Development Of Adaptive Immunity Research Articles

Developmental Programming of the Fetal Immune System by Maternal Western-Style Diet: Mechanisms and Implications for Disease Pathways in the Offspring.

Maternal obesity and over/undernutrition can have a long-lasting impact on offspring health during critical periods in the first 1000 days of life. Children born to mothers with obesity have reduced immune responses to stimuli which increase susceptibility to infections. Recently, maternal western-style diets (WSDs), high in fat and simple sugars, have been associated with skewing neonatal immune cell development, and recent evidence suggests that dysregulation of innate immunity in early life has long-term consequences on metabolic diseases and behavioral disorders in later life. Several factors contribute to abnormal innate immune tolerance or trained immunity, including changes in gut microbiota, metabolites, and epigenetic modifications. Critical knowledge gaps remain regarding the mechanisms whereby these factors impact fetal and postnatal immune cell development, especially in precursor stem cells in bone marrow and fetal liver. Components of the maternal microbiota that are transferred from mothers consuming a WSD to their offspring are understudied and identifying cause and effect on neonatal innate and adaptive immune development needs to be refined. Tools including single-cell RNA-sequencing, epigenetic analysis, and spatial location of specific immune cells in liver and bone marrow are critical for understanding immune system programming. Considering the vital role immune function plays in offspring health, it will be important to understand how maternal diets can control developmental programming of innate and adaptive immunity.

Type I Interferon Autoantibodies Correlate With Cellular Immune Alterations in Severe COVID-19.

Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can lead to severe disease with increased morbidity and mortality among certain risk groups. The presence of autoantibodies against type I interferons (aIFN-Abs) is one mechanism that contributes to severe coronavirus disease 2019 (COVID-19). This study aimed to investigate the presence of aIFN-Abs in relation to the soluble proteome, circulating immune cell numbers, and cellular phenotypes, as well as development of adaptive immunity. aIFN-Abs were more prevalent in critical compared to severe COVID-19 but largely absent in the other viral and bacterial infections studied here. The antibody and T-cell response to SARS-CoV-2 remained largely unaffected by the presence aIFN-Abs. Similarly, the inflammatory response in COVID-19 was comparable in individuals with and without aIFN-Abs. Instead, presence of aIFN-Abs had an impact on cellular immune system composition and skewing of cellular immune pathways. Our data suggest that aIFN-Abs do not significantly influence development of adaptive immunity but covary with alterations in immune cell numbers.

MRNA Vaccine Nanoplatforms and Innate Immunity.

mRNA-based vaccine technology has been significantly developed and enhanced, particularly highlighted by the authorization of mRNA vaccines for addressing the COVID-19 pandemic. Various biomaterials are developed in nano-scales and applied as mRNA vaccine delivery platforms. However, how these mRNA nanoplatforms influence immune responses has not been thoroughly studied. Hence, we have reviewed the current understanding of various mRNA vaccine platforms. We discussed the possible pathways through which these platforms moderate the host's innate immunity and contribute to the development of adaptive immunity. We shed light on their development in reducing biotoxicity and enhancing antigen delivery efficiency. Beyond the built-in adjuvanticity of mRNA vaccines, we propose that supplementary adjuvants may be required to fine-tune and precisely control innate immunity and subsequent adaptive immune responses.

Early innate cell interactions with Mycobacterium tuberculosis in protection and pathology of tuberculosis.

Tuberculosis (TB) remains a significant global health challenge, claiming the lives of up to 1.5 million individuals annually. TB is caused by the human pathogen Mycobacterium tuberculosis (Mtb), which primarily infects innate immune cells in the lungs. These immune cells play a critical role in the host defense against Mtb infection, influencing the inflammatory environment in the lungs, and facilitating the development of adaptive immunity. However, Mtb exploits and manipulates innate immune cells, using them as favorable niche for replication. Unfortunately, our understanding of the early interactions between Mtb and innate effector cells remains limited. This review underscores the interactions between Mtb and various innate immune cells, such as macrophages, dendritic cells, granulocytes, NK cells, innate lymphocytes-iNKT and ILCs. In addition, the contribution of alveolar epithelial cell and endothelial cells that constitutes the mucosal barrier in TB immunity will be discussed. Gaining insights into the early cellular basis of immune reactions to Mtb infection is crucial for our understanding of Mtb resistance and disease tolerance mechanisms. We argue that a better understanding of the early host-pathogen interactions could inform on future vaccination approaches and devise intervention strategies.

