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A systematic review of case reports in spontaneous regression of head and neck squamous cell carcinoma (SCC) was carried out to investigate the pattern and characteristics of this phenomenon.
Methods
A systematic search of case studies of spontaneously regressed head and neck SCC was carried out in Ovid Embase, Ovid Medline and Pubmed. Methodological quality was assessed by ascertainment of diagnosis and overall details of reports. Outcomes included patient demographics, head and neck SCC characteristics and clinical course of disease.
Results
A total of 8 cases were included and 50 per cent (n = 4) of the reported cases were SCC of the vocal folds. All cases received a surgical biopsy and three cases had possible febrile episodes preceding regression. The mean length of time to regression was 4.3 months.
Discussion
Spontaneous regression in head and neck SCC is likely to be under-reported. A better understanding of how the host immune system can instigate an antitumour response will shed light on the development of novel treatments.
A well-functioning immune system requires balanced immune responses. In vitro studies have shown that plant stanols contribute to restoring the T-helper (Th)1/Th2 ratio when it is imbalanced. However, effects of plant stanols on healthy immune responses are unknown. Therefore, we studied effects of recommended (2·5 g/d) or high (9·0 g/d) plant stanol intakes on the Th1/Th2 cytokine balance in immunologically healthy subjects. In two RCTs, peripheral blood mononuclear cells (PBMCs) were isolated, cultured, and stimulated with 5 µg/ml Phytohemagglutinin-M to study ex vivo cytokine production. In the first study, twenty participants consumed margarines (2·5 g/d plant stanols) or control for three weeks. In the second study, nineteen participants consumed margarines and yogurts (9·0 g/d plant stanols) or control for four weeks. T-cell cytokine concentrations were measured in culture medium and in study 2 a standardized Th1/Th2 index was calculated. Serum lipids and non-cholesterol sterols were also measured. Compliance was confirmed by significant increases in serum total cholesterol (TC)-standardized sitostanol and campestanol levels in both studies. Changes in ex vivo cytokine production and Th1/Th2 index did not differ between intervention and control groups. In the first study, no statistically significant changes were observed in lipid and lipoprotein concentrations. In the second study, LDL cholesterol significantly decreased compared to control (–0·77 (–1·11, –0·42) mmol/l; P < 0·001). Recommended (2·5 g/d) or high (9·0 g/d) intakes of plant stanols did not alter PBMC ex vivo cytokine production in immunologically healthy subjects. This suggests that plant stanols might only affect immune function when Th1/Th2 immune responses are imbalanced.
Zinc and copper are trace elements that have important roles in the function of the immune system. We aimed to compare serum zinc and copper levels in neonates with and without neonatal sepsis.
Methods:
This case–control study examined 54 newborns with sepsis and 54 matched healthy controls admitted to the neonatal intensive care unit of Children’s Hospital, Bandar Abbas, Iran. Neonates with the diagnosis of sepsis were regarded as cases and those admitted for other reasons were regarded as controls. Maternal and neonatal serum zinc and copper were measured on admission. Copper, zinc, and copper/zinc ratio differences between case and control groups were analyzed.
Results:
Neonatal zinc levels were significantly lower in the sepsis group versus controls (88.65 ± 40.64 vs 143.48 ± 69.57μg/dL, p < 0.001). Sepsis group mothers had lower zinc (66.04 vs 83.37μg/dL, p = 0.008) and copper (124.09 vs 157.74μg/dL, p < 0.001). Neonatal copper levels were slightly lower in the sepsis group. Copper/zinc ratio was significantly higher in the sepsis group (p < 0.001). In the sepsis group, the interval to the resolution of sepsis symptoms was significantly shorter in neonates with excess compared to sufficient copper levels (P = 0.023).
Conclusions:
Serum copper and zinc levels have an important role in the immune system’s response to the infection. Neonatal serum copper at levels higher than normal can lead to significantly shorter hospital stay. Also, higher Cu/Zn ratios can be found in neonatal sepsis, suggesting the potential utility of this index in the diagnosis of sepsis.
