Cancer immunotherapy, especially T-cell driven targeting, has significantly evolved and improved over the past decade, paving the way to treat previously refractory cancers. Hematologic malignancies, given their direct tumor accessibility and less immunosuppressive microenvironment compared to solid tumors, are better suited to be targeted by cellular immunotherapies. Gamma delta (γδ) T cells, with their unique attributes spanning the entirety of the immune system, make a tantalizing therapeutic platform for cancer immunotherapy. Their inherent anti-tumor properties, ability to act like antigen-presenting cells, and the advantage of having no major histocompatibility complex (MHC) restrictions, allow for greater flexibility in their utility to target tumors, compared to their αβ T cell counterpart. Their MHC-independent anti-tumor activity, coupled with their ability to be easily expanded from peripheral blood, enhance their potential to be used as an allogeneic product. In this review, the potential of utilizing γδ T cells to target hematologic malignancies is described, with a specific focus on their applicability as an allogeneic adoptive cellular therapy product.

Cutaneous homeostasis is maintained by dynamic cellular communications between different cell types in the skin through interactions with various mediators, including cytokines, chemokines and antimicrobial peptides/proteins (AMPs). Keratinocytes, as the major cell type of the epidermis, not only form a passive physical barrier, but also actively participate in the pathogenesis of many, if not all, inflammatory skin diseases. Keratinocytes highly interact with immune cells to shape, amplify or regulate inflammatory responses, thus triggering and/or sustaining these inflammatory skin diseases. In this review, crosstalk between keratinocytes and immune cells is summarized, and its contributions to two major inflammatory skin disorders including psoriasis and atopic dermatitis are highlighted.

Avidity of immunoglobulin G (IgG) is defined as its binding strength to its target antigen. As a consequence of affinity maturation of the IgG response, avidity is maturing as well. Therefore, acute infections are characterized by low-avidity IgG, whereas past infections are usually associated with high-avidity IgG. Avidity maturation is also observed as a consequence of optimal vaccination. Avidity has been shown to play a significant role in protective humoral immunity in many microbial systems. After severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, the situation is different compared to other viral infections, as the moderate degree of avidity reached in most cases of infection is similar to that reached after only one vaccination step. In contrast, two vaccination steps lead to a much higher avidity of IgG directed towards viral spike protein S1 (S1) in the majority of vaccinated individuals. Therefore, it seems that two vaccination steps allow for a more extended affinity/avidity maturation than natural infection. The degree of avidity maturation after two vaccination steps is heterogeneous. It can be further enhanced by a third vaccination step. Complete avidity maturation seems to depend on sustained availability of antigen during the maturation process. Variants of concern seem to increase the affinity of their receptor-binding domain (RBD) to angiotensin-converting enzyme-2 (ACE2) and/or to decrease the susceptibility for neutralizing antibodies. Classical neutralization tests do not necessarily reflect the avidity of neutralizing IgG, as they operationally dissect the binding reaction between S1 and IgG from the binding of the S1 to ACE2. This approach fades out critical competition reactions between IgG and ACE for RBD of the S1. Quantitative avidity determination might be an essential tool to define individuals that only possess suboptimal protective immunity after vaccination and therefore might benefit from an additional booster immunization.

Immunity is continuously evolving by evolutionary mechanisms shaped by pathogenic stimuli of different kinds. Man-made nanomaterials (NMs) have been developed in the last decades and represent a novel challenge for our immune system, especially when applied to medical science. Toxicological studies of such nanoparticles (NPs) revealed that size, shape, and surface chemistry are key parameters to understand their noxious effects on cellular mechanisms. Less is known on the immune reactions to NMs since prolonged exposure data are not so detailed as the results for acute administration. The importance of immunity to biocompatible NPs is underlined by their increasing use as drug or gene delivery carriers in common pharmaceutical preparations and vaccines. In the latter case, the immunomodulatory properties of NMs allow their use also as efficient adjuvants to enhance the innate immune response. In the current manuscript, the authors discuss the main concepts in this fast-growing field by restricting our view to NMs with consolidated application in biomedicine.

Mesenchymal stromal cells (MSCs) are a mesodermal stem cell population, with known self-renewal and multilineage differentiation properties. In the last century, MSCs have been widely used in regenerative medicine and tissue engineering approaches. MSCs initially were isolated from bone marrow aspirates, but currently have been identified in a great number of tissues of the human body. Besides their utilization in regenerative medicine, MSCs possess significant immunoregulatory/immunosuppressive properties, through interaction with the cells of innate and adaptive immunity. MSCs can exert their immunomodulatory properties with either cell-cell contact or via paracrine secretion of molecules, such as cytokines, growth factors and chemokines. Of particular importance, the MSCs’ immunomodulatory properties are explored as promising therapeutic strategies in immune-related disorders, such as autoimmune diseases, graft versus host disease, cancer. MSCs may also have an additional impact on coronavirus disease-19 (COVID-19), by attenuating the severe symptoms of this disorder. Nowadays, a great number of clinical trials, of MSC-mediated therapies are evaluated for their therapeutic potential. In this review, the current knowledge on cellular and molecular mechanisms involved in MSC-mediated immunomodulation were highlighted. Also, the most important aspects, regarding their potential application in immune-related diseases, will be highlighted. The broad application of MSCs has emerged their role as key immunomodulatory players, therefore their utilization in many disease situations is full of possibilities for future clinical treatment.

