Allergens are initiators of both innate and adaptive immune responses. They are recognised at the site of entry by epithelial and dendritic cells (DCs), both of which activate innate inflammatory circuits that can collectively induce Th2 immune responses. In an attempt to have a better understanding of the role of carbohydrates in the recognition and uptake of allergens by the innate immune system, we defined common glycosylation patterns in major allergens. This was done using labelled lectins and showed that allergens like Der p 1 (Dermatophagoides pteronyssinus group 1), Fel d 1 (Felis domisticus), Ara h 1 (Arachis hypogaea), Der p 2 (Dermatophagoides pteronyssinus group 2), Bla g 2 (Blattella germanica) and Can f 1 (Canis familiaris) are glycosylated and that the main dominant sugars on these allergens are 1–2, 1–3 and 1–6 mannose. These observations are in line with recent reports implicating the mannose receptor (MR) in allergen recognition and uptake by DCs and suggesting a major link between glycosylation and allergen recognition. We then looked at TSLP (Thymic Stromal Lymphopoietin) cytokine secretion by lung epithelia upon encountering natural Der p 1 allergen. TSLP is suggested to drive DC maturation in support of allergic hypersensitivity reactions. Our data showed an increase in TSLP secretion by lung epithelia upon stimulation with natural Der p 1 which was carbohydrate dependent. The deglycosylated preparation of Der p 1 exhibited minimal uptake by DCs compared to the natural and hyperglycosylated recombinant counterparts, with the latter being taken up more readily than the other preparations. Collectively, our data indicate that carbohydrate moieties on allergens play a vital role in their recognition by innate immune cells, implicating them in downstream deleterious Th2 cell activation and IgE production.
BackgroundAllergen recognition by dendritic cells (DCs) is a key event in the allergic cascade leading to production of IgE antibodies. C-type lectins, such as the mannose receptor and DC-SIGN, were recently shown to play an important role in the uptake of the house dust mite glycoallergen Der p 1 by DCs. In addition to mannose receptor (MR) and DC-SIGN the high and low affinity IgE receptors, namely FcϵRI and FcϵRII (CD23), respectively, have been shown to be involved in allergen uptake and presentation by DCs.ObjectivesThis study aims at understanding the extent to which IgE- and IgG-facilitated Der p 1 uptake by DCs influence T cell polarisation and in particular potential bias in favour of Th2. We have addressed this issue by using two chimaeric monoclonal antibodies produced in our laboratory and directed against a previously defined epitope on Der p 1, namely human IgE 2C7 and IgG1 2C7.ResultsFlow cytometry was used to establish the expression patterns of IgE (FcϵRI and FcϵRII) and IgG (FcγRI) receptors in relation to MR on DCs. The impact of FcϵRI, FcϵRII, FcγRI and mannose receptor mediated allergen uptake on Th1/Th2 cell differentiation was investigated using DC/T cell co-culture experiments. Myeloid DCs showed high levels of FcϵRI and FcγRI expression, but low levels of CD23 and MR, and this has therefore enabled us to assess the role of IgE and IgG-facilitated allergen presentation in T cell polarisation with minimal interference by CD23 and MR. Our data demonstrate that DCs that have taken up Der p 1 via surface IgE support a Th2 response. However, no such effect was demonstrable via surface IgG.ConclusionsIgE bound to its high affinity receptor plays an important role in Der p 1 uptake and processing by peripheral blood DCs and in Th2 polarisation of T cells.
Now nearly a century old, the Bacillus Calmette-Guérin (BCG) vaccine is used routinely in humans for the prophylaxis of tuberculosis and to clear up leprosy. As the immune response to the vaccine shows some degree of cross-antigenicity, the vaccine also affects a level of resistance to a range of unrelated diseases and pathogens.Clinical studies data have shown that the BCG vaccine has effects on autoimmune and inflammatory diseases.Although the vaccine does not possess any inherent antiviral activity, it engages in the host immune system such that many types of viral infections are considerably reduced. Hence, we expect that the frequency and severity of many microbial diseases, including COVID-19, will be lower in counties in which mass BCG vaccination programs are implemented. So the BCG vaccine may prove useful in the coming months especially in countries where already have mass BCG vaccination, as the COVID-19 pandemic has placed an unprecedented strain on health services across the world. Currently, countless front-line healthcare staff is in immediate danger of exposure to the SARS-CoV-2 virus. Furthermore, as oral zinc sulfate as immunomodulator has proved an effective means to treat various viral diseases (including viral warts and herpes), parasitic infections, and diseases with autoimmune reactions such as Behcet's disease and recurrent aphthous stomatitis, it could be employed in combination with the BCG vaccine to enhance the immunological functions of patients with COVID-19. So BCG immunotherapy combined with oral zinc sulfate will be encouraging protective programs in societies where coronavirus is going to spread.