Ocrelizumab is an effective anti-CD20 therapy approved for Relapsing Remitting (RRMS) and Primary Progressive Multiple Sclerosis (PPMS). In clinical trials, a proportion of patients developed hypogammaglobulinemia which could contribute to infection risk. This study aimed to identify hypogammaglobulinemia and its risk factors and evaluate potentially associated serious infection risk in a real-world cohort of patients.
Methods:
All MS patients treated with ocrelizumab in a Quebec City MS clinic from January 2017 to August 2021 were included and detailed patient characteristics were collected by chart review. Levels of immunoglobulins (IgM, IgA and IgG) were assessed prior to each treatment. Serious infection was defined as an infection requiring hospitalization or emergency room treatment. Association between hypogammaglobulinemia and serious infection was analyzed.
Results:
A total of 266 patients (average follow-up 2.05 years) were included (87% RRMS). After 6 infusions, 32.8%, 3.5% and 4.2% of patients had at least one IgM, IgA and IgG hypogammaglobulinemia event respectively. Aside from pre-treatment hypogammaglobulinemia, there were no variables associated with on-treatment hypogammaglobulinemia. There was a total of 21 serious infections (3.36 and 12.33 per 100-person-years in RRMS and PPMS). Developing hypogammaglobulinemia during treatment was not associated with serious infection. A regression analysis did not show associations between serious infection and key disease characteristics.
Conclusion:
Similar to ocrelizumab extension studies, our cohort demonstrated a significant rate of hypogammaglobulinemia over time, mostly with IgM. No association was found between hypogammaglobulinemia and serious infection.
This review will provide an overview of the immune system and then describe the effects of frailty, obesity, specific micronutrients and the gut microbiota on immunity and susceptibility to infection including data from the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic where relevant. A key role for the immune system is providing host defence against pathogens. Impaired immunity predisposes to infections and to more severe infections and weakens the response to vaccination. A range of nutrients, including many micronutrients, play important roles in supporting the immune system to function. The immune system can decline in later life and this is exaggerated by frailty. The immune system is also weakened with obesity, generalised undernutrition and micronutrient deficiencies, which all result in increased susceptibility to infection. Findings obtained during the SARS-CoV-2 pandemic support what was already known about the effects of ageing, frailty and obesity on immunity and susceptibility to infection. Observational studies conducted during the pandemic also support previous findings that multiple micronutrients including vitamins C, D and E, zinc and selenium and long-chain n-3 fatty acids are important for immune health, but whether these nutrients can be used to treat those already with coronavirus disease discovered in 2019 (COVID-19), particularly if already hospitalised, is uncertain from current inconsistent or scant evidence. There is gut dysbiosis in patients with COVID-19 and studies with probiotics report clinical improvements in such patients. There is an inverse association between adherence to a healthy diet and risk of SARS-CoV-2 infection and hospitalisation with COVID-19 which is consistent with the effects of individual nutrients and other dietary components. Addressing frailty, obesity and micronutrient insufficiency will be important to reduce the burden of future pandemics and nutritional considerations need to be a central part of the approach to preventing infections, optimising vaccine responses and promoting recovery from infection.
The SARS-CoV-2 pandemic persists with global repercussions. Initial COVID-19 symptoms encompass pneumonia, fever, myalgia, and fatigue. The human immune system produces IgM and IgG antibodies in response to SARS-CoV-2. Despite previous research, a comprehensive understanding of the interplay between clinical manifestations and humoral immune responses remains elusive. This study aims to scrutinize this association. 134 COVID-19 patients were enrolled, and stratified into mild, moderate, and severe symptom groups. Serum IgM and IgG levels were assessed thrice at one-month intervals using ELISA. The findings reveal significant elevation in serum IgG levels in moderate compared to mild cases (P < 0.001). Additionally, IgG production was significantly heightened in severe cases compared to both mild (P < 0.0001) and moderate (P < 0.05) groups. IgM and IgG levels peaked initially and diminished over time. While anti-SARS-CoV-2 antibodies are expected to confer protection, the direct correlation between IgG levels and symptom severity may arise from delayed immune activation, resulting in an intense antibody response in severe cases. Given evidence linking delayed immune function with a dysregulated innate immune response, comprehensive data collection should encompass not only serum IgG and IgM, but also early measurement of type I interferons at symptom onset. This could provide a more thorough understanding of COVID-19 progression.