Tracking the Host Response to Infection in Peritoneal Models of Acute Resolving Inflammation.

Antimicrobial host defense is dependent on the rapid recruitment of inflammatory cells to the site of infection, the elimination of invading pathogens, and the efficient resolution of inflammation that minimizes damage to the host. The peritoneal cavity provides an accessible and physiologically relevant system where the delicate balance of these processes may be studied. Here, we describe murine models of peritoneal inflammation that enable studies of competent antimicrobial immunity and inflammation-associated tissue damage as a consequence of recurrent bacterial challenge. The inflammatory hallmarks of these models reflect the clinical and molecular features of peritonitis seen in renal failure patients on peritoneal dialysis. The development of these models relies on the preparation of a cell-free supernatant derived from an isolate of Staphylococcus epidermidis (termed SES). Intraperitoneal administration of SES induces a Toll-like receptor 2-driven acute inflammatory response that is characterized by an initial transient influx of neutrophils that are replaced by a more sustained recruitment of mononuclear cells and lymphocytes. Adaptation of this model using a repeated administration of SES allows investigations into the development of adaptive immunity and the hallmarks associated with tissue remodelling and fibrosis. These models are therefore clinically relevant and provide exciting opportunities to study innate and adaptive immunity and the response of the stromal tissue compartment to bacterial infection and the ensuing inflammatory reaction.

Development of Adaptive Immunity and Its Role in Lung Remodeling.

Asthma is characterized by airflow limitations resulting from bronchial closure, which can be either reversible or fixed due to changes in airway tissue composition and structure, also known as remodeling. Airway remodeling is defined as increased presence of mucins-producing epithelial cells, increased thickness of airway smooth muscle cells, angiogenesis, increased number and activation state of fibroblasts, and extracellular matrix (ECM) deposition. Airway inflammation is believed to be the main cause of the development of airway remodeling in asthma. In this chapter, we will review the development of the adaptive immune response and the impact of its mediators and cells on the elements defining airway remodeling in asthma.

Immune gene expression analysis indicates the potential of a self-amplifying Covid-19 mRNA vaccine

Remarkable potency has been demonstrated for mRNA vaccines in reducing the global burden of the ongoing COVID-19 pandemic. An alternative form of the mRNA vaccine is the self-amplifying mRNA (sa-mRNA) vaccine, which encodes an alphavirus replicase that self-amplifies the full-length mRNA and SARS-CoV-2 spike (S) transgene. However, early-phase clinical trials of sa-mRNA COVID-19 vaccine candidates have questioned the potential of this platform to develop potent vaccines. We examined the immune gene response to a candidate sa-mRNA vaccine against COVID-19, ARCT-021, and compared our findings to the host response to other forms of vaccines. In blood samples from healthy volunteers that participated in a phase I/II clinical trial, greater induction of transcripts involved in Toll-like receptor (TLR) signalling, antigen presentation and complement activation at 1 day post-vaccination was associated with higher anti-S antibody titers. Conversely, transcripts involved in T-cell maturation at day 7 post-vaccination informed the magnitude of eventual S-specific T-cell responses. The transcriptomic signature for ARCT-021 vaccination strongly correlated with live viral vector vaccines, adjuvanted vaccines and BNT162b2 1 day post-vaccination. Moreover, the ARCT-021 signature correlated with day 7 YF17D live-attenuated vaccine transcriptomic responses. Altogether, our findings show that sa-mRNA vaccination induces innate immune responses that are associated with the development of adaptive immunity from other forms of vaccines, supporting further development of this vaccine platform for clinical application.

