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Dendritic cells capable of influencing immunity exist as functionally distinct subsets, T cell-tolerizing and T cell-immunizing subsets. The present paper reviews how these subsets of DCs develop, differentiate and function in vivo and in vitro at the cellular and molecular level. In particular, the role of DCs in the generation of regulatory T cells is highlighted. [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]

Background: Many factors influence the composition of the sinus microflora. The microbial balance is most disturbed by the use of antibacterial agents. Superinfections caused by more than one pathogen may then occur. Despite treatment, including surgery and long‐term antibiotic therapy, many patients with sinusitis do not experience significant relief from their symptoms. It has been hypothesized that an imbalance in the gut microbiota may also be responsible for the chronicity of sinusitis. Our goal was therefore to identify selected gut indicator bacteria that play a role in immunity in patients with chronic sinusitis. In addition, compare the number of selected bacteria in two groups of patients: with chronic sinusitis and with chronic rhinosinusitis (CRS) with concomitant diseases and/or symptoms other than CRS. Results: Significantly decreased numbers of Bifidobacterium spp. and Faecalibacterium prauznitzi bacteria were observed in patients from the G1 group. The majority of patients from this group (12 out of 13) had a significantly decreased number of Bifidobacterium and Akkermansia muciniphila bacteria, which are involved in the nutrition and regeneration of gut epithelium cells and have anti‐inflammatory properties. In group G2 (patients with chronic sinusitis and symptoms of comorbidities) a decreased number of F. prausnitzii, Bifidobacterium spp., A. muciniphila and Lactobacillus spp. bacteria was observed. A small percentage of patients in this group showed overgrowth of yeast‐like fungi. Conclusion: Although the more research is needed, possibly the gut microbiota indicator bacteria number analyses might enable to plan personalized prebiotic and probiotic treatment, which could support intestine microbiota and mucosal immunity patients suffering from chronic sinusitis. [ABSTRACT FROM AUTHOR]

Lipid droplet (LD) in vegetative tissues has recently been implicated in environmental responses in plants, but its regulation and its function in stress tolerance are not well understood. Here, we identified a Membrane Occupation and Recognition Nexus 1 (MORN1) gene as a contributor to natural variations of stress tolerance through genome‐wide association study in Arabidopsis thaliana. Characterization of its loss‐of‐function mutant and natural variants revealed that the MORN1 gene is a positive regulator of plant growth, disease resistance, cold tolerance, and heat tolerance. The MORN1 protein is associated with the Golgi and is also partly associated with LD. Protein truncations that disrupt these associations abolished the biological function of the MORN1 protein. Furthermore, the MORN1 gene is a positive regulator of LD abundance, and its role in LD number regulation and stress tolerance is highly linked. Therefore, this study identifies MORN1 as a positive regulator of LD abundance and a contributor to natural variations of stress tolerance. It implicates a potential involvement of Golgi in LD biogenesis and strongly suggests a contribution of LD to diverse processes of plant growth and stress responses. [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]

We aimed to estimate self‐reported vaccine coverage and SARS‐CoV‐2 anti‐N and anti‐S seroprevalence in Mexico overall and for five vaccine types. We used a nationally representative survey with 7236 dried blood spot samples for adults 18 years and older collected from August to November 2021. Anti‐N and anti‐S seroprevalence were estimated adjusting for the sensitivity and specificity of the immunoassay test. A multivariate Poisson regression model was used to estimate seroprevalence by vaccine type and by age group adjusting for confounders and test performance. Vaccination coverage was 74%, being higher in women compared to men, high socioeconomic status (SES) compared to low and middle SES, graduates compared to people with high school, and formal workers compared to other employment statuses. Anti‐N seroprevalence was 59.2%, compared to 84.1% anti‐S seroprevalence. Anti‐S seroprevalence was higher for vaccinated than unvaccinated participants. All vaccines were associated with more than 70% anti‐S seroprevalence, with the lowest being observed for CoronaVac and Ad5‐nCoV. Fully vaccinated participants over 60 years presented a lower seroprevalence (77.6%) compared to younger adults (91.1%), with larger differences for ChAdOx1 and CoronaVac vaccines. Between August and November 2021, three out of four Mexican adults had been vaccinated. Vaccination was associated with a higher positivity to anti‐S antibodies. While antibodies do not reflect immunity, our results suggest that booster doses should be offered to people over 60 years of age and to adults who received Ad5‐nCoV or CoronaVac as primary vaccination schemes. [ABSTRACT FROM AUTHOR]

The characteristic maximum lifespan varies enormously across animal species from a few hours to hundreds of years. This argues that maximum lifespan, and the ageing process that itself dictates lifespan, are to a large extent genetically determined. Although controversial, this is supported by firm evidence that semelparous species display evolutionarily programmed ageing in response to reproductive and environmental cues. Parabiosis experiments reveal that ageing is orchestrated systemically through the circulation, accompanied by programmed changes in hormone levels across a lifetime. This implies that, like the circadian and circannual clocks, there is a master 'clock of age' (circavital clock) located in the limbic brain of mammals that modulates systemic changes in growth factor and hormone secretion over the lifespan, as well as systemic alterations in gene expression as revealed by genomic methylation analysis. Studies on accelerated ageing in mice, as well as human longevity genes, converge on evolutionarily conserved fibroblast growth factors (FGFs) and their receptors, including KLOTHO, as well as insulin‐like growth factors (IGFs) and steroid hormones, as key players mediating the systemic effects of ageing. Age‐related changes in these and multiple other factors are inferred to cause a progressive decline in tissue maintenance through failure of stem cell replenishment. This most severely affects the immune system, which requires constant renewal from bone marrow stem cells. Age‐related immune decline increases risk of infection whereas lifespan can be extended in germfree animals. This and other evidence suggests that infection is the major cause of death in higher organisms. Immune decline is also associated with age‐related diseases. Taking the example of Alzheimer's disease (AD), we assess the evidence that AD is caused by immunosenescence and infection. The signature protein of AD brain, Aβ, is now known to be an antimicrobial peptide, and Aβ deposits in AD brain may be a response to infection rather than a cause of disease. Because some cognitively normal elderly individuals show extensive neuropathology, we argue that the location of the pathology is crucial – specifically, lesions to limbic brain are likely to accentuate immunosenescence, and could thus underlie a vicious cycle of accelerated immune decline and microbial proliferation that culminates in AD. This general model may extend to other age‐related diseases, and we propose a general paradigm of organismal senescence in which declining stem cell proliferation leads to programmed immunosenescence and mortality. [ABSTRACT FROM AUTHOR]

