Age-dependent disregulation of the immune response in humans

The review article analyzes literature data on the issues of immune response dysregulation during aging. It has been shown that impairment of innate and adaptive immune response in elderly and senile people under the conditions of spreading the new coronavirus infection is an aggravating factor in the course of the disease and recovery. Neuro-immuno-endocrine changes occurring in the organs of immune system, immunocompetent cells, molecules and receptor formations involved into the arising immune response have been traced. The imbalance of the brain-intestine-microbiota axis is considered in sufficient details, where a significant role is attributed to the changes occurring in hypothalamic-adrenal system under participation of biogenic neurotransmitters and neuromodulators. It is shown that intestinal microbiota may be involved into the neurodegeneration events, due to toxic effects on the brain via the neuro-immuno-endocrine and metabolic pathways. The data are presented, which show that adrenaline, norepinephrine, dopamine and serotonin are involved in the immune response dysregulation, thus making this process similar to the changes that occur during the general adaptation syndrome and stress response of the body. On the other hand, the review notes that chronic stress during aging not only alters the activity of macrophages, lymphocytes and dendritic cells, but also increases the level of proinflammatory cytokines in blood, thereby affecting permeability of the blood-brain barrier. The article emphasizes that with body aging, a neuroendocrine sensory pathway of immune response dysregulation is gradually formed. In this regard, it is noted that the afferent nerve endings and neurons of the vagus, adrenergic and peptidergic nerves are involved into dysfunction of immune system by affecting the processes occurring not only in thymus, but also in the brain. However, it is obvious that the pathodynamic “dysadapting circuit” formed in the higher compartments of nervous system is also involved in dysregulatory immune responses during aging. Hence, the work concludes that the signaling networks of the body's regulatory systems (nervous, immune and endocrine) are closely interconnected throughout the lifetime, but with aging and penetration of antigens into the body, this interaction is easily disrupted at different levels of organization of living matter, thus leading to dysregulation.

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Plant Phenolics and Lectins as Vaccine Adjuvants

Current Pharmaceutical Biotechnology ◽

10.2174/1389201020666190716110705 ◽

2019 ◽

Vol 20 (15) ◽

pp. 1236-1243 ◽

Cited By ~ 2

Author(s):

Hernández-Ramos Reyna-Margarita ◽

Castillo-Maldonado Irais ◽

Rivera-Guillén Mario-Alberto ◽

Ramírez-Moreno Agustina ◽

Serrano-Gallardo Luis-Benjamín ◽

...

Keyword(s):

Immune Response ◽

Immune System ◽

Innate Immune Response ◽

Adaptive Immune Response ◽

The Body ◽

Innate Immune ◽

Vaccine Adjuvants ◽

Plant Phenolics ◽

Adaptive Immune ◽

Foreign Substance

Background: The immune system is responsible for providing protection to the body against foreign substances. The immune system divides into two types of immune responses to study its mechanisms of protection: 1) Innate and 2) Adaptive. The innate immune response represents the first protective barrier of the organism that also works as a regulator of the adaptive immune response, if evaded the mechanisms of the innate immune response by the foreign substance the adaptive immune response takes action with the consequent antigen neutralization or elimination. The adaptive immune response objective is developing a specific humoral response that consists in the production of soluble proteins known as antibodies capable of specifically recognizing the foreign agent; such protective mechanism is induced artificially through an immunization or vaccination. Unfortunately, the immunogenicity of the antigens is an intrinsic characteristic of the same antigen dependent on several factors. Conclusion: Vaccine adjuvants are chemical substances of very varied structure that seek to improve the immunogenicity of antigens. The main four types of adjuvants under investigation are the following: 1) Oil emulsions with an antigen in solution, 2) Pattern recognition receptors activating molecules, 3) Inflammatory stimulatory molecules or activators of the inflammasome complex, and 4) Cytokines. However, this paper addresses the biological plausibility of two phytochemical compounds as vaccine adjuvants: 5) Lectins, and 6) Plant phenolics whose characteristics, mechanisms of action and disadvantages are addressed. Finally, the immunological usefulness of these molecules is discussed through immunological data to estimate effects of plant phenolics and lectins as vaccine adjuvants, and current studies that have implanted these molecules as vaccine adjuvants, demonstrating the results of this immunization.

