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Presents several developments in the veterinary medicine. Identification of keel and furculum damage in laying hens; Detection of antigens in fresh and autolysed tissue; Hypervaccination with marker vaccines against bovine herpesvirus type 1.

Immunoglobulin (Ig) is the one of the main anti‐infective components of blood, colostrum and breast milk. It is the unique glycoprotein that defends the body from harmful bacteria, viruses and other environmental pathogens by either binding to them or by forming an encapsulating barrier. The expansion of antimicrobial and immunomodulatory products from natural sources for dietary supplementation in both animals and humans is an ever growing and thriving area of research. Purified Ig from sheep serum (ovine serum Ig) is one such candidate product. Recent work has shown the various biological effects of oral Ig in different animal models including its effect on growth, immunity, intestinal growth and gut barrier function. The objective of this paper is to review the results of recent studies demonstrating the effects of oral Ig in both pathogenic and non‐pathogenic animal models and to suggest a possible mechanism of its action. Overall, purified oral Ig improves growth of healthy (and challenged) rats and defends against enteric infection by immunomodulation, mucin protein and/or modification of commensal microbial composition. The findings contribute to knowledge of how orally administered ovine Ig can influence and enhance key indicators of gut function and overall growth performance in an animal model. [ABSTRACT FROM AUTHOR]

The Steering Committee for the Prevention and Control of Infectious Diseases in Asia recently conducted a survey of primary-care physicians in Asia, which revealed that many physicians administer boosters in their clinical practice and that there is considerable variation and uncertainty among physicians regarding this practice. This paper serves as a response to physicians’ uncertainties by reviewing the literature regarding the administration of hepatitis B vaccine boosters in high endemicity areas and presenting the Steering Committee's guidelines for booster administration. While there are few data to support a need for routine hepatitis B vaccine boosters as a public health measure, they help to provide reassurance of immunity against breakthrough infection in certain risk groups. In clinical practice, primary-care physicians must exercise their judgment regarding the need for booster vaccination on an individual basis. This paper examines the available literature on the administration and value of hepatitis B vaccine boosters, explores the differences between the public health approach and clinical practice, and provides guidelines for those who use boosters in high endemicity Asian populations. Relevant articles were identified through searches of MEDLINE (1975–2003) and the Cochrane Library, using‘hepatitis B’ and‘booster’ as primary search terms. Guidelines for those who decide to administer hepatitis B vaccine boosters include: boosting approximately 10–15 years after primary vaccination; boosting rather than not when monitoring of antibody levels is not feasible; boosting immunocompromised patients when the antibody to hepatitis B surface antigen titer falls below 10 mIU/mL; and boosting healthcare workers based on the endemicity of the particular country. [ABSTRACT FROM AUTHOR]

Our understanding of immunity to filarial infection is enigmatic and continues to be passionately debated. The mechanisms whereby filarial nematodes are killed in vivo and how these parasites avoid these mechanisms are poorly understood. Although vaccination studies in permissive animals took off seven decades ago, the exact mechanisms driving protective immunity are extensively being investigated. Currently, little is known regarding the collective functions or counter-regulatory mechanisms of the antibody isotypes in filarial infection with respect to protective immunity. Establishing the functional role of antibody isotypes and cytokines in the various infection phenotypes can contribute immensely to current knowledge in filarial immunology. This paper reviews insight into protective immunity in filarial infection with focus on humoral and cellular responses from animal models and human studies. [ABSTRACT FROM AUTHOR]

Several hybridoma cell lines secreting NP-specific, murine IgE antibodies were generated by fusion of P3-X20 (γ,κ) tumour cells with spleen cells from (BALB/c x C57Bl/6)F1 (CB6F1) mice previously immunized with NP-ovalbumin. Four subclones (designated NP-ε-3.57, NP-ε-15,88, NP-ε-91,58 and NP-ε-95,31) were propagated in vivo and milligram quantities of the corresponding IgE antibodies were purified from ascitic fluid by gel filtration, ion exchange chromatography and affinity chromatography. Immunological analyses and sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDSPAGE) indicated that NP-ε-15,88, NP-ε-91,58 and NP-ε-95.31 all possessed λ1 (or possibly λ3) light chains; and that NP-ε-3,57 possessed λ2 light chains; NP-&elipson;-95,31 also expressed the P3-X20 derived, MOPC-21 κ light chain. Radioallergosorbent test (RAST) titration curves, generated from the interaction of the four monoclonal IgE antibodies with NP-BSA attached to paper discs (NP-BSA-P) were found to be non-overlapping. Measurements of the relative amounts of NP-ε-aminocaproic acid (NP-CAP) and 4-hydro-3-iodo-5-nitrophenylacetyl-ε- aminocaproic acid (NIP-CAP) that were required to inhibit by 50% the binding of the 4 IgE antibodies to NP-BSA-P indicated that these antibodies were all heteroclitic, since their affinity for NIP appeared to be higher than their affinity for NP. These results, in conjunction with other findings reported in the literature, suggested that the V regions of NP-specific IgE antibodies are similar to the V regions of NP-specific IgM and IgG antibodies, produced by the same mouse strains. Finally, in vitro histamine release measurements demonstrated that two of these monoclonal IgE antibodies could mediate antigen induced histamine release from passively sensitized rat peritoneal mast cells. [ABSTRACT FROM AUTHOR]

Heat and pH stability studies and experiments with organic solvents show that the A-antigens discussed in the preceding paper (Augustin, 1959c) are much more labile than the I-(‘inner ring’) antigens. Breakdown products and/or aggregates are produced which no longer precipitate with antisera to the original extracts, but act as inhibitors. Solutions of pollen allergens, on the other hand, are found to withstand even autoclaving for 15 min. at 20 atm. and vigorous boiling over the naked flame of a bunsen burner. None of the carbohydrates tested has a demonstrable effect on skin reactivity which is, however, destroyed by crystalline pepsin, crystalline trypsin, a crystalline mould protease and a tissue protease (a partially purified extract from rabbit spleen). It follows that the bulk of the allergens—if not all—are proteins. The relation of skin reactivity, immuno-electrophoretic patterns, carbohydrate and protein reactions to the selective destruction of the pollen antigens is investigated. Pollen components prove to have a somewhat wider range of electrophoretic mobilities than serum proteins and are probably as complicated a mixture. The most and least highly negatively charged components are without skin reactivity in allergic subjects. The skin reactive allergens appear to have the mobilities of α- and β-globulins. Not all the hay fever subjects react equally to all the components, and Cocksfoot and Timothy activity patterns vary in different subjects. [ABSTRACT FROM AUTHOR]