A Multimodal Single Cell Atlas of Human Tonsils Reveals New Insights into T and B Cell Differentiation

Palatine tonsils are secondary lymphoid organs under constant exposure to antigens via the upper respiratory tract which makes them a compelling organ for adaptive immunity development. They represent an important niche for lymphocyte maturation, where they differentiate into a wide variety of functional states, tailoring immune responses to different insults. However, although some efforts have been made to characterise the lymphocyte maturation process in human tonsils at single cell resolution, these studies lacked cell numbers and multimodal, i.e multiomics, information to comprehensively capture the cellular heterogeneity of the process. Here we generated a comprehensive human tonsil atlas of >357,000 cells profiled across five different data modalities, such as transcriptome, epigenome, proteome, adaptive immune repertoire and spatial location. We identified 121 cell subtypes and states across lineages and characterised the maturation process of both B and T lymphocytes. The high number of profiled cells allowed the detection of rare cell subtypes, such as precursor B and T cells, the latter representing <0.01% of detected cells, supporting an ongoing maturation of lymphoid cells outside the bone marrow and thymus, respectively. Beyond these rare precursor lymphocytes, the tonsil is the niche for multiple steps of mature T and B cell differentiation. With regard to mature T cells, we described 37 different T cell (TC) subpopulations being CD4 TC the more representative population with 58,783 cells, which illustrated the maturation process of this lineage. We identified an early bifurcation following antigen recognition by naïve CD4 TC, resulting in two distinct precursor populations of T follicular helper (fh) and non-Tfh cells. Tfh precursor cells continued their differentiation trajectory towards terminally differentiated populations, with functions in the production of mature B cells (BC) and in the enhancement of antibody secretion. On the other branch of the CD4 TC differentiation trajectory, our data revealed three transcriptional Treg subtypes, with functions in the suppression of antitumor responses, COVID-19 and the control of BC antibody production, respectively. The multimodal study design further enabled the interrogation of regulatory circuits driving TC specialization, describing a potential BCL6 superenhancer specifically active in follicular TC. Intriguingly, the same region has been previously linked to BCL6 gene activation in Germinal Center (GC) BC, indicating its function as follicle-specific rather than cell type-specific cis-regulatory element. Mature B cells corresponded to the greatest population of the dataset, with >70% cells assigned to the BC lineage allowing the fine-grained description of the BC maturation process. We identified 8 distinct naïve BC (NBC) subpopulations and comprehensively characterized the activation pathway upon first antigen recognition, further expanding previous findings focused on MYC. Additionally, by the combination of gene expression and chromatin accessibility profiles we disentangled the transcription factor (TF) hierarchy associated with the Light zone (LZ) to Dark Zone (DZ) reentry. We identified the activity NF-kB family genes as one of the first determinants of the TF hierarchy that drives this specialization, which seems to be shared in LZ cells reentering the DZ as well as activated NBCs that enter the DZ for the first time. However, this regulation was not observed in LZ GCBCs that further differentiate into plasma cells (PCs). This final maturation step towards an antibody secreting phenotype was also characterized, identifying the first stages of PC precursor cells derived from either memory or LZ-GCBC and their transcriptional dynamics was also spatially mapped in the tonsillar tissue. Charting the regulatory landscape in PCs we validated the presence of described PC TFs, but we also discovered SIX5 as a novel potential TF associated with the maturation, but not the commitment, of PCs. Moreover, we identified a higher activity of the regulatory network of SIX5 in multiple myeloma. This study presents a multimodal single cell view of the TC and BC maturation process taking place in the tonsil. We not only present our analysis as a resource but we discover a yet unappreciated cellular heterogeneity as well as novel gene regulatory mechanisms driving naive towards highly specialized lymphoid cells.

Transcriptome Analysis Identifies Accumulation of Natural Killer Cells with Enhanced Lymphotoxin-β Expression during Glioblastoma Progression.

Simple SummaryNatural killer (NK) cells play a pivotal role in anti-cancer immunity. We conducted an integrated analysis of single-cell RNA-sequencing datasets of malignant brain tumor-associated immune cells from a mouse glioma model and human newly diagnosed and recurrent glioblastomas. We found a robust increase in NK cells during brain tumor production. The cells showed a gene expression phenotype associated with NK cell dysfunction. Notably, the cytokine Lymphotoxin-β (LTB) was highly expressed in these cells. LTB receptors are found on myeloid and structural cells. In summary, we characterize a dysfunctional NK cell phenotype in advanced glioma.Glioblastomas are the most common primary brain tumors. Despite extensive clinical and molecular insights into these tumors, the prognosis remains dismal. While targeted immunotherapies have shown remarkable success across different non-brain tumor entities, they failed to show efficacy in glioblastomas. These failures prompted the field to reassess the idiosyncrasies of the glioblastoma microenvironment. Several high-dimensional single-cell RNA sequencing studies generated remarkable findings about glioblastoma-associated immune cells. To build on the collective strength of these studies, we integrated several murine and human datasets that profiled glioblastoma-associated immune cells at different time points. We integrated these datasets and utilized state-of-the-art algorithms to investigate them in a hypothesis-free, purely exploratory approach. We identified a robust accumulation of a natural killer cell subset that was characterized by a downregulation of activation-associated genes with a concomitant upregulation of apoptosis genes. In both species, we found a robust upregulation of the Lymphotoxin-β gene, a cytokine from the TNF superfamily and a key factor for the development of adaptive immunity. Further validation analyses uncovered a correlation of lymphotoxin signaling with mesenchymal-like glioblastoma regions in situ and in TCGA and CGGA glioblastoma cohorts. In summary, we identify lymphotoxin signaling as a potential therapeutic target in glioblastoma-associated natural killer cells.

