Trade-offs between immune investment and sexual signaling in male mallards

Allocation trade-offs between the immune system and sexual traits are central to current sexual selection hypotheses but remain contentious. Such trade-offs could be brought about by the dual action of testosterone that stimulates sexual signals but also suppresses immune functions and/or by competition for carotenoids that can be deposited in ornaments or used as antioxidants in support of immune functions. We investigated the trade-off between investment in immunity and maintenance of testosterone, carotenoids, and sexually selected, carotenoid-based bill color in male mallards. Following a nonpathogenic immune challenge, facultative immune investment resulted in a syndrome of changes in allocation. Plasma carotenoids disappeared from circulation proportional to antibody production. In addition, the reflectance spectrum of the bill was affected; greater antibody production was associated with an increase in relative UV reflectance. Although changes in bill reflectance and plasma carotenoids were related, the relationship appeared more complex than direct competition with immunity. Finally, maintenance of testosterone was affected by immune investment: testosterone levels declined substantially when males produced more antibodies. Because males with high testosterone are preferred by females, the decline in testosterone, in addition to carotenoid depletion and effects on bill reflectance, could constitute a significant cost of immune investment.     

Separate structural and functional domains of Tn4430 transposase contribute to target immunity

Like other transposons of the Tn3 family, Tn4430 exhibits target immunity, a process that prevents multiple insertions of the transposon into the same DNA molecule. Immunity is conferred by the terminal inverted repeats of the transposon and is specific to each element of the family, indicating that the transposase TnpA is directly involved in the process.However, the molecular mechanism whereby this protein promotes efficient transposition into permissive targets while preventing transposition into immune targets remains unknown. Here, we demonstrate that both functions of TnpA can be uncoupled from each other by isolating and characterizing mutants that are proficient in transposition (T+) but impaired in immunity (I-). The identified T+/I- mutations are clustered into separate structural and functional domains of TnpA, indicating that different activities of the protein contribute to immunity.Combination of separate mutations had synergistic effects on target immunity but contrasting effects on transposition. One class of mutations was found to stimulate transposition, whereas other mutations appeared to reduce TnpA activity. The data are discussed with respect to alternative models in which TnpA acts as a specific determinant to both establish and respond to immunity.     

Herpes simplex virus vectors elicit durable immune responses in the presence of preexisting host immunity

Herpes simplex virus (HSV) recombinants are being developed as vaccine vectors for the expression of heterologous antigens. There is concern, however, that preexisting HSV immunity may decrease their effectiveness. We have addressed this issue in an animal model. Immunized mice were inoculated with a replication-defective HSV-1 vector that expressed the Escherichia coli beta-galactosidase protein as a model antigen. We assessed vector efficacy by analyzing the immunoglobulin G (IgG) antibody response and cellular proliferative response directed against beta-galactosidase. We report that the ability of the vector to induce antibody or proliferative responses was not diminished by preexisting immunity to HSV. Of further note, the anti-HSV and anti-beta-galactosidase IgG responses following vector administration were extremely durable in both immunized and naive mice. These results indicate that the ability of a replication-defective HSV-derived vaccine vector to elicit long-lived immune responses in mice is not impaired by prior HSV exposure.     

The use of an E1-deleted, replication-defective adenovirus recombinant expressing the rabies virus glycoprotein for early vaccination of mice against rabies virus.

An E1-deleted, replication-defective adenovirus recombinant of the human strain 5 expressing the rabies virus glycoprotein, termed Adrab.gp, was tested in young mice. Mice immunized at birth with the Adrab.gp construct developed antibodies to rabies virus and cytokine-secreting lymphocytes and were protected against subsequent challenge. Maternal immunity to rabies virus strongly interferes with vaccination of the offspring with a traditional inactivated rabies virus vaccine. The immune response to the rabies virus glycoprotein, as presented by the Adrab.gp vaccine, on the other hand, was not impaired by maternal immunity. Even neonatal immunization of mice born to rabies virus-immune dams with Adrab.gp construct resulted in a long-lasting protective immune response to rabies virus, suggesting that this type of vaccine could be useful for immunization shortly after birth. Nevertheless, pups born to Adrab.gp virus-immune dams showed an impaired immune response to the rabies virus glycoprotein upon vaccination with the Adrab.gp virus, indicating that maternal immunity to the vaccine carrier affected the offspring's immune response to rabies virus.     