Follicular T helper (Tfh) cells are a subset of CD4+ T cells that play an important role in the formation of germinal centers and the maturation and differentiation of affinity‐matured B cells. Recent studies have demonstrated important functions of Tfh cells in tertiary lymphoid structures of tumors, revealing great potential of Tfh cells in tumor immunity. However, Tfh development is incompletely understood. The differentiation of Tfh cells is a complex, multistage process regulated at the DNA, RNA and protein levels. This review just summarizes current research on the molecular mechanisms of Tfh cell differentiation to better understand the role of Tfh cells in antitumor immunity. [ABSTRACT FROM AUTHOR]

SUMMARY: Plant cells possess a two‐layered immune system consisting of pattern‐triggered immunity (PTI) and effector‐triggered immunity (ETI), mediated by cell surface pattern‐recognition receptors and intracellular nucleotide‐binding leucine‐rich repeat receptors (NLRs), respectively. The CONSTITUTIVE EXPRESSION OF PR GENES 5 (CPR5) nuclear pore complex protein negatively regulates ETI, including ETI‐associated hypersensitive response. Here, we show that CPR5 is essential for the activation of various PTI responses in Arabidopsis, such as resistance to the non‐adapted bacterium Pseudomonas syringae pv. tomato DC3000 hrcC‐. In a forward‐genetic screen for suppressors of cpr5, we identified the mediator protein MED4. Mutation of MED4 in cpr5 greatly restored the defective PTI of cpr5. Our findings reveal that CPR5 plays opposite roles in regulating PTI and ETI, and genetically regulates PTI via MED4. [ABSTRACT FROM AUTHOR]

In 2014, the Brazilian National Immunization Program implemented the universal vaccination against the hepatitis A virus (HAV) for children aged 12 months and older, applying a single dose of the inactivated virus vaccine. It is essential to carry out follow‐up studies in this population, aiming to verify the longevity of HAV immunological memory. This study evaluated the humoral and cellular immune response of a cohort of children vaccinated between 2014 and 2015, and further investigated between 2015 and 2016, and who had their initial antibody response assessed after the single dose. A second evaluation took place in January 2022. We examined 109 children out of the 252 that took part in the initial cohort. Seventy (64.2%) of them had anti‐HAV IgG antibodies. Cellular immune response assays were performed in 37 anti‐HAV‐negative and 30 anti‐HAV‐positive children. Production of interferon‐gamma (IFN‐y) stimulated with the VP1 antigen was demonstrated in 34.3% of these 67 samples. Of the 37 negative anti‐HAV samples, 12 (32.4%) produced IFN‐y. Among the 30 anti‐HAV‐positive, 11 (36.7%) produced IFN‐y. In total, 82 (76.6%) children presented some type of immune response against HAV. These findings demonstrate the persistence of immunological memory against HAV in the majority of children vaccinated between 6 and 7 years with a single dose of the inactivated virus vaccine. [ABSTRACT FROM AUTHOR]

Effective vaccines have reduced the morbidity and mortality caused by severe acute respiratory syndrome coronavirus‐2 infection; however, the elderly remain the most at risk. Understanding how vaccines generate protective immunity and how these mechanisms change with age is key for informing future vaccine design. Cytotoxic CD8+ T cells are important for killing virally infected cells, and vaccines that induce antigen‐specific CD8+ T cells in addition to humoral immunity provide an extra layer of immune protection. This is particularly important in cases where antibody titers are suboptimal, as can occur in older individuals. Here, we show that in aged mice, spike epitope–specific CD8+ T cells are generated in comparable numbers to younger animals after ChAdOx1 nCoV‐19 vaccination, although phenotypic differences exist. This demonstrates that ChAdOx1 nCoV‐19 elicits a good CD8+ T‐cell response in older bodies, but that typical age‐associated features are evident on these vaccine reactive T cells. [ABSTRACT FROM AUTHOR]

Background: The impact of exposure to air pollutants, such as fine particulate matter (PM), on the immune system and its consequences on pediatric asthma, are not well understood. We investigated whether ambient levels of fine PM with aerodynamic diameter ≤2.5 microns (PM2.5) are associated with alterations in circulating monocytes in children with or without asthma. Methods: Monocyte phenotyping was performed by cytometry time‐of‐flight (CyTOF). Cytokines were measured using cytometric bead array and Luminex assay. ChIP‐Seq was utilized to address histone modifications in monocytes. Results: Increased exposure to ambient PM2.5 was linked to specific monocyte subtypes, particularly in children with asthma. Mechanistically, we hypothesized that innate trained immunity is evoked by a primary exposure to fine PM and accounts for an enhanced inflammatory response after secondary stimulation in vitro. We determined that the trained immunity was induced in circulating monocytes by fine particulate pollutants, and it was characterized by the upregulation of proinflammatory mediators, such as TNF, IL‐6, and IL‐8, upon stimulation with house dust mite or lipopolysaccharide. This phenotype was epigenetically controlled by enhanced H3K27ac marks in circulating monocytes. Conclusion: The specific alterations of monocytes after ambient pollution exposure suggest a possible prognostic immune signature for pediatric asthma, and pollution‐induced trained immunity may provide a potential therapeutic target for asthmatic children living in areas with increased air pollution. [ABSTRACT FROM AUTHOR]

