bluuebunny/crossref_metadata_2025 huggingface dataset:
The major histocompatibility complex and peptide vaccines in domestic animals
Authors: OUTTERIDGE P. M.
Published: July 2007

Three hypotheses are suggested to explain the phenomenon of low responsiveness in domestic animals after injection of peptide vaccines. The first hypothesis proposes involvement of MHC haplotype and the special case in livestock breeding, where inheritance of the sire's haplotype can be closely examined by injection of antigen into a large number of paternal half‐sib progeny. The second hypothesis examines the effect of repeated antigen injections in overcoming age and MHC haplotype effects and distinguishing these effects from those caused by deficiencies in the T cell repertoire. The third hypothesis concerns non‐MHC effects that influence the expression of MHC haplotype effects and enable the host to mount an effective immune response. It is suggested that the antigen recognition signal from T cell receptor/MHC interaction is amplified to a varying extent in animal populations. Deficiency in this amplification through myeloid cell or cytokine responses may be yet another factor limiting immune responsiveness.
Immunity and inflammation: The cosmic view
Authors: QUINTÁNS JOSÉ
Published: July 2007

This paper presents an overview of the evolution of defence reactions in multicellular animal life. The co‐evolution of hosts and pathogens provides the context to describe the major features of defence reactions and the countermeasures they evoke in their targets. Three major types of solutions to the riddle of self‐non‐self discrimination are discussed briefly: non‐clonal recognition mediated by lectins, the preferential accumulation of C3 in microbial surfaces and vertebrate clonal immunity. Vertebrate immunity is described as a specialized type of inflammation against infectious agents that evolved in response to countermeasures successfully used by intracellular pathogens against non‐specific defences.
Differential modulation of human multinegative (CD3− 4 − 8 −) thymocyte proliferation by monoclonal antibodies to CD45RA or to CD45
Authors: DEANS JULIE P. , LEDBETTER JEEEREY A. , PILARSKI LINDA M.
Published: July 2007

Human multinegative (CD3 −4 −8 − 19−; MN) thymocytes proliferate optimally in response to anti‐CD2 plus anti‐CD28 mAb plus PMA or IL‐7. The role of CD45 was assessed by the addition of mAb to a CD45 common determinant, or to CD45RA. MN thymocytes are unresponsive to anti‐CD2 mAb. Co‐stimulation with anti‐CD45RA generated 1.6–5.7‐fold enhancement of a proliferative response, with maximal enhancement by cross‐linkage of CD45RA molecules. The response to anti‐CD2/28 mAb was reproducibly enhanced only by immobilized anti‐CD45RA. Cross‐linking of CD45RA and CD28 through the use of heteroconjugates of mAb did not enhance the co‐stimulation by CD45RA. The most marked enhancement by anti‐CD45RA occurred in suboptimal activation conditions. In contrast, the response to anti‐CD2 or anti‐CD2/28 was inhibited by mAb to CD45 common determinants (anti‐CD45) in the presence or absence of PMA or IL‐7, with the most profound inhibition (6–8‐fold) detected in optimal proliferative conditions. Cross‐linking of CD45 and CD28 through heteroconjugates of mAb was required as soluble anti‐CD45 or immobilized anti‐CD45 were unable to mediate inhibition. This inhibitory effect of (anti‐CD45 × 28) was specific to MN thymocytes as no inhibition was detectable when peripheral blood T cells were treated with anti‐CD2/28 and the same heteroconjugate. The differential effects of anti‐CD45 and anti‐CD45RA may reflect either CD45 heterogeneity on MN thymocytes, or the physical modulation of a single CD45 molecules by interactions at different epitopes, and the avidity of the relevant CD45 mAb for thymocyte CD45 isoforms may play a role. We conclude that the molecular associations between signal transduction molecules on progenitor thymocytes differ significantly from those assembled on peripheral blood T cells.
Differences in epitopes recognized by T cells during oral tolerance and priming
Authors: HOYNE G. F. , CALLOW M. G. , KUO M‐C. , THOMAS W. R.
Published: July 2007

Feeding protein antigens to mice normally leads to the development of oral tolerance but under some circumstances, feeding can lead to immunity, for example, following pretreatment of mice with cyclophosphamide (CY). In both cases, however, it is possible to detect sensitized T cells in the spleen and mesenteric lymph nodes (MLN) by in vitro lymphokine release for granulocyte‐macrophage‐CSF (GM‐CSF) and IFN‐γ. This study examines the recognition of the immunodominant T cell epitope on ovalbumin (OVA) following intragastric priming and tolerance. T cells from CY/OVA treated mice and cells from mice injected subcutaneously with OVA in CFA responded well to both OVA and the H2d restricted peptide epitope pOVA323–339 releasing GM‐CSF. On the other hand MLN or spleen T cells from tolerized mice which responded to the protein in vitro did not recognize the immunodominant determinant. The cells responding from tolerized mice were restricted by the class II MHC so these results show there can be differential recognition of T cell epitopes between oral priming and tolerance.
Was exposure to directly antiviral cytokines during primary infection an important selective pressure in the evolution of unique immune evasion strategies by viruses?
Authors: LIDBURY BRETT A.
Published: July 2007

