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Edited by
Rebecca Leslie, Royal United Hospitals NHS Foundation Trust, Bath,Emily Johnson, Worcester Acute Hospitals NHS Trust, Worcester,Alex Goodwin, Royal United Hospitals NHS Foundation Trust, Bath,Samuel Nava, Severn Deanery, Bristol
Chapter 1.7 is focused on immunology relevant to anaesthesia and critical care. There is an outline of the structure of the human adaptive and innate immune systems including descriptions of the mechanism of acquired cellular immunity. We discuss the complement system and the inflammatory to surgery and critical illness.
Brain immune privilege for many years overshadowed investigation of interaction between the nervous and immune systems. Over time, however, evidence of their interdependence has emerged. In the 1970s, as antibody-mediated autoimmunity was being defined, the neurological disorder myasthenia gravis was shown to be due to autoantibodies that could be passively transferred to mice and removed from humans by plasma exchange. In the 1980s, Fink and Weihe showed that neurons innervate lymph nodes, and from the 1990s onwards, Rothwell and colleagues observed the impact of soluble inflammatory mediators on behaviour. For example, in a key experiment, her team showed that systemic and intraventricular injection of IL-1 led to fever and reduced food motivation in experimental animals, interpreted as “sickness behaviour”; this technique is now used as a model for inflammation-driven depression. Furthermore, IFN- α was unexpectedly found to cause depression when given as a treatment for hepatitis C. More recently, diseases have been identified in which autoantibodies interfere with neuronal function and cause severe psychiatric symptoms, such as N-Methyl D-Aspartate Receptor (NMDAR)-antibody encephalitis. There is now emerging interest in the patho-aetiological role of the immune system in various severe mental illnesses, and the use of immunotherapies in their treatment.
Autoimmune movement disorders, although relatively rare, are not to be missed because of the treatment implications. There is a broad clinical spectrum, but recognition of some characteristic forms, or associated red flags or other clues, can point to the diagnosis. This chapter covers the clinical spectrum of primary neurologic or systemic autoimmune disease presenting or mainly manifesting as a movement disorder, and addresses the underlying immune-pathophysiologic aspects.
We studied severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and vaccination status among six ethnic groups in Amsterdam, the Netherlands. We analysed participants of the Healthy Life in an Urban Setting cohort who were tested for SARS-CoV-2 spike protein antibodies between 17 May and 21 November 2022. We categorized participants with antibodies as only infected, only vaccinated (≥1 dose), or both infected and vaccinated, based on self-reported prior infection and vaccination status and previous seroprevalence data. We compared infection and vaccination status between ethnic groups using multivariable, multinomial logistic regression. Of the 1,482 included participants, 98.5% had SARS-CoV-2 antibodies (P between ethnic groups = 0.899). Being previously infected and vaccinated ranged from 36.2% (95% confidence interval (CI) = 28.3–44.1%) in the African Surinamese to 64.5% (95% CI = 52.9–76.1%) in the Ghanaian group. Compared to participants of Dutch origin, participants of South-Asian Surinamese (adjusted odds ratio (aOR) = 6.74, 95% CI = 2.61–17.45)), African Surinamese (aOR = 23.32, 95% CI = 10.55–51.54), Turkish (aOR = 8.50, 95% CI = 3.05–23.68), or Moroccan (aOR = 22.33, 95% CI = 9.48–52.60) origin were more likely to be only infected than infected and vaccinated, after adjusting for age, sex, household size, trust in the government’s response to the pandemic, and month of study visit. SARS-CoV-2 infection and vaccination status varied across ethnic groups, particularly regarding non-vaccination. As hybrid immunity is most protective against coronavirus disease 2019, future vaccination campaigns should encourage vaccination uptake in specific demographic groups with only infection.
This chapter provides details of serological tests which can be used to detect viral antibodies or antigens in serum, saliva or urine (e.g. ELISA, EIA, IF, CFT, HAI, neutralisation, Western blot, line immunoassays and avidity tests). It details the utility of each test.
In resource-limited countries, the lack of widespread screening masks the true situation of COVID-19. We conducted this study to assess SARS-CoV-2 spread by detection of specific antibodies and to determine associated factors. A population-based cross-sectional study was conducted. Subjects were tested for the presence of two antibodies (IgM and IgG) specific to SARS-CoV-2. Data collection was done using a smartphone with the KoboCollect application. Prevalence of antibodies was estimated with 95% confidence intervals. Logistic regression was used to determine factors associated with positive serological test. A total of 9,094 persons were tested in 4,340 households. The mean age was 30.18 ± 18.65 years, 46.5% male. The overall seroprevalence (prevalence, 95% CI) of SARS-CoV-2 antibodies was (48.2% [47.2%–49.2%]). Being vaccinated, having been in contact with a COVID-19 patient, being older than 50 years, living in a union, having secondary education and having tertiary education were factors independently associated with the likelihood of having anti-sars-CoV-2. We estimate in February 2022 that 48% persons had antibodies against the COVID-19 virus, more among those vaccinated. Vaccination intensification in low prevalence departments will reduce the risk of new outbreaks.