Special feature for the Olympics: effects of exercise on the immune system: exercise effects on systemic immunity

Heavy exertion has acute and chronic influences on systemic immunity. In the resting state, the immune systems of athletes and non-athletes are more similar than disparate with the exception of NK cell activity, which tends to be elevated in athletes. Many components of the immune system exhibit adverse change after prolonged, heavy exertion. These immune changes occur in several compartments of the immune system and body (e.g. the skin, upper respiratory tract mucosal tissue, lung, blood and muscle). Although still open to interpretation, most exercise immunologists believe that during this 'open window' of impaired immunity (which may last between 3 and 72 h, depending on the immune measure) viruses and bacteria may gain a foothold, increasing the risk of subclinical and clinical infection. The infection risk may be amplified when other factors related to immune function are present, including exposure to novel pathogens during travel, lack of sleep, severe mental stress, malnutrition or weight loss.     

种群内部因素对动物免疫功能的影响

动物的免疫状况与种群动态的关系是近年来动物生态学研究的热点之一。总结了种群内部因素对动物免疫功能的影响,并介绍了几种免疫调节假说,对于不同的研究对象,种群密度的高低对其可产生不同的影响。在一个种群中,优势个体往往具有较高的免疫水平;雌性个体的免疫水平高于雄性个体,这可部分归因于性激素的作用,动物处于繁殖期时免疫水平有所下降。婚配制度的作用效果是复杂的,为了能够成功进行繁殖而面临更大选择压力的性别可能具有更强的免疫水平有所下降,婚配制度的作用效果是复杂的,为了能够成功进行繁殖而面临更大选择压力的性别可能具有更强的免疫功能,许多研究者根据野外研究结果探讨了种群调节的免疫机制问题,认为个体的免疫能力受到遗传和环境因素的影响,其变化状况将关系到整个种群的数量波动,还介绍了生态学研究中采用的免疫学指标。评价了这些指标对实验结果的影响,并对今后的研究方向提出了几点建议。     

The immune system and the impact of zinc during aging

The trace element zinc is essential for the immune system, and zinc deficiency affects multiple aspects of innate and adaptive immunity. There are remarkable parallels in the immunological changes during aging and zinc deficiency, including a reduction in the activity of the thymus and thymic hormones, a shift of the T helper cell balance toward T helper type 2 cells, decreased response to vaccination, and impaired functions of innate immune cells. Many studies confirm a decline of zinc levels with age. Most of these studies do not classify the majority of elderly as zinc deficient, but even marginal zinc deprivation can affect immune function. Consequently, oral zinc supplementation demonstrates the potential to improve immunity and efficiently downregulates chronic inflammatory responses in the elderly. These data indicate that a wide prevalence of marginal zinc deficiency in elderly people may contribute to immunosenescence.     

Coordinated Neutralization and Immune Activation by the Cytosolic Antibody Receptor TRIM21

TRIM21 is a high-affinity antibody receptor uniquely expressed in the cytosol of mammalian cells. Here we summarize its role in extending antibody protection into the intracellular environment and allowing nonprofessional cells to benefit from adaptive immunity. We highlight recent work that has shed light on how TRIM21 acts as both an immune sensor and effector. We also review how TRIM21 synergizes with other innate immune receptors to promote an integrated antiviral response.     