Immunity parameters in adults with measles compared with healthy persons

Measles is a highly contagious viral infection transmitted by airborne droplets, characterized by fever, intoxication and specific rashes on the skin and mucous membranes. Despite the availability of highly effective vaccines and many years of efforts by the world medical community with active immunization of the worlds population against this infection under the auspices of WHO, measles still remains a serious problem. The aim of this work was to investigate the effect of measles infection in adults upon the wide range of lymphocyte subsets and blood cytokine profile in comparison with healthy controls.&#x0D; The venous blood samples from 50 adult measles patients aged 20 to 55 years, were taken 61 days after the onset of skin rash, being compared with blood samples from 50 healthy adults of similar age group. The 200 L plasma aliquotes resulting from spontaneous sedimentation of the formed elements in an Eppendorf tube were taken, frozen at -30 C and used within 3 months for the cytokine profile assays. 15 cytokines were tested by multiplex technique (MagPix, BioRad, USA). Mononuclear cells were isolated by gradient centrifugation and immunophenotyped using four-color staining by means of equipment and reagents from BD Biosciences (USA).&#x0D; In the group of measles patients, activation of innate immunity was revealed, i.e., the IL-1, IL-6, IL-23, IL-31 cytokines and TNF, which belong to early pro-inflammatory cytokines, were significantly increased. In measles patients, a significant increase in cytokines was found, suggesting active participation of epithelial cells in immune response to the measles virus. They produce danger signals (IL-25 and IL-33), inducing the development of adaptive immunity, activate their protective abilities via IL-17F production, and are involved in repair under the influence of IL-22. Some cells of adaptive immunity are infected with the measles virus and die, others actively respond to the viral infection and proliferate, thus leading to changing ratio of their subsets. Hence, the patients showed a significant decrease in T lymphocytes due to a decrease in CD4+ cells, an increased percentage of cells in senescent and exhaustion state, a significant decrease in TEMRO subpopulations, both among CD4+ and CD8+ lymphocytes, and an increase in CD8+TCM. The levels of B cell subpopulations (Bm, B1, Breg) in measles patients did not differ from healthy ones, and the level of plasmablasts was significantly increased. The level of CD4+ lymphocyte subpopulations and production of their cytokine markers varied greatly. In the patient group, a shift in the type of immune response towards Th2 and Th17 was found, activation of Tfh and Treg was detected, and increased expression of HLA-DR and CD38 activation markers was found.&#x0D; In response to measles infection, there are several independent, multidirectional processes observed in the patients. On the one hand, the measles virus attacks epithelial cells of mucous membranes and skin and immunocompetent cells, exerting a cytopathic effect and leading to lymphopenia and selective decrease in various lymphocyte subsets. On the other hand, the measles virus initiates activation of both innate and adaptive immunity, thus causing production of the corresponding cytokines, expression of activation markers, and an increase in effector cell subsets. Better understanding of the immunopathogenesis of measles infection and associated immunosuppression will help us to improve vaccination outcomes against this infection and prevent measles-related mortality.

Structural analysis of the basal state of the Artemis:DNA-PKcs complex.

