mutants have been isolated on recombinant plasmids by inserting transposable elements. Physical and phenotypic characterization of these mutants shows that a DNA region of 5 kilobases is required to produce microcin C7, and that two small regions located inside the producing region are also required to express immunity. Analysis of plasmids carrying mcc-lacZ gene fusions indicates that all microcin DNA is transcribed in the same direction. The results suggest that a structure like a polycistronic operon is responsible for microcin C7 production and immunity.     

Expression and identification of immunity determinants on linear DNA killer plasmids pGKL1 and pGKL2 in Kluyveromyces lactis.

The linear dsDNA plasmids, pGKL1 (8.9 kb) and pGKL2 (13.4 kb) discovered in Kluyveromyces lactis, confer killer and immunity characteristics upon various yeast strains. We have devised an immunity assay and have been able to show the expression of an immunity phenotype in the K. lactis transformants harbouring conventional circular plasmids which contain DNA fragments of pGKL1. Using this expression system, the immunity determinant on pGKL1 was identified as ORF5. In addition, the presence of pGKL2 was proved to be essential for the expression of the immunity phenotype. This is the first demonstration of this new pGKL2 function, as distinct from its known functions for the replication and maintenance of pGKL1 in yeast cells.     

Different levels of immunity to Schistosoma mansoni in the mouse: the role of variant cercariae.

Very variable levels of immunity to a second infection with Schistosoma mansoni were recorded in 7 strains of mice, 12--15 weeks following a small primary infection. When 2 or more strains of mice were assayed at the same time, less variation occurred within the experiment than between different experiments. This evidence suggested variation between pools of cercariae as the main cause of variability in immunity. In direct experiments in one strain of mouse, 2 different pools of cercariae stimulated widely different levels of immunity to the same challenge. Conversely, challenge infections drawn from different pools showed different susceptibility to immunity stimulated by the same primary infection. Individual clones of cercariae, from snails infected with single miracidia, showed a high level of susceptibility to immunity stimulated by a small bisexual infection, or were not susceptible at all. Antigenic polymorphism is the most likely explanation for the differences observed between clones of cercariae. However, indirect immunofluorescence showed the presence of at least 1 common antigen on the surface of schistosomula derived from different clones of cercariae and clone-specific antigens have not been detected.