scholarly journals COVID-19: The Emerging Immunopathological Determinants for Recovery or Death

2020 ◽  
Vol 11 ◽  
Author(s):  
Tanveer Ahmad ◽  
Rituparna Chaudhuri ◽  
Mohan C. Joshi ◽  
Ahmad Almatroudi ◽  
Arshad Husain Rahmani ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Cell Function ◽  
Critical Role ◽  
Adaptive Immune Response ◽  
Disease Outcome ◽  
Interferon Response ◽  
Host Immune System ◽  
Adaptive Immune ◽  
Holistic Understanding

Hyperactivation of the host immune system during infection by SARS-CoV-2 is the leading cause of death in COVID-19 patients. It is also evident that patients who develop mild/moderate symptoms and successfully recover display functional and well-regulated immune response. Whereas a delayed initial interferon response is associated with severe disease outcome and can be the tipping point towards immunopathological deterioration, often preceding death in COVID-19 patients. Further, adaptive immune response during COVID-19 is heterogeneous and poorly understood. At the same time, some studies suggest activated T and B cell response in severe and critically ill patients and the presence of SARS-CoV2-specific antibodies. Thus, understanding this problem and the underlying molecular pathways implicated in host immune function/dysfunction is imperative to devise effective therapeutic interventions. In this comprehensive review, we discuss the emerging immunopathological determinants and the mechanism of virus evasion by the host cell immune system. Using the knowledge gained from previous respiratory viruses and the emerging clinical and molecular findings on SARS-CoV-2, we have tried to provide a holistic understanding of the host innate and adaptive immune response that may determine disease outcome. Considering the critical role of the adaptive immune system during the viral clearance, we have presented the molecular insights of the plausible mechanisms involved in impaired T cell function/dysfunction during various stages of COVID-19.

Adaptive immunity

2010 ◽  
pp. 224-234
Author(s):  
Paul Klenerman
Keyword(s):  
Infectious Disease ◽  
Immune Response ◽  
Pattern Recognition ◽  
Adaptive Immunity ◽  
Adaptive Response ◽  
Critical Role ◽  
Adaptive Immune Response ◽  
Structural Features ◽  
Adaptive Immune ◽  
Single Organism

Following the innate immune response, which acts very rapidly, the adaptive immune response plays a critical role in host defence against infectious disease. Unlike the innate response, which is triggered by pattern recognition of pathogens, i.e. features that are common to many bacteria or viruses, the adaptive response is triggered by structural features—known as antigens or epitopes—that are typically unique to a single organism....

scholarly journals Mechanisms of Dysregulated Humoral and Cellular Immunity by SARS-CoV-2

Pathogens ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 1027
Author(s):  
Nima Taefehshokr ◽  
Sina Taefehshokr ◽  
Bryan Heit
Keyword(s):  
Immune Response ◽  
T Cells ◽  
T Cell ◽  
Cell Function ◽  
Adaptive Immune Response ◽  
Neutralizing Antibody ◽  
Humoral And Cellular Immunity ◽  
Cell Responses ◽  
Adaptive Immune ◽  
Antibody Titers

The current coronavirus disease 2019 (COVID-19) pandemic, a disease caused by severe acute respiratory syndrome corona virus 2 (SARS-CoV-2), was first identified in December 2019 in China, and has led to thousands of mortalities globally each day. While the innate immune response serves as the first line of defense, viral clearance requires activation of adaptive immunity, which employs B and T cells to provide sanitizing immunity. SARS-CoV-2 has a potent arsenal of mechanisms used to counter this adaptive immune response through processes, such as T cells depletion and T cell exhaustion. These phenomena are most often observed in severe SARS-CoV-2 patients, pointing towards a link between T cell function and disease severity. Moreover, neutralizing antibody titers and memory B cell responses may be short lived in many SARS-CoV-2 patients, potentially exposing these patients to re-infection. In this review, we discuss our current understanding of B and T cells immune responses and activity in SARS-CoV-2 pathogenesis.

