摘要:

SummaryRecent population‐based efficacy trials of the synthetic malaria vaccine SPf66 have shown restricted, if any, clinical protection againstPlasmodium falciparuminfection. Despite the well‐established role of antibodies in effector responses against asexual blood‐stage malaria parasites, the titres of anti‐SPf66 IgG antibodies do not correlate with the ability of sera from vaccine recipients to inhibit parasite growthin vitronor with partial clinical protection which could be detected in some trials. Qualitative or functional parameters of SP66‐induced antibody responses, such as IgG subclass composition and affinity, may be more predictive of clinical protection against malaria than quantitative estimates of antibody concentration or titre. Since these parameters are readily estimated by laboratory techniques currently available, and may be modulated by changes in vaccination protocols and by the use of different adjuvants, a better understanding of qualitative antibody responses induced by SPf66 and other asexual blood‐stage malaria vaccine candidates, and of their relationship with clinical protectionin vivo, is urgently needed for the improvement of currently used immunization schedules.

ISSN:0004-945X    

DOI:10.1038/icb.1996.54

出版商:Blackwell Publishing Ltd    

年代:2017

数据来源: WILEY

摘要:

SummaryStudies of phagocytic efficiency in cells of the macrophage lineage have assumed additional importance since the discovery that HIV infection of these cells impairs their immune function. A rapid method has been developed for measuring phagocytosis of the opportunistic pathogenMycobacterium aviumcomplex by human monocytes. FluoresceinatedM. aviumcomplex (F‐MAC) was incubated with whole blood at 37°C and the fluorescence of extra‐cellular F‐MAC was quenched using a vital blue stain. Monocytes were then stained with a monoclonal antibody (mAb) to human CD14 conjugated to phycoerythrin (PE) red cells were lysed, and the percentage of monocytes which had phagocytosed F‐MAC was measured by flow‐cytometry. The results were reproducible in samples of blood taken from individual donors over a period of 1or 2 weeks, and optimum F‐MAC concentrations and an optimum incubation time were determined by experiment. This method has the advantages of requiring only a small volume of blood, not necessitating manipulation of cells before testing, and using a phagocytic target relevant to the pathogenesis of HIV infection.

ISSN:0004-945X    

DOI:10.1038/icb.1996.55

出版商:Blackwell Publishing Ltd    

年代:2017

数据来源: WILEY

摘要:

SummaryDespite the potential for extensive diversity of γδ TCR, especially for δ‐chains, expression of the γδ TCR repertoire in various mouse epithelial tissues is highly restricted. This implies that the recognition of antigen by γδ T cells may also be limited. To date, however, few studies have examined γδ TCR diversity in peripheral lymphoid tissue. This report presents the Vδ usage and junctional region sequences of TCR δ‐chain transcripts derived from the lymph nodes of normal (PL/J × SJ/L) Fl mice. Rearranged TCR Vδ‐Cδ transcripts were amplified by PCR from TCR δ‐chain cDNA using oligonucieotide primers specific for the murine Vδl to Vγδ7 genes and the Cδ region. Following cloning of the polymerase chain reaction‐amplified TCR δ cDNA, the extent of junctional diversity was assessed by nucleotide sequencing of the V‐D‐J junctions of individual TCR cDNA clones. With the exception of Vδ3, all Vδ genes were expressed in mouse lymph node. Furthermore, predominant usage of Jδ1 was found in cDNA clones expressing Vδ2. Vδ4, Vδ5. Vδ6 and Vδ7 gene segments but despite this there was extensive junctional diversity of δ‐chains primarily due to the usage of multiple Dδ segments and N‐nucleotide sequence addition. In contrast, the Vδl cDNA clones had limited heterogeneity consisting mostly of Vδ1 directly spliced to γδ gene rearrangements. These results show that the expressed murine peripheral TCR δ‐chain repertoire is extremely diverse indicating that γδ T cells may potentially recognize a large number of antigens, and play an important role in contributing to host immune responses.

