bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immunological and structural similarities among allergens: Prerequisite for a specific and component‐based therapy of allergy
Authors: VALENTA RUDOLF , STEINBERGER PETER , DUCHÊNE MICHAEL , KRAFT DIETRICH 
Published: June 2007

SummaryIt is known that allergic patients are frequently co‐sensitized against different allergen sources. Progress made in the field of allergen characterization by molecular biological techniques has now revealed that sensitization against different allergen sources can be explained as cross‐reactivity of IgE antibodies with structurally and immunologically related components present in these allergen sources. This review defines groups of cross‐reactive plant allergens with significant sequence homology. The similarities among allergens may facilitate allergy diagnosis by using a few representative cross‐reactive allergens to determine the patient's IgE reactivity profile (allergogram). According to that typing, a few cross‐reactive allergens, carrying most of the relevant IgE epitopes, may then be selected for patient‐tailored specific therapy.
Atopy and the ectopic immune response
Authors: AALBERSE ROB C 
Published: June 2007

SummaryA hypothesis if formulated for the mode of action of the ‘atopy gene’: the gene(s) causing an increased tendency to mount an IgE immune response to trivial environmental antigens. It is postulated that some antigens are not efficiently transported to the lymphoid organs, the location of the ‘eutopic’ immune system; migratory lymphoid cells may occasionally react and start an inefficient immune response in sites not so destined. This is called an ectopic immune response. This response lacks the regulatory influences prevailing in the lymphoid organs, which results in approximately equal quantities of the various immunoglobulin isotypes, including IgE. The atopy gene(s) work by increasing the risk of such an ectopic immune response.
How is expression of the interleukin‐5 gene regulated?
Authors: KARLEN STEPHANE , MORDVINOV VIATCHESLAV A , SANDERSON COLIN J 
Published: June 2007

SummaryEosinophilia is a uniquely specific phenomenon regulated by interleukin‐5 (IL‐5), suggesting specific control for IL‐5 expression. However in eosinophilia IL‐5 is often co‐expressed with other lymphokines such as IL‐4, indicating that common, as well as independent, control mechanisms must exist. IL‐5 gene expression is regulated at the transcriptional level. The molecular analysis of the IL‐5 promoter region reveals the presence of positive regulatory sites that are common to many lymphokine genes. Results from immunosuppression studies suggest that the key control mechanism of IL‐5 regulation may not depend on specific regulatory factors but on how gene expression is activated.
The structure and function of hyaluronan: An overview
Authors: LAURENT TORVARD C , LAURENT ULLA BG , FRASER J ROBERT E 
Published: June 2007

SummaryHyaluronan is a major component of synovial tissue and fluid as well as other soft connective tissues. It is a high‐Mr polysaccharide which forms entangled networks already at dilute concentrations (< 1 mg/mL) and endows its solutions with unique rheological properties. Physiological functions of hyaluronan (lubrication, water homeostasis. macromolecular filtering, exclusion, etc.) have been ascribed to the properties of these networks. Recently a number of specific interactions between hyaluronan and a group of proteins named hyaladherins have also pointed towards a role of hyaluronan in recognition and the regulation of cellular activities. Many more or less well documented hypotheses have been proposed for the function of hyaluronan in joints, for example, that it should lubricate, protect cartilage surfaces, scavenge free radicals and debris, keep the joint cavities open, form flow barriers in the synovium and prevent capillary growth.
Susceptibility to Leishmania major in IL‐4 transgenic mice is not correlated with the lack of a Th1 immune response
Authors: ERB KLAUS J. , BLANK CHRISTINE , MOLL HEIDRUN 
Published: June 2007