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Suppression of the Peripheral Immune System Limits the Central Immune Response Following Cuprizone-Feeding: Relevance to Modelling Multiple Sclerosis

Cells ◽

10.3390/cells8111314 ◽

2019 ◽

Vol 8 (11) ◽

pp. 1314 ◽

Cited By ~ 7

Author(s):

Sen ◽

Almuslehi ◽

Gyengesi ◽

Myers ◽

Shortland ◽

...

Keyword(s):

Multiple Sclerosis ◽

Immune Response ◽

Immune System ◽

Adaptive Immune System ◽

Synaptic Function ◽

Adaptive Immune ◽

Splenic Atrophy ◽

The Impact ◽

The Brain ◽

Inside Out

Cuprizone (CPZ) preferentially affects oligodendrocytes (OLG), resulting in demyelination. To investigate whether central oligodendrocytosis and gliosis triggered an adaptive immune response, the impact of combining a standard (0.2%) or low (0.1%) dose of ingested CPZ with disruption of the blood brain barrier (BBB), using pertussis toxin (PT), was assessed in mice. 0.2% CPZ(±PT) for 5 weeks produced oligodendrocytosis, demyelination and gliosis plus marked splenic atrophy (37%) and reduced levels of CD4 (44%) and CD8 (61%). Conversely, 0.1% CPZ(±PT) produced a similar oligodendrocytosis, demyelination and gliosis but a smaller reduction in splenic CD4 (11%) and CD8 (14%) levels and no splenic atrophy. Long-term feeding of 0.1% CPZ(±PT) for 12 weeks produced similar reductions in CD4 (27%) and CD8 (43%), as well as splenic atrophy (33%), as seen with 0.2% CPZ(±PT) for 5 weeks. Collectively, these results suggest that 0.1% CPZ for 5 weeks may be a more promising model to study the ‘inside-out’ theory of Multiple Sclerosis (MS). However, neither CD4 nor CD8 were detected in the brain in CPZ±PT groups, indicating that CPZ-mediated suppression of peripheral immune organs is a major impediment to studying the ‘inside-out’ role of the adaptive immune system in this model over long time periods. Notably, CPZ(±PT)-feeding induced changes in the brain proteome related to the suppression of immune function, cellular metabolism, synaptic function and cellular structure/organization, indicating that demyelinating conditions, such as MS, can be initiated in the absence of adaptive immune system involvement.

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Proteomic and metabolomic signatures associated with the immune response in healthy individuals immunized with an inactivated SARS-CoV-2 vaccine

10.1101/2021.07.21.21260959 ◽

2021 ◽

Author(s):

Yi Wang ◽

Xiaoxia Wang ◽

Laurence Don Wai Luu ◽

Shaojin Chen ◽

Jin Fu ◽

...

Keyword(s):

Immune Response ◽

Immune System ◽

Systems Biology ◽

Complement Activation ◽

Metabolic Pathways ◽

Molecular Mechanisms ◽

Adaptive Immune Response ◽

Humoral Response ◽

Tca Cycle ◽

Adaptive Immune

CoronaVac (Sinovac), an inactivated vaccine for SARS-CoV-2, has been widely used for immunization. However, analysis of the underlying molecular mechanisms driving CoronaVac-induced immunity is still limited. Here, we applied a systems biology approach to understand the mechanisms behind the adaptive immune response to CoronaVac in a cohort of 50 volunteers immunized with 2 doses of CoronaVac. Vaccination with CoronaVac led to an integrated immune response that included several effector arms of the adaptive immune system including specific IgM/IgG, humoral response and other immune response, as well as the innate immune system as shown by complement activation. Metabolites associated with immunity were also identified implicating the role of metabolites in the humoral response, complement activation and other immune response. Networks associated with the TCA cycle and amino acids metabolic pathways, such as phenylalanine metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, and glycine, serine and threonine metabolism were tightly coupled with immunity. Critically, we constructed a multifactorial response network (MRN) to analyze the underlying interactions and compared the signatures affected by CoronaVac immunization and SARS-CoV-2 infection to further identify immune signatures and related metabolic pathways altered by CoronaVac immunization. These results suggest that protective immunity against SARS-CoV-2 can be achieved via multiple mechanisms and highlights the utility of a systems biology approach in defining molecular correlates of protection to vaccination.

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Exosomes Recovered From the Plasma of COVID-19 Patients Expose SARS-CoV-2 Spike-Derived Fragments and Contribute to the Adaptive Immune Response

Frontiers in Immunology ◽

10.3389/fimmu.2021.785941 ◽

2022 ◽

Vol 12 ◽

Author(s):

Elisa Pesce ◽

Nicola Manfrini ◽

Chiara Cordiglieri ◽

Spartaco Santi ◽

Alessandra Bandera ◽

...