Click here to view the accompanying paper in this issue. [ABSTRACT FROM AUTHOR]

Abstract: Females of the ectoparasitoid Habrobracon hebetor attack and envenomate numerous host individuals during oviposition. The vectoring of the entomopathogenic fungus Beauveria bassiana during the adhesion stage by ectoparasitoid females among the wax moth larvae Galleria mellonella was explored under laboratory conditions. Vectoring occurred both from infected parasitoids to wax moth larvae and from infected to healthy wax moth larvae by parasitoids. The efficacy of vectoring in both cases was dose dependent. Parasitoid females were unable to recognize infected larvae in a labyrinth test. In addition, the presence of H. hebetor females significantly (1.5–13 fold) increased the mycoses level in clusters of G. mellonella, with 40% of the larvae infected with fungal conidia. Envenomation by H. hebetor increased conidia germination on the cuticles of the wax moth larvae by 4.4 fold. An enhanced germination rate (2 fold) was registered in the n‐hexane epicuticular extract of envenomated larvae compared to that of healthy larvae. Both envenomation and mycoses enhanced the phenoloxidase (PO) activity in the integument of G. mellonella and, in contrast, decreased the encapsulation rate in hemolymphs. We hypothesize that changes in the integument property and inhibition of cellular immunity provide the highest infection efficacy of entomopathogenic fungi with H. hebetor. [ABSTRACT FROM AUTHOR]

This article presents an index of authors who have contributed to the publication of the "Journal of Fish Diseases." C. Agius, M.T. Horne and P.D. Ward contributed to the research paper "Immunization of Rainbow Trout, Salmo gairdneri Richardson, Against Vibriosis: Comparison of an Extract Antigen With Whole Cell Bacterins by Oral and Intraperitoneal Routes." D.F. Amend, K.A. Johnson, T.R. Croy and D.H. McCarthy presented the research paper "Some Factors Affecting the Potency of Yersinia ruckeri Bacterins."

`The O9-specific mannan of Escherichia coil was synthesized in vitro from GDP-[14C]mannose by membranes which were obtained from a phosphomannose isomerase-less mutant of E. coli O9:K29- :H-, Subsequent treatment of the membranes with dilute acid liberated a neutral product, whereas with aqueous phenol a charged product was obtained. Chromatography on DEAE-cellulose, incubation with alkaline phosphatase and microdetermination showed that the charged mannan was substituted with one phosphate per chain. The neutral 14C-labelled product of the incubation hr vitro was reduced with sodium boro[³H]hydride. After total acid hydrolysis, the radioactive material was chromatographed on paper in the presence of borate. It was found that [³H]glucitol, but no [³H, 14C]mannitol was present. When the neutral product, which was obtained after incubation of 14C-prelabelled membranes with nonradioactive GDP-mannose, was hydrolyzed with and without prior reduction with non-radioactive sodium borohydride, in subsequent paper chromatography, [14C]glucitol or [14C]glucose was found. The glucose was also converted enzymatically to gluconic acid, which was identified by paper electrophoresis. These results show that in the neutral O9-specific mannan glucose is at the reducing end and they indicate that the mannan chain grows at the non-reducing end. This is discussed with respect to the overall mechanism of the biosynthesis of the 09 antigen. [ABSTRACT FROM AUTHOR]

Psychosocial factors can influence immune functions: the brain intermediates between the outside world and the inside of the body. The functional interaction between the central nervous system and the immune system is effected by 2 different pathways: the nervous "wiring system" innervating lymphoid tissues and the "soluble connection" via the neuroendocrine system. The paper reviews data from the literature regarding changes in susceptibility to infections due to stressful conditions. Emphasis is given to information regarding infection of the oral cavity and the upper respiratory tract. [ABSTRACT FROM AUTHOR]

The lack of progress in development of vaccines to stimulate local protection in the urinary tract is attributable in part to the lack of information regarding mechanisms of local immunity and to the difficulty in antigen administration at this site. Experiments reported in this paper indicate that the urinary tract in rats forms part of an effector network linking mucosal organs (the common mucosal immune system). Concomitant immunization of the intestine and urinary tract with ovalbumin resulted in the appearance at both sites of antiovalbumin-containing cells (ACC) of IgA specificity. The gut origin of ACC in the urinary tract was confirmed by demonstrating in similarly immunized rats abrogation of the urinary tract response by chronic drainage of the thoracic lymphatic duct during the post-challenge period and by demonstrating the appearance of radio labelled ACC in the urinary tract after injection of labelled autologous thoracic duct lymphocytes collected during the post-challenge period. These experiments indicate a role for oral immunization in enhancing the local antibody response in the urinary tract against invading pathogens. [ABSTRACT FROM AUTHOR]

In the radiation immunity test for telecommunication equipment, an electromagnetic applicator such as chamber, a transmission electron microscopy (TEM) cell and a general transmission electron microscopy (GTEM) cell are used. Characteristics that include a semianechoic uniformity of the electromagnetic field without a device under test have been evaluated. However, characteristics that include an electromagnetic field in the presence of the device under test have not been reported. In this paper, it is recognized that these electromagentic application are designed in such a way that they can generate an electromagnetic field distribution generated by the plane wave incident on a conducting sphere, the electric field is evaluated and compared in the case in which the device under test is placed within the application. Further, evaluation results are include for the size of the device under test for which the immunity test is possible in each applicator. The evaluation method first derives the theoretical value of the scattered electric field when a plane wave is incident on the conducting sphere in free space. Next , these theoretical values are compared with the measured electric field values around the conducting sphere in each electromagnetic applicator. It was found that the difference between the measured and the theoretical results is the smallest and the frequency dependence is the lowest in a semianechoic chamber. In the case of a TEM cell and a GTEM cell, it was found that the difference between the measured and the theoritical values is less than +6 dB if the magnitude of the device under test is less than one-third the spacing between the inner and outer conductors. [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]

