BACKGROUND: The pathogenesis of migraine remains unclear; however, a large body of evidence supports the hypothesis that immunological mechanisms play a key role. Therefore, we aimed to review current studies on altered immunity in individuals with migraine during and outside attacks.
METHODS: We searched the PubMed database to investigate immunological changes in patients with migraine. We then added other relevant articles on altered immunity in migraine to our search.
RESULTS: Database screening identified 1,102 articles, of which 41 were selected. We added another 104 relevant articles. We found studies reporting elevated interictal levels of some proinflammatory cytokines, including IL-6 and TNF-α. Anti-inflammatory cytokines showed various findings, such as increased TGF-β and decreased IL-10. Other changes in humoral immunity included increased levels of chemokines, adhesion molecules, and matrix metalloproteinases; activation of the complement system; and increased IgM and IgA. Changes in cellular immunity included an increase in T helper cells, decreased cytotoxic T cells, decreased regulatory T cells, and an increase in a subset of natural killer cells. A significant comorbidity of autoimmune and allergic diseases with migraine was observed.
CONCLUSIONS: Our review summarizes the findings regarding altered humoral and cellular immunological findings in human migraine. We highlight the possible involvement of immunological mechanisms in the pathogenesis of migraine. However, further studies are needed to expand our knowledge of the exact role of immunological mechanisms in migraine pathogenesis.

BACKGROUND: With the emergence of newer SARS-CoV-2 variants and their substantial effects on the levels and duration of protection against infection, an understanding of these characteristics of the protection conferred by humoral and cellular immunity can aid in the proper development and implementation of vaccine and safety guidelines.
METHODS: We conducted a rapid literature review and searched five electronic databases weekly from 1 November 2021 to 30 September 2022. Studies that assessed the humoral or cellular immunity conferred by infection, vaccination or a hybrid (combination of both) in adults and risk groups (immunocompromised and older populations) were identified. Studies were eligible when they reported data on immunological assays of COVID-19 (related to vaccination and/or infection) or the effectiveness of protection (related to the effectiveness of vaccination and/or infection).
RESULTS: We screened 5103 studies and included 205 studies, of which 70 provided data on the duration of protection against SARS-CoV-2 infection. The duration of protection of adaptive immunity was greatly impacted by Omicron and its subvariants: levels of protection were low by 3-6 months from exposure to infection/vaccination. Although more durable, cellular immunity also showed signs of waning by 6 months. First and second mRNA vaccine booster doses increased the levels of protection against infection and severe disease from Omicron and its subvariants but continued to demonstrate a high degree of waning over time.
CONCLUSIONS: All humoral immunities (infection-acquired, vaccine-acquired and hybrid) waned by 3-6 months. Cellular immunity was more durable but showed signs of waning by 6 months. Hybrid immunity had the highest magnitude of protection against SARS-CoV-2 infection. Boosting may be recommended as early as 3-4 months after the last dose, especially in risk groups.

People living with HIV (PLWH) were not included in the first efficacy studies of mRNA vaccines against SARS-CoV-2. In this literature review, we investigate evidence of humoral and cellular immunity after a third dose of an mRNA vaccine in PLWH. We performed a literature search in PubMed, Embase, Web of Science and SCOPUS published between 1 January 2020 and 31 December 2022. Selection criteria were studies on immunological responses in PLWH, who were given an mRNA-based vaccine as a third vaccine dose against SARS-CoV-2. Eight articles complied with our selection criteria. All studies found a strong humoral response after the third dose. Five studies investigated cellular immunity and found an increased cellular response after the third vaccine dose in PLWH. No difference in humoral response was observed between PLWH and controls after three doses. However, some of the studies suggested a weaker cellular response among PLWH than in controls, which was associated with lower nadir or current CD4+ T-cell counts. In conclusion, we found evidence of strong humoral immunity in PLWH after receiving an mRNA-based COVID-19 vaccine as a third dose, while the cellular immunity may be impaired compared to controls.