One neurotransmitter, glutamate, has been implicated in the autoimmune demyelination seen in multiple sclerosis (MS). Glutamate is present in many tissues in the body, so consideration should be given to whether the serum level of glutamate is likely well correlated with the activity of the disease. This research aimed to compare the serum glutamate levels from patients diagnosed with MS with those from an age-matched control population. A review of this data could shed light upon whether the serum testing of glutamate using Enzyme-Linked Immunosorbent Assay (ELISA) is a reliable indicator of MS activity. Serum samples were obtained from 55 patients with different patterns of MS and from 25 healthy adults as a control group. The ELISA technique was used to determine the glutamate levels in the serum samples. The mean serum glutamate level for patients with MS was 1.318 ± 0.543 nmol/ml and that of the controls was 0.873 ± 0.341 nmol/ml. The serum glutamate levels showed an area under the curve via the receiver operating characteristics (ROC) of 0.738, which was significant (p value = 0.001). The present study is the first to establish a strong connection between the serum glutamate levels and MS patients, where there was statistically significant elevation of serum glutamate in MS patients; hence this elevation might be used as a monitor to help in the diagnosis of MS patients.
Interleukin‐38 (IL‐38) has recently been considered as a cytokine with anti‐inflammatory properties in viral respiratory infections, particularly coronavirus disease 19 (COVID‐19), but the evidence has not been well elucidated. Therefore, a case‐control study was conducted to determine IL‐38 serum levels in 148 patients with COVID‐19 (45 moderate, 55 severe, and 48 critical) and 113 controls. Results demonstrated that IL‐38 levels did not show significant differences between patients and controls (68.7 [interquartile range: 62.7–75.6] vs. 67.7 [58.0–82.6] pg/ml; probability = 0.457). Similarly, patients stratified by disease severity, age group, gender, or chronic disease showed no significant differences between IL‐38 levels in each stratum. Whereas, overweight/obese patients had a significantly lower median of IL‐38 compared to normal‐weight patients. Further, IL‐38 showed significantly higher levels in the age group ≥50 years of patients with critical illness than in the age group <50 years. Female patients with severe disease also showed significantly elevated levels of IL‐38 compared to male patients. In conclusion, the study indicated that serum IL‐38 levels were not affected by COVID‐19 infection, but the distribution of patients according to disease severity, age, gender, and body mass index may better reveal the role of IL‐38 in disease pathogenesis.
Background: Alopecia areata is a common autoimmune disease, where there are many topical and systemic therapies, during which hair growth appears in a uniform pattern. In certain cases, hair regrowth takes a polycyclic pattern simulating a target, so called targetoid phenomena. Objective: To screen all cases of treated alopecia areata for hair targetoid regrowth pattern. Methods: This is an observational study, was conducted in Dermatology Department of Baghdad Teaching Hospital in Iraq, during the period, August 2017 to October 2017. All cases treated for alopecia areata with IM triamcinolone 20-40 mg injection every 2 weeks with topical clobetasone ointment and zinc sulfate 2 mg/kg/day for 2 months, were examined for the targetoid concentric hair regrowth pattern. Result: Among all cases of alopecia areata, seven patients were recorded to have the targetoid concentric hair pattern, which seen 2-4 weeks after therapy, their ages ranged from 4 to 25 years old with a mean 14.5, all of them were males. All these patients returned back with hair growth in a form of rings of hair growth alternating with rings of little or no hair growth forming a typical picture of target. Conclusion: Targetoid polycyclic concentric hair regrowth pattern is an important phenomenon seen in patients receiving treatment for alopecia areata, which is a good sign of recovery where its etiopathogenesis could not well be elucidated but alternating immunological reactions could explain this targetoid pattern.
A shocking third species emerged from a family of coronaviruses (CoV) in late 2019 following viruses causing SARS (Severe Acute Respiratory Syndrome-CoV) in 2003 and MERS (Middle East Respiratory Syndrome-CoV) in 2012; it's a novel coronavirus now called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; formerly called 2019-nCoV). First emerging in China, it has spread rapidly across the globe, giving rise to significant social and economic costs and imposing severe strain on healthcare systems. Since many attempts to control viral spread has been futile, the only old practice of containment including city lockdown and social distancing are working to some extent. Unfortunately, specific antiviral drugs and vaccines remain unavailable yet. Many factors are encountered to play essential roles in viral pathogenesis. These include a broad viral-host range with high receptor binding affinity to various human tissues, viral adaptation to humans, a high percentage of asymptomatic but infected carriers, prolonged incubation, and viral shedding periods. There are also a wide variety of pulmonary and extrapulmonary tissue damage mechanisms including direct cell injury or immune-mediated damages involving the immune cells, upregulation of proinflammatory cytokines, and antibody dependent enhancement that can result in multi-organ failure. In this article, we summarise some evidence on the various steps in SARS-CoV-2 pathogenesis and immune evasion strategies to assess their contribution to our understanding of unresolved problems related to SARS-CoV-2 prevention, control, and treatment protocols.
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