Antigen 60 (A60), a member of the thermostable macromolecular antigen family (TMA) and main component of old tuberculin and purified protein derivative (PPD), has been purified from the cytoplasm of Mycobacterium bovis BCG; its structure and metabolism have already been described. In the present paper, the action of A60 on humoral immunity has been analysed by an ELISA type immunoassay, and that on cellular immunity by the mouse footpad swelling test. Injection of very low A60 doses into unprimed mice produced an undetectable level of anti-A60 antibodies: the effect or a booster inoculation was not appreciable in the absence of incomplete Freund's adjuvant, but was evident when the latter was added. Higher doses of the antigen produced an appreciable primary response, and a sharp and long-lasting secondary response, which had a 10-fold higher intensity in the presence of incomplete adjuvant. No detectable delayed hypersensitivity reactions were observed in unprimed mice after footpad injection of A60, whereas clear responses were elicited in primed mice. This effect was more pronounced when the footpad was injected after a secondary response than after a primary response, and it was invariably magnified by incomplete adjuvant. It is concluded that A60 is a powerful immunogen, which is able to induce primary and secondary responses and delayed hypersensitivity reactions, effects that are adjuvant-modulated and develop concurrently. [ABSTRACT FROM AUTHOR]

In a previous paper we described how the toxin ricin stimulates IgE but not IgG antibody responses in rats. In this study we have examined the cellular basis for this observation. The proportion of CD4- and CD8-positive cells present in the spleen at the peak of the IgE response was determined. Those animals injected with both ricin and antigen produced a substantial IgE response (50-fold increase). Their CD4+/CD8+ ratio was also markedly increased (P> 0.001l)compared with animals given toxin or antigen alone. In addition, mitogen-stimulated proliferation of mononuclear cells from spleens of the IgE-producing rats was enhanced nearly five-fold compared with cells from animals given toxin or allergen alone. The sensitivity of CD4- and CD8-positive rat spleen cells from unexposed animals to ricin in vitro was also studied. Spleen cells from untreated rats were co-cultured with optimal doses of mitogen and varying amounts of ricin. Mitogen-driven proliferation was inhibited at l0-3-10-6 mg/ml ricin. This effect was abrogated by the addition of as little as 0.01 m lactose but not by as much as 10 mg/mI mannan to the culture. Cultures depleted of CD4+ cells by rosetting were approximately 100 times more sensitive to ricin (P>0.01). Furthermore, the proportion of CD8 + to CD4+ cells present after culture of untreated cells with mitogen and ricin was significantly reduced. These results show (i) that the ability of ricin to increase the IgE response depends on the administration of antigen together with the toxin; (ii) that CD8+ spleen cells are more sensitive to ricin than CD4 + cells; (iii) that increased IgE responsiveness is associated with a reduction in the proportion of CD8- relative to CD4-positive cells in the spleen and increased responsiveness to mitogen. We believe that enhancement of the IgE responses by ricin may be due to inactivation of IgE-specific T-suppressor cells generated by immunization with antigen and speculate that these may be some or all of those bearing the CD8 marker. [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]

Previous work from this laboratory has shown that preimmunization of syngeneic hosts with Rous sarcoma virus (RSV)-transformed cells elicits a strong immune response against the growth of transplantable RSV sarcomas, mediated by T lymphocytes expressing the surface phenotype of helper cell precursors (Prat, Di Renzo & Comoglio, 1983). This paper shows that anti-tumour immunity may be elicited in tumour-bearing animals by triggering an experimentally pre-amplified T-helper cell population at the site of tumour growth. Mice were treated with cyclophosphamide (which inactivates suppressor T cells) followed by skin sensitization to trinitrochlorobenzene (TNCB) according to a protocol that has been shown to induce an appreciably amplified generation of trinitrophenyl (TNP)-reactive helper T cells (Fujiwara et al., 1984). Five weeks after TNCB painting, mice were transplanted s.c. with a lethal dose of RSV-induced syngeneic sarcoma cells; the injection at the tumour site of TNCB induced the regression of the tumour in mice in which the TNP-helper cell population has been amplified, but not in controls, including those injected with a non-related hapten or sensitized to TNCB without inactivation of suppressors. [ABSTRACT FROM AUTHOR]

This paper investigates desensitization in vitro, e.g. the inhibition of the transfer of contact sensitivity to picryl chloride by incubation of the passive transfer population with picrylated spleen cells. It asks whether desensitization is based on the same T-suppressor circuit which is responsible for the inhibition of passive transfer by antigen-specific T-suppressor factor (TsF). In this circuit, the T-suppressor cell which acts at the efferent stage (Ts-eff) makes TsF. This TsF depresses contact sensitivity indirectly by arming a T-acceptor cell (Tacc). The armed Tacc, when exposed to antigen (picrylated spleen cells), liberates a non-specific inhibitor which blocks the transfer of contact sensitivity. The three elements of this T-suppressor circuit occur in nylon wool-purified T cells prepared from the lymph nodes and spleens of mice four days after immunization with picryl chloride. This population transfers contact sensitivity and can be desensitized in vitro. It contains Ts-eff which can be isolated by panning (adherence) on picrylated albumin and detected by their ability to inhibit passive transfer. The 24 hr supernatant of cultures of these cells contains TsF. Finally the population contains Tacc which appear in the spleen 2 days after immunization and virtually disappear by 10 days. Further experiments demonstrated that the Ts-eff and the Tacc were not merely present but actually required for desensitization in vitro. Immune cells depleted of both Ts-eff (by panning on picrylated albumin) and Tacc (by arming with anti-oxazolone TsF and panning on oxazolonated albumin) cannot be desensitized. To restore desensitization both Ts-eff and Tacc must be added back. The Ts-eff were characterized as cyclophosphamide resistant, adult thymectomy sensitive cells (Cyr, ATx5), which adhered to antigen and were produced only by specific immunization. The Tacc were characterized as CF5, ATx5 cells which adhered to antigen only after arming with antigen-specific T-suppressor factor and were produced after immunization with an unrelated contact sensitizer, 'oxazolone'. It was concluded that desensitization in vitro was due to the interaction of two distinct T cells: the T-suppressor cell which acts at the efferent stage of the contact sensitivity reaction and the T-acceptor cell which becomes armed with the specific T-suppressor factor produced by the Ts-eff. [ABSTRACT FROM AUTHOR]