Artemis nuclease and DNA-dependent protein kinase catalytic subunit (DNA-PKcs) are key components in nonhomologous DNA end joining (NHEJ), the major repair mechanism for double-strand DNA breaks. Artemis activation by DNA-PKcs resolves hairpin DNA ends formed during V(D)J recombination. Artemis deficiency disrupts development of adaptive immunity and leads to radiosensitive T- B- severe combined immunodeficiency (RS-SCID). An activated state of Artemis in complex with DNA-PK was solved by cryo-EM recently, which showed Artemis bound to the DNA. Here, we report that the pre-activated form (basal state) of the Artemis:DNA-PKcs complex is stable on an agarose-acrylamide gel system, and suitable for cryo-EM structural analysis. Structures show that the Artemis catalytic domain is dynamically positioned externally to DNA-PKcs prior to ABCDE autophosphorylation and show how both the catalytic and regulatory domains of Artemis interact with the N-HEAT and FAT domains of DNA-PKcs. We define a mutually exclusive binding site for Artemis and XRCC4 on DNA-PKcs and show that an XRCC4 peptide disrupts the Artemis:DNA-PKcs complex. All of the findings are useful in explaining how a hypomorphic L3062R missense mutation of DNA-PKcs could lead to insufficient Artemis activation, hence RS-SCID. Our results provide various target site candidates to design disruptors for Artemis:DNA-PKcs complex formation.

Major Histocompatibility Complex Class I Chain-Related α (MICA) STR Polymorphisms in COVID-19 Patients.

The SARS-CoV-2 disease presents different phenotypes of severity. Comorbidities, age, and being overweight are well established risk factors for severe disease. However, innate immunity plays a key role in the early control of viral infections and may condition the gravity of COVID-19. Natural Killer (NK) cells are part of innate immunity and are important in the control of virus infection by killing infected cells and participating in the development of adaptive immunity. Therefore, we studied the short tandem repeat (STR) transmembrane polymorphisms of the major histocompatibility complex class I chain-related A (MICA), an NKG2D ligand that induces activation of NK cells, among other cells. We compared the alleles and genotypes of MICA in COVID-19 patients versus healthy controls and analyzed their relation to disease severity. Our results indicate that the MICA*A9 allele is related to infection as well as to symptomatic disease but not to severe disease. The MICA*A9 allele may be a risk factor for SARS-CoV-2 infection and symptomatic disease.

Innate Immune Responses and P. falciparum CS Repeat-Specific Neutralizing Antibodies Following Vaccination by Skin Scarification.

The skin is the site of host invasion by the mosquito-borne Plasmodium parasite, which caused an estimated 229 million infections and 409,000 deaths in 2019 according to WHO World Malaria report 2020. In our previous studies, we have shown that skin scarification (SS) with a P. falciparum circumsporozoite (CS) peptide in the oil-in-water adjuvant AddaVax containing a combination of TLR 7/8 and TLR 9 agonists can elicit sporozoite neutralizing antibodies. SS with AddaVax + TLR agonists, but not AddaVax alone, elicited CD4+ Th1 cells and IgG2a/c anti-repeat antibody. To explore the innate immune responses that may contribute to development of adaptive immunity following SS, we examined the skin at 4h and 24h post priming with CS peptide in AddaVax with or without TLR agonists. H&E stained and IHC-labeled dorsal skin sections obtained 24h post SS demonstrated a marked difference in the pattern of infiltration with F4/80+, CD11b+ and Ly6G+ cells at the immunization site, with the lowest intensity noted following SS with AddaVax + TLR agonists. Serum collected at 4h post SS, had reproducible increases in IL-6, MIP-3α, IL-22 and IP-10 (CXCL10) following SS with AddaVax + TLR agonists, but not with AddaVax alone. To begin to decipher the complex roles of these pro-inflammatory cytokines/chemokines, we utilized IP-10 deficient (IP-10 -/-) mice to examine the role of this chemokine in the development of anti-repeat antibody response following SS. In the absence of IP-10, the levels of Th1-type IgG2a/c antibody and kinetics of the primary anti-repeat antibody response were reduced following prime and boost. The IP-10 chemokine, present as early as 4h post prime, may provide an early serological marker for rapid screening of adjuvant formulations and delivery platforms to optimize SS-induced humoral immunity to CS repeats as well as other pathogens.

Helix-Loop-Helix Proteins in Adaptive Immune Development.