This study aimed to analyse the seroprevalence of SARS-CoV-2 in Kazakhstan. This is a cross-sectional study of adult population in Kazakhstan for the period from October 2021 to May 2022. For the study, 6 720 people aged 18 to 69 were recruited (from 17 regions). The demographic data were collected and analysed. Gender was evenly distributed (males 49.9%, females 50.1%). Women exhibited a higher seroprevalence than men (IgM 20.7% vs 17.9% and IgG 46.1% vs 41.5%). The highest prevalence of IgM was found in the age group of 30–39. However, the highest prevalence of IgG was detected in the age group of 60–69. The seroprevalence of IgG increased across all groups (from 39.7% in 18–29 age groups to 53.1% in 60–69 age groups). The odds for a positive test were significantly increased in older age groups 50–59 (p < 0.0001) and 60–69 (p < 0.0001). The odds of a positive test were 1.12 times higher in females compared to males (p = 0.0294). The odds for a positive test were significantly higher in eight regions (Astana, Akmola, Atyrau, Western Kazakhstan region, Kostanai, Turkestan, Eastern Kazakhstan region, and Shymkent) compared to Almaty city. The odds of a positive test were three times higher in Astana and the Western Kazakhstan region than in Almaty city. In urban areas, the odds of a positive test were 0.75 times lower than in rural areas (p < 0.0001). The study’s results showed an adequate level of seroprevalence (63%) that exceeds the essential minimum of herd immunity indicators in the country. There was significant geographic variability with a higher prevalence of IgG/IgM antibodies to SARS-CoV-2 in rural areas.
1. The innate immune system is immediate and non-specific, whilst the adaptive immune system mounts a slower, specific response to pathogens.
2. The complement system can be activated by either the innate or the adaptive immune system.
3. There are five classes of antibody, with variable roles.
4. Primary immunodeficiency disorders are genetic or congenital in origin, are present early in life and are rare.
5. Secondary acquired immunodeficiency is more common and linked to drug treatment, haematological disease, human immunodeficiency virus infection and critical illness.
Hemolytic disease of the fetus and newborn is a common cause of intrauterine death and increased neonatal morbidity. While this condition may occur as a result of maternal antibody formation to a variety of different antibodies,(alloimmunization), that which occurs in response to the Rhesus D antigen is the most common. Many centers now perform intrauterine fetal blood transfusion, a required mode of therapy for alloimunization, which is necessary to prevent fetal demise. The ability to accurately detect and treat fetuses affected by this condition depends on adequate prenatal care, astute maternal-fetal practitioners, and a robust center with the ability to analyze fetal blood samples which directs transfusion therapy. While intrauterine therapy is not without complications, and is commonly characterized by repeated fetal transfusions, the ability to transfuse fetuses in-utero has drastically improved the prognosis for affected babies.
We report the development of a regression model to predict the prevalence of severe acute respiratory syndrome coronavirus (SARS-CoV-2) antibodies on a population level based on self-reported symptoms. We assessed participant-reported symptoms in the past 12 weeks, as well as the presence of SARS-CoV-2 antibodies during a study conducted in April 2020 in Ischgl, Austria. We conducted multivariate binary logistic regression to predict seroprevalence in the sample. Participants (n = 451) were on average 47.4 years old (s.d. 16.8) and 52.5% female. SARS-CoV-2 antibodies were found in n = 197 (43.7%) participants. In the multivariate analysis, three significant predictors were included and the odds ratios (OR) for the most predictive categories were cough (OR 3.34, CI 1.70–6.58), gustatory/olfactory alterations (OR 13.78, CI 5.90–32.17) and limb pain (OR 2.55, CI 1.20–6.50). The area under the receiver operating characteristic curve was 0.773 (95% CI 0.727–0.820). Our regression model may be used to estimate the seroprevalence on a population level and a web application is being developed to facilitate the use of the model.