Changes in the risk of exposure to infectious disease agents can be tracked through variations in antibody prevalence in vertebrate host populations. However, information on the temporal dynamics of the immune status of individuals is critical. If antibody levels persist a long time after exposure to an infectious agent, they could enable the efficient detection of the past circulation of the agent; if they persist only a short time, they could provide snap shots of recent exposure of sampled hosts. Here, we explored the temporal dynamics of seropositivity against Lyme disease agent Borrelia burgdorferi sensu lato (Bbsl) in individuals of a widespread medium‐sized mammal species, the roe deer (Capreolus capreolus), in France. Using a modified commercially available immunoassay we tested 1554 blood samples obtained in two wild deer populations monitored from 2010 to 2020. Using multi‐event capture‐mark‐recapture models, we estimated yearly population‐, age‐, and sex‐specific rates of seroconversion and seroreversion after accounting for imperfect detection. The yearly seroconversion rates indicated a higher level of exposure in early (2010–2013) than in late years (2014–2019) to infected tick bites in both populations, without any detectable influence of sex or age. The relatively high rates of seroreversion indicated a short‐term persistence of antibody levels against Bbsl in roe deer. This was confirmed by the analysis of samples collected on a set of captive individuals that were resampled several times a few weeks apart. Our findings show the potential usefulness of deer as a sentinel for tracking the risk of exposure to Lyme disease Bbsl, although further investigation on the details of the antibody response to Bbsl in this incompetent host would be useful. Our study also highlights the value of combining long‐term capture‐mark‐recapture sampling and short‐time analyses of serological data for wildlife populations exposed to infectious agents of relevance to wildlife epidemiology and human health. [ABSTRACT FROM AUTHOR]

LINKED CONTENT This article is linked to Wunschi et al and Tornai & Papp papers. To view these articles, visit https://doi.org/10.1111/apt.16153 and https://doi.org/10.1111/apt.16201 [ABSTRACT FROM AUTHOR]

LINKED CONTENT This article is linked to Wunschi et al and Wunsch & Milkiewicz papers. To view these articles, visit https://doi.org/10.1111/apt.16153 and https://doi.org/10.1111/apt.16211 [ABSTRACT FROM AUTHOR]

The antibody response to a hapten conjugated to a protein can, in a number of situations, be suppressed by prior immunization with the carrier protein alone. The study of this finding appears to have been handicapped by previous literature on the subject having been consistently misquoted. It is to be hoped that recognition of this will allow a better understanding of the limitations to such suppression, and hence the mechanism by which it may act, [ABSTRACT FROM AUTHOR]

Background: Platelet refractoriness due to HLA immunization represents a problem in transfusion management of thrombocytopenic hematology patients. Refractory patients can be managed by HLA-selected platelet transfusions, but the optimal matching strategy is debated and how the degree of HLA mismatch influences transfusion outcome is poorly studied.Study Design and Methods: We studied 32 hematology patients who received 142 matched platelet units between 2007 and 2016. Four matching strategies were compared: 1) genomic HLA typing at the two digit level, performed using polymerase chain reaction-sequence-specific oligonucleotide probing; 2) serologic "eplet score" calculated using HLAMatchmaker; 3) cross-matching using lymphocyte cytotoxicity; and 4) matching based on donor-specific antibody (DSA) specificity, determined using Luminex. A 1-hour corrected count increment (CCI) of more than 7.5 × 109 /L was considered a successful response.Results: Selection of platelets with either a complete HLA match or an acceptable HLA mismatch based on genomic typing and DSA information, each predicted 86% successful transfusion responses. For HLA-mismatched transfusions, the eplet score correlated with CCI and the fraction of successful transfusions, but less well compared to DSA matching. Cytotoxic crossmatching was least predictive. For transfusions across one to four DSAs, the antibody reaction strength correlated with the 1-hour CCI, but many transfusions were successful despite the presence of DSA.Conclusion: A complete HLA-A and -B match or an acceptable mismatch based on DSA should guide identification of donors. Still, transfusions across DSAs are often successful, emphasizing that the presence of DSA is necessary but not sufficient for platelet clearance. [ABSTRACT FROM AUTHOR]

Please cite this paper as: De Vleeschauwer et al. (2011) Cross-protection between antigenically distinct H1N1 swine influenza viruses from Europe and North America. Influenza and Other Respiratory Viruses 5(2), 115-122. An avian-like H1N1 swine influenza virus (SIV) is enzootic in swine populations of Western Europe. The virus is antigenically distinct from H1N1 SIVs in North America that have a classical swine virus-lineage H1 hemagglutinin, as does the pandemic (H1N1) 2009 virus. However, the significance of this antigenic difference for cross-protection among pigs remains unknown. We examined protection against infection with a North American triple reassortant H1N1 SIV [A/swine/Iowa/H04YS2/04 (sw/IA/04)] in pigs infected with a European avian-like SIV [A/swine/Belgium/1/98 (sw/B/98)] 4 weeks earlier. We also examined the genetic relationships and serologic cross-reactivity between both SIVs and with a pandemic (H1N1) 2009 virus [A/California/04/09 (Calif/09)]. After intranasal inoculation with sw/IA/04, all previously uninfected control pigs showed nasal virus excretion, high virus titers in the entire respiratory tract at 4 days post-challenge (DPCh) and macroscopic lung lesions. Most pigs previously infected with sw/B/98 tested negative for sw/IA/04 in nasal swabs and respiratory tissues, and none had lung lesions. At challenge, these pigs had low levels of cross-reactive virus neutralizing and neuraminidase inhibiting (NI) antibodies to sw/IA/04, but no hemagglutination-inhibiting antibodies. They showed similar antibody profiles when tested against Calif/09, but NI antibody titers were higher against Calif/09 than sw/IA/04, reflecting the higher genetic homology of the sw/B/98 neuraminidase with Calif/09. Our data indicate that immunity induced by infection with European avian-like H1N1 SIV affords protection for pigs against North American H1N1 SIVs with a classical H1, and they suggest cross-protection against the pandemic (H1N1) 2009 virus. [ABSTRACT FROM AUTHOR]

Murine models of mucosal inflammation are frequently due to the inability of the mouse to mount a regulatory T cell response. To the extent that such responses arise from oral tolerance mechanisms, these models provide a unique way of studying oral tolerance. In this paper we focus on the regulatory cells generated in two of the most well-studied of such models, the cell-transfer model and the TNBS-colitis model. Our analysis leads to the view that regulatory cells generated by the oral tolerance seen in mucosal inflammation are, at least in part, cells that recognize self-antigens or antigens in the mucosal microflora whose effector function relies on the expression of TGF-β. [ABSTRACT FROM AUTHOR]

