The coronavirus disease-2019 (COVID-19) pandemic is a significant threat in the modern era. Clinical studies show that the most common symptom of severe COVID-19 is viral pneumonia-induced acute respiratory distress syndrome (ARDS). The underlying mechanisms by which severe respiratory disease syndrome-coronavirus-2 (SARS-CoV-2) results in ARDS and how certain host factors confer an increased risk of developing severe disease remain unknown. Therefore, identifying the distinctive features of this severe and fatal disease and the therapeutic approaches to COVID-19-induced ARDS remains an immediate need to serve as a basis for best practice models of standardized ARDS treatment. This review article aims to comprehensively discuss the immunopathology of ARDS and provides an overview of the precise role of both the innate and adaptive immune system, with emphasis on the current treatment strategies being tested in the COVID-19-induced ARDS patients. This knowledge will supposedly help in revealing further mechanistic insights into understanding COVID-19-induced ARDS.

The emergence and re-emergence of pathogens is a public-health concern, which has become more evident after the coronavirus disease 2019 (COVID-19) pandemic and the monkeypox outbreaks in early 2022. Given that vaccines are the more effective and affordable tools to control infectious diseases, the authors reviewed two heterologous effects of vaccines: the trained immunity and the cross-reactivity. Trained immunity, provided by attenuated vaccines, was exemplified in this article by the decreased the burden of COVID-19 in populations with high Bacille Calmette-Guerin (BCG) coverage. Cross-reactive responses were exemplified here by the studies which suggested that vaccinia could help controlling the monkeypox outbreak, because of common epitopes shared by orthopoxviruses. Although modern vaccination is likely to use subunit vaccines, the authors discussed how adjuvants might be the key to induce trained immunity and improve cross-reactive responses, ensuring that heterologous effects would improve the vaccine’s response.

In patients with autoimmune coagulation factor deficiency (AiCFD), the production of autoantibodies that inhibit coagulation factors in the blood reduces the activity of those relevant coagulation factors, resulting in severe bleeding symptoms. Recently, reports of patients with AiCFD have noted the concomitant detection of lupus anticoagulant (LA), a risk factor for thrombosis. LA-positive patients may show bleeding symptoms due to decreased activity of coagulation factor II (FII) caused by autoantibodies against FII, in addition to thrombotic symptoms, a condition termed LA-hypoprothrombinemia syndrome (LAHPS). Anti-FII antibodies in LAHPS cases are frequently cleared antibodies that can be detected using immunological techniques, such as enzyme-linked immunosorbent assay (ELISA). Recently, several cases of coagulation FV inhibitors, known as autoimmune FV deficiency, have been reported. Some of these cases may be complicated by LA, which can cause thrombosis. False-positive results for anticoagulant inhibitors are known to occur in LA cases; therefore, immunological confirmation of antibodies against coagulation factors is recommended. Additionally, acquired hemophilia A (AHA), caused by autoantibodies against FVIII, is a typical acquired hemorrhagic diathesis, although affected patients may present with thrombosis associated with LA. Thus, it is important to remember that hemorrhagic diathesis due to autoantibodies against clotting factors can also result in thrombosis, as demonstrated by the co-detection of LA. When clotting factor inhibitors are detected in LA-positive individuals, it is important to confirm the presence of autoantibodies against coagulation factors using immunological methods, such as ELISA, to avoid false-positive results.

