bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of rotation and input energy flux on convective overshooting
Authors: Käpylä Petri J. , Korpi M. J. , Stix M. , Tuominen I.
Published: May 2007

We study convective overshooting by means of local 3D convection calculations. Using a mixing length model of the solar convection zone (CZ) as a guide, we determine the Coriolis number (Co), which is the inverse of the Rossby number, to be of the order of ten or larger at the base of the solar CZ. Therefore we perform convection calculations in the range Co = 0. . .10 and interpret the value of Co realised in the calculation to represent a depth in the solar CZ. In order to study the dependence on rotation, we compute the mixing length parameters αT and αu relating the temperature and velocity fluctuations, respectively, to the mean thermal stratification. We find that the mixing length parameters for the rapid rotation case, corresponding to the base of the solar CZ, are 3-5 times smaller than in the nonrotating case. Introducing such depth-dependent α into a solar structure model employing a non-local mixing length formalism results in overshooting which is approximately proportional to α at the base of the CZ. Although overshooting is reduced due to the reduced α, a discrepancy with helioseismology remains due to the steep transition to the radiative temperature gradient.

In comparison to the mixing length models the transition at the base of the CZ is much gentler in the 3D models. It was suggested recently (Rempel 2004) that this discrepancy is due to the significantly larger (up to seven orders of magnitude) input energy flux in the 3D models in comparison to the Sun and solar models, and that the 3D calculations should be able to approach the mixing length regime if the input energy flux is decreased by a moderate amount. We present results from local convection calculations which support this conjecture.
Round table discussion of session F: convection and rotation
Authors: Roxburgh Ian W.
Published: May 2007

The Session F round table. and audience, considered the following questions:

(i)

what determines the differential rotation in stellar convective zones?

(ii)

If there really is a rapid inward increase in angular velocity in giants will it have significant effects in the late stages of stellar evolution?

(iii)

How effective is penetration above a convective core?

(iv)

Why is the solar core nearly uniformly rotating?
The redistribution of the regions in radiative and convective equilibrium of the stars of the main sequence with rotation
Authors: Kuzmanovska O.
Published: May 2007

We study the redistribution of the mechanisms of the energy transport with rotation in the interiors of young stars of the Main sequence. In that purpose, we did numerical modelling of the structure of zero age stars of the Main sequence for 26 stellar masses in the interval 0.8–120 Solar masses (M⊙), with constant chemical composition X = 0.75, Y = 0.23, Z = 0.02 (N = 0.3 Z). Rotation of a solid body type with angular velocity varied from zero (spherically symmetrical models) till critical one (models at the border of dynamical stability) for each stellar mass is considered. For numerical integration of the differential equations we used Henyey's method for spherically symmetrical stars, modified by the technique of Kippenhahn and Thomas for rotating stars, with the algorithm used by J. Petrovic. Additional algorithms determine the mass and radius of convective core.

Analysis of the results shows that the radius rf of the convective core decreases with increase of the angular velocity and has the lowest value for critical rotation. The radius of convective core has the lowest value for 1.2 M⊙ for spherically symmetric models, and in the interval 1–1.3 M⊙ for rotating stars at the border of dynamical stability. Absolute values (rf are in a range from 0.03–0.08, and increase with increase of the stellar mass for m >1.2 M⊙, while the relative changes are in the interval 15–22%. The lowest value of the mass qf of the convective core coincides with the lowest values of the radius. The change (qf >0, and increases with increase of the stellar mass for m >1.4 M⊙, while the greatest relative change with rotation is 7%. We show the dependence of qf from the structural parameters in the centre and on the surface of the star.

We emphasize a “critical” mass of the star, or a characteristic interval of stellar masses (1.2–1.4 M⊙), in which a qualitative change in the local structure and the distribution of mechanisms of energy transport of both, spherically symmetric and rotating stars occurs. It is connected with the change of the heat regime of the star in hydrostatic equilibrium. Rotation additionally changes the structure and redistributes the regions in radiative and convective equilibrium.
Differential rotation and angular momentum
Authors: Botha G. J. J. , Evangelidis E. A.
Published: May 2007

Differential rotation not only occurs in astrophysical plasmas like accretion disks, it is also measured in laboratory plasmas as manifested in the toroidal rotation of tokamak plasmas. A re-examination of the Lagrangian of the system shows that the inclusion of the angular momentum's radial variation in the derivation of the equations of motion produces a force term that couples the angular velocity gradient with the angular momentum. This force term is a property of the angular velocity field, so that the results are valid wherever differential rotation is present.
Challenges of magnetism in the turbulent Sun
Authors: Brun Allan Sacha , Miesch Mark S. , Toomre Juri
Published: May 2007

Three-dimensional global modelling of turbulent convection coupled to rotation and magnetism within the Sun are revealing processes relevant to many stars. We study spherical shells of compressible convection spanning many density scale heights using the MHD version of the anelastic spherical harmonic (ASH) code on massively parallel supercomputers. The simulations reveal that strong magnetic fields can be realized in the bulk of the solar convection zone while still attaining differential rotation profiles that make good contact with helioseismic findings. We find that the Maxwell and Reynolds stresses present in such a turbulent layer play an important role in redistributing angular momentum, with the latter maintaining the differential rotation, aided by baroclinic forcing at the base of the convection zone which is consistent with a tachocline there. The dynamo processes generate strong non-axisymmetric and intermittent fields and weak mean (axisymmetric) fields, but do not possess a regular cyclic magnetism. The explicit inclusion of penetrative convection into the tachocline below is modifying such behavior, serving to build strong toroidal magnetic fields there that may yield more prominent mean fields that have the potential of erupting upward.
“Negative magnetic buoyancy” effects and reconstruction of toroidal field in the solar convection zone
Authors: Krivodubskij Valery N.
Published: May 2007