This paper describes a method for in vitro measurement of specific cell-mediated immunity in the mouse. Animals were immunized parenterally with ovalbumin in Freund's incomplete or complete adjuvant, and a direct migration inhibition assay was performed, using lymphoid cells from the draining lymph nodes. Migration inhibition was found to be antigen specific, correlated with systemic delayed-type hypersensitivity measured in vivo by skin testing, and had a high degree of sensitivity for ovalbumin. The migrating cells were identified as lymphocytes. Lymph node lymphocyte migration inhibition provides a reliable in vitro assay for regional CMl in the mouse. [ABSTRACT FROM AUTHOR]

Macrophage agglutination factor (MAggF) is a T-cell-dependent guinea-pig lymphokine with pH stability, heat stability and isoelectric point similar to fibronectin (see preceeding paper for details). Further observations confirm the similarity between MAggF and fibronectin. MAggF in unconcentrated lymph node cell culture supernatants bound reversibly to gelatin and fibrinogen. On gel filtration chromatography, most MAggF activity in a pooled concentrated lymphokine preparation was associated with molecules of 370,000 Daltons; lesser amounts of activity were found at 240,000 and 50,000 Daltons. All molecular weight forms of MAggF bound reversibly to gelatin. Guinea-pig plasma fibronectin prepared by affinity chromatography over gelatin had a molecular weight of about 450,000, a sub-unit on reduction of about 240,000 Daltons, and showed partial antigenic identity with human plasma fibronectin. Human and guinea-pig plasma fibronectin preparations showed MAggF activity when tested using guinea-pig peritoneal macrophages, but their potencies relative to a culture supernatant standard did not correlate with the content of immunoprecipitable fibronectin measured by anti-human fibronectin antiserum. However, anti-human fibronectin immunoadsorbents specifically and reversibly bound MAggF activity in culture supernatants. On the basis of our observations, we suggest MAggF is a guinea-pig tissue fibronectin. [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]

This paper describes the application of numerical methods to the arrangement of four leishmanial strains according to their reactivity and cross-reactivity in tests of parasite agglutination, indirect immunofluorescence and passive cutaneous anaphylaxis with antisera prepared by immunization or infection of rabbits, guinea-pigs and mice. Using corresponding pools of animal sera as test 'reagents' the antigenic reactivity of the four leishmanial strains (L. enriettii, L. tropica major, L. aethiopica and L. mexicana amazonensis) was scaled by reference to end point serum titres; and antigenic relationships between individual strain pairs were expressed as mean similarity coefficients, giving equal weight to the results of the different serological tests. Overall analysis of the results revealed that L. mexicana amazonensis and L. tropica major were the two most closely related strains, clustering with an overall similarity coefficient of 89 per cent, whereas coefficients of similarity between other strain combinations fell between 75 and 80 per cent. Although different sera had different discriminatory capacity for the leishmanial strains, two combinations of serum reagent and test system yielded relationships between the four strains that most closely approximated to the overall values. These were: (a) immunofluorescence tests with mouse antisera; and (b) agglutination tests with selected rabbit antisera. The results illustrate the use of a number of immunological parameters in relatingmicro organisms of a given genus, and reveal a serological classification of the four leishmanial strains at variance with their geographical origin. [ABSTRACT FROM AUTHOR]

This work concerns the involvement of brown adipose tissue in the immune system of the rat. Wistar rats were thymectomized, adipectomized (surgical extirpation of the interscapular brown adipose tissue), thymectornited and adipectomized, and. sham,operated at birth, only 8-week-old females being employed in the experiment The production of antibody to bovine serum albumin (BSA). and sheep red blood cells (SRBC), delayed skin reactions to BSA, rejection of thyroid allograft implanted under the kidney capsule, and development of experimental allergic encephalomyelitis were investigated. Neonatal adipectomy did not affect the production of anti-BSA and anti-SRBC antibodies. On the other hand, delayed skin reactions to BSA, rejection of thyroid allograft, and incidence and severity of allergic encephalomyelitis were much more pronounced In adipectomized animals. It has been postulated that the immune function of brown adipose tissue is an expression of the secretory activity of the tissue. Since the immunosuppressive effect of neonatal thymectomy on demyelinating disease was neutralized by neonatal adipectomy, and vice versa, and since thymectomy rendered ineffective the immunopotentiating influence of adipectomy on this disease, as demonstrated in thymo-adipectomized rats, it was concluded that the brown adipose tissue is a natural antagonist of the thymus in cell-mediated immunity. This paper also describes the extra thymuses which were situated in the vicinity of the thyroid and parathyroid lobes of 23.2 per cent of rats. [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]