SummaryIL‐4 transgenic mice of C3H genetic background expressing IL‐4 under the control of an MHC class I promoter were infected with Leishmania major and the immune response was assessed. In contrast to littermate control mice, the transgenic mice were unable to restrict the growth of the parasites as shown by the strong increase in footpad swelling and parasite numbers in the spleen. The observed susceptibility was markedly less severe than that observed in BALB/c mice. Restimulation of lymph node cells with L. major antigen in vitro and subsequent analysis of cytokine secretion revealed that, in contrast to BALB/c mice, the cells from the IL‐4 transgenic mice secreted more IL‐5 and similar amounts of IFN‐γ as did the cells from litter mate control mice. These results demonstrate that the transgenic expression of IL‐4 in vivo leads to the generation of more Th2 cells without affecting the generation of IFN‐γ‐producing Th1 cells. This indicates that under certain conditions Th1 and Th2 immune responses during infection with L. majorare not mutually exclusive, and that other factors besides the secretion of IL‐4 determine whether only a Th1 or a Th2 immune response develops. The observed susceptibility of IL‐4 transgenic mice to L. major was not due to the lack of IFN‐γ production but presumably to the transgenic and Th2 cell‐derived IL‐4 counteracting the otherwise protective effect of IFN‐γ on infected macrophages. Our results might help explain why humans develop cutaneous leishmaniasis even though IFN‐γ‐producing ceils are readily detectable in the lesions.
Gene family use and somatic mutation in primary and secondary fluorescein‐specific IgM antibody responses
Authors: VAN DER KEYL H , HSU C , TOLAT A , KANSIL S , DALESANDRO MR , DORER DR , CATON A , OWEN JA 
Published: June 2007

SummaryA comparative analysis of the DNA sequences of primary and secondary IgM, fluorescein‐ specific antibodies was performed. These antibodies were secreted by hybridomas generated following fusion of immunized BALB/c mouse lymphocytes and SP2/0 myeloma cells. Our results show that primary and secondary fluorescein‐specific IgM antibodies use a variety of segments from the variable region of the immunoglobulin heavy chain locus (VH), with members of the J558 and 7183 VH gene families predominating in both populations, D regions from the DF116 and DSP2 families were used exclusively in our primary antibody sample and predominated in the secondary response. In the primary antibodies, 15 out of 18 definable D regions were transcribed in reading frame one, but in the secondary antibodies the three reading frames were used stochastically. Secondary IgM antibodies showed a higher frequency of somatic mutation than their primary counterparts, but we could detect no evidence of selection for mutations in the complementarity determining regions as compared with the framework regions. It appears that fusion of secondary cells, 3‐6 days after immunization, is able to‘capture’the IgM‐producing population of B cells at a stage in their development following mutation but prior to antigenic selection.
Similar abnormalities of idiotype and immunoglobulin light chain expression and of cell‐mediated cytotoxicity in HIV‐infected humans and simian immunodeficiency virus (SIV)‐infected rhesus macaques
Authors: GRANT MD , WHALEY MD , MAYNE A , HOFFMANN GW , ANSARI AA 
Published: June 2007

SummaryThe pathogenesis of AIDS in simian immunodeficiency virus (SIV)‐infected rhesus macaques models the pathogenesis of human AIDS. We investigated whether certain immunological abnormalities associated with HIV infection and implicated in disease progression also occur in SIV infection. We observed striking parallels between the rhesus macaque humoral immune response to SIV and unusual features of the human humoral immune response to HIV infection. Anti‐SIV envelope antibodies from SIV‐infected macaques exhibited skewed K/λ L chain usage relative to the ratio of K/λ L chain usage detected on total plasma Ig. In addition, the same idiotope conserved on human anti‐HIV gag, pol and env antibodies was detected with a similar distribution pattern on macaque anti‐SIV env, gag and pol antibodies. Skewed Ig L chain representation and selection of a highly conserved possible dominant regulatory idiotope on antibodies against key neutralizing antigens raise the possibility that the progressive failure of the humoral immune response to SIV and HIV involves skewed oligoclonal humoral immunity. We also found that SIV‐infected macaques, like HIV‐infected humans, have elevated levels of CD8+ lymphocyte‐mediated cytotoxicity. Cytotoxicity against human B cells was higher in CD8+ effector lymphocytes from SIV‐infected macaques than in those from uninfected macaques (P <0.05). Cell‐mediated cytotoxicity against human NK cell targets was not elevated in effector lymphocytes from the SIV‐infected macaques, suggesting that CTL activity was selectively elevated. Two out of seven SIV‐infected macaques tested had CD8+ cytotoxic lymphocytes that selectively killed activated uninfected CD4+ macaque lymphocytes. Oligoclonal B cell responses and persistently elevated CD+ lymphocyte‐mediated cytotoxicity are consistent features of primate retroviral infections leading to AIDS. Understanding immune predispositions to these features triggered by HIV and SIV may advance new prophylactic and therapeutic strategies.
How adaptive antibodies facilitate the evolution of natural antibodies
Authors: ANDERSON RUSSELL WAYNE 
Published: June 2007

