COEVOLUTION BETWEEN MATERNAL TRANSFER OF IMMUNITY AND OTHER RESISTANCE STRATEGIES AGAINST PATHOGENS

Among the wide variety of resistance mechanisms to parasitism, the transgenerational transfer of immunity from mother to offspring has largely been overlooked and never included in evolutionary or coevolutionary studies of resistance mechanisms. Here we study the evolution and coevolution of various resistance mechanisms with a special focus on maternal transfer of immunity. In particular we show that maternal transfer of immunity is only expected to evolve when cross immunity is high and when the pathogens have an intermediate virulence. We also show that the outcome of the coevolution between various resistance mechanisms depends critically on the life span of the host. We predict that short‐lived species should invest in avoidance strategies, whereas long‐lived species should invest in acquired resistance mechanisms. These results may help understanding the diversity of resistance strategies that have evolved in vertebrate species. Our framework also provides a general basis for the study of the evolution of other transgenerational resistance mechanisms.     

Host life span and the evolution of resistance characteristics

There is a wide variety of resistance mechanisms that hosts may evolve in response to their parasites. These can be functionally classified as avoidance (lower probability of becoming infected), recovery (faster rate of clearance), tolerance (reduced death rate when infected), or acquired immunity. It is commonly thought that longer lived organisms should invest more in costly resistance. We show that due to epidemiological feedbacks the situation is often more complex. Using evolutionary theory we examine how the optimal investment in costly resistance varies with life span in a broad range of scenarios. In the absence of acquired immunity, longer lived populations do generally invest more in resistance. If hosts have acquired immunity, the optimal resistance may either increase or decrease with increasing life span. In addition, there may be evolutionary bistability with high and low investments in avoidance or tolerance. The optimal investment in the duration of acquired immunity always increases with life span, and due to bistability, shorter lived hosts may commonly not evolve any immunity. In contrast, the optimal investment in the probability of acquiring immunity initially increases and then decreases with life span. Our results have important implications for the evolution of invertebrate and vertebrate immunity, and for the evolution of acquired immunity itself.     

Daytime variation in T-cell-mediated immunity of Eurasian kestrel Falco tinnunculus nestlings

Host-parasite interactions are central in evolutionary and behavioural ecology. In the last few years, skin injections of the mitogen Phytohaemagglutinin (PHA) have become one of the most important and widely used in-vivo assays of immune function in birds. However, there are no studies of the circadian variation suggesting that care should be taken interpreting results when using this technique. This 3-year study assessed PHA responses as a function of daylight time in 310 Eurasian kestrel Falco tinnunculus nestlings at 24 days of age in Central Spain. I found that T-cell-mediated immunity was positively related to nestling mass and varied among years. Controlling for these variables, I also found that T-cell-mediated immunity decreased with the hour of sampling, and that this pattern was consistent between years. In addition, I found that at the end of the day only, T-cell-mediated immunity decreased with brood size. Parasites seem not to be behind this pattern, but I suggest that the cumulative effect of sibling competition during the day might explain the decrease of cellular immunity with the hour of sampling. Thus, I strongly recommend that future studies of cellular immunity should control for this potential source of variation when nestling self-maintenance is evaluated by the PHA-induced skin-swelling response.     

流行性腮腺炎疫苗免后血清学效果及免疫方案探讨

选以往无流行性腮腺炎患病史和接种史的学龄及学龄前儿童２４３名,血清检测流腮ＨＩ抗体,阳性率为５５．６％,阳性率明显地随年龄增大而上升,而性别无差异。经用Ｓ生物所及Ｂ生物所生产的两种疫苗接种,免后ＨＩ抗体的跳高率及ＧＭＴ均较免前有明显上升。双份血清检测结果,免后ＨＩ抗体显著跳高率（≥４倍）为４４．８％;９８名免前阴性儿童免后ＨＩ阳转率５７．１％,ＧＭＴ为１１３．２９,两种疫苗均无显著差异,提示疫苗的质量和稳定性有待提高,笔者对当前免疫方案提出了改进意见。     

Immunity and the expression of a secondary sexual trait in a horned beetle

Resource-based trade-offs are known to be important in determininginvestment in both sexual ornamentation and immunity in insects.Because of the strict resource limitation experienced duringmetamorphosis, we predict that if insects are trading off ornamentsize and immunity this should be most apparent immediately aftereclosion and that the relationship between sexual ornament sizeand immunity should change with maturation feeding because ofthe changing patterns of resource availability during this process.We therefore present an investigation into the relationshipbetween morphology, sex, and two measures of immune response(phenoloxidase [PO] activity and encapsulation ability) in thehorned beetle Euoniticellus intermedius, immediately after eclosionand after maturation feeding. Both measures increased with maturation,with sex differences in PO activity becoming discernable aftermaturation feeding. PO activity was positively correlated withhorn length in male beetles both on eclosion and after maturationfeeding, and encapsulation ability was positively correlatedwith elytra length. We conclude that resource limitation inthe pupating insect does have effects on immunity but that thisresource limitation does not translate into a measurable trade-offbetween horn length and immunity. The correlation between hornlength and PO activity may arise because both horn length andPO activity are correlated with the same elements of the animal'sbiology that allow some animals both to grow a long horn andto sustain a higher level of PO activity.     