Keyword(s):

Infectious Disease ◽

Mass Spectrometry ◽

Immune Response ◽

Immune System ◽

Adaptive Immune Response ◽

Active Role ◽

Extracellular Vesicle ◽

Pathological State ◽

Cell Responses ◽

Adaptive Immune

Coronavirus disease 2019 (COVID-19) is an infectious disease caused by beta-coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that has rapidly spread across the globe starting from February 2020. It is well established that during viral infection, extracellular vesicles become delivery/presenting vectors of viral material. However, studies regarding extracellular vesicle function in COVID-19 pathology are still scanty. Here, we performed a comparative study on exosomes recovered from the plasma of either MILD or SEVERE COVID-19 patients. We show that although both types of vesicles efficiently display SARS-CoV-2 spike-derived peptides and carry immunomodulatory molecules, only those of MILD patients are capable of efficiently regulating antigen-specific CD4+ T-cell responses. Accordingly, by mass spectrometry, we show that the proteome of exosomes of MILD patients correlates with a proper functioning of the immune system, while that of SEVERE patients is associated with increased and chronic inflammation. Overall, we show that exosomes recovered from the plasma of COVID-19 patients possess SARS-CoV-2-derived protein material, have an active role in enhancing the immune response, and possess a cargo that reflects the pathological state of patients in the acute phase of the disease.

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Salmonella and the Immune System

10.5772/intechopen.95673 ◽

2021 ◽

Author(s):

Weam Saad Al-Hamadany

Keyword(s):

Immune Response ◽

Immune System ◽

Innate Immune Response ◽

Human Body ◽

Pathogenic Bacteria ◽

Adaptive Immune Response ◽

Resistance Mechanisms ◽

Personal Hygiene ◽

Disease Symptoms ◽

Adaptive Immune

The human body has many mechanisms to resist invaders like pathogenic bacteria to avoid harm according to the living creature’s law “survival for the best”. On the opposite; Salmonella as pathogenic bacteria have many weapons that they utilize to invade the human body. The resistance mechanisms expressed by the human body are called immunity which represented by the immune system that has many different types of resistance processes, either specific (adaptive immune response) or non-specific (Innate Immune Response) against certain pathogenic invaders. As far as these processes are strong they will be enough to avoid infections occurrence, otherwise, the human body will get infected with Salmonella, be ill, show the disease symptoms, transmit the disease to others, and may become a carrier for the pathogen according to many circumstances. Prevention is still stood the most effective way to avoid getting infected with Salmonella by personal hygiene or suitable vaccination if available.

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Snippets of virus integrated into human genome suggests possibility of CRISPR-like adaptive immune system in human cells

10.7287/peerj.preprints.27675v1 ◽

2019 ◽

Author(s):

Wenfa Ng

Keyword(s):

Immune Response ◽

Immune System ◽

Human Genome ◽

Adaptive Immune Response ◽

Adaptive Immune System ◽

Human Cells ◽

Rna Seq ◽

Viral Dna ◽

Adaptive Immune ◽

Foreign Dna

Snippets of virus that infect humans have been shown to be incorporated into the human genome. Could such virus snippets provide a form of adaptive immunity similar to that offered by CRISPR to bacterial cells? To answer the question, RNA-seq could be used to provide a broad view of the RNA transcribed from DNA in the genome. Using known genome sequence of viruses that infect humans as template, reads obtained from RNA-seq would be profiled for virus snippets integrated into human genome and subsequently transcribed as part of an adaptive immune system. Subsequently, viruses corresponding to the virus snippets in human genome would be used to infect human cell lines to obtain direct evidence of how virus snippets mediate an adaptive immune response at the cellular level. Specifically, successful defence of the cell by virus snippets triggering an adaptive immune response would manifest as viable cells compared to lysed cells unable to mount an immune response. Following demonstration of cell viability under viral challenge, in vitro biochemical assays using cell lysate would interrogate the specific proteins and enzymes that mediate possible cutting of the foreign DNA or RNA. To this end, beads immobilized with virus snippets would serve as bait for binding to complementary viral DNA or RNA as well as potential endogenous endonuclease protein. Following precipitation and recovery of beads, possible endonuclease that bind to both viral DNA or RNA and virus snippets immobilized on beads would be isolated through gel electrophoresis and subsequently purified. Purified endonuclease would be assayed for activity against a variety of nucleic acids (both DNA and RNA) from various sources with and without added virus snippets. This provides important information on substrate range and specificity of the potential endonuclease. Amino acid sequencing of the purified endonuclease would help downstream bioinformatic search for candidate protein in the human genome. Finally, cryo-electron microscopy could help determine the structure of the endonuclease in complex with viral nucleic acids and virus snippets. Such structural information would provide more insights into mechanistic details describing the binding and cleavage of viral DNA or RNA in a CRISPR-like adaptive immune response in human cells. Overall, tantalizing clues have emerged that a CRISPR-like adaptive immune response may exist in human cells for defending against viral attack. Combination of cell biological, biochemical and structural tools could lend insights into the potential endonuclease that mediate double strand break of foreign DNA or RNA using virus snippets transcribed from the human genome as guide RNA. If demonstrated to be true for a variety of human viruses across different cell lines, the newly discovered viral defence mechanism in human cells hold important implications for understanding the adoption and evolution of CRISPR in eukaryotic cells.