SUMMARY In an accompanying paper we show that antibodies in intestinal mucus that recognize a 35-kDa antigen from the surface of the L3 stage of the sheep intestinal nematode parasite, Trichostrongylus colubriformis, are strongly associated with immune rejection of L3 in a truncated infection model of immunity in sheep. Monoclonal antibody PAB-1 was used to immunopurify this antigen from T. colubriformis L3 . The antigen is resistant to digestion with a range of proteases including proteinase K and does not stain on gels or blots treated with protein-detecting reagents but does stain with carbohydrate-detecting reagents. The antigen is also resistant to degradation by the action of lipases and is not soluble in organic solvents, suggesting that lipid components are not present or not accessible. Treatment with glycosidases does not affect the antigen, indicating either that sialic acid and N-linked or O-linked sugars are not present or that they are not accessible to enzyme attack. The antigen is not destroyed by harsh alkaline degradation with up to 8 m NaOH with or without borohydride reducing agent, or by extensive hydrazinolysis. Strong acid hydrolysis with trifluoroacetic acid or boiling in hydrochloric acid for 20 min does destroy the antigen. The antigen migrates as a poorly defined high molecular weight complex on native electrophoresis gels, but is detected as a major band at 35 kDa on SDS PAGE either by carbohydrate staining or by immunoblotting with antibody from immune sheep intestinal mucus and with mAb PAB-1. Proteinase K digestion and alkaline degradation of extracts from L3 of 10 other parasitic nematode species revealed that L3 of each species contained a carbohydrate staining molecule which can be detected by mAb PAB-1 and by mucus antibody from immune sheep. Because antibodies in intestinal mucus are directed against these antigens and may be responsible for protective immunity, carbohydrate larval antigens (CarLA) could represent a new family... [ABSTRACT FROM AUTHOR]

Two main ideas have been put forward lo explain the unexpectedly low anti-hapten antibody titres which can result from pre-priming a mouse with carrier before hapten-carrier immunization. The first involves the interaction of a network of idiotype-specific suppressor T cells, the second instead arguing for the role of intrinsie B-cell anergy. This paper proposes that the data available can equally be interpreted as reflecting the suboptimal interaction between T and B cells at differing stages of maturity, provided that memory B cells can be divided into two subsets. Further, it is suggested that these considerations must be taken into account in the analysis of B-cell anergy in receptor transgenic mice. [ABSTRACT FROM AUTHOR]

This paper describes studies of genetic markers and immune functions in the first Icelandic family identified with X-linked agammaglobulinaemia (X-L,A). including three affected brothers. The eldest brother was diagnosed at the age of 9 in 1963. He suffered repeated infections and died at the age of 23. The other two affected brothers, diagnosed al 6 years and 1 year of age, are alive and well on immunoglobulin replacement therapy at the ages of 32 and 24. All were typed for HLA, complement, and various other markers. Pedigree analysis suggests an X-linked segregation of the disease. Their serum IgG is maintained at normal levels on therapy. Several parameters of immune function were studied. The following results were obtained for the X-LA brothers: B cells are absent in their peripheral blood samples, T-cell numbers arc normal, but monocytes are increased in numbers and activity. No immunoglobulin production could be elicited in vitro with PWM and no cells containing cytoplasmic Ig were detectable among PWM-stimulated blasts. Nevertheless the proliferative response was particularly vigorous, but the responding cells were shown to be exclusively T cells. No blast transformation could be achieved with EB virus. NK-cell activity was normal/high normal. Other cell-mediated immune functions were normal, In conclusion our data indicate that the differentiation of B cells is blocked in the two surviving XLA brothers. They have survived for a longer time and in better health than is generally reported- Early diagnosis and adequate replacement treatment with Ig is clearly crucial. Vigorous nonspecific immune mechanisms may help to compensate for the defective specific immune mechanisms may help to compensate for the defective specific immunity. [ABSTRACT FROM AUTHOR]

This paper examines the possibility of a functional linkage between class I MHC molecules and the T-cell receptor complex for antigen (T3-Ti). A newly developed anti-CD3 antibody (500A2) was used as an activation signal for EL4 lymphoma cells and allospecific cytotoxic T-cell clones (CTL), and the production of IL-2/IL-2 receptor in EL4 cells and serine esterase in CTL was determined. Anti-CD3 antibody-induced activation of both EL4+ and CTL cells was enhanced in the presence of immunologically cross-linked and immobilized anti-H-2 (class I) antibody reactive against the H-2 haplotype of the responding T cells. A number of H-2-negative and H-2-positive EL4 subclones were generated and tested for anti-CD3 antibody-induced IL-2/IL-2 receptor production. Although both H-2-positive and -negative subclones expressed CD3 antigen and produced IL-2 after activation with the phorbol ester TPA, only the H-2-positive cell clones produced IL-2 and expressed IL-2 receptor after anti-CD3 antibody induction. Our results are compatible with the existence of a functional linkage between the class I and the CD3 molecules on the surface of T cells. [ABSTRACT FROM AUTHOR]

This paper describes the induction of IgM immune memory to haptenated liposomes in mice. The tripeptide-enlarged haptens 3-(p-azo-benzene-arsonate)-N-acetyi-L-tyrosylglycyiglycine (A) and N-(2,4-dinitrophenyl)-β-alanylglycylglycine (J) were coupled to phosphatidylethanola mine (PE) and the conjugates A-PE and J-PE were incorporated into separate liposomal membranes (monofunctional A-PE-liposomes or J-PE-Liposomes) or into the same liposomal membranes [bifunctional (A,J)PE-liposomes]. The magnitude of the humoral response was measured by the appearance of direct and indirect plaque-forming cells in the spleens of immunized mice. Intracutaneous priming of mice with A-PE-liposomes mixed with the adjuvant dimethyl dioctadecyl ammonium bromide (DDA) and secondary immunization with bifunctional (A.J)-PE-liposomes resulted in enhanced hapten A- and J-specific IgM responses. However, no switch from IgM to IgG antibodies was observed in these mice. The J-specific IgM response was enhanced only when hapten I was incorporated into a bifunctional liposome which also contained A-epitopes. in mice primed with A-PE-liposomes in the absence of DDA, a greatly diminished memory to both hapten A and J was observed. This finding indicates a crucial role for the adjuvant in the induction of memory. J-PE-liposomes and DDA were not able to induce memory to monofunctional J-PE-liposomes or bifunctional (A,J)-PE-liposomes. The possibility that hapten A-specific B lymphocytes were responsible for the induction of memory was excluded by hapten-specific blockade of these cells with a B-cell tolerogen. These data, in addition to the observation that no IgM memory could be induced in congenitally athymic nude mice, suggest that the observed memory can be ascribed to priming of hapten A-specific T lymphocytes. [ABSTRACT FROM AUTHOR]

A mean of 6.9 per cent of small lymphocytes in peripheral blood preparations and between 1.8 and 2.4 per cent of small lymphocytes in lymph node, spleen, bone marrow and thymus preparations from unimmunized guinea-pigs bound 125I-labelled purified protein derivative of mammalian tuberculin (mammalian PPD). The percentage of these cells fluctuated but did not alter substantially after immunization with BCG or with BCG emulsified with human thyroglobulin (HTg) in Freund's incomplete adjuvant (FIA). Blocking experiments indicated that the binding of 125I-labelled mammalian PPD was specific and there was tentative evidence that the lymphocyte receptors may be IgG. A comparison is drawn between the observed time course of 125I-labelled mammalian PPD- binding small lymphocytes and the response of lymphocytes sensitive to strong histocompatibility antigens, and it is proposed that the propensity of certain anti- gens to induce a delayed hypersensitivity-type response is related to the presence of substantial numbers of antigen-binding cells in unimmunized animals. A noteworthy incidental finding was an unexplained depression in the cellular and humoral responses to mammalian PPD in guinea-pigs that had been immunized with HTg-BCG-FIA emulsion. [ABSTRACT FROM AUTHOR]