Different virus families are characterized by various immune evasion strategies. These viruses have co‐evolved with an increasingly sophisticated mammalian immune system which has continually placed pressure on their continued survival. This paper proposes that exposure to directly antiviral cytokines, namely TNF and members of the IFN family, during inflammatory and early immune responses, exerted particularly strong selective pressures on viruses, and has had a critical influence on the development of viral immune evasion strategies and pathogenesis. In the context of antiviral cytokine activity, this report concentrates on two DNA virus families with contrasting pathogenic and immune evasion strategies, namely poxviruses and HSV.
Effects of the anti‐inflammatory compounds castanospermine, mannose‐6‐phosphate and fucoidan on allograft rejection and elicited peritoneal exudates
Authors: BARTLETT MARK R. E. , WARREN HILARY S. , COWDEN WILLIAM B. , PARISH CHRISTOPHER R.
Published: July 2007

The glycoprotein processing inhibitor castanospermine (CS) and the monosaccharide mannose‐6‐phosphate (M6P), as well as some sulfated polysaccharides (SPS), have been shown to inhibit inflammation in rat models of experimental autoimmune encephalomyelitis and adjuvant‐induced arthritis. Here, the anti‐inflammatory effects of these agents have been further explored in murine models of allograft rejection and elicitation of peritoneal exudates. CS, M6P and the SPS, fucoidan, partially inhibited rejection of permanently accepted thyroid allografts induced by the i.p. injection of donor strain (H‐2d) spleen cells with a reduction in leucocyte infiltration of 25–36%. However none of these agents reduced the more extensive leucocyte infiltration induced by the i.p. injection of P815 (H‐2d) unless recipient mice were pretreated with the immunosuppressant. Cyclosporin A (CsA). Elicitation of peritoneal exudates by thioglycollate was inhibited by CS. M6P and fucoidan with sustained leucopenia being induced by CS. In contrast, CS and fucoidan, but not M6P, inhibited antigen‐elicited peritoneal exudates. These results suggest that CS, M6P and the SPS fucoidan exhibit subtle differences in their anti‐inflammatory activity but probably inhibit inflammation at the level of leucocyte extravasation.
Changes in epidermal Langerhans cells, γδ T cells and CD4 T cells after intradermal infection with recombinant vaccinia virus expressing cytokine genes
Authors: HERNANDO RICHARD A. , RUBY JANET C. , HALLIDAY GARY M.
Published: July 2007

Langerhans cells (LC) play a critical role in cutaneous immunity, and whereas Thy‐1− dendritic epidermal cells (Thy‐1+ dEC) are also present in murine epidermis, their role remains unknown. Antigens and cytokines influence the number of LC found in the epidermis. However, there has been no investigation into the effects of particular cytokines during resolution of a viral infection. In order to study this we infected mice subcutaneously with vaccinia virus (VV) constructs containing the genes encoding TNF‐α, IL‐6 or IFN‐γ and the density of LC, THY‐1+ dEC and CD4+ cells was determined. In this system the cytokines were produced locally at the site of viral replication. Cell densities were examined at day 1, while the response was being initiated, and at day 5 as the infection was being resolved. Infection with VV, like exposure to other antigens, decreased the density of epidermal LC at day 1, and they remained depressed at day 5. Production of TNF‐α during VV growth did not influence this response by LC, whereas IFN‐γ and IL‐6 both increased the number of epidermal Ia+ LC at day 1 but then caused a reduction at day 5. Thy‐1+ dEC were not affected by VV infection at any time‐point examined, nor did any cytokine influence the density of these cells at day 1. However, by day 5 IFN‐γ and IL‐6, but not TNE‐α, decreased the number of Thy‐1+ dEC. These changes in cell densities are consistent with LC but not Thy‐1+ dEC playing a role in initiation of immunity against VV and a complex interplay between cytokines and these cells during the response to VV. CD4+ T cells were also attracted into the epidermis by IEN‐γ and IL‐6 but not by TNE‐α
Targeting of pancreatic islets of severe combined immunodeficient mice by passive transfer of allogeneic spleen cells from non‐obese diabetic mice
Authors: REDDY S. , LIU W. , ELLIOTT R. B.
Published: July 2007

The precise role of immune cells in beta cell killing and their manner of invasion of pancreatic islets in insulin‐dependent diabetes meilitus (IDDM) are unclear. We have attempted to target pancreatic islets of severe‐combined immunodeficient (SCID) mice with spleen cells from diabetic and non‐diabetic female non‐obese diabetic (NOD) mice given i.p. or i.v. Pancreatic, liver and kidney sections of SCID mice were assessed histologically for the presence of donor cells. The presence of raised levels of serum Ig was also used as an index of engraftment of donor cells in the periphery of SCID mice. All six SCID mice which received i.v. spleen cells from normal Swiss mice died within 2 weeks from graft versus host disease (GVHD) whereas five out of nine mice survived for 30 days after i.p. injection. No deaths were recorded after i.v. or i.p. injection of spleen cells from NOD mice. Pancreatic islets of four out of six SCID recipients of diabetic and three out of five recipients of non‐diabetic spleen cells following i.p. injection showed lymphocytic infiltrates in the peri‐islet and perivascular regions. All SCID mice which received i.v. spleen cells from diabetic (six SCID recipients) and non‐diabetic NOD mice (seven SCID recipients) showed peri‐islet and perivascular infiltrates in their pancreas. Immunohistochemical analysis showed that the islet engrafted cells were of CD4 and CD8 phenotype. Donor cells were also observed in the exocrine pancreas of some recipients. A majority of mice showed various degrees of lymphocytic aggregates in the perivascular regions of the liver but not in the kidney. Two of the five mice which received i.p. cells from Swiss mice also showed some perivascular and peri‐islet lymphocytes in the pancreas. Significant but variable levels of mouse Ig were detected in all SCID sera which received spleen cells. These results demonstrate that spleen cells when passively transferred from NOD mice engraft islets of SCID recipients and reconstitute the periphery. However, additional studies are required to improve the specificity of homing of diabetogenic lymphocytes into the islets of these immunodeficient mice.
The expression of mycobacterial heat shock protein (HSP64) on Meth A tumour cells
Authors: SASAKI JIN‐ICHI , DEJEHANSART MICHEL , DE BRUYN JACQUELINE
Published: July 2007