Polyfunctional HIV-Specific Antibody Responses Are Associated with Spontaneous HIV Control

Elite controllers (ECs) represent a unique model of a functional cure for HIV-1 infection as these individuals develop HIV-specific immunity able to persistently suppress viremia. Because accumulating evidence suggests that HIV controllers generate antibodies with enhanced capacity to drive antibody-dependent cellular cytotoxicity (ADCC) that may contribute to viral containment, we profiled an array of extra-neutralizing antibody effector functions across HIV-infected populations with varying degrees of viral control to define the characteristics of antibodies associated with spontaneous control. While neither the overall magnitude of antibody titer nor individual effector functions were increased in ECs, a more functionally coordinated innate immune–recruiting response was observed. Specifically, ECs demonstrated polyfunctional humoral immune responses able to coordinately recruit ADCC, other NK functions, monocyte and neutrophil phagocytosis, and complement. This functionally coordinated response was associated with qualitatively superior IgG3/IgG1 responses, whereas HIV-specific IgG2/IgG4 responses, prevalent among viremic subjects, were associated with poorer overall antibody activity. Rather than linking viral control to any single activity, this study highlights the critical nature of functionally coordinated antibodies in HIV control and associates this polyfunctionality with preferential induction of potent antibody subclasses, supporting coordinated antibody activity as a goal in strategies directed at an HIV-1 functional cure.     

Trichinella spiralis: selective intestinal immune deviation in the rat

In rats, infections with 100-2000 Trichinella spiralis muscle larvae lead to a prompt immunity that is expressed in parasite expulsion within 14 days. Rats infected with more than 2000 larvae display impaired immunity with rejection delayed by 50% (7 days) or more. Suppression is selective for expulsive immunity as the antifecundity response of rats is directly proportional to dose and is expressed sooner in heavily infected subjects. Suppression of intestinal expulsive immunity was suggested by the fact that, with low doses (2000 larvae or less), worm rejection was inhibited by cortisone, whereas cortisone inhibited antifecundity but had no discernable effect on worm rejection in high-dose infections. Evidence for local immune deviation as opposed to systemic immunosuppression was obtained in experiments using parabiotic rats. When one partner was infected with 6000 worms and the other with 200, the rat infected with 200 parasites showed earlier rejection than was seen in single controls infected with 200 worms. The prolonged survival of high-dose adults was not accompanied by a change in the site of worm residence in the gut. Immunological parameters such as serum antibody levels, the number of activated cells or specific anti-T. spiralis lymphocytes in thoracic duct lymph were all increased in a dose-dependent manner. These experiments therefore demonstrate a novel autoprotective mechanism by which adult T. spiralis selectively reduce the expression of expulsive immunity in the gut.     

Immunological basis of anti‐Candida vaccines focused on synthetically prepared cell wall mannan‐derived manno‐oligomers

The increasing incidence of diseases caused by Candida species and complications in individuals with impaired immunity require new strategies for candidiasis treatment and prevention. The available therapies are often of limited effectiveness in immunocompromised patients, resulting in treatment failures, chronic infections and high mortality rates. Research directed at identifying the composition of an effective vaccine is required. Mannan forms the outermost layer of the Candida cell wall and has an essential role in modulation of anti‐Candida host immune responses. Therefore, Candida cell wall mannan and synthetically prepared manno‐oligomer‐based glycoconjugates are the foci of attention in vaccine candidate development. Almost all of the existing human vaccines mediate protection through neutralizing antibodies. Th1‐based and/or Th17‐based cellular immune responses, rather than antibody‐mediated immunity, mediate protection against candidiasis. Findings of published studies indicate that analysis of cellular immune responses as well as antibody responses is necessary when assessing the immunomodulatory properties of manno‐oligomer‐based glycoconjugates that are potential anti‐Candida vaccine candidates.     

Recent advances in the innate immunity of invertebrate animals

Invertebrate animals, which lack adaptive immune systems, have developed other systems of biological host defense, so called innate immunity, that respond to common antigens on the cell surfaces of potential pathogens. During the past two decades, the molecular structures and functions of various defense components that participated in innate immune systems have been established in Arthropoda, such as, insects, the horseshoe crab, freshwater crayfish, and the protochordata ascidian. These defense molecules include phenoloxidases, clotting factors, complement factors, lectins, protease inhibitors, antimicrobial peptides, Toll receptors, and other humoral factors found mainly in hemolymph plasma and hemocytes. These components, which together compose the innate immune system, defend invertebrate from invading bacterial, fungal, and viral pathogens. This review describes the present status of our knowledge concerning such defensive molecules in invertebrates.     