The E/ID protein axis is instrumental for defining the developmental progression and functions of hematopoietic cells. The E proteins are dimeric transcription factors that activate gene expression programs and coordinate changes in chromatin organization. Id proteins are antagonists of E protein activity. Relative levels of E/Id proteins are modulated throughout hematopoietic development to enable the progression of hematopoietic stem cells into multiple adaptive and innate immune lineages including natural killer cells, B cells and T cells. In early progenitors, the E proteins promote commitment to the T and B cell lineages by orchestrating lineage specific programs of gene expression and regulating VDJ recombination of antigen receptor loci. In mature B cells, the E/Id protein axis functions to promote class switch recombination and somatic hypermutation. E protein activity further regulates differentiation into distinct CD4+ and CD8+ T cells subsets and instructs mature T cell immune responses. In this review, we discuss how the E/Id proteins define the adaptive immune system lineages, focusing on their role in directing developmental gene programs.

What Is IL-1 for? The Functions of Interleukin-1 Across Evolution.

Interleukin-1 is a cytokine with potent inflammatory and immune-amplifying effects, mainly produced by macrophages during defensive reactions. In mammals, IL-1 is a superfamily of eleven structurally similar proteins, all involved in inflammation or its control, which mainly act through binding to specific receptors on the plasma membrane of target cells. IL-1 receptors are also a family of ten structurally similar transmembrane proteins that assemble in heterocomplexes. In addition to their innate immune/inflammatory effects, the physiological role of IL-1 family cytokines seems to be linked to the development of adaptive immunity in vertebrates. We will discuss why IL-1 developed in vertebrates and what is its physiological role, as a basis for understanding when and how it can be involved in the initiation and establishment of pathologies.

Molecular Signature of Tumor-Associated High Endothelial Venules That Can Predict Breast Cancer Survival.

High endothelial venules (HEV) are specialized post-capillary venules that recruit naïve lymphocytes to lymph nodes. HEVs are essential for the development of adaptive immunity. HEVs can also develop in tumors where they are thought to be important for recruiting naïve T cells and B cells into the tumors and locally enhancing antitumor immunity by supporting the formation of tertiary lymphoid structures. Herein, we used comparative transcriptome analysis of human breast cancer to investigate genes differentially expressed between tumor-associated HEVs and the rest of the tumor vasculature. Tumor vessels highly expressing HEV-upregulated genes, such as the homeobox gene MEOX2 and the tetraspanin gene TSPAN7, were associated with extensive infiltration of T and B cells and the occurrence of tertiary lymphoid structures, which is known to predict therapeutic responses to immune-checkpoint inhibitors. Moreover, high transcript counts of these genes in clinical tumor specimens were associated with a significant survival benefit in advanced breast cancer. The molecular signature of HEVs identified herein may be useful for guiding immunotherapies and provides a new direction for investigating tumor-associated HEVs and their clinical significance. See related Spotlight by Gallimore, p. 371.

Estrogens as immunotoxicants: 17α-ethinylestradiol exposure retards thymus development in zebrafish (Danio rerio).

Estrogenic endocrine disrupting compounds (EEDCs) can cause alterations in sexual development and reproductive function of fish. Growing evidence suggests that EEDCs can also interfere with development and function of innate immunity of fish. The present study examined a potential disruptive effect of EEDCs at field-relevant concentrations on the development of adaptive immunity, more specifically the thymus. Zebrafish (Danio rerio) were exposed from fertilization until 64 days post-fertilization (dpf) to environmentally relevant (3 and 10ng/L) concentrations of the synthetic estrogen 17α-ethinylestradiol (EE2). The exposure duration covered the period of initial thymus differentiation to maximum growth. Thymus development was assessed by histological and morphometric (thymus area) analysis, thymocyte number, and transcript levels of thymocyte marker genes. Additionally, transcript levels of the estrogen receptors (esr1 and esr2a) were determined. The EE2 exposure altered sexual development (gonad differentiation, transcript levels of hepatic vitellogenin and estrogen receptors) of zebrafish, as expected. At the same time, the EE2 treatment reduced the thymus growth (thymus area, thymocyte number) and transcript levels of thymus marker genes. The expression of the thymic estrogen receptors responded to the EE2 exposure but in a different pattern than the hepatic estrogen receptors. After the 64-day-exposure period, the juvenile fish were transferred into clean water for another 95 days to assess the reversibility of EE2-induced effects. The thymic alterations were found to be reversible in female zebrafish but persisted in males. The present study provides the first evidence that the development of the fish adaptive immune system is sensitive to EEDCs, and that this takes place at concentrations similar to those that disrupt sexual development.