Immunological cross‐reactivity between Mycobacterium bovis BCG stress protein (heat shock protein: HSP64) and Meth A tumour cells was analysed by using anti‐BCG HSP64 mAb whose recognition epitopes were characterized against BCG HSP64 peptides. By indirect immunofluorescence analysis (UFA), it was found that one of seven anti‐BCG HSP64 mAb, XVIIIGI, bound to the cell surface of Meth A in BALB/c mice. This result was further confirmed by western blot analysis, demonstrating the presence of a 64 kDa protein which reacted with mAb XVIIIGl that recognizes the 110–123 amino acid peptide of the BCG HSP64. Comparison of the amino acid sequence between the mouse HSP65 and BCG HSP64 recognized by mAb XVIIIGl revealed 50% amino acid sequence homology. It was concluded from these results that Meth A tumour cells continuously express the stress protein HSP64 as a kind of tumour‐associated antigen on the surface of tumour cells.
Thymus‐leukaemia antigens: The haemochromatosis gene product?
Authors: DORAK M. TEVFIK , BURNETT ALAN K. , WORWOOD MARK
Published: July 2007

The gene for hereditary haemochromatosis (HFE) lies telomeric to HLA‐A and is believed to be expressed in the intestinal mucosa. Its product has not been characterized, but iron overload and its pathological consequences occur only in homozygotes for this putative gene. The genes encoding the putative human counterparts of the mouse thymus‐leukaemia (TL) antigens map to the area where the HFE gene lies. Here, we postulate that a human TL gene may encode a protein acting as or interacting with the transferrin (Tf) receptor in the intestinal mucosa. This hypothesis is based on the following observations: (i) hereditary haemochromatosis (HH) is due to excessive absorption of iron through the intestinal mucosa. HH has a strong association with HLA‐A3, but HLA‐A3 has no direct role in the pathogenesis and reflects linkage disequilibrium with a telomeric gene, (ii) An HLA‐A3 homozygous genotype is associated with the highest relative risks for both early‐onset leukaemia and HH. In analogy to the susceptibility locus in mice, this genotype may reflect a TL gene association in leukaemia and raise the possibility of a TL gene involvement in HH. (iii) A TL antigen‐like human molecule encoded in the region telomeric to HLA‐A, TCA, is expressed in leukaemia and recognized by a Tf receptor‐specific monoclonal antibody. The Tf receptor is believed to have a role in the control of intestinal iron absorption, (iv) In mice, particular TL antigens are exclusively expressed in the intestinal mucosa. Therefore, an HLA‐A3‐linked TL‐like molecule, expressed in the intestinal mucosa and sharing a structural similarity with the Tf receptor, may be the yet unknown product of HEE.
Do lymphocytes require calibration?
Authors: Stc. SINCLAIR NICHOLAS R. , ANDERSON COLIN C.
Published: July 2007

Complexity in the activation/regulatory apparatus and the variable nature of the antigen‐binding site dictate that B and T cells establish and select, during their development, appropriate activation and control mechanisms beyond simple antigen‐binding specificity. These mechanisms are established partly by fixed interactions dictated by genetically defined structures, but they are also attained by calibration during ontogeny. This calibration depends on the ordered expression of early components (each of which is invariant), on their interaction with specific ligands, and on the receipt of invariant signals for calibration. Lymphocytes calibrate themselves by expressing various cell surface components, such as restricted heavy chain D‐regions and pseudo‐light chains. These are expressed in association with elements that will make up the antigen‐receptor complex of mature lymphocytes. Calibration by invariant signals results in the establishment, selection and active maintenance of cellular activities which serve to control lymphocyte function. Since these cellular activities are one of a number of possible conditions, they are referred to as variant controls. Effectively calibrated basic cellular functions, specialized responses and cellular interactions allow lymphocytes to attain self‐nonself discrimination. If calibration fails, lymphocytes will develop abnormalities, such as immunodeficiency and autoimmunity.
Novel structural features of autoantibodies in murine lupus: A possible superantigen binding site?
Authors: ZACK D. JESKE , WONG A. L. , WEISBART R. H.
Published: July 2007

The stimulus for the production of anti‐DNA autoantibodies in lupus remains unknown. Since double‐stranded DNA (dsDNA) is a weak immunogen, other stimuli such as B cell superantigens or anti‐idiotypic antibodies may provide an alternative mechanism for their production. The presence of regulatory determinants on autoantibodies might be revealed through their structural characterization, but they have eluded detection, perhaps because they may be three‐dimensional and require closer analysis. In this report we cloned and sequenced the heavy chain variable region (VH) of a monoclonal anti‐dsDNA antibody, mAb 3E10, derived from MRL/lpr mice with lupus nephritis previously shown to express an idiotype associated with nephritis in murine and human lupus. We now show that mAb 3E10 VH contains novel structural features unrelated to DNA binding which are shared only by a subset of autoantibodies expressed in murine lupus. These lupus autoantibodies can be distinguished from antibodies of non‐autoimmune strains by the presence of a specific sequence at the junction of the diversity and joining genes combined with the use of variable region genes with conserved sequences in framework 1 (FRl) and FR3. The location of the novel sequences indicates the possibility of a three‐dimensional solvent‐exposed determinant located distant from the classical antigen binding site that could regulate their production, possibly through binding B cell superantigens or other infectious agents.
Influence of compounds affecting synthesis, modification and transport of proteins on the expression and release of interleukin‐2 receptor
Authors: KARLSSON HÅKAN , NÄSSBERGER LENNART
Published: July 2007