Understanding the interactions of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) with humans is deeply grounded in immunology, from the diagnosis to pathogenesis, from the clinical presentations to the epidemiology, prevention, and treatment. However, the difficulty of capturing the complex and changeable array of immunological concepts and incorporating them into the strategies of control of the SARS-CoV-2 pandemic poses significant hindrances to establish optimal public health policies. The contribution of immunology to the control of the pandemic is to shed light on the features and mechanisms of the protective immunity elicited by SARS-CoV-2 infection and vaccines. Do they induce effective protective immunity? How? For how long? What is the effect of vaccination on individuals who were previously infected? To appropriately answer these questions, it is necessary to get rid of the outdated notion of a naïve, static, and closed immune system, which leads to misconceptions about susceptibility, specificity, immunological memory, and protective immunity. The present essay discusses these issues based on current immunological concepts.

A few pieces of research exist about the protective titer against severe acute respiratory syndrome (SARS) coronavirus 2 (CoV-2; SARS-CoV-2) in monkeys and humans in which the protection could be shown as dose-dependent. Early studies supposed that higher levels of pre-existing neutralizing antibodies (Nabs) against SARS-CoV-2 can potentially correlate with the protection to consequent infection. The data so far showed that cellular immunity is as essential as the humoral one. If needed, its presence can be beneficial if the titer of immunoglobulins is not optimal. It is also known that the immune response to the vaccine is similar to the one after natural infection with a production of very high naturalization titers antibodies. However, medical community is still unaware of the immunoglobulin titer needed for protection against the virus. The answers to the questions regarding correlates of protection are yet to be discovered. Still, no studies indicate a specific virus-Nab titer, so one can assume a patient is protected from being infected in the future. The evoked immunological response is indeed encouraging, but a future investigation is needed. Nonetheless, it remains a mystery how long the immunity lasts and whether it will be enough to shield the patients in the long run. Therefore, identifying immune protection correlations, including neutralization titer of antibodies and T cell immune response against SARS-CoV-2, could give a clue. Unfortunately, recent studies in the field have been more controversial than concise, and the data available is far from consensus.

Viral vectors have been frequently applied for vaccine development. It has also been the case for vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to tackle the coronavirus disease 2019 (COVID-19) pandemic. A multitude of different viral vectors have been mainly targeting the SARS-CoV-2 spike (S) protein as antigen. Intramuscular injection has been most commonly used, but also intranasal administration has been tested. Adenovirus vector-based vaccines are the most advanced with several vaccines receiving Emergency Use Authorization (EUA). The simian ChAdOx1 nCoV-19 vaccine applied as a prime-boost regimen has provided 62.1–90% vaccine efficacy in clinical trials. The Ad26.COV2.S vaccine requires only one immunization to provide protection against SARS-CoV-2. The rAd26-S/rAd5-S vaccine utilizes the Ad26 serotype for the prime immunization followed by a boost with the Ad5 serotype resulting in 91.2% vaccine efficacy. All adenovirus-based vaccines are used for mass vaccinations. Moreover, vaccine candidates based on vaccinia virus and lentivirus vectors have been subjected to clinical evaluation. Among self-replicating RNA viruses, vaccine vectors based on measles virus, rhabdoviruses, and alphaviruses have been engineered and tested in clinical trials. In addition to the intramuscular route of administration vaccine candidates based on influenza viruses and adenoviruses have been subjected to intranasal delivery showing antibody responses and protection against SARS-CoV-2 challenges in animal models. The detection of novel more transmissible and pathogenic SARS-CoV-2 variants added concerns about the vaccine efficacy and needs to be monitored. Moreover, the cause of recently documented rare cases of vaccine-induced immune thrombotic thrombocytopenia (VITT) must be investigated.

As the severe acute respiratory syndrome coronavirus (SARS-CoV)-2 is a new virus, the current knowledge on the immunopathogenesis of this newly emerged SARS-CoV-2 is beginning to unravel with intensive ongoing global research efforts. Although a plethora of new studies have been published in a short space of time describing how the virus causes disease and incurs insults on the host immune system and the underlying immunopathogenic mechanisms remain to be elucidated. Thus, the discussion in this review is based on the most current knowledge on the immunopathogenesis of SARS-CoV-2 that has emerged in the past 12 months. The main objective is to shed light on the most current concepts in immunopathological aspects of the lung, bloodstream, and brain caused by the SARS-CoV-2, which has led to the current pandemic resulting in > 100 million infections and > 2 million deaths, and ongoing.

Arginase-1 (Arg1) and the inducible nitric oxide synthase 2 (NOS2) compete for the common substrate L-arginine, semi-essential amino acid, and central intestinal metabolite. Both enzymes exhibit various, sometimes opposing effects on immune responses, tissue regeneration, or microbial growth and replication. In sub-mucosal tissues of patients suffering from inflammatory bowel disease (IBD), similar as in experimental colitis, the expression and activity of both enzymes, Arg1 and NOS2 are more prominent than in respective controls. Accordingly, the metabolism of L-arginine is altered in IBD patients. Thus, L-arginine represents a promising medical target for clinical intervention in these devastating diseases. Previous studies primarily focused on the host side of L-arginine metabolism. Initial reports using Arg1 inhibitors generated conflicting results in murine colitis models. Subsequently, only the generation of conditional Arg1 knockout mice allowed reliable functional analyses of Arg1 and the L-arginine metabolism in the immune system. Utilizing cell-specific conditional Arg1 knockouts, we have recently reported that Arg1, surprisingly, hampered the resolution of experimental colitis due to the restriction of the intraluminal availability of L-arginine. Reduced levels of L-arginine restrained the compositional diversity of the intestinal microbiota and subsequently the mutual metabolism between the microbiota and the host. Thus, the intraluminal microbiota represents a potential therapeutic target for L-arginine metabolism aside from host-dependent L-arginine consumption.