This investigation is devoted to study the turbulent convective transport of mean (large-scale) magnetic field in the solar convection zone (SCZ). For the SCZ model by Stix (1989) the reconstruction of the toroidal field was calculated as a result of the balance of mean-field magnetic buoyancy and two “negative magnetic buoyancy” effects: i) macroscopic turbulent diamagnetism and ii) the ∇ρ effect. It is shown that at high latitudes negative buoyancy effects block the magnetic fields, about 3000 – 4000 G, near the bottom of the SCZ. This may be the most plausible reason why a deep-seated field here could not become as apparent at the solar surface as sunspots. However, at the near equatorial domain in the deep layers the ∇ρ effect, with allowance for rotation, causes the upward magnetic transport, that facilitates penetration of strong fields to the surface where they emerge as sunspot patters in the “royal zone”.
Magnetic activity in the atmospheres of F-type binaries: V963 XSCyg, XZ CMi, V965 Cyg
Authors: Samec R. G. , Jones S. M. , Scott T. , Branning J. , Miller J. , Chamberlain H. , Faulkner D. R. , Hawkins N. C.
Published: May 2007

We have found photometric indications that Interacting Eclipsing Binaries of early to mid F spectral type (and possibly A) have strong magnetic activity which would arise from convective atmospheres. Light curve solutions and periodicity studies revealing spots, magnetic breaking and magnetic cycles are presented in XZ CMi, V965 Cyg and V963 Cyg.
Numerical simulations of sunspots
Authors: Botha G. J. J. , Rucklidge A. M. , Hurlburt N. E.
Published: May 2007

The origin, structure and evolution of sunspots are investigated using a numerical model. The compressible MHD equations are solved with physical parameter values that approximate the top layer of the solar convection zone. A three dimensional (3D) numerical code is used to solve the set of equations in cylindrical geometry, with the numerical domain in the form of a wedge. The linear evolution of the 3D solution is studied by perturbing an axisymmetric solution in the azimuthal direction. Steady and oscillating linear modes are obtained.
Super-equipartition fields in simulations of photospheric magnetoconvection
Authors: Bushby Paul J.
Published: May 2007

Observations of magnetic fields in the quiet Sun indicate that kilogauss-strength fields can be found in the intergranular lanes. Since the magnetic energy of these localised features greatly exceeds estimates of the kinetic energy of the surrounding granular convection, it is difficult to see how these features could be formed simply by convective flux concentration. Idealised, high-resolution simulations of three-dimensional compressible magnetoconvection are used to investigate the formation of these features numerically. Initially we take a fully developed non-magnetic convective state into which we insert a weak, uniform, vertical magnetic field. Magnetic flux is rapidly swept into the convective downflows, where it is concentrated into localised regions. As the field strength within these regions becomes dynamically significant, the high magnetic pressure leads to partial evacuation (via the convective downflows). Provided that the magnetic Reynolds number is large enough, the strength of the resulting magnetic fields significantly exceeds the (so called) “equipartition” value, with the dynamical effects of the surrounding convection playing an important role in confining these magnetic features to localised regions. These results can be related to the well-known convective collapse instability, although there are some important differences between the two models.
Autoimmunity and the highway to diabetes
Authors: Price Patricia
Published: May 2007

Insulin‐dependent diabetes mellitus (IDDM) is an immunopathological condition involving loss of β cell function, but views of how this arises are confusing and contradictory. For example, studies with non‐obese diabetic mice implicate abnormal cytokine production in disease pathogenesis, but give little insight into how this arises. Many genetic and environmental risk factors have been described, but no single factor predicts the development of disease. Moreover, the prevalence of auto‐antibodies suggests an autoimmune aetiology, but no antigen is recognized by all individuals. As an aid to understanding how IDDM develops, this review considers the risk factors as distinct starting points on a journey, and reviews current literature in search of the point where the roads from each origin merge into a highway to diabetes.
A brief history of the discovery of the immunoglobulins and the origin of the modern immunoglobulin nomenclature
Authors: Black C Allen
Published: May 2007

On the 30th anniversary of the discovery of IgE, the last immunoglobulin identified, the discovery and subsequent naming of the immunoglobulins is recounted. The first immunoglobulin‐like protein to be discovered was the Bence Jones protein or light chain in 1845. Over 100 years later, the final isotype, IgE, was discovered. During this century, there have been various names for what we now know as IgA, IgD, IgE, IgG and IgM. There was also confusion over what constituted a ‘new’ immunoglobulin and how u should be named. As a result the current nomenclature seems arbitrary; however, it reflects both a historical tradition of preserving the original name of the protein as well as a rational system designed in the early 1960s to codify the basic proteins of the humoral response.
Modulation of experimental allergic encephalomyelitis in mice by immunization with a peptide specific for the γδ T cell receptor
Authors: Olive Colleen
Published: May 2007