One of the most central events during lymphocyte activation is the synthesis and release of IL‐2. IL‐2 induces the synthesis and expression of the IL‐2 receptor α‐chain (IL‐2R) on the lymphocyte as well as the release of a truncated form of IL‐2R (sIL‐2R). The two proteins are identical except for the absence of the transmembrane and intracellular part on sIL‐2R. We have in an in vitro model investigated the influence of certain compounds, affecting different parts of the proliferative response, on the release and expression of IL‐2R. We found the generation of the two molecules to have different sensitivity to blocking of protein synthesis, glycosylation, microtubular assembly and proteolytic activity. However, blocking of intracellular transport from Golgi to the endoplasmic reticulum, disassembly of actin filaments and disturbances in the intracellular sodium/calcium balance had identical effects on expression and release of the respective IL‐2R. These findings indicate a more complex and specific mechanism behind the generation of sIL‐2R than simply by shedding through the action of proteases on the membrane‐bound IL‐2R.
Fine specificity analysis indicates that the primary and secondary fluorescein‐specific cytotoxic T cell receptor repertoires are indistinguishable
Authors: HUGHES E. A. , KINNEL G. , WICKERHAM C. , ATKESON B. , OWEN J. A.
Published: July 2007

Previous data from this laboratory have shown that fluorescein‐specific cytotoxic T cells derived from naive mice are capable of distinguishing between different isomeric forms of the fluorescein hapten, as well as between the iodoacetamido‐, isothiocyanate‐ and dichlorotriazinyl amino‐fluorescein derivatives. In this report, we show that T cells derived from previously immunized animals, while demonstrating a stronger and more cross‐reactive response overall, display identical fine specificity patterns to those of primary T cells for a panel of fluorescein homologues. We interpret this finding to indicate that the antigen receptor repertoires utilized by primary and secondary cytotoxic T cells are indistinguishable and that the enhanced response of memory as compared with naive CTL results from factors such as a higher density of cell surface receptors or receptor‐associated molecules and/or a higher frequency of antigen‐responsive T cells.
T cell response to grass pollen allergens: Correlation with skin test reactivity and serum IgE levels
Authors: BLAHER B. , McCLUSKEY J. , PUY R. , CZARNY D. , ROLLAND J. M.
Published: July 2007

T cell proliferative responses to rye and Bermuda grass pollen allergens have been studied in a series of 51 atopic and 18 non‐atopic subjects. Mean T cell responses were higher in the atopic group than in the non‐atopic group (P < 0.001). and there was a strong correlation between the magnitude of reaction in the T cell assay and in the skin test (rye P<0.001, Bermuda P < 0.05). A similar association was shown between T cell reactivity and serum levels of allergen‐specific IgE (rye P < 0.05. Bermuda P < 0.05), but no relationship was found between serum allergen‐specifie IgG levels and any other parameter studied, T cell reactivity was not found in three cord blood samples tested. Discordance between positivity for T cell responses and skin test reactions in some cases might reflect reactivity by T cell subsets that promote IgG antibody or cell‐mediated responses without IgE antibody production. A precise knowledge of T cell recognition of grass pollen allergens will provide exciting new prospects for more effective and safer immunotherapy strategies for allergic diseases including asthma.
Leukaemogenic progression: The importance of differentiation and associated genetic events
Authors: HO ELLEN S‐P , O'NEILL HELEN C
Published: July 2007

A feature common to many blood cell cancers is the uncoupling of normal proliferative and differentiative events, both of which are intimately linked in the cell's developmental programme. In some cancers, further differentiative events have been associated with oncogenic progression and, in other cancers, terminal differentiation of cells has been shown to result in reversal of malignancy and death of the cancer cell. Clearly the development of cancer is not the result of a single oncogenic event, but rather a myriad of events which appear to proceed in concert in a step‐wise fashion and which are likely to be influenced by the cellular environment.

Here we review some of the major genetic changes which occur in leukaemogenesis and discuss the possible role of differentiative events in the development of leukaemia.
Cell surface determinants on typhoid‐specific B cells isolated from peripheral blood after oral Ty2l a typhoid vaccination in humans
Authors: PENTTILA IA , GIBSON CE , LEONG AS‐Y , ZOLA H , LABROOY JT
Published: July 2007

Antigen specific B cells (ASC) that circulate after oral immunization with the typhoid vaccine Ty2 1a display cell surface determinants which are potentially involved in B cell differentiation and homing to mucosal sites. These ASC were isolated from peripheral blood after oral Ty21a, and dual labelled for binding of typhoid antigen and expression of various cell surface determinants: a4 integrin (CD49d), CD45RO, CD45RA, L‐selectin, CD44 and CDl la. Of particular interest was the finding of CD45RO expression on ASC. A comparison of cell surface determinants on typhoid‐specific cells was also made following binding to high endotheliai venules on peripheral and mesenteric lymph nodes, and venules in the lamina propria of the small intestine. Generally more typhoid ASC bound to mesenteric compared with peripheral lymph node. More ASC expressing CD45RO and a4 integrin (CD49d) were bound to mesenteric lymph node and small intestine than to peripheral lymph node. When expressed as a fraction of total ASC, the difference was statistically significant only for CD45RO binding to small intestine versus peripheral lymph node. No differences in expression of other homing markers on bound ASC were seen.
Purified rat peritoneal mast cells: Characteristics of the removal and binding of IgE
Authors: VALLY H , SAVIGNI DL , TURNER KJ
Published: July 2007

