Should we Try to Alleviate Immunosenescence and Inflammaging - Why, How and to What Extent?

2019 ◽  
Vol 25 (39) ◽  
pp. 4154-4162 ◽  
Author(s):  
Jacek M. Witkowski ◽  
Ewa Bryl ◽  
Tamas Fulop
Keyword(s):  
Immune System ◽  
Immune Responses ◽  
Immune Cells ◽  
Malignant Neoplasm ◽  
Human Beings ◽  
Therapeutic Approaches ◽  
Human Immune System ◽  
Immune Systems ◽  
Human Immune

With advancing age, immune responses of human beings to external pathogens, i.e., bacteria, viruses, fungi and parasites, and to internal pathogens - malignant neoplasm cells - become less effective. Two major features in the process of aging of the human immune system are immunosenescence and inflammaging. The immune systems of our predecessors co-evolved with pathogens, which led to the occurrence of effective immunity. However, the otherwise beneficial activity may pose problems to the organism of the host and so it has builtin brakes (regulatory immune cells) and - with age - it undergoes adaptations and modifications, examples of which are the mentioned inflammaging and immunosenescence. Here we describe the mechanisms that first created our immune systems, then the consequences of their changes associated with aging, and the mechanisms of inflammaging and immunosenescence. Finally, we discuss to what extent both processes are detrimental and to what extent they might be beneficial and propose some therapeutic approaches for their wise control.

scholarly journals A comprehensive logic-based model of the human immune system to study the dynamics responses to mono- and coinfections

2020 ◽  
Author(s):  
Bhanwar Lal Puniya ◽  
Robert Moore ◽  
Akram Mohammed ◽  
Rada Amin ◽  
Alyssa La Fleur ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Immune Responses ◽  
Immune Cells ◽  
Computational Models ◽  
Single Infection ◽  
Human Immune System ◽  
Adaptive Immune ◽  
Adaptive Immune Cells ◽  
Human Immune

AbstractThe human immune system, which protects against pathogens and diseases, is a complex network of cells and molecules. The effects of complex dynamical interactions of pathogens and immune cells on the immune response can be studied using computational models. However, a model of the entire immune system is still lacking. Here, we developed a comprehensive computational model that integrates innate and adaptive immune cells, cytokines, immunoglobulins, and nine common pathogens from different classes of virus, bacteria, parasites, and fungi. This model was used to investigate the dynamics of the immune system under two scenarios: (1) single infection with pathogens, and (2) various medically relevant pathogen coinfections. In coinfections, we found that the order of infecting pathogens has a significant impact on the dynamics of cytokines and immunoglobulins. Thus, our model provides a tool to simulate immune responses under different dosage of pathogens and their combinations, which can be further extended and used as a tool for drug discovery and immunotherapy. Furthermore, the model provides a comprehensive and simulatable blueprint of the human immune system as a result of the synthesis of the vast knowledge about the network-like interactions of various components of the system.

scholarly journals Development of a new patient-derived xenograft humanised mouse model to study human-specific tumour microenvironment and immunotherapy

Gut ◽  
2018 ◽  
Vol 67 (10) ◽  
pp. 1845-1854 ◽  
Author(s):  
Yue Zhao ◽  
Timothy Wai Ho Shuen ◽  
Tan Boon Toh ◽  
Xue Ying Chan ◽  
Min Liu ◽  
...  
Keyword(s):  
Immune System ◽  
Immune Responses ◽  
Immune Checkpoint ◽  
Drug Testing ◽  
Checkpoint Inhibitors ◽  
Tumour Microenvironment ◽  
Human Immune System ◽  
Patient Derived Xenograft ◽  
Human Immune ◽  
Human Specific