Tick-borne encephalitis (TBE) is a vector-borne infection associated with a variety of potentially serious complications and sequelae. Vaccination against TBE is strongly recommended for people living in endemic areas. There are two TBE vaccination schemes – standard and rapid – which differ in the onset of protection. With vaccination in a rapid schedule, protection starts as early as 4 weeks after the first dose and is therefore especially recommended for non-immune individuals travelling to endemic areas. Both schemes work reliably in immunocompetent individuals, but only little is known about how TBE vaccination works in people with HIV infection. Our aim was to assess the immunogenicity and safety of the rapid scheme of TBE vaccination in HIV-1 infected individuals. Concentrations of TBE-specific IgG > 126 VIEU/ml were considered protective. The seroprotection rate was 35.7% on day 28 and 39.3% on day 60. There were no differences between responders and non-responders in baseline and nadir CD4 + T lymphocytes. No serious adverse events were observed after vaccination. The immunogenicity of the TBE vaccination was unsatisfactory in our study and early protection was only achieved in a small proportion of vaccinees. Therefore, TBE vaccination with the rapid scheme cannot be recommended for HIV-1 infected individuals.
Bone marrow (BM) trephine biopsy (BMB) is a frequent and routine diagnostic investigation, as nicely described in the previous chapters, and is also widely used for follow-up of haematological disorders to judge the effectiveness of therapeutic interventions [1]. In addition, several drugs applied primarily for the treatment of non-haematological disorders may cause serious haematological side effects, such as pancytopaenia, agranulocytosis or anaemia. On occasion, the causative link between the haematological symptoms and the previous drug exposure is not perceived and it is not uncommon for BMB to be obtained in such circumstances without any information of a history of previous drug exposure being made available to the haematopathologist [2].
Determination of antibodies against ToRCH antigens at the beginning of pregnancy allows assessment of both the maternal immune status and the risks to an adverse pregnancy outcome. Age-standardised seroprevalences were determined in sera from 1009 women of childbearing age residing in Mexico, Brazil, Germany, Poland, Turkey or China using a multiparametric immunoblot containing antigen substrates for antibodies against Toxoplasma gondii, rubella virus, cytomegalovirus (CMV), herpes simplex viruses (HSV-1, HSV-2), Bordetella pertussis, Chlamydia trachomatis, parvovirus B19, Treponema pallidum and varicella zoster virus (VZV). Seroprevalences for antibodies against HSV-1 were >90% in samples from Brazil and Turkey, whereas the other four countries showed lower mean age-adjusted seroprevalences (range: 62.5–87.9%). Samples from Brazilian women showed elevated seroprevalences of antibodies against HSV-2 (40.1%), C. trachomatis (46.8%) and B. pertussis (56.6%) compared to the other five countries. Seroprevalences of anti-T. gondii antibodies (0.5%) and anti-parvovirus B19 antibodies (7.5%) were low in samples from Chinese women, compared to the other five countries. Samples from German women revealed a low age-standardised seroprevalence of anti-CMV antibodies (28.8%) compared to the other five countries. These global differences in immune status of women in childbearing age advocate country-specific prophylaxis strategies to avoid infection with ToRCH pathogens.
Borrelia burgdorferi (Bb) infection can affect the central nervous system and possibly lead to psychiatric disorders. We compared clinical and demographic variables in Bb seropositive and seronegative psychiatric patients and healthy controls.
Method.
Nine hundred and twenty-six consecutive psychiatric patients were screened for antibodies to Bb and compared with 884 simultaneously recruited healthy subjects.
Results.
Contrary to healthy controls, seropositive psychiatric patients were significantly younger than seronegative ones. None of the studied psychiatric diagnostic categories exhibited stronger association with seropositivity. There were no differences between seropositive and seronegative psychiatric patients in hospitalization length, proportion of previously hospitalized patients and proportion of subjects with family history of psychiatric disorders.
Conclusion.
These findings elaborate on potential association between Bb infection and psychiatric morbidity, but fail to identify any specific clinical ‘signature’ of Bb infection.
The past decade has seen a surge of reports and investigations into cases of autoimmune-mediated encephalitis. The increasing recognition of these disorders is especially of relevance to the fields of neurology and psychiatry. Autoimmune encephalitis involves antibodies against synaptic receptors, neuronal cell surface proteins and intracellular targets. These disorders feature prominent symptoms of cognitive impairment and behavioural changes, often associated with the presence of seizures. Early in the clinical course, autoimmune encephalitis may manifest as psychiatric symptoms of psychosis and involve psychiatry as an initial point of contact. Although commonly associated with malignancy, these disorders can present in the absence of an inciting neoplasm. The identification of autoimmune encephalitis is of clinical importance as a large proportion of individuals experience a response to immunotherapy. This review focuses on the current state of knowledge on n-methyl-d-aspartate (NMDA) receptor-associated encephalitis and limbic encephalitis, the latter predominantly involving antibodies against the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor, the γ-aminobutyric acid (GABA)B receptor and leucine-rich glioma-inactivated 1 (LGI1) protein. In addition, we briefly describe anti-dopamine D2 receptor encephalitis. A summary of the literature will focus on common clinical presentations and course, diagnostic approaches and response to treatment. Since a substantial proportion of patients with autoimmune encephalitis exhibit symptoms of psychosis, the relevance of this disorder to theories of psychosis and schizophrenia will also be discussed.