We have examined the emigration of chicken thymocytes after intrathymic fluorescein isothiocyanate (FITC) labelling in situ. In this paper we show that in young birds about 0.7% and 0.4% of thymocytes emigrate from the thymus to the blood and the spleen, respectively, per day. This suggests that, as in mammals, most thymocytes die within the thymus. At 3 weeks of age γδ and αβ T cells leave the thymus in comparable levels to their appearance in the blood. The phenotype of recent emigrants in peripheral tissues is similar to that of mature T cells. Interestingly, recent emigrants contain relatively much higher numbers of CD4+ and fewer CD8+ cells than is observed in peripheral tissues in a steady-state situation. [ABSTRACT FROM AUTHOR]

When lymphoid cells from hypersensitive rabbits are incubated with antigen, biologically active substances are formed and released which are capable of inhibiting the migration of normal non-sensitized mesenchymal cells. In the present paper some basic parameters of their production were determined. These substances were regularly obtained after 6 and 18 hours incubation, but not after 2 hours. Under more favourable cultivation conditions (lower density of lymphocyte suspension) an increased activity in the cell extracts as compared with the supernatants was observed. Another critical factor in the production of these substances is the quantity of antigen added. Ten micrograms of PPD leads to the production and liberation of a highly effective substance. A lower dose of antigen results in the liberation of a substance into the supernatant which by itself is almost inactive, but becomes more active when more antigen is added. The efficiency of the released substances was determined by serial dilution. The inhibiting activity was maintained at 1:5 and 1:20 and sometimes at 1:100 dilutions. [ABSTRACT FROM AUTHOR]

Rat liver microsomes were separated into three subfractions by means of ultracentrifugation through sucrose media of different densities and in the presence of different cations. Detergent extracts of these preparations were analysed by double diffusion in agar gel and immunoelectrophoresis with rabbit antisera against each of the subfractions. One subfraction was derived from the ‘rough’ and another from the ‘smooth’ part of the endoplasmic reticulum of the liver parenchymal cells. Their extracts contained at least thirteen soluble antigens in common. However, fraction-specific antigens were also present. Thus, the extracts of the rough (R) membranes contained at least one typical antigen, not found in any of the other fractions. An antiserum against this component also precipitated a non-migrating antigen present only in the extracts of smooth (Sa) membranes. These two antigens may represent different molecular forms of a substance involved in binding of the ribosomes or in the assembly of membrane subunits. At least eleven of the antigens common for the two fractions exhibited enzymatic activities when assayed after precipitation with antibody in the immunoelectro- phoretic plates. Six immunologically and electrophoretically distinct antigens had esterase activity with α-naphthyl propionate as substrate. Two of these esterases also split indoxyl acetate. Three other antigens with acid phosphatase activity split both α-naphthyl acid phosphate and β-glycerophosphate. Three antigens had nucleoside diphosphatase activity when tested with uridine- or inosine-diphosphate. Preliminary experiments also suggested that two additional antigens possessed NADH-diaphorase activity and thus could belong to the microsomal electron trans- port systems. The third subfraction consisted of electron-microscopically smooth membranes (Sb), enzymatically different from those of the endoplasmic reticulum. The antigens typical for the latter were either absent or present only in minor and variable concentrations. Its extracts contained at least two typical antigens. One of these was identified as contaminating ferritin. The nature and origin of the other antigen has not yet been established. All antigens described in this paper were immunologically different from the common rat serum proteins. [ABSTRACT FROM AUTHOR]

The objective of this cohort study was to assess the relationship between perinatal calf management practices relevant to the control of paratuberculosis and passive transfer of immunoglobulin in calves born in an endemically infected Irish dairy herd. Data from 176 calves were used to assess the effect of time spent in the calving area, individual versus nondesignated calving and colostrum pasteurisation on serum total protein, zinc sulphate turbidity, globulin and γ-glutamyltransferase. In addition, the effects of colostrum quality, volume of colostrum fed, method of colostrum administration and calving season on passive transfer were quantified. Serum samples were collected as part of routine herd health monitoring from calves aged between one and seven days. Multivariate linear and logistic regression models were used to assess the effect of each variable on the test result and failure of passive transfer as determined using a cut-off point for each diagnostic test. Colostrum pasteurisation and calving area were not significantly associated with passive transfer, whereas increased time spent in the calving pen was consistently associated with a detrimental effect. In addition, a strong seasonal effect was apparent, which appeared to be unrelated to colostrum quality and calf management. The authors are unaware of published studies documenting such a significant seasonal effect on passive transfer. [ABSTRACT FROM AUTHOR]

The article focuses on purification and characterization of atopic allergens. In the past two decades, several atopic allergens, which induce IgE antibody-mediated immediate hypersensitivity in man have been purified to near homogeneity and studied for their immunochemical properties. In this paper will be reviewed some of the general findings drawn from such studies. Allergen characterization studies with extracts from these sources have confirmed the views of allergists that all extracts are multi-allergen systems and that individuals can have varying patterns of sensitivity to different allergens.

Background: There is incomplete information regarding evolution of antibody titers against SARS‐CoV‐2 after a two‐dose strategy vaccination with BNT162b2 in older adults in long‐term care facilities (LTCFs) with frailty, disability, or cognitive impairment. We aimed to determine IgG antibody titer loss in older adults in LTCFs. Methods: This is a multicenter longitudinal cohort study including 127 residents (90 females and 37 males) with a mean age of 82.7 years (range 65–99) with different frailty and disability profiles in two LTCFs in Albacete, Spain. Residents received two doses of BNT162b2 as per label, and antibody levels were determined 1 and 6 months after the second dose. Age, sex, previous history of coronavirus disease 2019 (COVID‐19), comorbidity (Charlson Index), performance in activities of daily living (Barthel Index), frailty (FRAIL instrument), and cognitive status were assessed. Results: The mean antibody titers 1 and 6 months after the second vaccine dose were 32,145 AU/ml (SD 41,206) and 6182 AU/ml (SD 13,316), respectively. Across all participants, the median antibody titer loss measured 77.6% (interquartile range [IQR] 23.8%). Notably, the decline of titers in individuals with pre‐vaccination COVID‐19 infection was significantly lower than in those without a history of SARS‐CoV‐2 infection (72.2% vs. 85.3%; p < 0.001). The median titer decrease per follow‐up day was 0.47% (IQR 0.14%) and only pre‐vaccination COVID‐19 was associated with lower rate of antibody decline at 6 months (hazard ratio 0.17; 95% confidence interval 0.07–0.41; p < 0.001). Frailty, disability, older age, cognitive impairment, or comorbidity were not associated with the extent of antibody loss. Conclusions: Older adults in LTCFs experience a rapid loss of antibodies over the first 6 months after the second dose of BNT162b2 vaccine. Only pre‐vaccination COVID‐19 is associated with a slower rate of antibody decrease. Our data support immunization with a third dose in this vulnerable, high‐risk population. [ABSTRACT FROM AUTHOR]