scholarly journals Hypercholesterolemia Impairs Immunity to Tuberculosis

2008 ◽  
Vol 76 (8) ◽  
pp. 3464-3472 ◽  
Author(s):  
Gregory W. Martens ◽  
Meltem Cevik Arikan ◽  
Jinhee Lee ◽  
Fucheng Ren ◽  
Therese Vallerskog ◽  
...  
Keyword(s):  
Immune Response ◽  
Ex Vivo ◽  
Bacterial Load ◽  
Elevated Serum ◽  
Adaptive Immune Response ◽  
Interferon Response ◽  
Lung Pathology ◽  
Inflammatory Cytokine Production ◽  
Adaptive Immune ◽  
Elevated Serum Cholesterol

ABSTRACT We demonstrate that apolipoprotein E -deficient (ApoE −/ −) mice are highly susceptible to tuberculosis and that their susceptibility depends on the severity of hypercholesterolemia. Wild-type (WT) mice and ApoE −/ − mice fed a low-cholesterol (LC) or high-cholesterol (HC) diet were infected with ∼50 CFU Mycobacterium tuberculosis Erdman by aerosol. ApoE −/ − LC mice were modestly more susceptible to tuberculosis than WT LC mice. In contrast, ApoE −/ − HC mice were extremely susceptible, as evidenced by 100% mortality after 4 weeks with tuberculosis. The lung pathology of ApoE −/ − HC mice was remarkable for giant abscess-like lesions, massive infiltration by granulocytes, elevated inflammatory cytokine production, and a mean bacterial load ∼2 log units higher than that of WT HC mice. Compared to WT HC mice, the gamma interferon response of splenocytes restimulated ex vivo with M. tuberculosis culture filtrate protein was delayed in ApoE −/ − HC mice, and they failed to control M. tuberculosis growth in the lung. OT-II cells adoptively transferred into uninfected ApoE −/ − HC mice had a weak proliferative response to their antigen, indicating impaired priming of the adaptive immune response. Our studies show that ApoE −/ − deficiency is associated with delayed expression of adaptive immunity to tuberculosis caused by defective priming of the adaptive immune response and that elevated serum cholesterol is responsible for this effect.

scholarly journals Insights into Innate Immune Response Against SARS-CoV-2 Infection

2021 ◽  
Vol 29 (3) ◽  
pp. 255-269
Author(s):  
Adina Huțanu ◽  
Anca Meda Georgescu ◽  
Akos Vince Andrejkovits ◽  
William Au ◽  
Minodora Dobreanu
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Innate Immune Response ◽  
Innate Immune System ◽  
Time Course ◽  
Adaptive Immune Response ◽  
Innate Immune ◽  
Interferon Response ◽  
Humoral Factors ◽  
Key Steps

Abstract The innate immune system is mandatory for the activation of antiviral host defense and eradication of the infection. In this regard, dendritic cells, natural killer cells, macrophages, neutrophils representing the cellular component, and cytokines, interferons, complement or Toll-Like Receptors, representing the mediators of unspecific response act together for both activation of the adaptive immune response and viral clearance. Of great importance is the proper functioning of the innate immune response from the very beginning. For instance, in the early stages of viral infection, the defective interferon response leads to uncontrolled viral replication and pathogen evasion, while hypersecretion during the later stages of infection generates hyperinflammation. This cascade activation of systemic inflammation culminates with cytokine storm syndrome and hypercoagulability state, due to a close interconnection between them. Thus an unbalanced reaction, either under- or over- stimulation of the innate immune system will lead to an uncoordinated response and unfavorable disease outcomes. Since both cellular and humoral factors are involved in the time-course of the innate immune response, in this review we aimed to address their gradual involvement in the antiviral response with emphasis on key steps in SARS-CoV-2 infection.

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

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.

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

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.

scholarly journals Salmonella and the Immune System

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.

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

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.

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

Viruses ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 816 ◽  
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.

scholarly journals SARS-CoV-2 and interferon blockade

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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