This study investigated the role of γδ T cells in experimental allergic encephalomyelitis (EAE), a chronic inflammatory disease of the central nervous system (CNS) that resembles multiple sclerosis. The strategy was to assess the effect on EAE of TCR peptide immunization directed against Vγ6 T cells, shown recently to predominate in the CNS of mice during the early stages of EAE. The data show that TCR peptide immunization specific for Vγ6 chains does not induce protection against EAE, since the incidence of EAE in TCR treated animals was similar to control mice, and therefore does not affect disease susceptibility per se, but rather alters the development of the disease, Specifically, there was a delay in the onset of EAE and a reduction in disease severity in TCR treated animals, although the effects were not highly significant. These findings suggest a role for γδ T cells in the development of EAE; however, further studies are necessary to confirm the specificity of TCR peptide immunization.
Human cytokines suppress apoptosis of leukaemic CD5+ B cells and preserve expression of bcl‐2
Authors: Tangye Stuart G , Raison Robert L
Published: May 2007

Leukaemic CD5+ B cells obtained from B cell chronic lymphocytic leukaemia (B‐CLL) patients rapidly undergo apoptosis during in vitro culture. This is associated with down‐regulation in expression of bcl‐2. Spontaneous apoptosis of these cells contrasts their enhanced longevity in vivo and suggests that apoptosis‐inhibitory factors may be responsible for the accumulation of leukaemic cells in B‐CLL. The effect of different cytokines on apoptosis and bcl‐2 expression was examined in six populations of leukaemic CD5+ B cells. Consistent with previous data, IL‐4 and IFN‐γ suppressed apoptosis in 6/6 and 5/6 cell populations, respectively. Interestingly, the ability to suppress apoptosis in leukaemic CD5+ B cells was also found to be a property of IL‐2, IL‐6, IL‐13 and TNF‐α. In the presence of these cytokines, 10‐40% more viable cells were detected, compared with unstimulated cultures. Enhancement of cell viability and suppression of apoptosis were associated with a delay in down‐regulation of bcl‐2. These results suggest a role for autocrine and paracrine growth factors in the pathogenesis of B‐CLL, and indicate that cytokines which prevent apoptosis in vitro may be targets for treating this malignancy.
Enhancement of macrophage‐mediated bactericidal activity by macrophage‐mannose receptor‐ligand interaction
Authors: Lefkowitz Dorls L , Lincoln John A , Lefkowitz Stanley S , Bollen Alex , Moguilevsky Nicole
Published: May 2007

Neutrophils represent one of the host's primary defenses against invading organisms. These cells often arrive at the site of infection prior to macrophages (MØ). Neutrophils release myeloperoxidase (MPO) into the micro‐environment during phagocytosis. Previous studies by the present investigators have shown that MØ bactericidal activity is enhanced by exposure to MPO. A recent report suggests that as much as 40% of this protein is enzymatically inactive once it is released into the micro‐environment. In the present study, exposure of MØ to an enzymatically inactive form of MPO (iMPO) or another mannosylated protein, mannoslyated bovine serum albumin (mBSA). can induce the same enhanced MØ‐mediated bacterial cell killing observed with the active form of MPO. Furthermore, this phenomenon is limited as galactosylated BSA (gBSA) did not induce enhancement of bacterial killing. The data suggest that interaction of either enzymatically active or inactive mannosylated proteins with the MØ mannose receptor (MMR), is sufficient to enhance MØ bactericidal activity and further underscores the binding of the MMR and resultant responses as a major host defense mechanism.
Pertussis toxin pretreatment alters the in vivo cell division behaviour and survival of B lymphocytes after intravenous transfer
Authors: Lyons A Bruce
Published: May 2007

Pertussis toxin (PT), produced by the causative agent of whooping cough. Bordetella pertussis, contributes to the immune dysfunction seen in infected patients. Treatment of laboratory animals with purified toxin reproduces many of the biological effects exhibited in the disease state, which include lymphocytosis, adjuvant effects for IgE secretion and delayed‐type hypersensitivity reactions. In previous studies, we have demonstrated that PT pretreatment of intravenously transferred lymphocytes not only results in them being held up in the blood, but also causes a profound alteration in their positioning within the spleen. Pertussis toxin pretreated lymphocytes fail to traverse the layer of marginal zone macrophages encircling the white pulp, resulting in their exclusion from the lymphoid area of the spleen. Using a novel flow cytometric assay of cell division, the studies presented here show that a significant proportion of B, but not T. lymphocytes underwent proliferation after intravenous transfer of donor splenic lymphocytes to syngeneic recipients. This proliferation was markedly reduced by PT pretreatment of lymphocytes before transfer. In contrast, the in vitro proliferative responses of B lymphocytes to anti‐IgM, LPS and antibody engagement of CD40 were unimpaired by exposure to the same levels of PT. Furthermore, the rate of in vivo decay of transferred B cells was accelerated by pretreatment with PT. Together, these data suggest PT impairs the receipt of signals which promote survival and proliferation of B cells, due to altered recirculation and positioning of lymphocytes.
Sequential activation of alveolar macrophages by IFN‐γ and LPS is required for enhanced growth inhibition of virulent Mycobacterium bovis but not M. bovis BCG
Authors: Aldwell FE , Wedlock DN , Buddle BM
Published: May 2007