Immune Investment Is Explained by Sexual Selection and Pace-of-Life,but Not Longevity in Parrots (Psittaciformes)

Investment in current reproduction should come at the expense of traits promoting future reproduction, such as immunity and longevity. To date, comparative studies of pace-of-life traits have provided some support for this, with slower paced species having greater immune function. Another means of investment in current reproduction is through secondary sexual characters (SSC). Investment in SSC''s is considered costly, both in terms of immunity and longevity, with greater costs being borne by species with more elaborate traits. Yet within species, females prefer more ornate males and those males are typically immunologically superior. Because of this, predictions about the relationship between immunity and SSC''s across species are not clear. If traits are costly, brighter species should have reduced immune function, but the opposite is true if SSC''s arise from selection for more immunocompetent individuals. My approach was to investigate immune investment in relation to SSC''s, pace-of-life and longevity while considering potentially confounding ecological factors. To do so I assessed leukocyte counts from in a novel group, the Psittaciformes. Investment in SSC''s best explained investment in immunity: species with brighter plumage had higher leukocyte counts and those with a greater degree of sexual dichromatism had fewer. Ecological variables and pace-of-life models tended to be poor predictors of immune investment. However, shorter incubation periods were associated with lower leukocyte counts supporting the notion that species with a fast pace-of-life invest less in immunity. These results suggest that investment in reproduction in terms of fast pace-of-life and sexual dichromatism results in reduced immunity; however, investment in plumage colour per se does not impose a cost on immunity across species.     

Ecological and evolutionary implications of immunological priming in invertebrates

Invertebrates have an immune response that differs considerably from the acquired immune response found in vertebrates. However, new studies indicate that past experience with a pathogen can provide individual invertebrates, or their descendants, with enhanced immunity. This prophylactic effect, termed immunological priming, is functionally similar to the acquired immune response in vertebrates. This newfound complexity of invertebrate immunity begs investigation into the conditions under which immunological priming should evolve, and its consequences for population dynamics.     

Loss of susceptibility as a novel breeding strategy for durable and broad-spectrum resistance

Recent studies on plant immunity have suggested that a pathogen should suppress induced plant defense in order to infect a plant species, which otherwise would have been a nonhost to the pathogen. For this purpose, pathogens exploit effector molecules to interfere with different layers of plant defense responses. In this review, we summarize the latest findings on plant factors that are activated by pathogen effectors to suppress plant immunity. By looking from a different point of view into host and nonhost resistance, we propose a novel breeding strategy: disabling plant disease susceptibility genes (S-genes) to achieve durable and broad-spectrum resistance.     

Chemical warfare or modulators of defence responses - the function of secondary metabolites in plant immunity

In plants, a host's responses to an attempted infection include activation of various secondary metabolite pathways, some of which are specific for particular plant phylogenetic clades. Phytochemicals that represent respective end products in plant immunity have been stereotypically linked to antimicrobial properties. However, in many cases, owing to the lack of unequivocal evidence for direct antibiotic action in planta, alternative functions of secondary metabolites should be considered. Correspondingly, recent findings have identified novel, and rather unexpected, functions of phytochemicals in plant immunity that mediate regulatory pathways for conserved defence responses. It also seems likely that these conserved responses can be regulated by clade-specific phytochemicals.     

Vaccine delivery: lipid-based delivery systems

Needle-free delivery of vaccines should not only increase compliance, but should also prove to be a safer and less traumatic method of vaccine delivery. One of the potential ways to achieve needle-free delivery is with the use of lipid-based delivery systems. To demonstrate the utility of these systems, we have shown them to be effective with proteins produced by recombinant DNA technology, plasmid-based vaccines, as well as conventional vaccines. Furthermore, these lipid-based delivery systems were shown to be effective in inducing mucosal immunity if delivered to mucosal surfaces or systemic immunity if different transdermally. These approaches have the potential to revolutionize vaccine delivery in humans and animals.     

Lassa fever: implications of T-cell immunity for vaccine development.