Mast cells were purified by discontinuous density gradient centrifugation to greater than 90% and subsequently exposed to lactic acid in order to dissociate endogenous IgE. Unfortunately no removal of this IgE was achieved, despite previous reports of lactic acid exposure dissociating IgE from human basophils. Only a minimal level of endogenous IgE was found on the surface of mast cells, however, which allowed investigations of IgE binding to proceed without the initial removal of this endogenous IgE. Conditions for binding of normal rat IgE and myeloma IgE were established while efforts to bind human IgE to purified rat mast cells were unsuccessful. Our results suggest that while purified rat mast cells have the potential to play an important role in the study of the IgE requirement of various stimuli including histamine‐releasing factor, this role is limited at present.
Effect of cisplatin administration on the proliferation and differentiation of bone marrow cells of tumour‐bearing mice
Authors: KUMAR ASHOK , SINGH SUKH MAHENDRA
Published: July 2007

In the present study the effect of tumour growth with respect to two tumour systems (Dalton's lymphoma [DL] and P815) on the in vitro, colony‐forming ability (CFA) and proliferation of the bone marrow cells (BMC) of C3H/He mice was investigated. The P815‐bearing mice showed an enhanced bone marrow colony forming ability in vitro, in response to L929 conditioned medium (L929 CM) used as a source of CSF. On the other hand, DL‐bearing mice did not have any significant alteration in this process compared to normal mice. In vivo, administration of cisplatin resulted in a significant rise in the CFA of normal as well as DL‐ or P815‐bearing mice. The tumour‐conditioned medium (TCM) and ascitic fluid (AF) of P815 but not of DL, was found to support the in vitro colony formation of BMC obtained from cisplatin‐treated or untreated mice. The number of CFU‐granulocyte‐macrophage was predominantly high in the cultures of BMC incubated with TCM or AF of P815. The TCM and AF of P815 also enhanced the in vitro proliferation of BMC obtained from cisplatin‐treated or untreated mice. In vivo, administration of cisplatin in normal mice resulted in enhanced numbers of peritoneal exudate macrophages (PEM) and PBL. Similarly, the number of PEM and PBL was augmented in both the P815‐ and DL‐bearing mice. However, cisplatin administration in the tumour‐bearing mice decreased the count of PEM, while the number of leucocytes remain unaffected. This study indicates that the cancer chemotherapeutic drug cisplatin can influence the differentiation of the bone marrow progenitor cells in response to tumour growth in situ.
IL‐8 enhances antibody‐dependent cellular cytotoxicity in human neutrophils
Authors: REALI EVA , SPISANI SUSANNA , GAVIOLI RICCARDO , LANZA FRANCESCO , MORETTI SABRINA , TRANIELLO SERENA
Published: July 2007

Human neutrophils are able to kill in vitro colorectal carcinoma cell line SW11‐16 coated with mAb 17‐1A, but they are not cytotoxic towards a non‐immunized tumour target. Neutrophil exposure to the inflammatory cytokine, IL‐8, produces a significant increase in antibody‐dependent cellular cytotoxicity, which is related to IL‐8 concentration. Oxyradical production is one of the lytic mechanisms used by phagocytes, and IL‐8 is shown to activate this function, which does not occur if neutrophils are pretreated with the protein kinase C inhibitor, staurosporine, but is increased by R59022, a dyacylglycerol kinase inhibitor. The IL‐8 effect is mediated by protein kinase C, which is potentiated by the calcium flux induced by the interaction between antibody coating tumour target and FcγRIII on effector cells, as previously demonstrated. Data suggest a possible new role for IL‐8 in tumour surveillance.
Expression and immune recognition of stress proteins in sarcoidosis and other chronic interstitial lung diseases
Authors: STATON J. M. , DENCH J. E. , CURRIE B. , FITZPATRICK D. R. , HIMBECK R. P. , ALLEN R. , BRUCE J. , ROBINSON B. W. S. , BIELEFELDT‐OHMANN H.
Published: July 2007

Stress proteins (SP) are major immunogens in a number of microbial infections and have been implicated in some autoimmune diseases. The aetiology of sarcoidosis, a non‐caseating granulomatous disease, remains unknown, but mycobacteria as well as autoimmunity have been considered. In the present study, patients diagnosed with sarcoidosis and other interstitial lung diseases (ILD), as well as healthy volunteers were studied to determine; (i) the level of expression of SP in alveolar macrophages and blood monocytes; (ii) the serum levels of antibodies specific for mycobacterial SP65 and SP70; and (iii) the reactivity of peripheral blood and alveolar lymphocytes to mycobacterial SP65. Our results suggest that SP are expressed constitutively at high levels in alveolar macrophages, retrieved by bronchoalveolar lavage, from all individuals regardless of health status. In contrast, freshly isolated blood monocytes express low levels of SP, which are, however, readily upregulated following exposure to IFN‐γ and TNF‐α. Lymphocyte reactivity and presence of antibodies against mycobacterial SP may reflect the current state of in vivo inflammation rather than the cause of inflammation.
Cell mediated immunity in Antarctic wintering personnel; 1984–1992
Authors: MULLER HK , LUGG DJ , QUINN D
Published: July 2007