ISSN:0004-945X    

DOI:10.1038/icb.1996.56

出版商:Blackwell Publishing Ltd    

年代:2017

数据来源: WILEY

摘要:

SummaryInvasive aspergillosis is a significant cause of death in immunocompromised individuals. The majority of strains of the main causative agent,Aspergillus fumigatus, produce gliotoxin, a secondary metabolite with demonstratedin vitroimmunosuppressive activity. Pretreatment of normally resistant mice with a single injection of a sublethal dose of gliotoxin was sufficient to make them susceptible to infection and subsequent death, after challenge withA. fumigatusspores. Animals infected with the non‐gliotoxin producing strain survived significantly longer than those infected with a gliotoxin producer. We propose that the release of gliotoxin byA. fumigatushyphae during infection can exacerbate the pathogenesis of aspergillosis.

ISSN:0004-945X    

DOI:10.1038/icb.1996.57

出版商:Blackwell Publishing Ltd    

年代:2017

数据来源: WILEY

摘要:

SummaryThe present study reports the influence of bovine β‐casein onin vitroandin vivoimmune responses. Bovine β‐casein showed an inhibitory effect on ovine neutrophil chemotaxis but had an enhancing effect on superoxide production by neutrophils. In response to mitogenic stimulation, the proliferative response of both T and B lymphocytes was significantly enhanced by β‐casein. While β‐casein had no significant effects on IFNγ production by ovine blood lymphocytes, and TNFα production and MHC Class II antigen expression by ovine bronchoalveolar macrophages, it enhanced IL‐1β production by the macrophages. β‐casein also had no influence on bovine NK cell activity against a virally‐infected cell line. Interestingly, β‐casein was found to reduce the adjuvant effect of matrix immune stimulating complexes (ISCOM) on anti‐ovalbumin antibody response in mice when given intramuscularly. Taken together, the results suggest that bovine β‐casein had selective modulating effectsin vitroon both innate and adaptive immune responses in ruminants, whereas systemic administration of β‐casein, that might have a depressive effect on adjuvant activity, requires further study.

ISSN:0004-945X    

DOI:10.1038/icb.1996.58

出版商:Blackwell Publishing Ltd    

年代:2017

数据来源: WILEY

摘要:

SummaryThe strong association between polymorphisms in an intronic microsatellite and the coding sequences for (BoLA)‐DRB3genes, previously described for demonstrating alleles of class II major histocompatibility complex (MHC) in the cow, was examined in sheep to see if similar polymorphisms could be demonstrated in theDRBregion of the MHC. The bovine primers LA53 and LA54, previously used to amplify the bovineDRB3microsatellites, were used with DNA from Australian sheep, eightDRBalleles were identified by length polymorphisms of polymerase chain reaction (PCR) products amplified from theDRBmicrosatellite region. Incomplete amplification of both alleles was sometimes found for sheep DNA samples using bovine primers, so a modified primer (LA53b) was used, and found to amplify the microsatellite next to intron 2 of the MHC more reliably than the LA53 primer. Two additional primers (LA31 and LA32), used in amplification of the exon 2 region of bovineDRB3, were used in the sheep, and the PCR products were analysed by single‐stranded conformation polymorphism (SSCP). These primers successfully amplified the variable region of the ovineDRBregion coded by exon 2, and the SSCP technique demonstrated polymorphisms with sheep DNA. Family studies demonstrated the segregation of alleles, by amplification both of intronic microsatellites and of the exon 2 variable region. Close correspondence was found between the two regions for several alleles, suggesting that the intronic microsatellites were closely linked toDRB‐variable region alleles. Three families of Merino sheep with different antibody responses to intestinal nematode parasites were examined. The sire group with the highest antibody levels possessed two microsatellite alleles of closely similar length (alleles 3 and 4) inherited from the sire and present in high frequency in the lambs. In contrast, the other two sires did not possess these two alleles and the alleles were in low frequency in their progeny. Further studies are required in unrelated sheep to confirm whether these two alleles are associated with resistance to nematode parasites.