Accurate lupus anticoagulant (LA) detection is crucial to antiphospholipid syndrome (APS) diagnosis. Detection is based on LA functional behavior in coagulation assays irrespective of epitope specificity. LA screening tests employ dilute phospholipids to accentuate in vitro inhibition by LAs, although they are not LA-specific and can be elevated by other coagulation abnormalities. Elevated screening tests are reflexed to mixing tests to distinguish between factor deficiency and inhibition. Confirmatory tests with high phospholipid concentration swamp LA to generate shorter clotting times than screening tests, whilst prolongation persists with non-phospholipid-dependent inhibitors. LA heterogeneity means that no single screening test detects every LA and the screen/mix/confirm medley must be applied to at least two assay types, usually dilute Russell’s viper venom time (dRVVT) and an LA-sensitive activated partial thromboplastin time (aPTT). Most laboratories restrict LA testing to these two assays, yet others, such as dilute prothrombin time (dPT), can perform with equal diagnostic efficacy, and additionally detect LA unreactive with dRVVT and aPTT. Converting clotting times to normalized ratios improves assay performance, and practitioners must choose between normal pooled plasma (NPP) clotting time denominators to reflect on-the-day assay performance, or reference interval (RI) mean clotting times to negate the effects of NPP variation. Cut-offs can be generated parametrically from normally distributed data, or different percentiles applied depending on the preferred balance between sensitivity and specificity. Sourcing sufficient donors for accurate cut-off estimations is problematic and transference exercises can be undertaken on low donor numbers. Analytical limitations of mixing tests have led to the adoption of alternative algorithms to the screen/mix/confirm test order, whilst some continue to rigidly apply the latter despite those limitations. Strategies to reduce or eliminate the effects of therapeutic anticoagulation have limitations, whilst the Taipan snake venom time (TSVT) screening test with an ecarin time (ET) confirmatory test is insensitive to vitamin K antagonist (VKA) and direct activated factor X anticoagulation.

Interest in the mechanisms of aging of the immune system has not faded over the past 100 years, and it is caused by the immune-mediated development of age-related pathology, including autoimmune organ damage, reduced vaccination efficiency, atherosclerosis, the development of cardiovascular pathology, etc. In contrast to many other organs and systems, the immune system aging begins at an early age and has more pronounced changes that lead to the development of secondary pathology, which significantly affects life expectancy. But an effective strategy to restore immune function has not been developed yet. During this time, the mechanisms of age-related dysfunction of organs and cells of both the adaptive and innate immune systems were studied in detail-thymus involution, a decrease in the potential of hematopoietic stem cells, impaired differentiation and functions of immunocompetent cells, as well as the ways of their interaction. Numerous potential therapeutic targets have been identified and various approaches have been used to implement such therapeutic interventions. The review is devoted to replacement therapy using transplantation of hematopoietic stem cells (HSCs) and young lymphoid cells and tissues, cellular and systemic factor exchange in heterochronic parabiosis, and some other widely used life extension approaches. It has been proven that cell therapy using young cells to rejuvenate the old immune system, unfortunately, often turns out to be ineffective because it does not eliminate the root cause of age-related changes. The phenomenon of inflamm-aging that develops with age can significantly affect both the aging of the organism in general and the functioning of immunocompetent cells in particular. Therefore, the most promising direction in the restoration of immune functions during aging is systemic approaches that have a complex effect on the organism as a whole and can slow down the aging process.

Changes occurring in the immune system along the ageing process increase the risk of infection, susceptibility to tumor development, and autoimmunity. Interventions such as physical exercise, supplements, and probiotics have been proposed in order to circumvent these conditions. Vitamin D supplementation could contribute to the immune system homeostasis in older adults since a large proportion of this population has low levels of circulating vitamin D. Additionally, observational studies have shown the association between vitamin D status and infections, chronic diseases such as cancer, diabetes, and cardiovascular disease. Recently it was observed that old patients with COVID-19 and vitamin D deficiency had enhanced severity of lung damage, longer stay at the hospital, and increased risk of death, suggesting that vitamin D plays an important role in the patient outcome from COVID-19. A high dose of vitamin D supplementation improved clinical recovery in a case-series report but in another study, no evident link between levels of vitamin D and risk of COVID-19 infection was found. Results also remain debatable for vitamin D supplements and improvement of immune response after vaccination, tuberculosis, pneumonia, and sepsis. It has been hypothesized that vitamin D could modulate the immune system and thus provide both efficacies in the immune response to pathogens/vaccinations and reduction of the inflammatory phenotype. This review will discuss vitamin D and homeostasis of the immune system; the literature-based clinical data on vitamin D and infections; and the possible link between vitamin D and immune response after vaccination.