Cell‐mediated immune responses were studied in 12 Antarctic and sub‐Antarctic wintering groups at quarterly intervals over the period 1948–1992, using the cutaneous CMI Multitest. These populations are among the most isolated on earth. While the sub‐Antarctic population at Macquarie Island had levels of responsiveness and hypoergy (9%) comparable to healthy populations in temperate zones, the Antarctic Continental group showed a level of hypoergy of 36%. There was no seasonal variation in the pattern of responses. It is concluded that the extreme and isolated environment and stress factors are responsible for the decreased immunological responsiveness but the mechanisms are presently unclear. On review, one factor appears to be perceived anxiety. The high rate of hypoergy in Antarctica, where medical care is limited, may have health implications. These groups provide an excellent analogue for immunological investigations in longer term space flight.
Spontaneous generation of human CD8+ TCRαβ+ cells derived from precursors within the double negative compartment
Authors: FUJIMIYA YOSHIAKI , NAKAYAMA MASAYUKI , SHIBATA TORU , ABE JUN , SHIMADA MUNEHIRO , KOHSAKA TAKAO
Published: July 2007

Flow cytometric analysis demonstrated that fresh human thymocytes contain only a low level of mature CD8αβ+ TCRαβ+ or CD8+ TCRγδ+ cells and that they consist of − 70% double positive (DP) and − 10% double negative (DN) cells. These unfractionated thymocytes could be selectively expanded in vitro by stimulation with 12‐o‐tetradecanoylphorbol 13‐acetate (TPA) and PHA in the presence of IL‐2. The majority of the cells expanded from unfractionated thymocytes expressed CD3, TCRαβ and CD8 molecules after long‐term culture (18 days). When highly purified DN thymocytes were expanded over a period of 18 days in the presence of DP cells, they also co‐expressed CD3, TCRγδ and CD8 molecules on their surface. However, when pruified DN thymocytes were expanded alone, that is, in the absence of DP cells for 18 days, they expressed CD3‐assoeiated TCRαβ, but not CD8 or TCRαβ. Despite the expression of measurable levels of IL‐2 α and β receptors, as well as a significant level of TCRαβ, purified DP cells failed to proliferate. These findings provide the first evidence, in humans, that the progression of precursor cells in the DN compartment to a later stage of differentiation can be induced outside the thymus and that DP cells can affect the development of TCR expression in proliferating DN thymocytes.
Immune response to hepatitis C virus core protein in mice
Authors: HARASE ICHIRO , MORIYAMA TAKASHI , KANEKO TAKASHI , KITA HIROTO , NOMURA MASAYUKI , SUZUKI GEN , OHNISHI HIROO , MUTO YASUTOSHI , YAZAKI YOSHIO , IMAWARI MICHIO
Published: July 2007

To analyse the immune response to the hepatitis C virus (HCV) core protein, we immunized mice with the protein. BALB/c (H‐2d) and C3H/He (H‐2k) mice were high responders, while C57BL/6 (H‐2b) mice were low responders in terms of Th cell proliferative responses. All the strains showed comparable levels of antibody responses to the HCV core protein. The Th cell lines recognized residues 61–90 of the HCV core protein in the context of I‐Ad (BALB/c) and residues 11–30 in the context of I‐Ek (C3H/He), respectively. The Th cell lines were restricted by I‐Ab in C57BL/6 mice but recognized no synthetic peptide that spanned the region, although derivative clones from the line recognized residues 1–20 and 91–110 of the HCV core protein, respectively. The Th cell lines were Thl subset in all three strains based on the profile of lymphokine secretion. The major B cell epitope of the protein was found to be within residues 21–40 of the HCV core protein in all three strains. These observations should be useful for better understanding of the immune response to the HCV core protein in vivo.
Deficiency in T cell responses of human fetal lymph node cells: A lack of accessory cells
Authors: VON HOEGEN* PAUL , SARIN SUJATA , KROWKA JOHN F
Published: July 2007

Lymph node and spleen cells of human foetuses from the 18th to the 24th week of gestation were analysed with regard to their phenotypes and their functional capacities. Fetal mesenteric lymph nodes contain high percentages of CD45RA+ T cells and few B cells and monocytes, whereas the fetal spleen is comprised of equal numbers of T and B cells as well as monocytes/macrophages. Functional analysis of lymph node T cells revealed a lack of proliferative response to PHA or CD3 specific mAb, despite induction of expression of the activation marker CD69. Proliferation of LN cells and thymocytes was observed upon addition of exogenous IL‐2. An allogeneic EBV transformed tumour cell line, known to be an effective antigen presenting cell, could induce proliferation of LN cells without exogenous IL‐2 and fetal spleen cells could proliferate in response to all stimuli tested without additional IL‐2. Splenic non‐T cells could restore the proliferation of lymph node cells as efficiently as IL‐2 or the EBV transformed B cell line. Separated B cells were more effective than plastic adherent cells on a per cell basis. Naivity of the fetal immune system is therefore not only reflected by the expression of markers representative for naive lymphocytes but can also be due to the absence of potential accessory cells in the different lymphoid organs.
Search for linkage disequilibrium between alleles in the T cell receptor α and β chain loci and susceptibility to rheumatic fever
Authors: ABBOTT WGH , GEURSEN A , PEAKE JS , SIMPSON IJ , SKINNER MA , TAN PLJ
Published: July 2007

A population‐based linkage disequilibrium study was conducted to search for associations between alleles in T cell receptor a and p chain polymorphic loci and susceptibility to rheumatic fever. The allele frequencies of four T cell receptor locus restriction fragment length polymorphisms were measured in 47 European and 51 Maori subjects with a history of rheumatic fever. These allele frequencies were compared to the allele frequencies in three or four independently recruited, race‐matched control groups totalling 125 Europeans and 117 Maoris with no history of rheumatic fever. The polymorphisms studied were (locus/ enzyme/probe) Cα/Taq1/Y14, Vα/Taq1/Y14, Vβ/BAMHI/Vβ7.4 and Vβ8/BAMHI/Vβ8.1. There was no evidence for linkage disequilibrium between rheumatic fever and these Tcr alleles in either the Maori or European subjects.
The immune system and integrated homeostasis
Authors: HUSBAND ALAN J
Published: July 2007