In 1941, techniques using fluorescent antibodies to locate antigens were used for the first time by Coons, Crech and Jones. Intercellular and epithelial antibodies in pemphigus vulgaris were demonstrated initially by Beutner and Jordan in 1964. The relationship between clinical severity and titers of serum antibodies has been a controversial subject. Antibodies are located in the intercellular spaces of the epidermis, where intraepidermal bullae with acantholytic cells develop. The antibodies are specific and present in almost all patients with active Brazilian pemphigus foliaceus.

The principal aim of this work was to analyze the host systemic immune response to an oral infection of A. viscosus T14V. Previous work had established a Balb/c mouse model for A. viscosus T14V oral infection. Animals were infected and the splenocyte response to A. viscosus T14V antigens, LPS, and Con A were assessed in the lymphoblast assay. Splenocytes from mice infected with A. viscosus T14V exhibited an altered response pattern to the antigens and mitogens. The responses were enhanced or suppressed when compared to the uninfected control splenocyte response. The effluent cells from a nylon wool column were unresponsive to A. viscosus antigens but LPS did respond to Con A. This response pattern was true for splenocytes from infected and uninfected animals. These results suggest that A. viscosus T14V is a potent immunomodulater when analyzed within the BaIb/c mouse model system. [ABSTRACT FROM AUTHOR]

The article discusses ligands and receptors in autoimmune systems. Brief information regarding ligands and receptors; Theories of idiotype network; Lists of diseases that involves autoimmunity to receptors; Utilization of the cellular receptor repertoire.

Primed LD typing cells were prepared against single HLA baplotypes within families and used to type a random panel of 48 individuals. PLT cells could be grouped on the basis of highly correlated responses with the panel test cells; the 21 different PLT cells could be used to define 6 different PL antigens. One of these, PL 3, was split by the responses of two of the 21 PLT cells which measured an antigen called PL 3.1. [ABSTRACT FROM AUTHOR]

Four allergologically important fungi, viz. Aspergillus fumigatus, Penicillium notalum Alternaria altermata, and Cladosporium herbarum were cultured in a liquid synthetic me with or without addition of 0.1 % yeast extract (YE). After 10 and 28 days of cultivation, immunochemical properties of the fungal extracts, characterised by precipitation pattern and IgG- and IgE-binding capacity, were studied. In pure synthetic medium no large differences were observed in number of precipitates, as measured by DID, among the four antigenic fractions of each fungus (metabolic and mycelial antigens of both early and late phase cultures). Addition of YE to the growth medium hardly changed the number of precipitates and generally caused a decrease in lgG-binding capacity of the extracts. In contrast to these observations were the findings with the IgE-binding capacities of the fungal extracts as measured by RAST. Most allergenic fractions demonstrated an increase (sometimes strong) in lgE-binding capacity after YE was added to the growth medium. It is concluded that the time of cultivation influences the immunochemical characteristics of fungal extracts and that mycelial as well as metabolic antigens of both early and late phase cultures should be used in order to obtain a wide spectrum of allergens in extracts used for diagnostic purposes. [ABSTRACT FROM AUTHOR]

IgE and IgG antibodies (ab) and lymphocyte transformation (LT) were studied in untreated and hyposensitized birch pollen allergic subjects and in non-a topic controls using whole extract and fractions obtained by gel filtration of birch pollen extract. All the allergic subjects had positive IgE ab, IgG ab and LT responses to the whole extract. Both the untreated and the hyposensitized subjects had peak IgE ab and LT responses against the allergenic fractions of the extract, while negative responses were obtained in the non-atopic controls. Only hyposensitized subjects had developed high IgG ab responses to the allergenic fractions. Most of the treated and untreated subjects showed IgG ab and LT responses to the high molecular weight fractions with low allergenic activity. Significantly higher IgE ab responses to these fractions were observed in the treated subjects than in the untreated ones, indicating potentiation of IgE ab responses against some antigens during immunotherapy. Some of the allergic subjects also responded to the fractions of low molecular size (mol.wt. 2000-5000) with low allergenic activity. Both IgE ab, IgG ab and LT responses to these fractions were observed. [ABSTRACT FROM AUTHOR]

The immunological responses of rabbits to HSA, HGG or BSA were tested at various times later in animals which had received the corresponding antigens before or shortly after birth. As judged by the criterion of failure to show immune elimination of antigen, a high proportion of the rabbits remained unresponsive at times when it was calculated that all the originally administered antigen would have been eliminated from the circulation. Furthermore, removal of antigen by passively administered antibody failed to restore the capacity to respond. It is concluded that, in respect of the antigens used, their persistence in the extracellular body fluids is not a prerequisite for maintenance of immunological unresponsiveness.
Further administration of the same antigen to rabbits which had escaped from a state of specific immunological unresponsiveness generally produced a very weak response, and in a few instances resulted in a return to the unresponsive state.
When the cross-reacting antigens HSA and BSA were administered adsorbed on alum to rabbits made unresponsive by neonatal contact with BSA and HSA respectively, and at the same time a further dose of the original antigen was given, antibodies were formed which were specific for the second antigen and did not cross-react with the first. In only 1/9 animals was responsiveness to the first antigen restored. The significance of these results is discussed. [ABSTRACT FROM AUTHOR]

Summary. Rabbit circulating lymphocytes have been examined for the a locus allotypic markers As1, As2 and As3 using the mixed antiglobulin reaction. These determinants cannot be as easily demonstrated as the b locus determinants As4, As5 and As6. Undiluted antiserum is required and even then the percentage of reacting cells is low. The specificity of the reaction was checked by an inhibition procedure. [ABSTRACT FROM AUTHOR]

The enhancement effect of some antigens on in vitro colony formation by normal mouse bone marrow cells is mediated through a normal serum αmacroglobulin (αM) which is present in newborn animals and shows no immunological specificity. The proportion of antigen and αM affects colony enhancement, and it has also been shown that specific antibody successfully competes with αM for the antigen. It seems likely that antigen-αM complex acts directly on the colony forming cell, rather than indirectly through release of colony stimulating factor. The possible relevance of this phenomenon to immune induction and, to the effect of antigens in promoting irradiation survival is discussed. [ABSTRACT FROM AUTHOR]