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Distinct immune responses in patients infected with influenza or SARS-CoV-2, and in COVID-19 survivors, characterised by transcriptomic and cellular abundance differences in blood.

10.1101/2021.05.12.21257086 ◽

2021 ◽

Author(s):

Jelmer Legebeke ◽

Jenny Lord ◽

Rebekah Penrice-Randal ◽

Andres F Vallejo ◽

Stephen Poole ◽

...

Keyword(s):

Immune Response ◽

T Cell Activation ◽

Cell Activation ◽

Topological Analysis ◽

Adaptive Immune Response ◽

Influenza Virus Infection ◽

The Body ◽

Nucleosome Assembly ◽

Bioinformatic Tools ◽

Adaptive Immune

Background The worldwide pandemic caused by SARS-CoV-2 has claimed millions of lives and has had a profound effect on global life. Understanding the pathogenicity of the virus and the body′s response to infection is crucial in improving patient management, prognosis, and therapeutic strategies. To address this, we performed functional transcriptomic profiling to better understand the generic and specific effects of SARS-CoV-2 infection. Methods Whole blood RNA sequencing was used to profile a well characterised cohort of patients hospitalised with COVID-19, during the first wave of the pandemic prior to the availability of approved COVID-19 treatments and who went on to survive or die of COVID-19, and patients hospitalised with influenza virus infection between 2017 and 2019. Clinical parameters between patient groups were compared, and several bioinformatic tools were used to assess differences in transcript abundances and cellular composition. Results The analyses revealed contrasting innate and adaptive immune programmes, with transcripts and cell subsets associated with the innate immune response elevated in patients with influenza, and those involved in the adaptive immune response elevated in patients with COVID-19. Topological analysis identified additional gene signatures that differentiated patients with COVID-19 from patients with influenza, including insulin resistance, mitochondrial oxidative stress and interferon signalling. An efficient adaptive immune response was furthermore associated with patient survival, while an inflammatory response predicted death in patients with COVID-19. A potential prognostic signature was found based on a selection of transcript abundances, associated with circulating immunoglobulins, nucleosome assembly, cytokine production and T cell activation, in the blood transcriptome of COVID-19 patients, upon admission to hospital, which can be used to stratify patients likely to survive or die. Conclusions The results identified distinct immunological signatures between SARS-CoV-2 and influenza, prognostic of disease progression and indicative of different targeted therapies. The altered transcript abundances associated with COVID-19 survivors can be used to predict more severe outcomes in patients with COVID-19.

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Predicting the risk of re-infection from SARS-CoV-2 using the known pattern of adaptive immune response to previous human coronavirus outbreaks

10.31219/osf.io/7ctze ◽

2020 ◽

Author(s):

Ademola Samuel Ojo ◽

Paul Toluwatope Okediji ◽

Ayotemide P. Akin-Onitolo ◽

Olusegun S. Ojo ◽

Oluyinka Oladele Opaleye

Keyword(s):