Alveolar macrophages (AM) form the first line of defence against most respirators’ pathogens and, unlike tissue macrophages, are constantly exposed to a wide variety of antigenic stimuli. In this study we investigated the in vitro effects of IFN‐γ and LPS on growth of virulent Mycobacterium bovis and M. bovis bacille Calmette‐Guérin (BCG) in bovine AM. Bovine AM were purified from bronchial lavage fluid and cultured in serum‐free medium. Pretreatment of bovine AM with IFN‐γ resulted in growth inhibition of M. bovis BCG but only partially inhibited growth of virulent M. bovis. Enhanced inhibition of virulent M. bovis by bovine AM required sequential stimulation with IFN‐γ and LPS and was associated with increased induction of nitric oxide (NO) and IL‐12 mRNA. Growth inhibition of M. bovis was not affected by treatment of macrophages with the L‐arginine analogue. NG‐monomethyl‐L‐arginine although this treatment decreased NO production. These results suggest that a second activation signal in the form of TNF‐α or LPS may be required to induce bacteriostasis of virulent M. bovis by bovine AM in vivo. The ability of bovine AM to respond to activation stimuli in vitro suggests that these cells may play an important role in preventing establishment of intracellular bacterial infections in the lung.
A possible role of pre‐existing IgM/IgG antibodies in determining immune response type
Authors: Seledtsov Victor I , Seledtsova Galina V
Published: May 2007

On the basis of the data indicating the existence of two types of immuno‐protection, namely macrophage‐mediated and mast cell‐basophil‐mediated, it is argued that by reacting with potential pathogens, pre‐existing IgM and IgG antibodies (both natural and induced by environmental microflora) might promote involvement of macrophages in the presentation process, favouring the generation of pathogen‐specific T helper 1 (Th 1), hut not Th2, responses. Alternatively, the failure of these antibodies to effectively recognize pathogens might be associated with active involvement of pathogen‐specific B cells in presenting Ag and, as a consequence, with the predominant development of Th2. rather than Th 1, responses.
Sexual behaviour and increased anal cancer
Authors: Ablin Richard J , Stein‐Werblowsky Rachel
Published: May 2007

An increase in epidermoid anal cancer has been observed in the past 30 years (1959‐89). This increase in anal cancer has been noted to be more pronounced in women than men. The absence of a significant interactive effect of the HIV and human papillomaviruses and the incidence of anal cancer has been noted in some studies. These observations provide the rationale for consideration of other aetiologic agents that may contribute to the increase of anal cancer in men and women. Within the context of their ability to serve as cancer initiating and promoting factors, spermatozoa and seminal plasma are suggested as aetiologic agents and/or cofactors which are common to men and women practising anal intercourse in whom an increase in anal cancer has been observed. It is further suggested that sexual behaviour, that is. Anal intercourse, not sexual preference, is one of the primary factors in the development of anal cancer.
Plant immunomodulators for termination of unwanted pregnancy and for contraception and reproductive health
Authors: Talwar GP , Vanshi Poonam Raghu , Misra Rachna , Mukherjee Sutapa , Shah Sangeeta
Published: May 2007

Neem (Azadirachta indica) seed and leaf extracts have spermicidal, anti‐microbial, anti‐fungal and anti‐viral properties. They are also immunomodulators that induce primarily a TH, type response. These properties are being exploited to develop two different useful methods of fertility control. Neem extracts given orally at early post‐implantation stage terminate pregnancy in rodents and primates. Treatment has no residual permanent effect and fertility is regained in subsequent cycles. The mechanism by which the action occurs is not fully clear. A transient increase in CD4 and more significantly in CD8 cells is noticed in mesenteric lymph nodes and spleen. A rise in immunoreactive and bioactive TNF‐α and IFN‐γ in draining lymph nodes, serum and foetal‐placental tissue is observed.

A polyherbal cream and pessary have been developed containing three active ingredients of plant origin. These have synergistic spermicidal properties on human sperm as determined by the Sander Cramer test. Their use before mating has high contraceptive efficacy in rabbits and baboons. Another interesting property is their inhibitory action on a wide spectrum of micro‐organisms, including Candida albicans. C. tropicalis, Neisseria gonorrhoeae, the multidrug‐resistant Slaphylococcus aureus and urinary tract Escherichia coli. Herpes simplex‐2 and HIV‐1, Phase I clinical trials have been completed in India, Egypt and the Dominican Republic, and indicate the safety of the formulation, its acceptability and beneficial action invaginosis due to infections.
How did the primordial T cell receptor and MHC molecules function initially?
Authors: Kurosawa Yoshikazu , Hashimoto Keiichiro
Published: May 2007

Two genes, designated Trsc‐UAA and Trsc‐UBA, which encode highly polymorphic major histocompatibility complex (MHC) class I molecules in the shark Trtakis scyllia were isolated. The identification of these genes indicates that the classical MHC class I was already established at the level of elasmobranches during animal evolution. At the emergence of the MHC/T cell receptor recognition system, the number of genes for T cell receptors (TCR) must have been just one. In this brief review, the way in which a small number of TCR could have recognized MHC‐oligopeptide complexes initially, based on recent progress in the phylogenetic analysis of the immune systems in primitive vertebrates, is discussed.
Regulation of T cell function in mucosal tolerance
Authors: Hoyne Gerard F , Lamb Jonathan R
Published: May 2007