ObjectiveAs the current therapeutic strategies for human hepatocellular carcinoma (HCC) have been proven to have limited effectiveness, immunotherapy becomes a compelling way to tackle the disease. We aim to provide humanised mouse (humice) models for the understanding of the interaction between human cancer and immune system, particularly for human-specific drug testing.DesignPatient-derived xenograft tumours are established with type I human leucocyte antigen matched human immune system in NOD-scid Il2rg−/− (NSG) mice. The longitudinal changes of the tumour and immune responses as well as the efficacy of immune checkpoint inhibitors are investigated.ResultsSimilar to the clinical outcomes, the human immune system in our model is educated by the tumour and exhibits exhaustion phenotypes such as a significant declination of leucocyte numbers, upregulation of exhaustion markers and decreased the production of human proinflammatory cytokines. Notably, cytotoxic immune cells decreased more rapidly compared with other cell types. Tumour infiltrated T cells have much higher expression of exhaustion markers and lower cytokine production compared with peripheral T cells. In addition, tumour-associated macrophages and myeloid-derived suppressor cells are found to be highly enriched in the tumour microenvironment. Interestingly, the tumour also changes gene expression profiles in response to immune responses by upregulating immune checkpoint ligands. Most importantly, in contrast to the NSG model, our model demonstrates both therapeutic and side effects of immune checkpoint inhibitors pembrolizumab and ipilimumab.ConclusionsOur work provides a model for immune-oncology study and a useful parallel-to-human platform for anti-HCC drug testing, especially immunotherapy.

scholarly journals Characterization of Human Antiviral Adaptive Immune Responses during Hepatotropic Virus Infection in HLA-Transgenic Human Immune System Mice

2013 ◽  
Vol 191 (4) ◽  
pp. 1753-1764 ◽  
Author(s):  
Eva Billerbeck ◽  
Joshua A. Horwitz ◽  
Rachael N. Labitt ◽  
Bridget M. Donovan ◽  
Kevin Vega ◽  
...  
Keyword(s):  
Immune System ◽  
Virus Infection ◽  
Immune Responses ◽  
Human Immune System ◽  
Adaptive Immune Responses ◽  
Adaptive Immune ◽  
Human Immune

scholarly journals Mathematical model of a personalized neoantigen cancer vaccine and the human immune system

2021 ◽  
Vol 17 (9) ◽  
pp. e1009318
Author(s):  
Marisabel Rodriguez Messan ◽  
Osman N. Yogurtcu ◽  
Joseph R. McGill ◽  
Ujwani Nukala ◽  
Zuben E. Sauna ◽  
...  
Keyword(s):  
Mathematical Model ◽  
T Cells ◽  
Immune System ◽  
Immune Responses ◽  
Cancer Vaccine ◽  
Tumor Size ◽  
Cancer Vaccines ◽  
Patient Specific ◽  
Human Immune System ◽  
Human Immune

Cancer vaccines are an important component of the cancer immunotherapy toolkit enhancing immune response to malignant cells by activating CD4+ and CD8+ T cells. Multiple successful clinical applications of cancer vaccines have shown good safety and efficacy. Despite the notable progress, significant challenges remain in obtaining consistent immune responses across heterogeneous patient populations, as well as various cancers. We present a mechanistic mathematical model describing key interactions of a personalized neoantigen cancer vaccine with an individual patient’s immune system. Specifically, the model considers the vaccine concentration of tumor-specific antigen peptides and adjuvant, the patient’s major histocompatibility complexes I and II copy numbers, tumor size, T cells, and antigen presenting cells. We parametrized the model using patient-specific data from a clinical study in which individualized cancer vaccines were used to treat six melanoma patients. Model simulations predicted both immune responses, represented by T cell counts, to the vaccine as well as clinical outcome (determined as change of tumor size). This model, although complex, can be used to describe, simulate, and predict the behavior of the human immune system to a personalized cancer vaccine.

scholarly journals Ikaros-Associated Diseases: From Mice to Humans and Back Again

2021 ◽  
Vol 9 ◽  
Author(s):  
Brigette Boast ◽  
Cristiane de Jesus Nunes-Santos ◽  
Hye Sun Kuehn ◽  
Sergio D. Rosenzweig
Keyword(s):  
Immune System ◽  
Immune Dysregulation ◽  
Single Amino Acid ◽  
Human Immune System ◽  
Immune Systems ◽  
Associated Diseases ◽  
Normal Expression ◽  
Extreme Phenotypes ◽  
Human Immune ◽  
Entire Gene