Five tissue specific antigens in guinea-pig epidermis were characterized by heat treatment, enzyme digestion, DEAE-cellulose chromatography, (NH4)2SO4 precipitation, ethanol precipitation and gel filtration. These antigens appeared to be proteins although one was fairly resistant to proteinases. Two antigens (Sp2a and Sp2b) were heat-stable and precipitated at high (NH4)2SO4 concentration (3.0 M—saturation): Sp2b was also precipitated at very high ethanol concentration (50-90 per cent). On electrophoresis, Sp2a was shown to have three distinct molecules, while Sp2b showed two. The molecular weight of one component of Sp2a was 71,000 and that of one component of Sp2b was 13,500, as determined by gel filtration. A third antigen behaved electrophoretically and chromatographically like γ-globulin, but was separated from it by (NH4)2SO4 precipitation. The other two antigens did not show any characteristic features and behaved like many other non-specific tissue antigens. [ABSTRACT FROM AUTHOR]

Lymph node tissue from guinea-pigs immunized against one of several antigens was cultured in different media in order to determine conditions under which maximal amounts of antibody are formed in vitro. The amounts of antibody formed were variable and bore no relation m the level of serum antibody in the tissue donor. Heterologous sera of several origins, when included in the culture medium, varied very markedly in their capacity to support antibody production in vitro. [ABSTRACT FROM AUTHOR]

Background: Blood donors represent a healthy population, whose red blood cell (RBC) alloantibody persistence or evanescence kinetics may differ from those of immunocompromised patients. A better understanding of the biologic factors impacting antibody persistence is warranted, as the presence of alloantibodies may impact donor health and the fate of the donated blood product.Methods: Donor/donation data collected from four US blood centers from 2012 to 2016 as part of the Recipient Epidemiology and Donor Evaluation Study-III (REDS-III) were analyzed. Clinically significant antibodies from blood donors with more than one donation who underwent at least one follow-up antibody screen after the initial antibody identification were included. Of 632,378 blood donors, 481 (128 males and 353 females) fit inclusion criteria.Results: Antibody screens detected 562 alloantibodies, with 368 of 562 (65%) of antibodies being persistently detected and with 194 of 562 (35%) becoming evanescent. Factors associated with antibody persistence included antibody specificity, detection at the first donation, reported history of transfusion, and detection of multiple antibodies concurrently. Anti-D, C, and Fya were most likely to persist, while anti-M, Jka , and S were most frequently evanescent.Conclusions: These data provide insight into variables impacting the duration of antibody detection, and they may also influence blood donor center policies regarding donor recruitment/acceptance. [ABSTRACT FROM AUTHOR]

A mathematical antidrug antibody (ADA) model was developed to quantitatively assess immunogenicity for therapeutic proteins. The ADA model was built with antibody titer data in subjects from 10 clinical trials. The time course of the antibody titers was quantitatively characterized with a two‐component semimechanistic model describing the double peaks of ADA titers. The relationship between antibody titer and incidence was also explored. The ADA incidences in subjects from 12 clinical trials were used for internal and external validations. The ADA titers reasonably predicted the incidence of antibody. The model‐predicted elimination rate constant for antibody titer was 14.1 × 10−3 day−1 and 8.1 × 10−3 day−1 in healthy subjects and patients, respectively. This research provided a useful tool to quantitatively evaluate immunogenicity and its impact for therapeutic proteins. [ABSTRACT FROM AUTHOR]

Background: Therapeutic intervention strategies in complement-mediated hemolytic diseases are still inappropriate, and lethal events cannot be reliably prevented. As an in vitro model of intravascular hemolysis, a sensitive flow cytometric assay was designed using red blood cells (RBCs) of patients with paroxysmal nocturnal hemoglobinuria (PNH) as target cells. Complement activation by human allo- and autoantibodies directed against RBC antigens and the effect of different complement inhibitors were studied.Study Design and Methods: RBCs of patients with a PNH III RBC clone of more than 20% were coated with different human allo- or autoantibodies. Hemolysis was initiated with pooled normal human AB serum with or without the addition of complement inhibitors. Loss of PNH III RBCs was estimated by flow cytometry.Results: RBC antibodies of 174 different patients representing 37 different specificities were tested for their potency to activate complement. In correlation with blood group specificities roughly three different patterns were observed: 1) strong and regular, 2) sporadic, and 3) weak or absent complement activation. Remarkably strong complement activators were among antibodies directed against high-prevalence blood group antigens. The C5 inhibitor eculizumab abrogated mild but not strong complement activation, even in presence of excess inhibitor. However, this residual complement activity could be further depressed by combining eculizumab with other inhibitors.Conclusion: The PNH hemolysis assay offers a sensitive tool for in vitro analyses of classical pathway-mediated complement activation. The recognition of additive effects of complement inhibitors may guide novel intervention strategies against unwanted complement damage. [ABSTRACT FROM AUTHOR]

Background: Patients treated with intravenous immunoglobulins (IVIG) rarely experience symptomatic hemolysis. Although anti-A and anti-B isoagglutinins from the product are involved in most cases, the actual mechanisms triggering hemolysis are unclear.Study Design and Methods: A prospective, open-label, multicenter, single-arm clinical trial in 57 patients with immune thrombocytopenia treated with IVIG (Privigen, CSL Behring) was conducted.Results: Twenty-one patients received one infusion (1 g/kg) and 36 received two infusions (2 × 1 g/kg) of IVIG. After a study duration of more than 2 years, no cases of clinically significant hemolysis as defined in the protocol were identified. Data of patients with mild hematologic and biochemical changes were analyzed in more detail. Twelve cases (10/23 patients with blood group A1 and 2/11 patients with blood group B, all having received 2 g/kg IVIG) were adjudicated as mild hemolysis (median hemoglobin [Hb] decrease, -3.0 g/dL); Hb decreases were transient, with partial or full recovery achieved by last visit. Eighteen patients (31.6%), all with non-O blood group, of whom 16 (88.9%) received 2 g/kg IVIG, fulfilled post hoc criteria for hemolytic laboratory reactions. Red blood cell (RBC) eluates of all direct antiglobulin test-positive samples were negative for non-ABO blood group antibodies. Blood groups A and B antigen density on RBCs appeared to be a risk factor for hemolytic laboratory reactions. Platelet response to treatment was observed in 42 patients (74%); eight of 12 patients with complete response had blood group A1.Conclusion: Isoagglutinins are involved in clinically nonsignificant hemolysis after treatment with IVIG, but individual susceptibility varies greatly. [ABSTRACT FROM AUTHOR]