Why do hosts vary so much in parasite burden, how does this variation translate to variation in host demographic rates and parasite transmission, and how does varied transmission intensity impact selection upon immune defence of individuals? The theoretical foundations of disease ecology provide predictions for the answers to these questions, yet testing such predictions with empirical data poses many challenges. We show how the long-term ecological and genetic study of the unmanaged Soay sheep of St Kilda has addressed fundamental questions in disease ecology, with longitudinal data on parasite burden, immune defence, condition, survival, and fecundity of >10,000 individuals. The rich individual-scale data are complemented by >30 years of data on sheep population dynamics and genetic diversity as well as parasite dynamics and diversity. Population-scale work has documented the range of parasite species present and the contribution of the most prevalent and virulent parasites to regulating sheep dynamics. Individual-scale work has identified drivers of variation in parasite burden and tested hypotheses about costs and benefits of defence in a quest to determine how natural selection has shaped immune function of the sheep.
The relationship between epilepsy and the presence of visceral larva migrans caused by Toxocara canis in Mexican children remains uncertain; however, this relationship needs to be elucidated because these parasite larvae can invade the human central nervous system. Accordingly, this study aimed to determine the frequency and specificity of anti-T. canis antibodies in the sera of children with epilepsy to determine the relationship between this parasite and epilepsy. The sera samples of 214 children were examined: 111 children diagnosed with epilepsy and 103 clinically healthy children without neurological disorders. In the sera of each group, the presence and specificity of anti-T. canis and anti-Ascaris lumbricoides antibodies, as well as the cross-reactivity between them, were assessed using enzyme-linked immunosorbent assay and Western blotting analysis. Among the children with epilepsy, 25.2% exhibited seropositivity to T. canis. Cross-reactivity against the A. lumbricoides antigen was present in 46.8% of the children with epilepsy, whereas 11.7% of the children with epilepsy and anti-T. canis antibodies did not exhibit cross-reactivity against this antigen. The Western blotting analysis of the sera from the children with epilepsy demonstrated the presence of T. canis proteins, with molecular weights of 24, 35, 55, 70, 120 and 210 kDa, and A lumbricoides proteins with molecular weights of 70, 80 and 110 kDa. Our results revealed the presence of anti-T. canis antibodies in the children with epilepsy; furthermore, cross-reactivity tests with A. lumbricoides showed the importance of the presence of anti-T. canis antibodies in revealing the relationship between this parasite and epilepsy in children.
Outbreaks of Old World cutaneous leishmaniasis (CL) have significantly increased due to the conflicts in the Middle East, with most of the cases occurring in resource-limited areas such as refugee settlements. The standard methods of diagnosis include microscopy and parasite culture, which have several limitations. To address the growing need for a CL diagnostic that can be field applicable, we have identified five candidate neoglycoproteins (NGPs): Galα (NGP3B), Galα(1,3)Galα (NGP17B), Galα(1,3)Galβ (NGP9B), Galα(1,6)[Galα(1,2)]Galβ (NGP11B), and Galα(1,3)Galβ(1,4)Glcβ (NGP1B) that are differentially recognized in sera from individuals with Leishmania major infection as compared with sera from heterologous controls. These candidates contain terminal, non-reducing α-galactopyranosyl (α-Gal) residues, which are known potent immunogens to humans. Logistic regression models found that NGP3B retained the best diagnostic potential (area under the curve from receiver-operating characteristic curve = 0.8). Our data add to the growing body of work demonstrating the exploitability of the human anti-α-Gal response in CL diagnosis.
Malaria is one the most serious infectious diseases with over 200 million clinical cases annually. Most cases of the severe disease are caused by Plasmodium falciparum. The blood stage of Plasmodium parasite is entirely responsible for malaria-associated pathology. The population most susceptible to severe malaria are children under the age of 5, with low levels of immunity. It is only after many years of repeated exposure that individuals living in endemic areas develop clinical immunity. This form of protection prevents clinical episodes by substantially reducing parasite burden. Naturally acquired immunity predominantly targets blood-stage parasites with antibody responses being the main mediators of protection. The targets of clinical immunity are the extracellular merozoite and the infected erythrocyte surface, with the extremely diverse PfEMP1 proteins the main target here. This observation provides a strong rationale that an effective anti-malaria vaccine targeting blood-stage parasites is achievable. Thus the identification of antigenic targets of naturally acquired immunity remains an important step towards the formulation of novel vaccine combinations before testing their efficacy in clinical trials. This review summarizes the main findings to date defining antigenic targets present on the extracellular merozoite associated with naturally acquired immunity to P. falciparum malaria.