ISSN:0004-945X    

DOI:10.1038/icb.1996.59

出版商:Blackwell Publishing Ltd    

年代:2017

数据来源: WILEY

摘要:

SummaryThis paper analyses the association between infection with helminth parasites, the elevated production of IgE and the expression of allergies. Interpretations of this interaction have taken place in a scientific environment whose most secure element is the immunochemistry of allergic reactions resulting in a substantial body of literature that has sought a biological role for allergic reactivity in protective immunity directed against helminth parasites. While the association between helminth infections and elevated levels of IgE, mast cells and eosinophils is well established, a functional role for allergic reactions in protection against helminths has eluded experimental proof. Instead of this hypothesis, it is proposed that allergic reactivity is rarely present in helminth‐infected individuals because allergic reactions do not function to regulate helminth infections. Data from many sources are used to establish that the ‘normal’ state of all mammals is to be infected with helminth parasites from shortly after birth until well into adulthood. Only in the last 100 years or so have people living in areas of high development with sophisticated water and sewage systems been able to escape helminth infection. Allergies are as conspicuously present in these human populations as they are absent in populations that are still regularly exposed to helminths. Furthermore, in populations with endemic helminthoses there is little overt expression of allergic pathology that could be connected to the acquisition or elimination of helminth parasites. Based on these observations, it is suggested that endemic helminthoses activate the Th2 system, particularly at mucosal surfaces, to provide a different level of immunological homeostasis than currently occurs in developed societies. Under these conditions, mast cells, eosinophils and IgE rarely participate in reactions that we would recognize as ‘allergic’, although their participation in the control of helminth infections is still envisaged. Allergic reactions are considered to be a purely pathologic consequence of the disruption of this homeostatic mechanism and are not protective at all for the individual expressing them. This interpretation is derived from the immunobiology of the host‐parasite interaction rather than the biology of allergies and should lead to new concepts regarding both allergic disease and the role of helminth infections in human and animal populations.

ISSN:0004-945X    

DOI:10.1038/icb.1996.60

出版商:Blackwell Publishing Ltd    

年代:2017

数据来源: WILEY

摘要:

SummaryInfection of animals with species ofEimeriainduces a hyper‐reactivity to endotoxin as manifest by a greatly increased capacity of infected animals to produce TNF in response to LPSin vivocompared with uninfected animals. This finding indicates priming for hyperactivation of macrophages byEimeriainfection and raises the possibility that non‐specific triggering of macrophages by agents such as Bacille Calmette‐Guerin (BCG), zymosan orCoxiella burnettiextract may be a simple means of control for coccidiosis. However, all of these agents enhanced oocyst excretion in mice, rats or chickens infected withEimeria vermiformis. Eimeria nieschulziorEimeria tenella, respectively, without affecting the patent period.

ISSN:0004-945X    

DOI:10.1038/icb.1996.61

出版商:Blackwell Publishing Ltd    

年代:2017

数据来源: WILEY

摘要:

SummaryThe classical major histocompatibility complex (MHC) class I genes are conserved in higher primates. Motifs common to human, chimpanzee and gorilla alleles indicate that class I alleles diverged from ancestral sequences that existed before separation of these species. Analysis of native human populations such as Australian Aborigines and Amerindians shows that HLA‐B is characterized by rapid generation of new alleles. HLA‐A and ‐C appear to be evolving more slowly. Comparison of alleles for orthologous class I genes in humans and other primates confirms that similar mechanisms contribute to the generation of new alleles in these species.

ISSN:0004-945X    

DOI:10.1038/icb.1996.62

出版商:Blackwell Publishing Ltd    

年代:2017

数据来源: WILEY

摘要:

SummaryWe determined the sequence of 18 DNA clones encoding VHregions of sandbar shark and bull shark. All of these sequences exhibit key structural coding features characteristic of known VHgenes of higher vertebrates. These VHsequences disclosed considerable diversity, and can be divided into six families according to the criterion of 80% DNA sequence identity. The overlapping of some VHgene clones to two or more families is a particular feature found in carcharhine sharks, which suggests that VHdiversification is a continuing process. The basic sequence patterns of heavy‐chain V regions found in all representative gnathanstomes and in VHof the shark heavy immunoglobulin igW provides evidence for selection of canonical residues in all VHstructures, Elasmobranch VHsequences can be divided into two classes or clans, one comprising the ‘classical’ VHset and the other comprising VHs related to those of IgW (Vω). Phylogenetic analyses place the VHcluster as the root of all the classic VHs and indicates that the Vω set is most probably that of the primordial heavy chain.

ISSN:0004-945X    

DOI:10.1038/icb.1996.63

出版商:Blackwell Publishing Ltd    

年代:2017

数据来源: WILEY