Our immune system is our greatest ally when it comes to protecting us from harm. It is designed to fight off infections, heal our wounds, and protect us from malignancy and autoimmune disease. Like all the other systems of our body, this system changes progressively through our lives. Unfortunately, its performance and skills of detection wane as we grow older. This makes us more vulnerable to infections. Some of these effects are inevitable. Others are not. There are things we can do to protect our immune system and mitigate some of the normal forces of aging. This becomes especially important when we reach 70 and older. Chapter outlines seven actions we can do to strengthen our immune system: Mediterranean Diet. Exercise. Keep up to date on vaccinations. Practice good hygiene. Sleep. Lower stress. Practice optimism.
Methionine (MET) supplementation is a current strategy to achieve shrimp requirement. Notwithstanding, the efficiency of the precisely formulated feeds can be diminished since shrimps are slow eaters and masticate feed externally that results in nutrient leaching. In this regard, a methionine dipeptide (DL-methionyl DL-methionine) benefits the feed industry by reducing MET water solubility while increasing its bioavailability. Therefore, the effects of feeding whiteleg shrimp (Penaeus vannamei) with increasing levels of methionine dipeptide were evaluated on zootechnical performance and methionine-, immune- and antioxidant-related pathways. A 74 d growth trial was conducted by feeding a control diet and four diets supplemented with AQUAVI® Met-Met at 0·08, 0·12, 0·24 and 0·32% of DM. Diet digestibility, body amino acids (AA) composition and nitrogen metabolites, metabolic enzymes, oxidative status and gene expression were evaluated. It can be concluded that graded dietary increase of methionine dipeptide up to 0·24 % for 74 d translated in significant gains on the growth performance, feed efficiency, nutrient and nitrogen gain and shrimp survival. Moreover, it was showed that Met-Met dietary spare leads to an improvement of free-AA pool and nitrogen metabolites concentration and reduces the signs of oxidative stress. Finally, in a closer look to the MET-related pathways passive to be altered by Met-Met spare, a clear modulation of the described antioxidant and cell proliferation routes was detected.
None of us can really remember anything about our lives before the age of two years. How much of what makes us what we are has been set by that time? We challenge the widely-accepted idea that what we are is ‘determined’ by inherited genes and we start to explore how interaction with parents/carers establishes our behaviour. We use examples drawn from fiction and the real world to explore how the brain learns from the conditions in early life. We explain why this adaptability underpins development of our senses, our behaviour and our self-control. This introduces control as one of the themes of the book – how much we are in control of our bodies and how control develops based on environmental cues. We question what effect today’s exposure to digital media may have on the developing brain, and explore new ideas about the development of defence mechanisms, from immunity to the gut microbiome. Through the quote from JM Barrie, author of ‘Peter Pan’: ‘You always know after you are two. Two is the beginning of the end’, we ask whether age two is the beginning of the end or the end of the beginning of development.
Schizophrenia affects approximately 1% of the world population, having a devastating impact not only in patients but in all society. As a result, it has been subject of extensive investigation and the presence of certain genes was associated with an increased risk of developing schizophrenia. However, the presence of these genes is not sufficient, therefore, other factors are necessarily involved.Observation of the association between schizophrenia and inflammatory states of the Central Nervous System led to the hypothesis that a dysfunction of the immune system may play a central role in this process.
Objectives
In this work we intend to make a brief review of the existing literature related to the immunological theory of schizophrenia.
Methods
A bibliographic research was conducted in Medline library using the following terms: “schizophrenia and immune system”; “schizophrenia and inflammation” and “schizophrenia and neuroinflammation”.
Results
The survey results reveal increasing evidence of the key role of the immune system in schizophrenia. Several studies show benefits of treatment with anti-inflammatory drugs in patients at an early stage of the disease. In the same way, it was verified that pro and anti-inflammatory cytokines influence glutamatergic transmission and tryptophan metabolism. Furthermore, the decrease in microglial activity appears to have a beneficial effect on schizophrenia.