IMPACT OF DIETARY GUIDELINES AGAINST COVID-19

Coronavirus illness 2019 is a contagious disease that has become pandemic after rapidly spreading around the world. Diet is a key factor of happiness. The prevalence of coronavirus disease and the illnesses associated with it Severe Acute Respiratory Syndrome 2 is caused by the Coronavirus Virus (COVID-19) and can be treated with a healthy diet. Data was gathered using Google Scholar, Medline, Embase, Science Direct and books from studies conducted between 2020 and 2021. Many studies have indicated that eating a nutrient-dense diet and making wise food choices can aid in the development of adaptive immunity. Improvement of micronutrient deficiencies in current COVID-19 infections may promote the immune response to infection in individuals at greatest risk. Supplementation with vitamins D and C, as well as selenium and zinc, has been proven to be potentially beneficial for persons suffering from or at risk of developing respiratory virus diseases, as well as those suffering from nutritional deficiencies. A healthy diet of iron, zinc, and vitamins B12, B6, A, and E is essential for immune function maintenance. Therefore, the aim of this study is to promote healthy eating pattern, a better lifestyle, maintaining a healthy weight, getting adequate sleep, and exercising in their spare time during the COVID-19 pandemic.

Seroprevalence of Toxoplasma gondii, Rubella, Group A Streptococcus, CMV and HSV-1 in COVID-19 Patients with Vitamin D Deficiency.

&lt;b&gt;Background and Objective:&lt;/b&gt; In recent years, respiratory tract viral infections have caused many pandemics that impact the whole world. To investigate the seropositivity of &lt;i&gt;Toxoplasma gondii&lt;/i&gt;, rubella, CMV, HSV-1 and group A &lt;i&gt;Streptococcus&lt;/i&gt; in recovered COVID-19 patients and correlate these findings with vitamin D levels. &lt;b&gt;Materials and Methods:&lt;/b&gt; A total of 417 COVID-19 patients with diarrhoea were enrolled in this study. Vitamin D and seroprevalence for &lt;i&gt;Toxoplasma gondii&lt;/i&gt;, rubella, CMV, HSV-1 and group A &lt;i&gt;Streptococcus&lt;/i&gt; were evaluated and correlated. &lt;b&gt;Results:&lt;/b&gt; It was found that recent infection in COVID-19 patients with HSV-1, rubella, &lt;i&gt;Toxoplasma&lt;/i&gt; and CMV, respectively. IgG was detected indicating the development of adaptive immunity with all microbes. &lt;b&gt;Conclusion:&lt;/b&gt; Current study detected a correlation between vitamin D levels and HSV-1 and no correlation between this infection and vitamin D deficiency with the other microbes.

From innate to adaptive immunity: Abomasal transcriptomic responses of merino sheep to Haemonchus contortus infection

Although many important mediators and critical pathways are found to be involved in host immune responses to Haemonchus contortus infection, the initial responses to infection in the naïve and in the previously exposed state have not been compared at the transcriptional level. To further understand the development of adaptive immunity to H. contortus infection, we compared the early abomasal gene expression patterns between a primary and a tertiary challenge for four lines of sheep to discover differentially expressed genes (DEGs). The sheep were from the resistant (R) and susceptible (S) lines of two flocks of sheep selected for divergent responses to gastro-intestinal parasites (HSF and TSF). The flocks have separate origins and were initiated using two different strains of Merino sheep. One of the DEGs, mast cell proteinase 1, had significantly lower expression in tertiary compared to primary infections for all four lines of sheep. This gene was not identified in previous studies where resistant and susceptible sheep samples were compared within infection time points. Comparing the differentially expressed genes (DEGs) for the two R lines reveals that responses differed very little between the primary and tertiary challenges for HSFR and only two genes were identified, in contrast to the TSFR where there were 134 genes identified including the two identified using the HSFR animals. Similarly, comparing the primary and tertiary challenges for HSFS identified 15 DEGs, whilst for TSFS there were 128 DEGs identified. It is surprising that so few genes respond similarly between the two challenge regimes across the four lines of sheep, and suggests significant differences in immune mechanisms between the two flocks (across the lines) and also between the lines within flocks. Our results offer a quantitative snapshot comparing the transcriptome in the ovine abomasum between primary and tertiary infections with H. contortus in both genetically resistant and susceptible sheep.