Administering antigens through mucosal surfaces leads to the induction of antigen‐specific T cell unresponsiveness. This property of the mucosal immune system is now beginning to be exploited in the design of immunotherapeutic strategies aimed at targeting disease‐inducing T cell populations. The induction of high dose mucosal tolerance leads to the induction of T cell anergy. Recent studies have suggested that the induction of anergy in vivo may not neccessarily be due to a lack of costimulation by APC. Instead, recognition of mucosal antigen leads to transient T cell activation which eventually gives rise to a population of regulatory T cells whose function is to modulate, rather than promote antigen‐specific immune responses. These regulatory T cells mediate linked suppression in vivo thus enabling T cell responses directed to a multideterminant protein to be effectively controlled. The manner in which T cell responses to mucosally delivered antigens are regulated are examined herein.
Specific transcription of the unrearranged TCR Vβ8.2 gene in lymphoid tissues occurs independently of V(D)J rearrangement
Authors: Jolly Christopher J , O'Neill Helen C
Published: May 2007

A truncated T cell receptor (TCR) Vβ8.2 polypeptide expressed on the surface of a precursor lymphoid cell line and on a subset of mesenteric lymph node cells has previously been shown to be encoded by transcripts from unrearranged Vβ8 genes. Germline Vβ8 transcription has now been demonstrated in multiple lymphoid and non‐lymphoid tissues in mice of varying ages and in cultured cell lines by reverse transcription polymerase chain reaction (RT‐PCR). Significant levels of Vβ8 germline transcription were found in thymus. spleen, liver and bone marrow and in all lymphoid cell lines studied. Germline Vβ8 transcription in the liver dropped as mice aged, and increased in the bone marrow. Germline Vβ8 transcription was also detectable in thymus, spleen, liver and bone marrow RAG‐l‐/‐ mice. This indicated that it is not dependent upon the presence of mature lymphoid cells, nor necessarily related to V(D)J rearrangement events. Semi‐quantitative polymerase chain reaction (PCR) and hybridization with oligonucleotides specific for Vβ8.1, 8.2 and 8.3 showed that the Vβ8.2 gene produced at least 90% of all the germline Vβ8 transcripts in all of the tissues examined. The significance of these results in lymphoid cell development and for models of the regulation of V(D)J rearrangement are discussed.
Dendritic cells as antigen‐presenting cells in vivo
Authors: Inaba Kayo
Published: May 2007

Antigen‐presenting cells are of central importance for the generation and regulation of T cell mediated immune responses. The specialized features of dendritic cells as antigen‐presenting cells in selecting rare clones of antigen‐specific T cells and activating them in vivo are described.
The roles of preB cell receptor in early B cell development and its signal transduction
Authors: Karasuyama H , Nakamura T , Nagata K , Kuramochi T , Kitamura F , Kuida K
Published: May 2007

The preB cell receptor is expressed for a short period after μ heavy chain is produced, that is, at the large preB cell stage in B cell development. The severe impairment of B cell differentiation observed in mice deficient for the preB cell receptor clearly demonstrated the importance of the preB cell receptor m B cell development. Analyses of bone marrow precursor B cells in normal and B cell‐deficient mutant mice indicated the preB cell receptor transduced signals to drive cell cycle and to induce allelic exclusion. The proliferation of the preB cell receptor‐expressing cells leads to the selective expansion of cells which have succeeded in the productive rearrangement of μ heavy chain gene. This process builds up a preB cell pool large enough to generate sufficient numbers of mature B cells. The preB cell receptor appears to induce allelic exclusion by shutting off the expression of recombinase activation gene (RAG). In order to analyse the signal transduction pathway downstream of the preB cell receptor, we have developed a new system in which cross‐linking of Igβ expressed on bone marrow proB cells mimics the signalling through the preB cell receptor to induce differentiation from proB to small preB cells.
Down‐regulation of an established immune response via chemical carcinogen or UVB‐altered skin
Authors: Chen Yi‐Peng , Woods Gregory M , Dandie Geoffrey W , Muller H Konrad
Published: May 2007

The ability to produce antigen‐specific down‐regulation of an established immune response was investigated in 2,4,6‐trinitrochlorobenzene (TNCB)‐immune mice by delivery of antigen through chemical carcinogen‐ or ultraviolet B (UVB)‐treated skin. When TNCB‐immune mice were treated on the dorsal trunk skin with 7,12‐dimethylbenz(a)anthracene (DMBA) followed by TNCB there was an antigen‐specific reduction in both contact sensitivity and antibody production. Further, immune mice that received spleen cells from naive syngeneic donors treated with DMBA followed by TNCB also exhibited a reduction in both contact sensitivity and antibody production. In contrast, mice treated with UVB irradiation followed by TNCB had a reduction in contact sensitivity but not antibody production. These results provide evidence that an ongoing immune response can be manipulated by immunization through a modified skin immune system. This may provide a beneficial approach for the treatment of autoimmune disease.
B cell responses to a peptide epitope. II: Multiple levels of selection during maturation of primary responses
Authors: Tuteja Renu , Agarwal Anshu , Vijayakrishnan Lalitha , Nayak Bishnu P , Gupta Satish K , Kumar Vijay , Rao Kanury VS
Published: May 2007