Background: Anti-human neutrophil antigen (HNA) antibodies have been implicated in the development of neonatal alloimmune neutropenia (NAN) and autoimmune neutropenia (AIN). There are many conventional assay methods that detect anti-HNA antibodies. However, a method to measure multiple samples and detect several anti-HNA antibodies simultaneously is needed.Study Design and Methods: We developed a new method, the extracted granulocyte antigen immunofluorescence assay (EGIFA), to analyze anti-HNA-1a, -1b, and -2 antibodies in sera. The results obtained by EGIFA were evaluated in comparison with those from several standard assay methods. Anti-HNA antibodies in serum samples from nine familial cases with suspected NAN (n = 19) and children with suspected AIN (n = 88) were also measured by EGIFA.Results: The evaluation of nine serum samples with anti-HNA antibodies suggested that EGIFA demonstrated equivalent specificity and superior sensitivity to monoclonal antibody-specific immobilization of granulocyte antigens and had comparable sensitivity to the granulocyte indirect immunofluorescence test. EGIFA successfully detected anti-HNA-1a or -1b antibodies in seven of nine familial cases with suspected NAN. EGIFA detected anti-HNA antibodies in 40.9% of children with suspected AIN. Among them, isolated anti-HNA-1a or -1b antibody was detected in 4.5 or 12.5% of children, respectively, and anti-HNA-2 antibody was identified in 3.4% of children. The 30.8% (16 of 52) of children negative for anti-HNA antibody by EGIFA were positive for anti-HLA antibody.Conclusion: EGIFA facilitated the measurement of anti-HNA-1a, -1b, and/or -2 antibodies in sera. The prompt measurement of anti-HNA antibodies will improve the diagnosis and clinical management of patients with suspected NAN or AIN. [ABSTRACT FROM AUTHOR]

Background When dogs are transfused, blood compatibility testing varies widely but may include dog erythrocyte antigen ( DEA) 1 typing and rarely cross-matching. Objectives Prospective study to examine naturally occurring alloantibodies against red blood cells ( RBCs) and alloimmunization by transfusion using 2 antiglobulin-enhanced cross-match tests. Animals Eighty client-owned anemic, 72 donor, and 7 control dogs. Methods All dogs were typed for DEA 1 and some also for DEA 4 and DEA 7. Major cross-match tests with canine antiglobulin-enhanced immunochromatographic strip and gel columns were performed 26-129 days post-transfusion (median, 39 days); some dogs had an additional early evaluation 11-22 days post-transfusion (median, 16 days). Plasma from alloimmunized recipients was cross-matched against RBCs from 34 donor and control dogs. Results The 2 cross-match methods gave entirely concordant results. All 126 pretransfusion cross-match results for the 80 anemic recipients were compatible, but 54 dogs died or were lost to follow up. Among the 26 recipients with follow-up, 1 dog accidently received DEA 1-mismatched blood and became cross-match-incompatible post-transfusion. Eleven of the 25 DEA 1-matched recipients (44%) became incompatible against other RBC antigens. No naturally occurring anti- DEA 7 alloantibodies were detected in DEA 7− dogs. Conclusions and clinical importance The antiglobulin-enhanced immunochromatographic strip cross-match and laboratory gel column techniques identified no naturally occurring alloantibodies against RBC antigens, but a high degree of post-transfusion alloimmunization in dogs. Cross-matching is warranted in any dog that has been previously transfused independent of initial DEA 1 typing and cross-matching results before the first transfusion event. [ABSTRACT FROM AUTHOR]

Background: Transfusion-related acute lung injury (TRALI) is a major complication of hemotherapy that may occur after the transfusion of any blood type component. Several clinical reports have suggested the presence of anti-HLA antibodies in the blood product. This study sought to examine the role of anti-HLA-A2 antibodies in polymorphonuclear neutrophil (PMN) activation and thus in endothelial permeability.Study Design and Methods: PMN activation was assessed by both nicotinamide adenine dinucleotide phosphate oxidase (NADPH oxidase) activity and reactive oxygen species (ROS) production. A coculture assay of EA.hy926 endothelial cells with PMNs or differentiated-PLB-985 cells, a model of neutrophil-like cells, was performed to estimate the impact of ROS on endothelial permeability.Results: Anti-HLA-A2 antibodies significantly increased PMN activation, with subsequent endothelial dysfunction. Phagocyte NADPH oxidase (NOX2) activity was shown to be involved in this process and ROS themselves were demonstrated to induce VE-cadherin cleavage and endothelial permeability.Conclusion: Our data may support the existence of a critical anti-HLA-A2 antibody threshold for PMN activation, with NOX2 activity and subsequent endothelial permeability in the two-hit model of TRALI. [ABSTRACT FROM AUTHOR]

Background: A general understanding of allergic transfusion reaction mechanisms remains elusive. Multiple mechanisms have been proposed, but none have been compared experimentally.Study Design and Methods: We used histamine release (HR) from healthy human donor basophils to model allergic transfusion reactions. Platelet component supernatant (plasma), platelet lysate, and manipulated platelet lysates (dialyzed, delipidated, trypsinized, mild heat-inactivated, and ultracentrifuged) were used to characterize allergic stimuli. Immunoglobulin-dependent mechanisms were investigated through cell surface immunoglobulin depletion and ibrutinib signaling inhibition. HR induced by platelet mitochondria was compared with HR by platelet lysate with or without DNase treatment.Results: Robust, dose-responsive HR to platelet lysate was observed in two of eight nulliparous, never-transfused, healthy donors. No HR was observed with plasma. Among manipulated platelet lysates, only trypsin treatment significantly reduced HR (39% reduction; p = 0.008). HR in response to platelet lysate significantly decreased with either cell surface immunoglobulin depletion or ibrutinib pretreatment. Platelet mitochondria induced minimal basophil HR, and DNase treatment did not inhibit platelet lysate-induced HR.Conclusion: Type I immediate hypersensitivity to platelet proteins may be an allergic transfusion reaction mechanism. Prior sensitization to human proteins is not required for basophil responses to platelet proteins. Further study into the relative contributions of hypersensitivity to platelet versus plasma proteins in transfusion is warranted. [ABSTRACT FROM AUTHOR]

Background: Acquired thrombotic thrombocytopenia purpura (TTP) is a life-threatening illness caused by autoantibodies that decrease the activity of ADAMTS13, the von Willebrand factor-cleaving protease. Despite efficacy of plasma exchange, mortality remains high and relapse is common. Improved therapies may come from understanding the diversity of pathogenic autoantibodies on a molecular or genetic level. Cloning comprehensive repertoires of patient autoantibodies can provide the necessary tools for studying immunobiology of disease and developing animal models.Study Design and Methods: Anti-ADAMTS13 antibodies were cloned from four patients with acquired TTP using phage display and characterized with respect to genetic origin, inhibition of ADAMTS13 proteolytic activity, and epitope specificity. Anti-idiotypic antisera raised to a subset of autoantibodies enabled comparison of their relatedness to each other and to polyclonal immunoglobulin (Ig)G in patient plasma.Results: Fifty-one unique antibodies were isolated comprising epitope specificities resembling the diversity found in circulating patient IgG. Antibodies directed both to the amino terminal domains and to those requiring the ADAMTS13 cysteine-rich/spacer region for binding inhibited proteolytic activity, while those solely targeting carboxy-terminal domains were noninhibitory. Anti-idiotypic antisera raised to a subset of antibody clones crossreacted with and reduced the inhibitory activity of polyclonal IgG from a set of unrelated patients.Conclusions: Anti-ADAMTS13 autoantibodies isolated by repertoire cloning display the diversity of epitope specificities found in patient plasma and provide tools for developing animal models of acquired TTP. Shared idiotypes of inhibitory clones with circulating IgG from multiple patients suggest common features of pathogenic autoantibodies that could be exploited for developing more targeted therapies. [ABSTRACT FROM AUTHOR]