Impairment of T cell-mediated immunity to Listeria monocytogenes in pregnant mice

In order to study pregnancy-induced changes in cell-mediated immunity to Listeria monocytogenes, acquired resistance and T cell functions in pregnant mice were compared with those in nonpregnant mice after immunization with viable listerial cells. Impaired generation of acquired resistance was evident in pregnant mice from the impaired elimination of bacteria and poor survival after secondary challenge. Delayed footpad reactivity to listerial antigen was also lower in the pregnant mice. When immune spleen cells were examined for their ability to produce macrophage activating factor in vitro, culture supernatants from pregnant-mouse spleen cells with listerial antigen showed far less ability to render macrophages cytostatic for P815 mastocytoma cells. To elucidate further the impairment of listeria-immune T cell generation in pregnant mice, a local transfer experiment was carried out. When a given number of immune spleen cells was transferred locally into the footpads of naive mice, both delayed footpad reaction and local protection were much lower in the pregnant mice. This local transferability of the reactions was abrogated after treatment of cells with anti-Thy 1 antibody plus complement. These findings indicate that pregnancy impairs the generation of specific T cells capable of contributing to acquired resistance to L. monocytogenes. Possible mechanisms for this impairment and the relationship to macrophage functions are discussed.     

IVIg Immune Reconstitution Treatment Alleviates the State of Persistent Immune Activation and Suppressed CD4 T Cell Counts in CVID

Common variable immunodeficiency (CVID) is characterized by defective B cell function, impaired antibody production, and increased susceptibility to bacterial infections. Here, we addressed the hypothesis that poor antibody-mediated immune control of infections may result in substantial perturbations in the T cell compartment. Newly diagnosed CVID patients were sampled before, and 6–12 months after, initiation of intravenous immunoglobulin (IVIg) therapy. Treatment-naïve CVID patients displayed suppressed CD4 T cell counts and myeloid dendritic cell (mDC) levels, as well as high levels of immune activation in CD8 T cells, CD4 T cells, and invariant natural killer T (iNKT) cells. Expression of co-stimulatory receptors CD80 and CD83 was elevated in mDCs and correlated with T cell activation. Levels of both FoxP3+ T regulatory (Treg) cells and iNKT cells were low, whereas soluble CD14 (sCD14), indicative of monocyte activation, was elevated. Importantly, immune reconstitution treatment with IVIg partially restored the CD4 T cell and mDC compartments. Treatment furthermore reduced the levels of CD8 T cell activation and mDC activation, whereas levels of Treg cells and iNKT cells remained low. Thus, primary deficiency in humoral immunity with impaired control of microbial infections is associated with significant pathological changes in cell-mediated immunity. Furthermore, therapeutic enhancement of humoral immunity with IVIg infusions alleviates several of these defects, indicating a relationship between poor antibody-mediated immune control of infections and the occurrence of abnormalities in the T cell and mDC compartments. These findings help our understanding of the immunopathogenesis of primary immunodeficiency, as well as acquired immunodeficiency caused by HIV-1 infection.     

Iron status, immune capacity and resistance to infections

1. The importance of iron on immune functions is reviewed. 2. The consequences of iron deficiency upon resistance to infection in men (adults and children) and animals are controversial. 3. Cellular immunity is often altered in iron-deficient humans and in murine species. 4. Humoral immune responses seem far less affected in iron-deficient humans than is cellular immunity, but is impaired in iron-deficient animals. Results on complement are scarce and controversial. 5. There is almost no perturbation of phagocytosis but bactericidal activity is decreased in most studies on iron-deficient subjects. 6. Natural Killer activity is decreased in iron-deficient mice. Iron deficiency also affects lymphokine production in mice and rats.     