This report analyses murine primary humoral recognition of a linear domain (MEP 17–31) within a 100 amino acid polypeptide. MEP‐I. An analysis of the early primary IgM response revealed that MEP 17–31 presented at least two distinct domains for pre‐immune B cell recognition represented by MEP‐1 residues 19–23 and 26–28. However, subsequent maturation into an IgG response saw an exclusive selection for the anti‐MEP 19–23 component with loss of all alternate specificities. The IgM response to MEP 19–23 was oligoclonal and composed of diverse paratope phenotypes as evidenced by varied heavy chains of immunoglobulin V–D‐J combinations and CDR3 sequences. In contrast to the oligoclonality of IgM niAb. the mature IgG response to MEP 19–23 appeared to derive predominantly from a single progenitor. It therefore appears that maturation of primary humoral responses to polypeptide antigens involves two distinct levels of selection. While there is selection for a restricted subset of the initially induced antibody fine‐specificities, progression of the response also entails a reduction in clonal heterogeneity of B cells responding to the dominant epitope.
Hepatitis B virus binding to leucocyte plasma membranes utilizes a different region of the preS1 domain to the hepatocyte receptor binding site and does not require receptors for opsonins
Authors: Atkins Gerald J , Qiao Ming , Coombe Deirdre R , Gowans Eric J , Ashman Leonie K
Published: May 2007

A quantitative assay of hepatitis B virus (HBV) binding to hepatocyte plasma membranes was adapted to show that leucocyte plasma membranes bind serum‐derived HBV saturably, and that this binding is inhibited using synthetic peptides representative of the large envelope protein of HBV. Using a panel of ligand‐ blocking monoclonal antibodies (mAb) to opsonin receptors, it was shown that the three classes of FcyR and CR3 are not major receptors for HBV on leucocytes or hepatocytes. It was also shown that HBV docs not utilize the receptor for IgA, FcαR, for attachment to leucocytes, despite reported sequence homology between the large envelope protein of HBV and the Fc portion of human IgA. Evidence is presented that the receptor for HBV on leucocytes may differ from the hepatocyte receptor(s). based on synthetic peptide inhibition assays of HBV binding. Furthermore, it was observed that glycosaminoglycans influence the HBV‐liver and leucocyte interactions, providing evidence that HBV attachment may be a multi‐stage process.
Differential expression of protein tyrosine kinases and their phosphorylation in murine Th1 cells anergized with class II MHC‐peptide complexes
Authors: Yu Sheue Ching T , Nag Bishwajit
Published: May 2007

In resting T cell clones, antigen presentation with immobilized anti‐CD3 or anti‐T cell receptor (TCR) is known to result in a state of anergy as characterized by unresponsiveness to normal antigenic restimulation. Similarly, T cell unresponsiveness could be induced by immobilized (plate‐coated) complexes of purified class II MHC and antigenic peptide. It is not clearly defined whether the engagement of TCR by immobilized anti‐TCR or immobilized class II MHC‐peptide complexes generates similar or differential signals during the induction of T cell unresponsiveness. In order to address the initial signalling events induced by TCR occupancy with anti‐TCR and class II MHC‐peptide molecules, the expression of three critical protein tyrosine kinases (PTK) and their phosphorylation were investigated in the present study using a murine T cell clone (HS17) restricted for IAS and myelin basic protein (MBP (91–103)) peptide. The anergic T cells induced by immobilized IAS‐MBP (91–103) complex or anti‐TCR (H57) showed differential expression of lck (56 kDa) and Zap‐70 (70 kDa) proteins. In both systems, however, the induction of T ceil unresponsiveness was accompanied by increased level of fyn (59 kDa) expression. When analysed for the total tyrosine phosphorylation of PTK. anergic HS17 T cells induced by both molecules showed increased phosphorylation associated with only the fyn protein. These results suggest that the signal transduction events induced by immobilized class II MHC‐peptide complexes and anti‐TCR are distinct, although both can initiate signals that lead to increased fyn expression and phosphorylation. In addition, the present study supports the evidence for the important functional association of fyn protein with direct TCR engagement in T cell signalling.
Hypothesis: MHC class I, rather than just a flagpole for CD8+ T cells is also a protease in its own right
Authors: Müllbacher Arno
Published: May 2007

Ever since the discovery of MHC class I restriction and the onslaught of the dual receptor hypothesis. MHC class I has been perceived as a passive entity in TCR recognition and the appropriate antigen processing and presentation pathways. However, numerous experimental observations and theoretical considerations are difficult or unable to be explained by the accepted mechanism of class T antigen presentation. Proteases within and outside the endoplasmic reticulum (ER) are evoked to be solely responsible for the generation of the appropriate 8–10 amino acid‐long peptides associated with MHC class I. A MHC class I with site restricted ER protease activity would overcome most of the present difficulties in explaining MHC class I antigen presentation.
The spleen, IgG antibody subsets and immunity to Plasmodium berghei in rats
Authors: Smith NC , Favila‐Castillo L , Monroy‐Ostria A , Hirunpetcharat C , Good MF
Published: May 2007