The immune system is usually viewed as an effector mechanism reacting to environmental antigenic challenge with defensive responses designed to eliminate ‘foreign’ substances and return to standby or surveillance mode. However, there is now substantial evidence to suggest that immunity is not effector‐biased but is also a sensory organ and forms part of an integrated homeostatic network. Evidence that communication pathways exist between the immune and central nervous systems which support bi‐directional information flow, and that the output of the immune system influences other physiological adjustments to environmental change, is discussed in this paper. The proposition that an endocrine‐immune gradient determines the homeostatic response to combined microbial and other ambient stressors is established and the potential for management of this gradient is explored.
Antibacterial proteins from porcine polymorphonuclear neutrophils
Authors: ALBERDI FERNANDO , ALDERTON MALCOLM R. , KOROLIK VICTORIA , COLOE PETER J. , SMITH STUART C.
Published: July 2007

Antibacterial peptides were purified from porcine neutrophil granules collected from healthy pigs. Granule proteins, extracted with 0.2 mol/L sodium acetate, were subjected to ion‐exchange chromatography and five peaks (designated A to E) were detected. Individual porcine neutrophil granule proteins were shown to inhibit the growth of target organisms Escherichia coli and Staphylococcus aureus. The antimicrobial activity was shown to be concentration and time dependent. Peak D showed strong antimicrobial activity against S. aureus and peak C (with a greater number of eluted proteins) was shown to be active against both S. aureus and E. coli. One of the peptides was purified further by reverse‐phase HPLC from peak fraction C. The MW of this peptide was approximately 5500 Da as determined by SDS‐PAGE and mass spectral analysis and was active against both E. coli and S. aureus in vitro sustaining a > 90% decrease, respectively, in CFU after a 2 h exposure with 50 μg of this peptide. Amino acid analysis showed the peptide was rich in aspartate/aspartic acid, glutamine/glutamic acid, proline, arginine and threonine. The antimicrobial activity of this peptide and other novel proteins in porcine neutrophilic granules demonstrates the probable role of these proteins and peptides in host defence of porcine neutrophils against bacterial infection.
Acute on chronic bronchitis: A model of mucosal immunology
Authors: CLANCY ROBERT , PANG GERALD , DUNKLEY MARGARET , TAYLOR DIANA , CRIPPS ALLAN
Published: July 2007

Acute bronchitis has been studied as a model of disturbed mucosal immunoregulation. A new hypothesis relating to the pathogenesis of acute bronchitis has been developed, based on altered host response as the prime mover. Infection‐prone subjects had low levels of lysozyme. Effective oral immunization, especially if early, reduced levels of bacterial colonization. Future attention focuses on intra bronchial inflammation and its link to the host‐parasite relationship.
Pulmonary immunity to Pseudomonas aeruginosa
Authors: CRIPPS ALLAN W , DUNKLEY MARGARET L , CLANCY ROBERT L , KYD JENNELLE
Published: July 2007

Pseudomonas aeruginosa, an oportunistic bacterial pathogen, is a major course of morbidity and mortality in subjects with compromised respiratory function despite the significant advances in therapeutic practices. The bacteria produces an armoury of products which modify its infective niche to ensure bacterial survival. The role of antibody in protection against pulmonary infection remains poorly defined. Protection appears to be associated with opsonizing antibody whilst some other antibody responses may be deleterious and promote further lung damage. Cell mediated responses are clearly important in protection against infection. This review proposes a vaccine strategy aimed at enhancing specific T cell responses in the lung which, through T cell‐derived cytokines, drive the recruitment of neutrophils to the lung and the subsequent activation of these cells results in the clearance of bacteria from the lung.
Phorbol ester activates CD5+ leukaemic B cells via a T cell‐independent mechanism
Authors: TANGYE STUART G. , WESTON KATHRYN M. , RAISON ROBERT L.
Published: July 2007

B cell chronic lymphocytic leukaemia (B‐CLL) is characterized by the proliferation and accumulation of sIgM+ CD5+ lymphocytes that fail to progress to the final stages of B cell development. Stimulation of unfractionated PBL from three patients with B‐CLL with the phorbol ester PMA and the mitogens PHA and PWM resulted in significant increases in cell proliferation, RNA synthesis and IgM secretion when compared to unstimulated cell populations. PMA was the most potent inducer of IgM secretion and this occurred irrespective of the presence of residual T cells. PMA‐induced proliferation and RNA synthesis was also independent of T cells. However, in the presence of T cells, these parameters of cellular activation were enhanced during in vitro culture. Thus, the inductive ability of PMA on CD5+ CLL B cells was independent of T cells. In contrast, activation and differentiation of the malignant CD5+ B cells into IgM‐secreting cells following culture with mitogens did not occur in the absence of T cells.
Hind III genomic polymorphism of the C3b receptor (CR1) in patients with SLE: Low erythrocyte CR1 expression is an acquired phenomenon
Authors: KUMAR AMIT , KUMAR ASHOK , SINHA SUBRATA , KHANDEKAR PS , BANERJEE KAKOLI , SRIVASTAVA LM
Published: July 2007