When the Coronavirus Disease 2019 (COVID-19) appeared, it was unknown what impact it would have on the condition of patients with autoimmunological disorders. Attention was focused on the course of infection in patients suffering from multiple sclerosis (MS), specially treated with disease-modifying therapies (DMTs) or glucocorticoids. The impact of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection on the occurrence of MS relapses or pseudo-relapses was important. This review focuses on the risk, symptoms, course, and mortality of COVID-19 as well as immune response to vaccinations against COVID-19 in patients with MS (PwMS). We searched the PubMed database according to specific criteria. PwMS have the risk of infection, hospitalization, symptoms, and mortality due to COVID-19, mostly similar to the general population. The presence of comorbidities, male sex, a higher degree of disability, and older age increase the frequency and severity of the COVID-19 course in PwMS. For example, it was reported that anti-CD20 therapy is probably associated with an increased risk of severe COVID-19 outcomes. After SARS-CoV-2 infection or vaccination, MS patients acquire humoral and cellular immunity, but the degree of immune response depends on applied DMTs. Additional studies are necessary to corroborate these findings. However, indisputably, some PwMS need special attention within the context of COVID-19.

COVID-19 vaccines exhibit high levels of immunogenicity in the overall population. Data on the effects of immunomodulators on the consequences of COVID-19 in patients with Immune-mediated inflammatory diseases (IMIDs) remains scarce. This systematic review aimed to evaluate the immune responses to the COVID-19 vaccines in IMID patients receiving methotrexate (MTX) compared to healthy individuals. A comprehensive literature search was carried out using electronic databases such as PubMed, Web of Science, Scopus, Google Scholar, and Embase up to August 2022 to identify eligible RCTs evaluating the effect of MTX on immune responses in patients with COVID-19. The PRISMA checklist protocol was applied for the quality assessment of the selected trials. Our findings demonstrated that MTX lowered the responses of T cells and antibodies in IMID patients compared to healthy controls. We also discovered that young age (<60 years) was the main parameter influencing the antibody response after vaccination, while MTX had little effect. Following vaccination, MTX-hold and age were considered the main factors influencing the antibody response. In patients older than 60 years of age, the time point of 10 days of MTX discontinuation was critical to boosting the humoral response to anti-SARS-CoV-2 IgG. Because many IMID patients did not have adequate humoral and cellular responses, our findings highlighted the importance of second or booster doses of vaccine and temporary MTX discontinuation. As a result, it implies that individuals with IMIDs should be subjected to more research, particularly humoral and cellular immunity efficiency trials after COVID-19 vaccination, until credible information is achieved.

Saponins, which exhibit many different biological and pharmacological activities, are present in a wide range of plant species and in some marine organisms. Notably, the researchers have found that saponins can activate the immune system in mammals. The strength of this function is closely related to the chemical structure of saponins. The present study of the structure-activity relationship suggests that aglycones, glycochains on aglycones and special functional groups of saponins affect the immune activity of saponins. This paper reviews the effects of different saponins on cellular immunity. As well as the structure-activity relationship of saponins. It is hoped that the information integrated in this paper will provide readers with information on the effects of saponins on cellular immunity and promote the further study of these compounds.

T cells are critical orchestrators of the adaptive immune response that optimally eliminate a specific pathogen. Aberrant T-cell development and function are implicated in a broad range of human disease including immunodeficiencies, autoimmune diseases, and allergic diseases. Accordingly, therapies targeting T cells and their effector cytokines have markedly improved the care of patients with immune dysregulatory diseases. Newer discoveries concerning T-cell-mediated antitumor immunity and T-cell exhaustion have further prompted development of highly effective and novel treatment modalities for malignancies, including checkpoint inhibitors and antigen-reactive T cells. Recent discoveries are also uncovering the depth and variability of T-cell phenotypes: while T cells have long been described using a subset-based classification system, next-generation sequencing technologies suggest an astounding degree of complexity and heterogeneity at the single-cell level.

