Role of Immature Red Blood Cells in Neonatal Immunity

Newborns are highly susceptible to diseases. Infections such as Bordetella Pertussis (i.e. whooping cough) and Listeria (i.e. food poisoning) can result in the death of neonates while causing little harm to older children and adults. Although previously attributed to an underdeveloped immune system, recent research has shown that this susceptibility is due to the high presence of immature red blood cells or CD71+ cells. These cells possess immunosuppressive properties. By interfering with the function of other immune cells, they can prevent an effective pathogenic immune response. In this study, the changes in the amount of CD71+ cells were observed throughout the different age points of mice as well as in mice infected with Bordetella pertussis and Listeria. This study aimed to gain a better understanding of the development of the immune system as to better aid neonates in fighting infection. Flow cytometry was used to determine the amount of CD71+ cells in the spleens of mice at different age points. The results showed that overall the amount of CD71+ cells decreased as the age of the mouse increased, paralleling the decrease in susceptibility of the immune system. Furthermore, the change in CD71+ cells was also observed in the spleens of mice infected with Bordetella pertussis and mice infected with Listeria. There was no significant change for the Listeria infected mice, as CD71+ cells play no immunological role in fighting Listeria, an intracellular bacteria. However, there was a significant increase in CD71+ cells in Bordetella Pertussis infected mice since this infection was extracellular. These results show that CD71+ cells react differently to different infections and play a different immunological role in the presence of different pathogens. Furthermore, the results shows a direct correlation between age and the amount of CD71+ cells present in the spleen. The changes in the amount of CD71+ cells was most likely due to different pathological conditions and requirements at different ages

Too Much of a Good Thing: High T Cell Count Can Kill Newborns

Neonates have a weakened immune system that could be due to low exposure to pathogens resulting in low adaptive immunity and/or purposeful immune suppression to protect the weak neonate from a robust immune response. The purpose of this project is to find preliminary data to further investigate why the immune system of neonates are weaker, and to possibly improve neonatal immunity while protecting against a powerful immune response in the future.  Using processed mice spleen cells that were stained for CD4 and CD8 to be subjected to flow cytometry, an increase in the percent of helper CD4 and killer CD8 T cells were observed as the mice aged. This indicates that neonates do have a weaker immune system. Between healthy mice and mice infected with either Bordetella pertussis or Listeria, a decrease in the percent of CD4 and CD8 T cells were found, which could be because not enough time had passed for an adaptive immune response

Metabolomic and immune alterations in long COVID patients with chronic fatigue syndrome

IntroductionA group of SARS-CoV-2 infected individuals present lingering symptoms, defined as long COVID (LC), that may last months or years post the onset of acute disease. A portion of LC patients have symptoms similar to myalgic encephalomyelitis or chronic fatigue syndrome (ME/CFS), which results in a substantial reduction in their quality of life. A better understanding of the pathophysiology of LC, in particular, ME/CFS is urgently needed.MethodsWe identified and studied metabolites and soluble biomarkers in plasma from LC individuals mainly exhibiting ME/CFS compared to age-sex-matched recovered individuals (R) without LC, acute COVID-19 patients (A), and to SARS-CoV-2 unexposed healthy individuals (HC).ResultsThrough these analyses, we identified alterations in several metabolomic pathways in LC vs other groups. Plasma metabolomics analysis showed that LC differed from the R and HC groups. Of note, the R group also exhibited a different metabolomic profile than HC. Moreover, we observed a significant elevation in the plasma pro-inflammatory biomarkers (e.g. IL-1α, IL-6, TNF-α, Flt-1, and sCD14) but the reduction in ATP in LC patients. Our results demonstrate that LC patients exhibit persistent metabolomic abnormalities 12 months after the acute COVID-19 disease. Of note, such metabolomic alterations can be observed in the R group 12 months after the acute disease. Hence, the metabolomic recovery period for infected individuals with SARS-CoV-2 might be long-lasting. In particular, we found a significant reduction in sarcosine and serine concentrations in LC patients, which was inversely correlated with depression, anxiety, and cognitive dysfunction scores.ConclusionOur study findings provide a comprehensive metabolomic knowledge base and other soluble biomarkers for a better understanding of the pathophysiology of LC and suggests sarcosine and serine supplementations might have potential therapeutic implications in LC patients. Finally, our study reveals that LC disproportionally affects females more than males, as evidenced by nearly 70% of our LC patients being female

Downregulated regulatory T cell function is associated with increased peptic ulcer in Helicobacter pylori-infection