SummaryIt is shown how Ig specificities, randomly generated in conventional B cells, come to be expressed in the genetically‐determinate B1 population. Thus the adaptive antibody population facilitates the evolution of the natural antibody repertoire, in accordance with the Baldwin effect in the evolution of instinct. The evolution of these two populations is discussed under both the‘proximal usage’and‘preferential expression’hypotheses of biased Ig gene segment usage. This process is independent of theories of B1 function.
Expression of the T cell receptor δ‐chain repertoire in mouse lymph node
Authors: OLIVE COLLEEN 
Published: June 2007

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.
The PCR typing of MHC‐DRB genes in the sheep using primers for an intronic microsatellite: Application to nematode parasite resistance
Authors: OUTTERIDGE PM , ANDERSSON L , DOUCH PGC , GREEN RS , GWAKISA PS , HOHENHAUS MA , MIKKO S 
Published: June 2007

SummaryThe strong association between polymorphisms in an intronic microsatellite and the coding sequences for (BoLA)‐DRB3 genes, 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 the DRB region of the MHC. The bovine primers LA53 and LA54, previously used to amplify the bovine DRB3 microsatellites, were used with DNA from Australian sheep, eight DRB alleles were identified by length polymorphisms of polymerase chain reaction (PCR) products amplified from the DRB microsatellite 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 bovine DRB3, 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 ovine DRB region 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 to DRB‐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.
Bacterial metabolism, cytokine mRNA transcription and viability of bovine alveolar macrophages infected with Mycobacterium bovis BCG or virulent M bovis
Authors: ALDWELL FE , WEDLOCK DN , BUDDLE BM 
Published: June 2007

Summary Mycobacterium bovis causes tuberculosis in cattle and many other animals including humans while BCG, an attenuated form of M. bovis, has been used widely as a safe vaccine. Both strains infect host macrophages and their fate is determined by their ability to survive within these phagocytic cells. We compared interactions of these two strains with bovine alveolar macrophages in order to gain an understanding of virulence mechanisms involved in the early pathogenesis of M. bovis infection. Macrophages were infected with bacilli at varying multiplicities of infection and cultured for 1‐4 days. Bacterial metabolism within macrophages was assessed by [3H]‐uracil uptake and bacterial growth was assessed by culture and acid‐fast staining. Induction of TNF‐α, IL‐1β and IL‐6 cytokine mRNA transcription in macrophages was determined by reverse transcriptase‐polymerase chain reaction. Infection of macrophages by virulent M. bovis resulted in enhanced bacterial metabolism, enhanced induction of macrophage cytokines and reduced viability of macrophages when compared to M. bovis BCG‐infected macrophages. These differences may reflect virulence mechanisms contributing to the early pathogenesis of bovine tuberculosis.
IgE, allergies and helminth parasites: A new perspective on an old conundrum
Authors: BELL RG 
Published: June 2007