The introduction of vaccines preventing a severe course of COVID-19 disease is particularly important in immunocompromised patients, among whom organ recipients and patients awaiting transplantation constitute a large group. The article is a critical review of 68 recent publications on the impact of the SARS-CoV-2 pandemic on transplantology worldwide. The study discusses research results concerning various aspects of SARS-CoV-2 vaccination in transplant patients; it also lists important factors influencing vaccination effectiveness. A suboptimal immune response to 2 doses of vaccine in this group of patients is a major challenge prompting further research. Therefore, this review aims to provide an update on the humoral and cellular immune responses to SARS-CoV-2 vaccination following solid organ transplantation.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has undergone multiple mutations since its emergence, and its latest variant, Omicron (B.1.1.529), is the most contagious variant of concern (VOC) which poses a major and imminent threat to public health. Since firstly reported by World Health Organization (WHO) in November 2021, Omicron variant has been spreading rapidly and has become the dominant variant in many countries worldwide. Omicron is the most mutated variant so far, containing 60 mutations in its genome, including 37 mutations in the S-protein. Since all current COVID-19 vaccines in use were developed based on ancestral SARS-CoV-2 strains, whether they are protective against Omicron is a critical question which has been the center of study currently. In this article, we systemically reviewed the studies regarding the effectiveness of 2- or 3-dose vaccines delivered in either homologous or heterologous manner. The humoral and cellular immune responses elicited by various vaccine regimens to protect against Omicron variant are discussed. Current understanding of the molecular basis underlying immune escape of Omicron was also analyzed. These studies indicate that two doses of vaccination are insufficient to elicit neutralizing antibody responses against Omicron variant. Nevertheless, Omicron-specific humoral immune responses can be enhanced by booster dose of almost all type vaccines in certain degree, and heterologous vaccination strategy may represent a better choice than homogenous regimens. Intriguingly, results of studies indicate that all current vaccines are still able to elicit robust T cell response against Omicron. Future focus should be the development of Omicron variant vaccine, which may induce potent humoral as well as cellular immune responses simultaneously against all known variants of the SARS-CoV-2 virus.

Immune responses on SARS-CoV-2 vaccination in patients receiving anti-CD20 therapies are impaired but vary considerably. We conducted a systematic review and meta-analysis of the literature on SARS-CoV-2 vaccine induced humoral and cell-mediated immune response in patients previously treated with anti-CD20 antibodies.
We searched PubMed, Embase, Medrxiv and SSRN using variations of search terms \'anti-CD20\', \'vaccine\' and \'COVID\' and included original studies up to 21 August 2021. We excluded studies with missing data on humoral or cell-mediated immune response, unspecified methodology of response testing, unspecified timeframes between vaccination and blood sampling or low number of participants (≤3). We excluded individual patients with prior COVID-19 or incomplete vaccine courses. Primary endpoints were humoral and cell-mediated immune response rates. Subgroup analyses included time since anti-CD20 therapy, B cell depletion and indication for anti-CD20 therapy. We used random-effects models of proportions.
Ninety studies were assessed. Inclusion criteria were met by 23 studies comprising 1342 patients. Overall rate of humoral response was 0.40 (95% CI 0.35 to 0.47). Overall rate of cell-mediated immune responses was 0.71 (95% CI 0.57 to 0.87). A time interval >6 months since last anti-CD20 therapy was associated with higher humoral response rates with 0.63 (95% CI 0.53 to 0.72) versus <6 months 0.2 (95% CI 0.03 to 0.43); p=0<01. Similarly, patients with circulating B cells more frequently showed humoral responses. Anti-CD20-treated kidney transplant recipients showed lower humoral response rates than patients with haematological malignancies or autoimmune disease.
Patients on anti-CD20 therapies can develop humoral and cell-mediated immune responses after SARS-CoV-2 vaccination, but subgroups such as kidney transplant recipients or those with very recent therapy and depleted B cell are at high risk for non-seroconversion and should be individually assessed for personalised SARS-CoV-2 vaccination strategies. Potential limitations are small patient numbers and heterogeneity of studies included.
This study was funded by Bern University Hospital.