Vaccination has made an enormous contribution to global health. Treatment resistance for infectious diseases is growing quickly, and chemotherapeutic toxicity in cancer means that vaccines must be made right away to save humanity. But subunit vaccinations alone don’t give enough strong and long-lasting protection against infections that can kill. Nanoparticle (NP)-based delivery vehicles, such as dendrimers, liposomes, micelles, virosomes, nanogels, and microemulsions, offer interesting ways to get around the problems with traditional vaccine adjuvants. The nanovaccines (50-250 nm in size) are most efficient in terms of tissue targeting, staying in the bloodstream for a long time. Nanovaccines can improve antigen presentation, targeted delivery, stimulation of the body’s innate immune system, and a strong T-cell response without putting people at risk. This can help fight infectious diseases and cancers. Also, nanovaccines can be very helpful for making cancer treatments that use immunotherapy. So, this review highlights the various types of NPs used in the techniques that have worked in the new paradigm in viral vaccinology for infectious diseases. It gives a full rundown of the current NP-based vaccines, their potential as adjuvants, and the ways they can be delivered to cells. In the future, the best nanovaccines will try to be more logically designed, have more antigens in them, be fully functionalized, and be given to the right people.

Cancer stem cells (CSCs) are a small subpopulation of cells that drive the formation and progression of tumors. However, during tumor initiation, how CSCs communicate with neighbouring immune cells to overcome the powerful immune surveillance barrier in order to form, spread, and maintain the tumor, remains poorly understood. It is, therefore, absolutely necessary to understand how a small number of tumor-initiating cells (TICs) survive immune attack during (a) the “elimination phase” of “tumor immune-editing”, (b) the establishment of regional or distant tumor after metastasis, and (c) recurrence after therapy. Mounting evidence suggests that CSCs suppress the immune system through a variety of distinct mechanisms that ensure the survival of not only CSCs but also non-stem cancer cells (NSCCs), which eventually form the tumor mass. In this review article, the mechanisms via which CSCs change the immune landscape of the tissue of origin, which contains macrophages, dendritic cells (DCs), myeloid-derived suppressor cells (MDSCs), natural killer (NK) cells, and tumor-infiltrating lymphocytes, in favour of tumorigenesis were discussed. The failure of cancer immunotherapy might also be explained by such interaction between CSCs and immune cells. This review will shed light on the critical role of CSCs in tumor immune evasion and emphasize the importance of CSC-targeted immunotherapy as a cutting-edge technique for battling cancer by restricting communication between immune cells and CSCs.

Aim: A number of questions remain unanswered concerning how infected individuals regulate their immune response to Plasmodium falciparum ( P. falciparum) parasites at varying levels of exposure. Due to the interactions of inflammatory mediators and cytokines with the P. falciparum parasite complex density, several mediators influence parasitaemia and may give some indications of disease severity and represent effective signs in clinical manifestations of malaria disease. Methods: In this study, various levels of immune response mediators of interleukin 8 (IL-8), tumor necrosis factor-beta (TNF-β, also known as lymphotoxin-α), interferon-gamma (IFN-γ), IL-6, and IL-10 were investigated to the different phases of infection with P. falciparum in hyperendemic states in Sudan (White Nile, Blue Nile). This study vetted the association between certain inflammatory mediators during malaria infection and parasite density. This study was based on a total of 108 cases, in which 86 patients (62.0%) were uncomplicated and (17.6%) were severe, all met the diagnostic criteria and were clinically admitted for malaria infections. Commercial enzyme-linked immunosorbent assay (ELISA) kits were employed to determine the inflammatory mediator’s serum concentration. Results: The analysis of data indicated that older infected children had substantially raised levels of IFN-γ ( P < 0.05), among study groups, levels of IFN-γ, TNF-β, and IL-8 were strongly linked with the severity of malaria, in severe and uncomplicated cases ( P < 0.001), IL-6 and IL-10 were significantly associated with severe malaria cases uniquely ( P < 0.001). Furthermore, we reported a positive correlation between IL-8 and TNF-β during all infection cases ( r = 0.760, P < 0.001). Additionally, in severe malaria cases IL-6 was positively correlated with IL-10 ( r = 0.575, P = 0.010). Conclusions: Eliminating P. falciparum blood-stage infection needs effective, specific, and tuned immune response strategies, which may present in the mediator’s correlations and depend on the density of the infection. Besides the effective levels contribution of certain cytokines that play protective roles during different stages of an infection.