Aim It has been reported that the innate immune system plays a pivotal role in the pathogenesis of immunoglobulin A nephropathy (IgAN). To explore non-invasive monitoring of disease activity in children with IgAN, we examined whether expressions of mRNA for innate immunity-associated functional molecules: CC ligand chemokine 5 ( CCL5), fractalkine/ CX3 CL1, interferon-γ-induced protein 10 ( IP-10), monocyte chemoattractant protein 1 ( MCP-1), retinoic acid-inducible gene- I ( RIG- I), and toll-like receptor 3 ( TLR3) in urinary sediment from patients with IgAN correlate with histologic parameters. Methods Twenty consecutive children with IgAN and four children with thin basement membrane disease (serving as a non-inflammatory control) were enrolled in this pilot study. Urinary mRNA expressions of target genes were examined real-time quantitative polymerase chain reaction. Results The expressions of CCL5, fractalkine and RIG- I were significantly increased in IgAN (all P < 0.05). Although no significant correlation was observed between mRNA expressions of these three molecules and clinical parameters, such as levels of urinary protein excretion, degrees of occult blood in urine and serum albumin, the expression of fractalkine was significantly correlated with the histological activity index ( P = 0.022) and the chronicity index ( P = 0.005). Furthermore, intense glomerular immune activity of fractalkine was observed in biopsy specimens in patients with moderately to severe proliferative IgAN. Conclusion Regional expression of fractalkine may be involved in the pathogenesis of childhood IgAN. Although our present findings remain preliminary, measurement of mRNA expression of fractalkine in urinary sediment could be used as a non-invasive method for predicting histologic severity in IgAN in children. Further studies of this issue are needed. [ABSTRACT FROM AUTHOR]

Fundamentally new approaches are required for the development of vaccines to pre-empt and protect against emerging and pandemic influenzas. Current strategies involve post-emergent homotypic vaccines that are modelled upon select circulating 'seasonal' influenzas, but cannot induce cross-strain protection against newly evolved or zoonotically introduced highly pathogenic influenza (HPI). Avian H5N1 and the less-lethal 2009 H1N1 and their reassortants loom as candidates to seed a future HPI pandemic. Therefore, more universal 'seasoned' vaccine approaches are urgently needed for heterotypic protection ahead of time. Pivotal to this is the need to understand mechanisms that can deliver broad strain protection. Heterotypic and heterosubtypic humoral immunities have largely been overlooked for influenza cross-protection, with most 'seasoned' vaccine efforts for humans focussed on heterotypic cellular immunity. However, 5 years ago we began to identify direct and indirect indicators of humoral-herd immunity to protein sites preserved among H1N1, H3N2 and H5N1 influenzas. Since then the evidence for cross-protective antibodies in humans has been accumulating. Now proposed is a rationale to stimulate and enhance pre-existing heterotypic humoral responses that, together with cell-mediated initiatives, will deliver pre-emptive and universal human protection against emerging epidemic and pandemic influenzas. [ABSTRACT FROM AUTHOR]

Summary B lymphoblastic leukaemia (B-ALL) cells are characterized by the expression of various B-cell antigens. Expression of T/Natural Killer-cell antigens, however, has rarely been reported in B-ALL (TAg+ B-ALL), and the significance of this aberrant antigen expression is unclear. We thus analysed the frequency of TAg+ B-ALL at our institution and investigated its significance in the context of immunophenotypes, cytogenetic/molecular findings, and prognosis. We reviewed 134 consecutive cases of B-ALL and found 18 cases (13·4%) of TAg+ B-ALL. The most common aberrant T-cell antigens expressed were CD2, CD5, and CD7 at equivalent rates (each in six cases), CD4 (two cases), and CD56 (three cases). Adverse cytogenetic abnormalities were seen in a significantly larger proportion of the TAg+ cases (72·2%) than the TAg− cases (32·2%; P = 0·003). Multivariate Cox-regression analysis showed that the risk of relapse over time was higher in the TAg+ cases, independent of high risk status (based on age and white blood cell count) and the presence of adverse cytogenetic abnormalities (hazard ratio = 2·256, P = 0·065). These findings suggest that T-cell antigen expression in B-ALL may be an independent predictor of poor prognosis, and a useful marker to identify patients at increased risk for relapse and for harbouring adverse cytogenetic abnormalities. [ABSTRACT FROM AUTHOR]

The article presents a report documenting the additions and revisions to the nomenclature of HLA specificities. It states that a number of HLA gene fragments have been reported and named which includes HLA-T previously known as HLA-16 and HLA-V previously known as HLA-75. It further discusses the conditions for acceptance of new genes and allele sequences for official names. It also presents lists of the serological specificities or antigens associated with the alleles.

OBJECTIVES: To determine whether cardiovascular exercise training resulted in improved antibody responses to influenza vaccination in sedentary elderly people who exhibited poor vaccine responses. DESIGN: Single-site randomized parallel-arm 10-month controlled trial. SETTING: University of Illinois at Urbana-Champaign. PARTICIPANTS: One hundred forty-four sedentary, healthy older (69.9 ± 0.4) adults. INTERVENTIONS: Moderate (60–70% maximal oxygen uptake) cardiovascular exercise was compared with flexibility and balance training. MEASUREMENTS: The primary outcome was influenza vaccine response, as measured according to hemagglutination inhibition (HI) anti-influenza antibody titer and seroprotective responses (HI titer ≥40). Secondary measures included cardiovascular fitness and body composition. RESULTS: Of the 160 participants enrolled, 144 (90%) completed the 10-month intervention with excellent compliance (∼83%). Cardiovascular, but not flexibility, exercise intervention resulted in improvements in indices of cardiovascular fitness, including maximal oxygen uptake. Although not affecting peak (e.g., 3 and 6 weeks) postvaccine anti-influenza HI titers, cardiovascular exercise resulted in a significant increase in seroprotection 24 weeks after vaccination (30–100% dependent on vaccine variant), whereas flexibility training did not. CONCLUSION: Participants randomized to cardiovascular exercise experienced improvements in influenza seroprotection throughout the entire influenza season, whereas those in the balance and flexibility intervention did not. Although there were no differences in reported respiratory tract infections, the exercise group exhibited reduced overall illness severity and sleep disturbance. These data support the hypothesis that regular endurance exercise improves influenza vaccine responses. [ABSTRACT FROM AUTHOR]