Optimal proliferative response of T lymphocytes to purified protein derivative of tuberculin (PPD) in vitro requires that antigen be presented by autologous macrophages or allogeneic macrophages sharing HLA-D/DR determinants with the T cell donor. In some cases, however, T cells may respond to a limited extent to PPD in association with macrophages expressing different HLA-D/DR determinants. In this paper experiments are presented where various combinations of T cells and HLA-D/DR disparate macrophages were stimulated with PPD. We often found a strong PPD-specific response in HLA-D/DR-incompatible combinations in which the macrophages carried HLA-DR antigens known from serological studies to be cross-reactive with those of the T cell donor than in combinations in which this was not the case. Thus, the cross-reactions detected by serology may sometimes be reflected on a functional level in T lymphocyte/macrophages cooperation. [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]

Peripheral lung tissue contains large numbers of T cells, strategically located for immune surveillance at the blood-air interface. Given the intensity of antigenic exposure at this site, it is clear that local T-cell activation events require strict control, in order to maintain tissue homeostasis. How this control is achieved in this unique tissue microenvironment is unknown, and the present study sought to elucidate the process via detailed analysis of the surface phenotypic characteristics of freshly isolated lung T cells. We report below that these cells display typical characteristic of ‘postactivation’, notably elevated basal Ca2+ concentrations, down-modulated T-cell receptors, expression of Ia and ‘late’ activation antigens and concomitant CD4/CD8. However, levels of interleukin-2 receptor and CD2 expression were below those expected of ‘activated’ T-cell populations, and virtually all of the cells were found to be in the G0/G1 phases of the cell cycle. These properties bear a remarkable similarity to those of T cells activated in the presence of endogenous tissue (alveolar) macrophages from the lung (see accompanying paper). We hypothesize that they reflect the in vivo operation of an endogenous macrophage-mediated T-cell anergy-induction process, the function of which is to limit the local clonal expansion of T cells in peripheral lung tissue after in situ activation. [ABSTRACT FROM AUTHOR]

This paper investigates major histocompatibility complex (MHC) regulation of the class of the immune response given in vitro and in vivo following immunization of the congenic BALB/k (H-2k) and BALB/c (H-2d) mice with the hapten trinitrophenyl (TNP). TNP-immune lymph node cells from BALB/k mice produced high levels of interferon-γ (IFN-γ), interleukin-5 (IL-5) and IL-2 when stimulated with TNP-antigen-presenting cells (APC) in vitro, while TNP-immune lymph node cells from BALB/c mice produced very low levels of these cytokines. No significant difference was found in antigen-specific production of IL-3, IL-4 and tumour necrosis factor-α (TNF-α). There was a strong correlation between the pattern of cytokine production in vitro and the secondary antibody production in vivo. Sera from BALB/k mice had anti-TNP IgG2a, IgG2b and IgG3 levels threefold greater, and anti-TNP IgA levels eightfold greater, than BALB/c mice. The level of specific IgG1 and IgE was only marginally raised in BALB/k mice. In contrast to these strain differences in cytokine and antibody production, there was no difference in two measures of cellular immunity: contact sensitivity in vivo and antigen-specific lymphocyte response in vitro. Our results suggest that there is a good correlation between the production of cytokines in vitro and antibody response in vivo, but not with measures of cellular immunity. Moreover, this MHC control of the class of the immune response to TNP does not fit into the T-helper type-1 (Th1)-Th2 paradigm. [ABSTRACT FROM AUTHOR]

Two factors essential for the lysis of EAC'142 cells are described and designated as Β and d. These factors are distinct from the C'3-subunits a, b and c described earlier; they can be separated by chemical procedures. A simple assay method for both factors is given. Four highly reactive intermediates, EAC'142,a; EAC'142,a,b; EAC'142,a,b,Β and EAC'142,a,b,Β,c can be prepared and characterized by their lytic reactivity pattern against different systems of incomplete C'3. Evidence is presented that the subunits of the C'3-system interact with EAC'142 in a sequential order corresponding to the formula a-b-Β-c-d. [ABSTRACT FROM AUTHOR]

The experiments described in this paper extend the observations of previous work in vitro demonstrating a decrease in the frequency of antigenreactive units specific for horse RBC in spleen cells from mice primed with KLH. It was observed that the addition of lymphoid cells having T-cell function reconstituted the anti-HRBC response to normal values. Significant enhancement of the response beyond the normal values could be evoked using two dissimilar methods, (i) addition of allogeneic thymus cells, and (ii) restimulation in vitro with the priming antigen. The latter type enhancement was elicited by the addition of small doses of KLH to cultures of spleen cells from mice recently primed with KLH, including cultures otherwise demonstrating antigen-induced suppression. The stimulus required to enhance the response to HRBC in these cultures was specific for the priming antigen, KLH. These results are discussed in the light of current theories of 'antigenic competition' and specific heterologous enhancement. [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]

This paper describes a form of red cell lysis differentiated from classical complement haemolysis by its occurrence in the absence of antibody on the cells and in the presence of EDTA. This type of haemolysis has been called reactive haemolysis. It is the result of the interaction, in the presence of red cells, of at least two serum factors called ‘reactor’ and ‘indicator’, respectively. Reactor only becomes active after incubation at 37° of serum with certain agents, notably antibody-coated bacteria, zymosan and agarose, in conditions similar to those required for complement activation. The potential for the formation of activated reactor could be demonstrated infrequently in healthy subjects but more frequently in sera from hospital patients. Activated reactor behaved as a protein sedimenting between 7S and 19S, and of α2-β1, electrophoretic mobility in agar. Indicator factors were present in all human sera studied, as well as in the sera of a number of mammalian species. They were demonstrable at high dilutions of the serum and required no prior activation for their action. They occurred maximally in the 7S fractions of serum proteins and migrated in the β2 position on electrophoresis. Reactive haemolysis was first observed and can most conveniently lie demonstrated in a red cell-agarose gel. It can also be demonstrated in the test tube following partial purification of activated reactor and indicator factors. Studies in the test tube indicated that a .soluble labile lytic factor was responsible for this type of haemolysis, [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]