Immune Response ◽

T Cells ◽

Severe Acute Respiratory Syndrome ◽

Immune Responses ◽

Adaptive Immune Response ◽

The Body ◽

Short Term ◽

Adaptive Immune ◽

Short And Long Term

This paper attempts to answer the question: are recovered COVID-19 patients protected from re-infection? This review draws evidence from comparisons between immune responses to Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) and Middle East Respiratory Syndrome coronavirus (MERS-CoV), which are phylogenetically closely related to Severe Acute Respiratory Syndrome coronavirus type 2 (SARS-CoV-2). Relevant studies were identified and reviewed based on searches conducted using PubMed. Full-text original studies on short- and long-term immune responses to human coronaviruses were included. The immune dysfunction and clinical manifestations in SARS-CoV-2, SARS-CoV, and MERS-CoV were found to be similar. Infections with SARS-CoV and MERS-CoV trigger the production of antibodies and memory B- and T-cells. Serum IgM is detectable within 7 days, peak at 21-30 days and become undetectable by 180 days. IgG is detectable at 7 days, peak at 90 days, and decline to undetected levels by 2 years post-infection. Memory B- and T-cells persist in the body for up to 2 and 6 years respectively after initial infection. The short-term risk of SARS-CoV-2 re-infection is predictably low based on similarities in the short term adaptive immune response to kindred coronaviruses. However, more research will be required to determine the long-term adaptive immunity to SARS-CoV-2 and factors that may influence the existence of short- and long-term immunity against the virus.

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Fetal Lymphoid Organ Immune Responses to Transient and Persistent Infection with Bovine Viral Diarrhea Virus

Viruses ◽

10.3390/v12080816 ◽

2020 ◽

Vol 12 (8) ◽

pp. 816 ◽

Cited By ~ 2

Author(s):

Katie J. Knapek ◽

Hanah M. Georges ◽

Hana Van Campen ◽

Jeanette V. Bishop ◽

Helle Bielefeldt-Ohmann ◽

...

Keyword(s):

Immune Response ◽

Immune System ◽

Innate Immune Response ◽

Adaptive Immune Response ◽

Innate Immune ◽

Bovine Viral Diarrhea ◽

Diarrhea Virus ◽

Viral Diarrhea ◽

Adaptive Immune ◽

Viral Diarrhea Virus

Bovine Viral Diarrhea Virus (BVDV) fetal infections occur in two forms; persistent infection (PI) or transient infection (TI), depending on what stage of gestation the fetus is infected. Examination of lymphoid organs from both PI and TI fetuses reveals drastically different fetal responses, dependent upon the developmental stage of the fetal immune system. Total RNA was extracted from the thymuses and spleens of uninfected control, PI, and TI fetuses collected on day 190 of gestation to test the hypothesis that BVDV infection impairs the innate and adaptive immune response in the fetal thymus and spleen of both infection types. Transcripts of genes representing the innate immune response and adaptive immune response genes were assayed by Reverse Transcription quatitative PCR (RT-qPCR) (2−ΔΔCq; fold change). Genes of the innate immune response, interferon (IFN) inducible genes, antigen presentation to lymphocytes, and activation of B cells were downregulated in day 190 fetal PI thymuses compared to controls. In contrast, innate immune response genes were upregulated in TI fetal thymuses compared to controls and tended to be upregulated in TI fetal spleens. Genes associated with the innate immune system were not different in PI fetal spleens; however, adaptive immune system genes were downregulated, indicating that PI fetal BVDV infection has profound inhibitory effects on the expression of genes involved in the innate and adaptive immune response. The downregulation of these genes in lymphocytes and antigen-presenting cells in the developing thymus and spleen may explain the incomplete clearance of BVDV and the persistence of the virus in PI animals while the upregulation of the TI innate immune response indicates a more mature immune system, able to clear the virus.

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SARS-CoV-2 and interferon blockade

Molecular Medicine ◽

10.1186/s10020-020-00231-w ◽

2020 ◽

Vol 26 (1) ◽

Author(s):

Betty Diamond ◽

Bruce T. Volpe ◽

Sonya VanPatten ◽

Yousef Al Abed

Keyword(s):

Immune Response ◽

Immune System ◽

Innate Immune System ◽

Neutralizing Antibodies ◽

Cytotoxic T Cells ◽

Adaptive Immune Response ◽

Innate Immune ◽

Interferon Production ◽

Therapeutic Implications ◽

Adaptive Immune

Abstract The response to viral infection generally includes an activation of the adaptive immune response to produce cytotoxic T cells and neutralizing antibodies. We propose that SARS-CoV-2 activates the innate immune system through the renin-angiotensin and kallikrein-bradykinin pathways, blocks interferon production and reduces an effective adaptive immune response. This model has therapeutic implications.

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