Expression of the human erythrocyte C3b receptor (CR1‐CD35) and its Hind III RFLP was studied in a group of 37 patients with SLE, 15 consanguineous relatives of the patients and 48 healthy normal subjects. The CR1 number on erythrocytes was quantitated by ELISA using a mAb to CR1. Serum levels of complement proteins (C3, C4, C3d) and circulating immune complexes (CIC) were estimated simultaneously in controls and relatives. The patients were followed up during the course of the treatment. The CR1/erythrocyte (CR1/E) in patients were found to be significantly low in comparison to controls. The gene frequencies for the alleles H and L (7.4 and 6.9 kb Hind III restriction fragments) in the patients were 0.75 and 0.25. respectively, which did not differ significantly from the controls (0.77 and 0.23 in normal subjects and 0.79 and 0.21 in consanguineous relatives of the patients). However, patients expressed fewer CR1/E within each genotype than their relatives and healthy subjects. CR1/E was found to be stable in consecutive samples in controls. In patients, the numbers varied between low and high during the course of the treatment. The variation in the numbers was significantly correlated with C3d and CIC as well as with the severity of the disease. Our results suggest that low levels of CR1 on erythrocytes in SLE patients are acquired during the course of the disease and that the 6.9 kb restriction fragment does not play a role in causing susceptibility to the disease.
Prolactin as an immunoreactive agent
Authors: DRAČA S
Published: July 2007

Prolactin (PRL), an endocrine hormone from the anterior pituitary, is also synthesized and secreted by activated immunocytes, mostly T cells and thymocytes. In vitro PRL acts as an autocrine or paracrine growth factor which regulates the proliferation of previously stimulated immunocompetent cells. PRL acts through its specific cell surface receptors expressed on different immunocytes including T cells, B cells, monocytes, NK cells and neutrophils. In vivo the immunoregulatory role of PRL is still the subject of intense investigation, especially in the conditions of stress and reproduction. The conflicting results suggest that PRL concentration, sex hormones and some other factors influence the immunomodulatory role of PRL.
Interferon‐γ downregulates the proliferative response of hapten‐specific B cells stimulated by antigen and cytokines
Authors: VOGEL LOTHAR , PIKE BEVERLEY L.
Published: July 2007

IFN‐γ plays a role in many aspects of cellular interactions, both positive and negative. Among its functions during the immune response, the antagonistic effects of IFN‐γ and IL‐4 are well documented. Observations in our laboratory suggested that IFN‐γ could also interfere with the activation of single, antigen‐specific B cells by antigen and other cytokines. Closer examination revealed that IFN‐γ reduced the number of proliferating cell clones in response to antigen and a variety of cytokines, alone or in combination. Cell viability remained at the initial level and the cells were still able to produce Ig, albeit to a lesser extent than in the absence of IFN‐γ. On the other hand, the frequency of IgM secreting clones was not affected, whereas the total amount of secreted IgM was lower in the presence of IFN‐γ, probably due to the reduced cell number and a decrease in Ig production. In addition, proliferation was prevented when B cells were pre‐incubated with IFN‐γ and then stimulated by other cytokines. Kinetic studies revealed that INF‐γ had to be present from the onset of culture because delayed addition did not inhibit the proliferation of the B cells. After its initial action, IFN‐γ could be removed without abolishing the negative signal for proliferation. From these results it can be concluded that IFN‐γ transmits a signal that causes B cells to stop proliferating and prevents them from forming large clones.
Characterization of immunorelated peptides to porcidin P1
Authors: ALBERDI FERNANDO , ALDERTON MALCOLM R , COLOE PETER J , SMITH STUART C
Published: July 2007

Porcidin P1, an antimicrobial peptide purified from the granules of porcine polymorphonuclear neutrophils (PMN) using ultrafillration and reverse phase high performance liquid chromatography (RPHPLC), was covalently conjugated to BSA and used to generate monospecific polyclonal ascites. Antibodies raised against porcidin P1 were covalently coupled to an Affi‐gel Hz affinity column and used for immunoaffinity chromatography of peptides from porcine PMN cell extract. Eleven immunorelated peptides were eluted from the column from neutrophil cell extracts and purified to homogeneity by HPLC. The molecular weights of the immunorelated peptides were determined by mass spectral analysis and ranged in size from 1.91 to 10.65 kDa. Of the II immunorelated peptides which were bound to the affinity column, only six peptides were recognized by the anti‐porcidin antibodies after HPLC purification. Three immunoreactive peptides displayed potent antibacterial activity towards Staphylococcus aureus and Escherichia coli. reducing viability by as much as 99.9% (> 3 log reduction in CFU) when 5 μg/mL of each purified peptide was used. The polydonal monospecific antibodies also reacted with proteins from ovine and human PMN, illustrating possible structural relationships between small antibacterial peptides from the different species.
Role of the PS integrins in Drosophila development
Authors: BROWER DANNY L , BRABANT MARC C , BUNCH THOMAS A
Published: July 2007

The PS1 and PS2 integrins of Drosophila are heterodimers of αPS1βPS and αPS2βPS subunits, respectively, with very strong structural similarity to vertebrate integrins. Cell transfection experiments indicate that the PS integrins are receptors for extracellular matrix components and are functionally analogous to vertebrate integrins. Matrix ligands from Drosophila tissues have been identified for PS1 and PS2 integrins, using transformed cells and a cell‐spreading assay. Mutations in all three subunit genes have been identified, and the phenotypes of mutants indicate that PS integrins are required for the proper morphogenesis of a number of embryonic tissues. Using methods to produce genetic mosaics and transformation of integrin transgenes into whole animals, integrin functions in adult morphogenesis also have been examined. In the pupal wing, integrins are critically required to maintain the connection between dorsal and ventral epithelia, and recent results suggest that in early pupal development, the integrins are acting as specific receptors, as opposed to a non‐specific cell‐matrix glue.