Objective: This study aimed at evaluating the safety of administering immune checkpoint inhibitors (ICIs) and monitoring for immune‐related adverse events (irAEs) using the Teleoncology model of care. Design: A retrospective cohort study comparing two patient groups. Setting: The North Queensland Teleoncology Network (NQTN) operated by the Townsville (THHS) and Cairns Hospital Health Services (CHHS) with the Townsville Cancer Centre (TCC) acting as the control group setting. Participants: Patients who received ICI treatment via the NQTN between January 2015 and April 2019. Patients who received ICI at the TCC over the same time period were used for comparison. Main Outcome Measures: Rates of high‐grade irAEs and irAE‐related deaths. Results: Fifty‐two patients received a total of 822 cycles of ICIs via the Teleoncology model through NQTN. Over the same time period, 142 patients received a total of 1521 cycles at the TCC. There were no significant differences in all demographic characteristics between either group, including tumour profile and Indigenous status. There were no statistically significant differences between the rates of high‐grade irAE across multiple body organ systems (p = 0.151) and rate of hospital admissions (13.5% (NQTN) vs 5.6% (TCC), p = 0.702). There were no irAE‐related deaths in either group. Conclusions: The results suggest that with adequate governance and clinical resources, ICIs can be administered safely using Teleoncology models to rural and remote towns. [ABSTRACT FROM AUTHOR]

Background: Delayed graft function is a manifestation of acute kidney injury unique to transplantation usually related to donor ischemia or recipient immunological causes. Ischemia also considered the most important trigger for innate immunity activation and production of non‐HLA antibodies. While ischemia is inevitable after deceased donor transplantation, this complication is rare after living transplantation. Heterologous Immunity commonly used to describe the activation of T cells recognizing specific pathogen‐related antigens as well unrelated antigens is common post‐viral infection. In transplant‐setting induction of heterologous immunity that cross‐react with HLA‐antigens and subsequent reactivation of memory T cells can lead to allograft rejection. Methods: Here we describe a non‐sensitized child with ESRD secondary to lupus nephritis and recent history of COVID‐19 infection who experienced 17 days of anuria after first kidney living transplantation from her young HLA‐haploidentical uncle donor. Graft histology showed acute cellular rejection, evidence of mild antibody‐mediated rejection and vascular wall necrosis in some arterioles suggesting possibility of intraoperative graft ischemia. Both pre‐ and post‐transplant sera showed very high level of several non‐HLA antibodies. Results: The patient was treated for cellular and antibody‐mediated rejection while maintained on hemodialysis before her graft function started to improve on day seventeen post transplantation. Conclusion: The cellular rejection likely trigged by ischemia that activated T‐cells‐mediated immunity. The high level of non‐ HLA‐antibodies further aggravated the damage and the rapid onset of rejection may be partly related to memory T‐cell activation induced by heterologous immunity. [ABSTRACT FROM AUTHOR]

Keywords: Allergic inflammation; Alveolar macrophages; Aspergillus fumigatus; CARD9 EN Allergic inflammation Alveolar macrophages Aspergillus fumigatus CARD9 659 663 5 06/09/23 20230601 NES 230601 Key message CARD9 enhances pro-inflammatory immune response, but inhibits pulmonary type 2 immunity after I A. fumigatus i exposure. Moreover, we sorted out alveolar macrophages from WT and CARD9 deficient mice infected with/without I A. fumigatus i , and further confirmed that RelB activation only occurred in CARD9 deficient alveolar macrophages. Simultaneously, we found that the expression of CD80, CD86 and MHC-II were comparable between WT and CARD9 deficient mice with/without I A. fumigatus i exposure, hinting that CARD9 did not affect the antigen presentation capacity of alveolar macrophages. CARD9 balances Aspergillus fumigatus-induced anti-fungal immunity and allergic inflammation. [Extracted from the article]

Platelet factor 4 (PF4, synonym: CXCL4) is an evolutionary old chemokine with proposed roles in hemostasis and antimicrobial defense. In addition, PF4 has attracted considerable attention as a crucial mediator of one of the most prothrombotic adverse drug effects affecting blood cells, heparin‐induced thrombocytopenia (HIT). Interest in PF4 substantially increased in 2021 when it was identified as the target antigen in the life‐threatening adverse effect, vaccine‐induced immune thrombotic thrombocytopenia (VITT). We address the concept that a major biological function of PF4—a strongly cationic chemokine—is to bind to negatively‐charged prokaryotic microorganisms, resulting in structural changes in PF4 that trigger a danger signal recognized by the adaptive immune system. Application of biophysical tools has provided substantial insights into the molecular mechanisms by which PF4 becomes immunogenic, providing insights into a new mechanism of autoimmunity. Binding of autoantibodies with high affinity induces conformational change(s) in the endogenous protein, which are then recognized as foreign antigen, as exemplified by the prothrombotic disorders, autoimmune HIT and VITT. The final part of our review summarizes current assays for HIT and VITT, explaining how structural aspects of anti‐PF4 pathobiology relate to assay design and performance characteristics. Currently, functional (platelet activation) assays using washed platelets detect HIT antibodies when heparin is added, and VITT antibodies when PF4 is added. Solid‐phase PF4‐dependent immunoassays using microtiter plates are sensitive for both HIT and VITT antibodies, while rapid immunoassays, in which the PF4/heparin antigen is coated on beads, are sensitive and specific for HIT, but not for VITT antibodies. [ABSTRACT FROM AUTHOR]