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.
The effect of BCG, zymosan and Coxiella burnetti extract on Eimeria infections
Authors: SMITH NC , OVINGTON KS 
Published: June 2007

SummaryInfection of animals with species of Eimeria induces a hyper‐reactivity to endotoxin as manifest by a greatly increased capacity of infected animals to produce TNF in response to LPS in vivo compared with uninfected animals. This finding indicates priming for hyperactivation of macrophages by Eimeria infection and raises the possibility that non‐specific triggering of macrophages by agents such as Bacille Calmette‐Guerin (BCG), zymosan or Coxiella burnetti extract may be a simple means of control for coccidiosis. However, all of these agents enhanced oocyst excretion in mice, rats or chickens infected with Eimeria vermiformis. Eimeria nieschulzi or Eimeria tenella, respectively, without affecting the patent period.
Evolution of MHC class I genes in higher primates
Authors: LIENERT KRISTIN , PARHAM PETER 
Published: June 2007

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.
Heavy‐chain variable regions in carcharhine sharks: Development of a comprehensive model for the evolution of VH domains among the gnathanstomes
Authors: SHEN SHAN XIANG , BERNSTEIN RALPH M , SCHLUTER SAMUEL F , MARCHALONIS JOHN J 
Published: June 2007

SummaryWe determined the sequence of 18 DNA clones encoding VH regions of sandbar shark and bull shark. All of these sequences exhibit key structural coding features characteristic of known VH genes of higher vertebrates. These VH sequences disclosed considerable diversity, and can be divided into six families according to the criterion of 80% DNA sequence identity. The overlapping of some VH gene clones to two or more families is a particular feature found in carcharhine sharks, which suggests that VH diversification is a continuing process. The basic sequence patterns of heavy‐chain V regions found in all representative gnathanstomes and in VH of the shark heavy immunoglobulin igW provides evidence for selection of canonical residues in all VH structures, Elasmobranch VH sequences can be divided into two classes or clans, one comprising the ‘classical’ VH set and the other comprising VHs related to those of IgW (Vω). Phylogenetic analyses place the VH cluster as the root of all the classic VHs and indicates that the Vω set is most probably that of the primordial heavy chain.
NK‐like activity against allogeneic tumour cells demonstrated in the spleen of control and thymectomized Xenopus
Authors: HORTON TRUDY L , RITCHIE PAMELA , WATSON MARTIN D , HORTON JOHN D 
Published: June 2007

SummaryThis paper addresses the issue of natural killer (NK) cell evolution by searching for NK‐like activity in an amphibian representative, the immunologically well‐characterized clawed frog. Xenopus laevis. Using in vitro6 h 51 chromium release assays, we have shown that splenocyte effectors from early thymectomized (Tx) year‐old frogs, but not from control siblings, are able to spontaneously lyse allogeneic thymus tumour cell lines that lack MHC antigen expression. Such lytic capacity can be readily induced in control Xenopus and elevated in Tx frogs by a single injection of tumour cells, with maximal splenocyte cytotoxicity occurring 3 days postinjection, the amount of 51 Cr‐release correlating directly with effector: target ratios. Splenocytes, even those from tumour‐injected frogs, are unable to lyse allogeneic splenic lymphoblasts or erythrocyte targets, even when the latter are coated with IgY (the Xenopus IgG equivalent); moreover, we were unable to demonstrate any splenocyte‐induced lysis of the human NK cell target K562. Lymphokine‐activated killing (LAK) in Xenopus is suggested, since Tx splenocytes cultured in cytokine‐rich medium (from concanavalin A‐stimulated control splenocytes) display significantly elevated killing of allogeneic tumour targets. Flow cytometric analysis highlights the loss of T cell markers from the spleen of Tx frogs and reveals a variable staining pattern of both control and Tx splenocytes when treated with a mAb that binds to both fish non‐specific cytotoxic cells and human NK cells. Prospects for identifying the cellular basis of NK‐like activity in Xenopus are discussed in the light of these experiments.