The development of IgG subclass‐specific antibody responses to Plasmodium berghei in spleen‐chimeric rats were monitored to determine if there was any relationship between IgG subset profiles and resistance. Strongly immune eusplenic rats respond to challenge with P. berghei by producing high levels of parasite‐ specific IgG2a, IgG2b and IgG2c but only modest levels of IgG I. Splenectomy profoundly affects the antibody response to infection. Thus, in splenectomized immunized rats, which harbour chronic parasitaemia of 1%, the IgG2a, IgG2b and IgG2c responses peak 1 week later than in eusplenic immunized rats although the size of the peak is similar. More marked effects are apparent in the IgG1 response, the magnitude of which is far greater in splenectomized immunized rats than eusplenic immunized rats. Similar antibody profiles are seen in splenectomized immunized rats transplanted with naive spleen. In contrast, splenectomized naive rats receiving either transplant of spleen from an immune rat or transfer of immune spleen cells have high levels of IgG2a, IgG2b and lgG2c but modest levels of IgG1. However, only the former group of rats completely clears the parasite, the latter maintaining chronic 1% parasitaemia. Thus, although complete resistance to P. berghei is always associated with high levels of parasite‐specific IgG2a, IgG2b and IgG2c plus modest levels of IgG 1. this is not sufficient set of conditions to guarantee complete immunity. The IgG subset profile may be related to cytokine production; IFN‐y was detected in the sera of rats receiving spleens from rats immune to P. berghei (modest IgG1 responses) but not in rats receiving spleens from naive animals (pronounced IgG1 responses).
Different statistical models used in the calculation of the prevalence of insulin‐dependent diabetes mellitus according to the polymorphism of the HLA‐DQ region
Authors: Martín JL Santos , Pérez‐Bravo F , Carrasco E , Icaza G , Calvillán M , Albala C
Published: May 2007

The use of three statistical models yielded different estimates of the odds ratio relative to the association between the polymorphism in the HLA‐DQ region and insulin‐dependent diabetes mellitus (IDDM). The models used were: (1) the allele‐dosage model which assumes that the number of susceptibility alleles has a linear effect on the logarithm of the odds; (2) the reference cell coding method used with alleles of susceptibility as a risk factor; or (3) a model that uses a classification of α/β heterodimers as a susceptibility factor. We suggest that models which imply a log‐linear relationship between a susceptibility marker and disease such as the first model are not appropriate in the assessment of the HLA‐IDDM association. In contrast, although both latter models are valid, the third model is more compatible with current hypotheses of the pathological process of the disease. Once an estimation of the odds ratio is chosen, we use such an estimation to calculate an approximation of the prevalence of IDDM according to the polymorphism in HLA‐DQ region using the iterative procedure of Newton‐Raphson. These approaches are illustrated with data from a case‐control study previously conducted in the city of Santiago, Chile.
Regulation of the expression of Mycobacterium avium complex proteins differs according to the environment within host cells
Authors: Bermudez Luiz E , Petrofsky Mary
Published: May 2007

Mycobacterium avium is an intracellular organism that can infect a number of cell types such as macrophages and epithelial cells. Each one of these cells represents a different environment that requires specific adaptation from the bacterium. The effect of uptake of M. avium and M. smegmatis by both human monocyte‐derived macrophages in culture for 6 days, and HT‐29 intestinal mucosal cell line on the bacterial synthesis of proteins were comparatively examined. Incorporation of [35S]‐methionine by the bacterium was measured at 30 min, 2, 4, and 24 h after infection. Effect of the uptake by cells was compared with bacteria not exposed to cells and bacteria submitted to different stresses such as heat, hyperosmolarity and acid pH. Uptake of M. avium by macrophages triggered the synthesis of 93, 65, 55 and 33 kDa, among other proteins in the bacteria. Between 2 and 4 h of exposure to the intracellular millieu, a number of additional proteins have their synthesis up‐regulated such as 39, 31, 43, 42, 61 and 70 kDa. In contrast, uptake by epithelial cells is associated with the up‐regulation of 27, 65, 71 and 72 kDa proteins, among others. In this case, exposure to the intracellular environment was associated with expression of a number of proteins that do not vary with time. The results of this study suggest that regulation of the expression of proteins in M avium varies according to the mammalian cell bacteria they are exposed to, and is influenced by the stage of intracellular infection.
Gene gun‐based nucleic acid immunization alone or in combination with recombinant vaccinia vectors suppresses virus burden in rhesus macaques challenged with a heterologous SIV
Authors: Fuller Deborah Heydenburg , Simpson Laura , Cole Kelly Stefano , Clements Janice E , Panicali Dennis L , Montelaro Ronald C , Murphey‐Corb Michael , Haynes Joel R
Published: May 2007

Gene gun‐based DNA immunization alone or in combination with recombinant vaccinia vectors was evaluated for the ability to elicit protective immune responses in rhesus macaques challenged with a pathogenic, heterologous simian immunodeficiency virus (SIV). Six monkeys primed with seven consecutive doses of DNA encoding SIV mac239 gpl20 and gpl60 (DNA+DNA) were divided into two groups. Three of these animals received another DNA booster immunization and the remaining three received a booster immunization containing a homologous, live recombinant vaccinia virus expressing SIV mac251gpl60 (DNA+VAC). In addition, a group of 15 animals primed with recombinant vaccinia vectors were divided into two groups. One group of six monkeys received another immunization of vaccinia (VAC+VAC) and the other nine animals received a DNA (mac239) booster immunization (VAC+DNA). Geometric mean end‐point IgG titres in the DNA+VAC and VAC+DNA groups were substantially higher than the responses seen in the DNA+VAC and VAC+DNA groups, demonstrating a synergistic relationship between DNA‐based vaccines and recombinant vaccinia virus‐based vaccines. All vaccinates and five naive controls were challenged 19 weeks after the final booster immunization with 10 animal infectious doses of SIVdelta/b670. The vaccines did not prevent infection. However, all vaccine groups showed significant virus load reductions from seven to 56 days post challenge when compared to controls. Although the DNA+DNA group developed the lowest prechallenge antibody responses, the most significant reduction (200‐fold) in virus load was associated with this group. In addition, a significant delay in CD4+ T cell loss relative to controls was observed in the DNA+DNA group. These results demonstrate that a gene gun‐based DNA vaccine provided some attenuation of infection and CD4+ T cell loss after a heterologous challenge.
Multi‐epitope DNA vaccines
Authors: Suhrbier A
Published: May 2007