Conclusions
Future will say if neuroimmunology mechanisms are primary or a secondary consequence in Schizophrenia. Recent discoveries in this area are encouraging and open the possibility of new therapeutic targets and new therapeutic approaches to this disease.
We have previously shown that the association between frequent cannabis use and psychosis is more likely in subgroups with low-grade inflammation than subgroups without (PMID: 33736715). The role of immune-related polymorphisms remains unknown.
Objectives
To explore whether polymorphisms affecting the function of key immune regulatory proteins moderate the association between cannabis and psychosis, namely: ENTPD1 and NT5E, involved in the synthesis of CD39, CD73, respectively, and anti-inflammatory adenosine; CTLA4 and FOXP1, essential for Treg functional capacity.
Methods
We genotyped blood samples from 283 community-based controls and 140 recent-onset psychosis patients in Brazil (EU-GEI consortium, Ribeirão Preto/SP) for twelve polymorphisms (ENTPD1: rs3814159, rs3176891, rs10748643; NT5E: rs9444348, rs2295890; CTLA4: rs3087243, rs231775, rs5742909, rs4553808; FOXP1: rs6803008, rs6786408, rs830599; Illumina Human Core Exome-24). Cannabis frequency (daily, less than daily, never) was assessed by self-report (Cannabis Experience Questionnaire). Binary logistic regression models (OR,95%CI) included case status as the outcome, genotype (dominant model), cannabis frequency, and an interaction term between the two as exposure, adjusting for confounders (age, sex, ethnicity, tobacco smoking).
Results
We found significant interactions between cannabis use and polymorphisms for ENTPD1 (rs3814159), NT5E (rs9444348), and FOXP1 (rs6786408). Less than daily or daily use were, in a dose-response fashion, only associated with psychosis in those with the variant and heterozygous genotypes; less than daily: ENTPD1 AG/GG (3.34,1.71-6.50); NT5E AG/AA (3.71,1.87-7.33); FOXP1 AC/CC (2.98,1.54-5.77); daily: ENTPD1 AG/GG (16.81;5.89-47.96); NT5E AG/AA (21.20,6.81-66.01); FOXP1 AC/CC (13.75,5.22-36.21).
Conclusions
Variation in genes that affect Treg function appears to modify the effect of cannabis consumption on psychosis in keeping with Treg hypofunction hypothesis (PMID:33713699).
A new therapy that uses the patient's own blood to cure blood cancers (leukaemias) is the focus of this chapter. The history of its detection and diagnosis is related, along with the long and arduous search for effective treatment, arriving at successful employment of bone marrow transplantation in the later twentieth century. More recent developments in chemotherapy are reviewed, leading to a contemporary account of the encouraging progress with T-cell therapies.
Acute rheumatic fever is an autoimmune disease that develops due to streptococcal infection. The positive effect of breastfeeding on the development of the child’s immune system is well documented. In this study, we aimed to investigate the effect of breast milk intake period on the development of carditis.
Materials and methods:
Patients (n: 182) who were diagnosed with acute rheumatic fever between 2010 and 2019 were enrolled in the study. The patients were divided into groups according to carditis development. The demographic, socio-economic, and breastfeeding data were compared between groups.
Results:
The mean age of the patients was 10.5 ± 3.4, and 43.4 % (n: 79) of them were female. Independent predictors of the development of carditis in the first acute rheumatic fever episode were the number of children at home (OR: 1.773, CI 95%: 1.105, 2.845; p: 0.018) and breast milk intake less than 6 months (OR: 0.404, CI 95%: 0.174, 0.934; p: 0.034). Independent predictors of the development of carditis in any of the acute rheumatic fever episodes were the number of children at home (OR: 1.858, CI 95%: 1.100, 3.137; p: 0.021) and female gender (OR: 3.504, CI 95%: 1.227, 10.008; p: 0.019). The only independently predictor of the development of chorea during acute rheumatic fever was female gender (OR: 3.801, CI 95%: 1.463, 9.874; p: 0.006).