The normal expression of Ikaros (IKZF1) is important for the proper functioning of both the human and murine immune systems. Whilst our understanding of IKZF1 in the immune system has been greatly enhanced by the study of mice carrying mutations in Ikzf1, analyses of human patients carrying germline IKZF1 mutations have been instrumental in understanding its biological role within the human immune system and its effect on human disease. A myriad of different mutations in IKZF1 have been identified, spanning across the entire gene causing differential clinical outcomes in patients including immunodeficiency, immune dysregulation, and cancer. The majority of mutations in humans leading to IKAROS-associated diseases are single amino acid heterozygous substitutions that affect the overall function of the protein. The majority of mutations studied in mice however, affect the expression of the protein rather than its function. Murine studies would suggest that the complete absence of IKZF1 expression leads to severe and sometimes catastrophic outcomes, yet these extreme phenotypes are not commonly observed in patients carrying IKZF1 heterozygous mutations. It is unknown whether this discrepancy is simply due to differences in zygosity, the role and regulation of IKZF1 in the murine and human immune systems, or simply due to a lack of similar controls across both groups. This review will focus its analysis on the current literature surrounding what is known about germline IKZF1 defects in both the human and the murine immune systems, and whether existing mice models are indeed accurate tools to study the effects of IKZF1-associated diseases.

scholarly journals The immune system as a biomonitor: explorations in innate and adaptive immunity

2013 ◽  
Vol 3 (2) ◽  
pp. 20120099 ◽  
Author(s):  
Niclas Thomas ◽  
James Heather ◽  
Gabriel Pollara ◽  
Nandi Simpson ◽  
Theres Matjeka ◽  
...  
Keyword(s):  
Immune System ◽  
Immune Responses ◽  
Lymphoid Tissue ◽  
Tissue Injury ◽  
Great Sensitivity ◽  
The Body ◽  
Human Immune System ◽  
Ligand Interactions ◽  
Human Immune ◽  
Body Self

The human immune system has a highly complex, multi-layered structure which has evolved to detect and respond to changes in the internal microenvironment of the body. Recognition occurs at the molecular or submolecular scale, via classical reversible receptor–ligand interactions, and can lead to a response with great sensitivity and speed. Remarkably, recognition is coupled to memory, such that responses are modulated by events which occurred years or even decades before. Although the immune system in general responds differently and more vigorously to stimuli entering the body from the outside (e.g. infections), this is an emergent property of the system: many of the recognition molecules themselves have no inherent bias towards external stimuli (non-self) but also bind targets found within the body (self). It is quite clear that the immune response registers pathophysiological changes in general. Cancer, wounding and chronic tissue injury are some obvious examples. Against this background, the immune system ‘state’ tracks the internal processes of the body, and is likely to encode information regarding both current and past disease processes. Moreover, the distributed nature of most immune responses (e.g. typically involving lymphoid tissue, non-lymphoid tissue, bone marrow, blood, extracellular interstitial spaces, etc.) means that many of the changes associated with immune responses are manifested systemically, and specifically can be detected in blood. This provides a very convenient route to sampling immune cells. We consider two different and complementary ways of querying the human immune ‘state’ using high-dimensional genomic screening methodologies, and discuss the potentials of these approaches and some of the technological and computational challenges to be overcome.

scholarly journals Molecular mimicry of HIV gp120: Possible implications on prevention and therapy of AIDS

2005 ◽  
Vol 13 (3-4) ◽  
pp. 126-130
Author(s):  
Nevena Veljkovic
Keyword(s):  
Immune System ◽  
Immune Responses ◽  
Molecular Mimicry ◽  
Human Immune System ◽  
Host Cell Proteins ◽  
Immunodeficiency Virus ◽  
Human Proteins ◽  
Human Immune ◽  
Hiv Gp120 ◽  
Hiv 1

A broad range of similarities between HIV-1 gp120 and human proteins-especially those participating in immune responses-highlight gp120 as a pleiotropic protein which can influence many important functions of the human immune system. The molecular mimicry that serves to the human immunodeficiency virus as potent destructive arms against immune system could be the weak point we are in search of over decades. Examples involving sequence and informational similarities of HIV-1 gp120 and immunerelated host cell proteins important for prevention and treatment of HIV infection are presented. .