Lassa fever is a re-emerging viral hemorrhagic fever, which causes significant human morbidity in endemic regions of West Africa. Attempts to vaccinate against this virus in animal models including non-human primates have revealed that eliciting a strong cellular immune response protects from clinical disease, but not infection, in the absence of measurable neutralizing antibodies. As there is renewed interest in developing a vaccine against Lassa fever for use in humans, several questions should be addressed in view of the scarce knowledge of the mechanisms of natural immunity against this disease. MHC-dependency of a vaccine relying mainly on the induction of T-cell immunity and its ability to cross-protect against different Lassa virus strains will be important issues. Furthermore, the question whether the vaccine can prevent human-to-human transmission of the virus should be discussed and the possibility that vaccination could predispose to immunopathology should be excluded. We are addressing some of the above mentioned problems concerning natural immunity through field studies in the Republic of Guinea, West Africa, and are presently studying the CD4 cell responses of Lassa antibody positive subjects on the basis of T-cell proliferation assays using recombinant Lassa virus proteins.     

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.     

Dendritic-cell interactions with HIV: infection and viral dissemination

Dendritic cells (DCs) are crucial for the generation and the regulation of adaptive immunity. Because DCs have a pivotal role in marshalling immune responses, HIV has evolved ways to exploit DCs, thereby facilitating viral dissemination and allowing evasion of antiviral immunity. Defining the mechanisms that underlie cell-cell transmission of HIV and understanding the role of DCs in this process should help us in the fight against HIV infection. This Review highlights the latest advances in our understanding of the interactions between DCs and HIV, focusing on the mechanisms of DC-mediated viral dissemination.     

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.     

Polynucleotide vaccines: potential for inducing immunity in animals.

Polynucleotide immunization has been described as the Third Revolution in Vaccinology. Early studies suggest the potential benefits of this form of immunization including: long-lived immunity, a broad-spectrum of immune responses (both cell mediated immunity, and humoral responses) and the simultaneous induction of immunity to a variety of pathogens through the use of multivalent vaccines. Using a murine model, we studied methods to enhance and direct the immune response to polynucleotide vaccines. We demonstrated the ability to modulate the magnitude and direction of the immune response by co-administration of plasmid encoded cytokines and antigen. Also, we clearly demonstrated that the cellular components (cytosolic, membrane-anchored, or extracellular) to which the expressed antigen is delivered determines the types of immune responses induced. Since induction of immunity at mucosal surfaces (route of entry for many pathogens) is critical to prevent infection, various methods of delivering polynucleotide vaccines to mucosal surfaces have been attempted and are described. Expansion of studies in various species, using natural models, should be extremely helpful in demonstrating the universality of this approach to immunization and more importantly, accurately identify parameters that are critical for the development of protective immunity.     

The complexity of protective immunity against liver-stage malaria

Sterile protective immunity against challenge with Plasmodium spp. sporozoites can be induced in multiple model systems and humans by immunization with radiation-attenuated Plasmodium spp. sporozoites. The infected hepatocyte has been established as the primary target of this protection, but the underlying mechanisms have not been completely defined. Abs, CD8+ T cells, CD4+ T cells, cytokines (including IFN-gamma and IL-12), and NO have all been implicated as critical effectors. Here, we have investigated the mechanisms of protective immunity induced by immunization with different vaccine delivery systems (irradiated sporozoites, plasmid DNA, synthetic peptide/adjuvant, and multiple Ag peptide) in genetically distinct inbred strains, genetically modified mice, and outbred mice. We establish that there is a marked diversity of T cell-dependent immune responses that mediate sterile protective immunity against liver-stage malaria. Furthermore, we demonstrate that distinct mechanisms of protection are induced in different strains of inbred mice by a single method of immunization, and in the same strain by different methods of immunization. These data underscore the complexity of the murine host response to a parasitic infection and suggest that an outbred human population may behave similarly. Data nevertheless suggest that a pre-erythrocytic-stage vaccine should be designed to induce CD8+ T cell- and IFN-gamma-mediated immune responses and that IFN-gamma responses may represent an in vitro correlate of pre-erythrocytic-stage protective immunity.     

Disentangling extrinsic from intrinsic factors in disease dynamics: a nonlinear time series approach with an application to cholera

Alternative explanations for disease and other population cycles typically include extrinsic environmental drivers, such as climate variability, and intrinsic nonlinear dynamics resulting from feedbacks within the system, such as species interactions and density dependence. Because these different factors can interact in nonlinear systems and can give rise to oscillations whose frequencies differ from those of extrinsic drivers, it is difficult to identify their respective contributions from temporal population patterns. In the case of disease, immunity is an important intrinsic factor. However, for many diseases, such as cholera, for which immunity is temporary, the duration and decay pattern of immunity is not well known. We present a nonlinear time series model with two related objectives: the reconstruction of immunity patterns from data on cases and population sizes and the identification of the respective roles of extrinsic and intrinsic factors in the dynamics. Extrinsic factors here include both seasonality and long-term changes or interannual variability in forcing. Results with simulated data show that this semiparametric method successfully recovers the decay of immunity and identifies the origin of interannual variability. An application to historical cholera data indicates that temporary immunity can be long-lasting and decays in approximately 9 yr. Extrinsic forcing of transmissibility is identified to have a strong seasonal component along with a long-term decrease. Furthermore, noise appears to sustain the multiple frequencies in the long-term dynamics. Similar semiparametric models should apply to population data other than for disease.     