Aim: To understand Baduanjin rehabilitation therapy in mild COVID‐19 patients. Design: A narrative review. Methods: A literature search for COVID‐19 and Baduanjin treatments was conducted on Chinese and English electronic databases: China National Knowledge Infrastructure, Wanfang Data, Embase, PubMed, Scopus, Science Direct, Ebscohost, SPORTDiscus and ProQuest. Results: Twelve studies on the Baduanjin rehabilitation for COVID‐19 patients have been included. We acknowledged the considerable published research and current clinical practice using Baduanjin for COVID‐19 treatment in the following areas: anxiety, depression, insomnia, lung function rehabilitation, immunity and activity endurance. Conclusion: The use of Baduanjin as adjuvant therapy for COVID‐19 patients' rehabilitation is still limited, therefore, more clinical studies are needed to confirm its efficacy. [ABSTRACT FROM AUTHOR]

This study aimed to examine the impact of the Jerusalem Artichoke extract (JAEx) as a feed additive on the performance, blood biochemistry, antioxidant indices, immunity, and intestinal microbiota in growing Japanese quails. In total, 270 birds were randomly divided into three groups, with six replicates of 15 birds each. The first group was fed a control diet without JAEx. The second and third groups received the control diet plus 200 and 400 ppm JAEx, respectively. The groups fed the diet containing 200 and 400 ppm JAEx had the best body weight, body weight gain and feed conversion ratio, and faster growth rate with the best performance index, compared with the control group (p < 0.05). The control quails had a lower feed intake than the JAEx‐treated quails. The groups fed JAEx 200 and 400 ppm had the lowest lipid profile, blood glucose, liver enzymes, Salmonella and Escherichia coli population and the highest antioxidant indices, immune responses and Lactobacilli population number compared to the control group (p < 0.05). In conclusion, the addition of JAEx at 400 ppm followed by 200 ppm improved the productive performance, antioxidant capacity, blood biochemical and immunological indices, and intestinal microbiota in growing Japanese quails. [ABSTRACT FROM AUTHOR]

Summary: Deep‐frying oil intake is considered to destroy body health. In this review, a meta‐analysis was performed to assess the effects of deep‐frying oil intake on the risk of intestinal barrier dysfunction. Following Preferred Reporting Items for Systematic Reviews and Meta‐Analyses guidelines, a systematic literature search was conducted in PubMed, Embase and Cochrane Central updated till April 2022 (CRD42022326306). A total of nine studies were included. The pooled results revealed that deep‐frying oil intake significantly exaggerated crypt damage of colon [weighted mean difference (WMD) = 4.55; 95% CI: 2.87, 6.24, P < 0.05], increased proinflammatory cytokine expression in plasma and colon tissue, and enhanced intestinal permeability [lipopolysaccharides content (WMD: 10.11 μg mL−1, 95% CI: 7.44, 12.79 μg mL−1, P < 0.05)]. Moreover, deep‐frying oil intake could change the gut microbiota and decrease the content of microbiota‐derived short‐chain fatty acids. In conclusion, our findings provide insights into the effect of deep‐frying oil intake on the intestinal barrier dysfunction. [ABSTRACT FROM AUTHOR]

Virus neutralization at respiratory mucosal surfaces is important in the prevention of infection. Mucosal immunity is mediated mainly by extracellular secretory immunoglobulin A (sIgA) and its role has been well studied. However, the protective role of intracellular specific IgA (icIgA) is less well defined. Initially, in vitro studies using epithelial cell lines with surface expressed polymeric immunoglobulin receptor (pIgR) in transwell culture chambers have shown that icIgA can neutralize influenza, parainfluenza, HIV, rotavirus and measles viruses. This effect appears to involve an interaction between polymeric immunoglobulin A (pIgA) and viral particles within an intracellular compartment, since IgA is transported across the polarized cell. Co‐localization of specific icIgA with influenza virus in patients' (virus culture positive) respiratory epithelial cells using well‐characterized antisera was initially reported in 2018. This review provides a summary of in vitro studies with icIgA on colocalization and neutralization of the above five viruses. Two other highly significant respiratory infectious agents with severe global impacts viz. SARS‐2 virus (CoViD pandemic) and the intracellular bacterium—Mycobacterium tuberculosis—are discussed. Further studies will provide more detailed understanding of the mechanisms and kinetics of icIgA neutralization in relation to viral entry and early replication steps with a specific focus on mucosal infections. This will inform the design of more effective vaccines against infectious agents transmitted via the mucosal route. [ABSTRACT FROM AUTHOR]

The low response rate to immunosuppressant is mainly due to the lack of adequate knowledge about the tumor microenvironment (TME) and screening biomarkers for gliomas. We aimed to identify the promising immune biomarkers and new immune classification of glioma. In this study, multiple‐immune algorithms were used to calculate immune‐infiltration scores. Unsupervised and supervised machine learning methods were used to perform the classification. We observed that OLFML3 overexpression was indicated in gliomas and linked to poor prognosis. OLFML3 knockdown inhibited proliferation, invasion and increased the sensitivity of glioma cells to temozolomide. OLFML3 expression could also reflect the aberrant immune status. Based on the immune‐related signature, patients were divided into three immune subtypes via consensus clustering. Patients with C2 subtype presented poorer prognosis and shorter progression free survival than patients with other two subtypes. The TME patterns among subtypes were different. C2 and C3 subtypes are the immune‐inflamed and immune‐desert tumors, respectively. Additionally, compared with C3 subtype, patients with C1/C2 subtypes were more likely to respond to immunotherapy. The pRRophetic algorithm indicated patients with C1/C2 subtypes were more resistant to temozolomide, but sensitive to paclitaxel and cisplatin. To conclude, OLFML3 overexpression affects glioma cell proliferation, invasion, and TMZ sensitivity and has been proved to be an independent prognostic‐ and immune‐related biomarker. Additionally, the novel immune subtype's classification could provide the prognostic and predictive predictors for glioma patients and may guide physicians in selecting potential responders. [ABSTRACT FROM AUTHOR]