Background: Helicobacter pylori (H. pylori) chronically colonizes gastric/duodenal mucosa and induces gastroduodenal disease such as gastritis and peptic ulcer and induces vigorous innate and specific immune responses; however, the infection is not removed, a state of chronic active gastritis persists for life if untreated. The objective of this study was to determine the number of regulatory T cells (Tregs) in gastric mucosa of patients with gastritis and peptic ulcer and determined the relationship between main virulence factor of H. pylori and Tregs. Methods and materials: A total of 89 patients with gastritis, 63 patients with peptic ulcer and 40 healthy, H. pylori-negative subjects were enrolled in this study. Expression of CD4 and Foxp3 was determined by immunohistochemistry. Antrum biopsy was obtained for detection of H. pylori, bacterial virulence factors and histopathological assessments. TGF-b1, IL-10 and FOXP3 expressions were determined by real-time polymerase chain reaction (qPCR). Results: The numbers of CD4þ and Foxp3þ T cells as well as the expression of IL-10, TGF-b1, FOXP3, INF-g and IL-17A in infected patients were significantly higher than the ones in uninfected patients. Also, the number of CD4þ T cells was independent on the vacuolating cytotoxin A (vacA) and outer inflammatory protein A (oipA), but it was positively correlated with cytotoxin-associated gene A (cagA). Instead, the number of Foxp3þ T cells was dependent on the vacA and oipA, but it was independent on cagA. The number of Foxp3þ T cells and the expression of IL-10, TGF-b1 and FOXP3 in infected patients with gastritis were significantly higher than the ones in infected patients with peptic ulcer. Moreover, the number of CD4þ T cells and the expression of IL-17A and INF-g was the lowest in the gastritis patients, however, increased progressively in the peptic ulcer patients. Additionally, the numbers of CD4þ and Foxp3þ T cells as well as the expression of IL-10, TGF-b1, FOXP3 and INF-g were positively correlated with the degree of H. pylori density and chronic inflammation. Conclusion: Tregs are positively associated with vacA alleles and oipA status of H. pylori and histological grade but negatively associated with peptic ulcer disease

Association of HLA-alleles with the immune regulation of chronic viral infections

The increased influx of refugees in 2015 has led to challenges in transition and destination countries such as Germany, Sweden and Denmark. Volunteer-led initiatives providing urgent relief played a crucial role in meeting the needs of arriving refugees. The work of the volunteers in central stations and transition shelters was mainly organised with the help of Facebook, both in terms of inward and outward communication. This article examines the role of social media for civic participation drawing on Swedish volunteer initiatives that emerged in the context of the migration crisis in 2015 as a case study. Theoretically the article provides an analytical framework including power relations, technological affordances, practices, and discourses that helps to shed light on the interrelation between social media and civic participation

Coinhibitory Receptor Expression and Immune Checkpoint Blockade: Maintaining a Balance in CD8+ T Cell Responses to Chronic Viral Infections and Cancer

In cancer and chronic viral infections, T cells are exposed to persistent antigen stimulation. This results in expression of multiple inhibitory receptors also called “immune checkpoints” by T cells. Although these inhibitory receptors under normal conditions maintain self-tolerance and prevent immunopathology, their sustained expression deteriorates T cell function: a phenomenon called exhaustion. Recent advances in cancer immunotherapy involve blockade of cytotoxic T lymphocyte antigen-4 and programmed cell death 1 in order to reverse T cell exhaustion and reinvigorate immunity, which has translated to dramatic clinical remission in many cases of metastatic melanoma and lung cancer. With the paucity of therapeutic vaccines against chronic infections such as HIV, HPV, hepatitis B, and hepatitis C, such adjunct checkpoint blockade strategies are required including the blockade of other inhibitory receptors such as T cell immunoreceptor with immunoglobulin (Ig) and immunoreceptor tyrosine-based inhibitory motif domains, T cell Ig and mucin-domain containing-3, lymphocyte activation gene 3, and V-domain Ig-containing suppressor of T cell activation. The nature of different chronic viral infections and cancers is likely to influence the level, composition, and pattern of inhibitory receptors expressed by responding T cells. This will have implications for checkpoint antibody blockade strategies employed for treating tumors and chronic viral infections. Here, we review recent advances that provide a clearer insight into the role of coinhibitory receptor expression in T cell exhaustion and reveal novel antibody-blockade therapeutic targets for chronic viral infections and cancer. Understanding the mechanism of T cell exhaustion in response to chronic virus infections and cancer as well as the nature of restored T cell responses will contribute to further improvement of immune checkpoint blockade strategies

Maternal Immunity Provides Protection against Pertussis in Newborn Piglets

Pertussis continues to be a significant cause of morbidity and mortality in infants and young children worldwide. Methods to control the disease are based on vaccination with either whole-cell or acellular vaccines or treatment with antibiotics. However, despite worldwide vaccination infants are still at the highest risk for the disease. Here we used our newly developed newborn-piglet model to investigate whether transfer of maternal immunity can protect newborn piglets against infection with Bordetella pertussis. Pregnant sows were vaccinated with heat-inactivated B. pertussis or treated with saline (controls). Newborn piglets were allowed to suckle colostrum and milk for 4 to 5 days before they were challenged with 5 × 10(9) CFU of bacteria intrapulmonarily. Elevated levels of B. pertussis-specific secretory immunoglobulin A (S-IgA) and IgG antibodies were found in the colostrum and serum of vaccinated sows but not in those of control sows. Subsequently, significant levels of specific IgG and S-IgA were detected in the serum and bronchoalveolar lavage fluid of piglets born to vaccinated sows. Following infection with 5 × 10(9) CFU of B. pertussis, clinical symptoms, pathological alterations, and bacterial shedding were significantly reduced in piglets that had received passively transferred immunity. Thus, our results demonstrate that maternal immunization might represent an alternative approach to provide protection against pertussis in young infants