TLR-independent induction of dendritic cell maturation and adaptive immunity by negative-strand RNA viruses

TLR signaling leads to dendritic cell (DC) maturation and immunity to diverse pathogens. The stimulation of TLRs by conserved viral structures is the only described mechanism leading to DC maturation after a virus infection. In this report, we demonstrate that mouse myeloid DCs mature normally after in vivo and in vitro infection with Sendai virus (SeV) in the absence of TLR3, 7, 8, or 9 signaling. DC maturation by SeV requires virus replication not necessary for TLR-mediated triggering. Moreover, DCs deficient in TLR signaling efficiently prime for Th1 immunity after infection with influenza or SeV, generating IFN-gamma-producing T cells, CTLs and antiviral Abs. We have previously demonstrated that SeV induces DC maturation independently of the presence of type I IFN, which has been reported to mature DCs in a TLR-independent manner. The data presented here provide evidence for the existence of a novel intracellular pathway independent of TLR-mediated signaling responsible for live virus triggering of DC maturation and demonstrate its critical role in the onset of antiviral immunity. The revelation of this pathway should stimulate invigorating research into the mechanism for virus-induced DC maturation and immunity.     

Immunogenicity of heterologous recombinant adenovirus prime-boost vaccine regimens is enhanced by circumventing vector cross-reactivity

The high prevalence of preexisting immunity to adenovirus serotype 5 (Ad5) in human populations has led to the development of recombinant adenovirus (rAd) vectors derived from rare Ad serotypes as vaccine candidates for human immunodeficiency virus type 1 and other pathogens. Vaccine vectors have been constructed from Ad subgroup B, including rAd11 and rAd35, as well as from Ad subgroup D, including rAd49. However, the optimal combination of vectors for heterologous rAd prime-boost vaccine regimens and the extent of cross-reactive vector-specific neutralizing antibodies (NAbs) remain poorly defined. We have shown previously that the closely related vectors rAd11 and rAd35 elicited low levels of cross-reactive NAbs. Here we show that these cross-reactive NAbs correlated with substantial sequence homology in the hexon hypervariable regions (HVRs) and suppressed the immunogenicity of heterologous rAd prime-boost regimens. In contrast, vectors with lower hexon HVR homology, such as rAd35 and rAd49, did not elicit detectable cross-reactive vector-specific NAbs. Consistent with these findings, rAd35-rAd49 vaccine regimens proved more immunogenic than both rAd35-rAd5 and rAd35-rAd11 regimens in mice with anti-Ad5 immunity. These data suggest that optimal heterologous rAd prime-boost regimens should include two vectors that are both rare in human populations to circumvent preexisting antivector immunity as well as sufficiently immunologically distinct to avoid cross-reactive antivector immunity.     

Vaccination against Feline Panleukopenia: implications from a field study in kittens

ABSTRACT: BACKGROUND: Feline Panleukopenia (FPL) is a serious disease of cats that can be prevented by vaccination. Kittens are routinely vaccinated repeatedly during their first months of life. By this time maternally derived antibodies (MDA) can interfere with successful vaccination and inhibit the development of active immunity. The efficacy of primary vaccination under field conditions was questioned by frequent reports to the Paul-Ehrlich-Institut on outbreaks of FPL in vaccinated breeding catteries. We therefore initiated a field study to investigate the development of immunity in kittens during primary vaccination against FPL. 64 kittens from 16 litters were vaccinated against FPL at the age of 8, 12 and 16 weeks using three commercial polyvalent vaccines. Blood samples were taken before each vaccination and at the age of 20 weeks. Sera were tested for antibodies against feline panleukopenia virus (FPV) by hemagglutination inhibition test and serum neutralisation assay in two independent diagnostic laboratories. RESULTS: There was a good correlation between the results obtained in different laboratories and with different methods. Despite triple vaccination 36.7% of the kittens did not seroconvert. Even very low titres of maternally derived antibodies (MDA) apparently inhibited the development of active immunity. The majority of kittens displayed significant titres of MDA at 8 and 12 weeks of age; in some animals MDA titres that interfered with vaccination were still detected at 20 weeks of age. Interestingly, the vaccines tested differed significantly in their ability to overcome low levels of maternal immunity. CONCLUSIONS: In the given situation it is recommended to quantify antibodies against FPV in the serum of the queen or of the kittens before primary vaccination of kittens. The beginning of primary vaccination should be delayed until MDA titres have declined. Unprotected kittens that have been identified serologically should be revaccinated.