Babesia rodhaini: effects of the immune system in mice

Possible functions of antibody in controlling multiplication of B. rodhaini in mice have been investigated. The infectivity of parasites which have been circulating in the blood of immune hosts for 4 hr is not impaired. Clearance of parasitized red cells from the blood of immune hosts is not impaired if the parasites are prevented from leaving the red cells by the effects of radiation damage. The rate of clearance of parasitized red cells by immune hosts is very slow compared with the clearance of foreign red cells by normal hosts.     

Cooperativity of adaptive and innate immunity: implications for cancer therapy

The dichotomy of immunology into innate and adaptive immunity has created conceptual barriers in appreciating the intrinsic two-way interaction between immune cells. An emerging body of evidence in various models of immune rejection, including cancer, indicates an indispensable regulation of innate effector functions by adaptive immune cells. This bidirectional cooperativity in innate and adaptive immune functions has broad implications for immune responses in general and for regulating the tumor-associated inflammation that overrides the protective antitumor immunity. Mechanistic understanding of this two-way immune cross-talk could provide insights into novel strategies for designing better immunotherapy approaches against cancer and other diseases that normally defy immune control.     

Selenium Supplementation Restores Innate and Humoral Immune Responses in Footrot-Affected Sheep

Dietary selenium (Se) alters whole-blood Se concentrations in sheep, dependent upon Se source and dosage administered, but little is known about effects on immune function. We used footrot (FR) as a disease model to test the effects of supranutritional Se supplementation on immune function. To determine the effect of Se-source (organic Se-yeast, inorganic Na-selenite or Na-selenate) and Se-dosage (1, 3, 5 times FDA-permitted level) on FR severity, 120 ewes with and 120 ewes without FR were drenched weekly for 62 weeks with different Se sources and dosages (30 ewes/treatment group). Innate immunity was evaluated after 62 weeks of supplementation by measuring neutrophil bacterial killing ability. Adaptive immune function was evaluated by immunizing sheep with keyhole limpet hemocyanin (KLH). The antibody titer and delayed-type hypersensitivity skin test to KLH were used to assess humoral immunity and cell-mediated immunity, respectively. At baseline, FR-affected ewes had lower whole-blood and serum-Se concentrations; this difference was not observed after Se supplementation. Se supplementation increased neutrophil bacterial killing percentages in FR-affected sheep to percentages observed in supplemented and non-supplemented healthy sheep. Similarly, Se supplementation increased KLH antibody titers in FR-affected sheep to titers observed in healthy sheep. FR-affected sheep demonstrated suppressed cell-mediated immunity at 24 hours after intradermal KLH challenge, although there was no improvement with Se supplementation. We did not consistently prevent nor improve recovery from FR over the 62 week Se-treatment period. In conclusion, Se supplementation does not prevent FR, but does restore innate and humoral immune functions negatively affected by FR.     

SURVIVAL COST OF AN EARLY IMMUNE SOLICITING IN NATURE

If immune functions confer obvious benefits to hosts, life-history theory assumes that they also induce costs, leading to trade-offs between immunity and other fitness components. However, whether substantial fitness costs are associated with immune systems in the wild is debatable, as numerous factors may influence the costs and benefits associated with immune activation. Here, we explore the survival cost of immune deployment in postfledging birds. We injected Eurasian collared dove nestlings ( Streptopelia decaocto ) with antigens from Escherichia coli , and examined whether this immune challenge affected survival after fledging. To assess survival, birds were fitted with radiotags and the fate of each individual was monitored regularly. Our results show that mimicking a bacterial infection in nestlings lowered their survival prospects after fledging, in comparison to controls. The main identified cause of mortality (by examination of dead birds) was presumed to be predation. This study provides experimental evidence that immune activation may entail dramatic survival costs in a free-ranging vertebrate, and emphasizes the potential role that environmental factors such as predation may play in this interaction.