Conclusion:
Although the occurrence of carditis is less common during the first acute rheumatic fever attack in patients with breast milk intake less than six months, this advantage is lost in recurrent attacks. This study showed that breast milk does not have a negative effect on acute rheumatic fever carditis.
Coronavirus disease 2019 (COVID-19) is an acute respiratory disease associated with severe systemic inflammation. The optimal status of vitamins and microelements is considered crucial for the proper functioning of the immune system and necessary for successful recovery. Most patients with respiratory distress in COVID-19 are vitamin and microelement deficient, with vitamin D and Se deficiency being the most common. Anyway, various micronutrient supplements are widely and arbitrarily used for prevention or in the treatment of COVID-19. We aimed to summarise current knowledge about molecular and physiological mechanisms of vitamins (D, A, C, B6, B9 and B12) and microelements (Se, Zn, Cu and Fe) involved in the immune system regulation in consideration with COVID-19 pathogenesis, as well as recent findings related to their usage and effects in the prevention and treatment of COVID-19. In the early course of the pandemic, several, mainly observational, studies reported an association of some micronutrients, such as vitamin C, D and Zn, with severity reduction and survival improvement. Still, emerging randomised controlled trials showed no effect of vitamin D on hospitalisation length and no effect of vitamin C and Zn on symptom reduction. Up to date, there is evidence neither for nor against the use of micronutrients in the treatment of COVID-19. The doses that exceed the recommended for the general population and age group should not be used, except in clinical trials. Benefits of supplementation are primarily expected in populations prone to micronutrient deficiencies, who are, as well, at a higher risk of worse outcomes in COVID-19.
The appearance on the skin of herpes virus lesions, concomitantly with the coronavirus disease 2019 (COVID-19) pandemic, leads us to suspect an underlying infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Diagnostic reverse transcriptase polymerase chain reaction tests and immunoglobulin M (IgM) and IgG seroconversion studies have therefore been carried out. We present three cases of herpes virus infections in immunocompetent patients: one of the infections was herpes simplex 1 in a 40-year-old woman, and the other two were herpes varicella-zoster infections in a 62-year-old man and a 25-year-old woman. The patients were in the care of the southern health district of Seville of the SAS (Andalusian Health Service) during the Spanish state of alarm over the COVID-19 pandemic. The SARS-CoV-2 infection was confirmed in only one of the three cases. In this study, we briefly review the etiopathogenic role of the COVID-19 pandemic situation, whereby immunodeficiencies are generated that favour the appearance of other viral infections, such as herpes virus infections.
We study a mathematical model proposed in the literature with the aim of describing the interactions between tumor cells and the immune system, when a periodic treatment of immunotherapy is applied. Combining some techniques from non-linear analysis (degree theory, lower and upper solutions, and theory of free-homeomorphisms in the plane), we give a detailed global analysis of the model. We also observe that for certain therapies, the maximum level of aggressiveness of a cancer, for which the treatment works (or does not work), can be computed explicitly. We discuss some strategies for designing therapies. The mathematical analysis is completed with numerical results and conclusions.
Altered expression of the complement component C4A gene is a known risk factor for schizophrenia. Further, predicted brain C4A expression has also been associated with memory function highlighting that altered C4A expression in the brain may be relevant for cognitive and behavioral traits.
Methods
We obtained genetic information and performance measures on seven cognitive tasks for up to 329 773 individuals from the UK Biobank, as well as brain imaging data for a subset of 33 003 participants. Direct genotypes for variants (n = 3213) within the major histocompatibility complex region were used to impute C4 structural variation, from which predicted expression of the C4A and C4B genes in human brain tissue were predicted. We investigated if predicted brain C4A or C4B expression were associated with cognitive performance and brain imaging measures using linear regression analyses.
Results
We identified significant negative associations between predicted C4A expression and performance on select cognitive tests, and significant associations with MRI-based cortical thickness and surface area in select regions. Finally, we observed significant inconsistent partial mediation of the effects of predicted C4A expression on cognitive performance, by specific brain structure measures.
Conclusions
These results demonstrate that the C4 risk locus is associated with the central endophenotypes of cognitive performance and brain morphology, even when considered independently of other genetic risk factors and in individuals without mental or neurological disorders.