The evolution of vaccine strategies has seen a move from whole organisms to recombinant proteins, and further towards the ultimate in minimalist vaccinology, the epitope. The epitope‐based approach is clearly compelling as only a relatively tiny, but immunologically relevant, sequence is often capable of inducing protective immunity against a large and complex pathogen. The post‐reductionist era in epitope‐based vaccinology has seen a quest to re‐construct complexity and design vaccines containing many epitopes. The hope is that such multi‐epitope vaccines might induce immunity against multiple antigenic targets, multiple strain variants, and/or even multiple pathogens. The ability of DNA vaccination to co‐deliver a series of antibody and/or CD4 T cell epitopes remains largely unexplored. Successful viral vector and DNA‐based experimental vaccines coding for multiple contiguous CDS CTL epitopes have, however, recently been described. This simple CTL poly‐epitope (or polytope) strategy may find application in the design of vaccines against several diseases including EBV, HIV and cancer.
DNA vaccines for the treatment of autoimmune disease
Authors: Ramshaw Ian A , Fordham Susan A , Bernard Claude CA , Maguire Deborah , Cowden William B , Willenborg David O
Published: May 2007

DNA vaccines represent one of the most significant developments in vaccine technology in recent years. Although, in general, studies have primarily focused on the induction of protective immune responses against infectious pathogens, the technology may prove useful for other immune‐related diseases, including autoimmunity. Autoimmune disease results from a breakdown in tolerance to self antigens; however, the same fundamental immunological reactions that control immune responses to foreign antigens are also likely to operate during the course of autoimmune disease. These include the reciprocal regulation of Thl cell subsets. Thl cells appear to be involved in many organ‐specific autoimmune diseases while suppression of disease is associated with cells of the Th2 phenotype. It has been possible, therefore, to suppress many of the pathological consequences of autoimmunity by manipulating the Th1/Th2 cell balance. The induction of Th2 responses by DNA immunization might therefore be expected to have a profound effect on the course of autoimmune disease. Indeed, we have demonstrated that DNA immunization can protect animals against the autoimmune central nervous system inflammatory disease, experimental autoimmune encephalomyelitis (EAE). As many other autoantigens have now been identified, the application of this technology to other autoimmune diseases warrants investigation.
Postnatal Changes in mucosal immune response: A physiological perspective of breast feeding and weaning
Authors: Cummins Adrian G , Thompson Fiona M
Published: May 2007

There are profound changes of immune activity during infancy from suppression during breast feeding, activation with weaning, and later intrinsic down‐regulation after weaning. Breast feeding, as well as protecting against infections, seems to have a fundamental role in modifying the immune system against certain disease states. Transforming growth factor (TGF)β in breast milk may mediate this immunosuppressive effect. Although the infant immune system is not in an adult state, the notion that the infant immune system is immature is difficult to reconcile with evidence that most infants respond appropriately to immunization and to infections. The systemic immune system of neonates may be subject to Th2 immune deviation, while the mucosal immune system, particularly of the gastrointestinal tract and probably the respiratory tract, is upregulated with physiological inflammation during infancy. Weaning is associated with a peak of intestinal immune activation which includes mucosal mast cells and T cells. The physiological effects of this activation are promotion of epithelial growth of the small intestine and initial activation of mechanisms leading to subsequent down‐regulation of the physiological heightened immune activity. This coincides with the development of mucosal (oral) tolerance to food and bacterial antigens.
The protective efficacy of a liposomal encapsulated 30 kDa secretory protein of Mycobacterium tuberculosis H37Ra tuberculosis in mice
Authors: Sinha RK , Khuller GK
Published: May 2007

The immunoprotective efficacy of the 30 kDa secretory protein isolated from mid‐log phase culture filtrate of Mycobacterium tuberculosis H37Ra was investigated using Liposomes as adjuvant. Immunization of animals with the 30 kDa protein entrapped in liposomes prepared by a freeze‐thaw method and adsorbed on alum induced both cellular (monitored by T cell proliferation assay and cytokine, secretion, viz. IL‐2. IFN‐7) and humoral (evaluated by ELISA) responses which were comparable to those induced in the 30 kDa IFA‐immunized group. The protection induced by liposome‐encapsulated 30 kDa secretory protein was slightly lower than that induced in 30 kDa IFA‐immunized animals on the basis of higher survival rates and decreased viable counts of M tuberculosis H37Rv in various organs (spleen, lung and liver) after 30 days of infection compared to the controls. The results strongly indicate that liposomes are an ideal vaccine delivery system which can effectively replace IFA for the delivery of the immunoprotective 30 kDa secretory protein of M. Tuberculosis H37Ra.