scholarly journals Gene Expression Analysis Reveals Age and Ethnicity Signatures Between Young and Old Adults in Human PBMC

2021 ◽  
Author(s):  
Yang Hu ◽  
Yudai Xu ◽  
Lipeng Mao ◽  
Wen Lei ◽  
Jan Jian Xiang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Immune System ◽  
Large Scale ◽  
Mononuclear Cells ◽  
Immune Cell ◽  
Human Immune System ◽  
Immune Systems ◽  
Network Analyses ◽  
Age Related ◽  
Human Immune

Abstract Background: Human immune system functions over an entire lifetime, yet how and why the immune system becomes less effective with age are not well understood. Therefore, the aim of this study is to exploit a large-scale population-based strategy to systematically identify genes and pathways differentially expressed as a function of chronological age. Despite the importance of age and race in shaping immune cell numbers and functions, it is unclear whether Asian and Caucasian immune systems go through similar gene expression changes throughout their lifespan, and to what extent these aging-associated variations are shared among ethnicities. Results: Here, we characterize peripheral blood mononuclear cells transcriptome from 19 healthy adults of RNA-seq data and 153 healthy subjects of micoarray data with 21~90 years of age using the weighted gene correlation network analyses (WGCNA). These data reveal a set of insightful gene expression modules and representative gene biomarkers for human immune system aging from Asian and Caucasian ancestry, respectively. Among them, the aging-specific modules may show an age-related gene expression variation spike around early-seventies. In addition, we find the top hub genes including NUDT7, CLPB, OXNAD1 and MLLT3 are shared between Asian and Caucasian aging related modules and further validated in human PBMCs from different age groups. Conclusion: Overall, our findings reveal how age and race differentially affect the immune systems between Asian and Caucasian, as well as discovered a common genetic variant that greatly impacts normal PBMC aging between Asian and Caucasian.

Immune response by the human body to SARS-CoV 2 infection

2021 ◽  
Vol 6 (1) ◽  
pp. 30-31
Author(s):  
PD Gupta
Keyword(s):  
Immune System ◽  
Lymphatic System ◽  
The Body ◽  
Human Beings ◽  
Human Immune System ◽  
First Line ◽  
Organ Systems ◽  
Mucous Membranes ◽  
Human Immune ◽  
Lymphatic Organs

A new virus SARS-CoV2 is responsible for Covid-19. Many existing drugs were tried but failed to treat Covid-19 patients. To begin with our immune system also couldn’t cope with Covid-19, therefore within no time it became pandemic. It is a well-known fact that our body fights against all infections and inflammations through well-organized immune system. The human immune system is made up of individual cells (T and B cells) and proteins as well as entire organs and organ systems. The organs of the immune system include skin and mucous membranes, and the organs of the lymphatic system. The skin and mucous membranes are the first line of defense against germs entering from outside the body and once the infection enter in the organs and tissues lymphatic organs take over. Additionally, here we also described gut bacteria and food to build up immunity. In this way human beings are fight against the new virus SARS-CoV2 infections.

scholarly journals Computational Modeling of Microabscess Formation

2012 ◽  
Vol 2012 ◽  
pp. 1-16 ◽  
Author(s):  
Alexandre Bittencourt Pigozzo ◽  
Gilson Costa Macedo ◽  
Rodrigo Weber dos Santos ◽  
Marcelo Lobosco
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Computational Modeling ◽  
Bacterial Infection ◽  
Computational Model ◽  
Immune Cells ◽  
Bacterial Infections ◽  
Distinct Pattern ◽  
Human Immune System ◽  
Human Immune

Bacterial infections can be of two types: acute or chronic. The chronic bacterial infections are characterized by being a large bacterial infection and/or an infection where the bacteria grows rapidly. In these cases, the immune response is not capable of completely eliminating the infection which may lead to the formation of a pattern known as microabscess (or abscess). The microabscess is characterized by an area comprising fluids, bacteria, immune cells (mainly neutrophils), and many types of dead cells. This distinct pattern of formation can only be numerically reproduced and studied by models that capture the spatiotemporal dynamics of the human immune system (HIS). In this context, our work aims to develop and implement an initial computational model to study the process of microabscess formation during a bacterial infection.

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