This meta-analysis on peripheral blood compounds in drug-naïve first-episode patients with either schizophrenia or major depressive disorder (MDD) examined which compounds change following psychopharmacological treatment.
Methods
The Embase, PubMed and PsycINFO databases were systematically searched for longitudinal studies reporting measurements of blood compounds in drug-naïve first-episode schizophrenia or MDD.
Results
For this random-effects meta-analysis, we retrieved a total of 31 studies comprising 1818 schizophrenia patients, and 14 studies comprising 469 MDD patients. Brain-derived neurotrophic factor (BDNF) increased following treatment in schizophrenia (Hedges' g (g): 0.55; 95% confidence interval (CI) 0.39–0.70; p < 0.001) and MDD (g: 0.51; CI 0.06–0.96; p = 0.027). Interleukin (IL)-6 levels decreased in schizophrenia (g: −0.48; CI −0.85 to −0.11; p = 0.011), and for MDD a trend of decreased IL-6 levels was observed (g: −0.39; CI −0.87 to 0.09; p = 0.115). Tumor necrosis factor alpha (TNFα) also decreased in schizophrenia (g: −0.34; CI −0.68 to −0.01; p = 0.047) and in MDD (g: −1.02; CI −1.79 to −0.25; p = 0.009). Fasting glucose levels increased only in schizophrenia (g: 0.26; CI 0.07–0.44; p = 0.007), but not in MDD. No changes were found for C-reactive protein, IL-1β, IL-2 and IL-4.
Conclusions
Psychopharmacological treatment has modulating effects on BDNF and TNFα in drug-naïve first-episode patients with either schizophrenia or MDD. These findings support efforts for further research into transdiagnostic preventive strategies and augmentation therapy for those with immune dysfunctions.
Rumen fluid from slaughtered animals is one of the wastes of slaughterhouses released to the environment that, due to its high nitrogen and phosphorus contents, can lead to soil and groundwater pollution. Meanwhile, it contains ruminal microbes and some bioactive compounds such as enzymes, minerals, vitamins and organic acids. This study was designed to examine the potential of rumen fluid as a feed additive. Therefore, the effects of spray-dried rumen fluid (SDR) with 1% maltodextrin on the performance, blood metabolites and some cytokines of sucking dairy calves during the pre-weaning phase were investigated. Forty male Holstein calves, with a mean weight of 39.4 ± 3.7 kg and 7 ± 1 days old, were randomly assigned to four groups (n = 10 calves per group) in a completely randomized design. Experimental treatments were: control diet with no additive (CON); control diet with 0.5 g/day of SDR (SDR0.5); control diet with 1 g/day of SDR (SDR1); and control diet with 1.5 g/day of SDR (SDR1.5). Daily feed intake and average daily gain of calves were not affected by feeding SDR as a feed additive. Cholesterol concentration was significantly affected by the 20th and 40th days of the experiment and decreased linearly by increasing SDR feeding level. Levels of liver enzymes, including aspartate aminotransferase and alanine aminotransferase, in the blood decreased by feeding SDR at day 40 of the experiment. Serum concentration of interleukin-6 at day 20 was not affected by dried rumen fluid feeding, whereas at day 40, a significant effect was observed among experimental treatments. The lowest value was recorded for SDR1.5 v. control calves. At day 20, the serum concentration of interferon-γ was influenced by supplementing SDR, and the highest value was recorded for SDR1.5 calves. The inclusion of SDR with 1% maltodextrin in suckling dairy calves had beneficial effects on the stimulation of calves’ immune system.
Immunology is central to contemporary biology and medicine, but it also provides novel philosophical insights. Its most significant contribution to philosophy concerns the understanding of biological individuality: what a biological individual is, what makes it unique, how its boundaries are established and what ensures its identity through time. Immunology also offers answers to some of the most interesting philosophical questions. What is the definition of life? How are bodily systems delineated? How do the mind and the body interact? In this Element, Thomas Pradeu considers the ways in which immunology can shed light on these and other important philosophical issues. This title is also available as Open Access on Cambridge Core.