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 ◽  
...  

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.

Gut ◽  
2018 ◽  
Vol 67 (10) ◽  
pp. 1845-1854 ◽  
Author(s):  
Yue Zhao ◽  
Timothy Wai Ho Shuen ◽  
Tan Boon Toh ◽  
Xue Ying Chan ◽  
Min Liu ◽  
...  

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.


2013 ◽  
Vol 191 (4) ◽  
pp. 1753-1764 ◽  
Author(s):  
Eva Billerbeck ◽  
Joshua A. Horwitz ◽  
Rachael N. Labitt ◽  
Bridget M. Donovan ◽  
Kevin Vega ◽  
...  

2021 ◽  
Vol 17 (9) ◽  
pp. e1009318
Author(s):  
Marisabel Rodriguez Messan ◽  
Osman N. Yogurtcu ◽  
Joseph R. McGill ◽  
Ujwani Nukala ◽  
Zuben E. Sauna ◽  
...  

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.


Author(s):  
D. Goldblatt ◽  
M. Ramsay

Immunization is one of the most successful medical interventions ever developed: it prevents infectious diseases worldwide. Mechanism of effect—the basis for the success of immunization is that the human immune system is able to respond to vaccines by producing pathogen-specific antibody and memory cells (both B and T cells) which protect the body should the pathogen be encountered....


2005 ◽  
Vol 13 (3-4) ◽  
pp. 126-130
Author(s):  
Nevena Veljkovic

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. .


2020 ◽  
Author(s):  
Bhanwar Lal Puniya ◽  
Robert Moore ◽  
Akram Mohammed ◽  
Rada Amin ◽  
Alyssa La Fleur ◽  
...  

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.


2021 ◽  
Vol 6 (1) ◽  
pp. 30-31
Author(s):  
PD Gupta

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.


2019 ◽  
Vol 25 (39) ◽  
pp. 4154-4162 ◽  
Author(s):  
Jacek M. Witkowski ◽  
Ewa Bryl ◽  
Tamas Fulop

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.


Author(s):  
Muhammad Tahir Khan ◽  
Toar Imanuel ◽  
Yelnil Gabo ◽  
C. W. de Silva

The human immune system is a network of cells, tissues, and other organs that defend the body against foreign invaders called antigens. Jerne’s Idiotypic network theory concerns how an antibody in the immune system stimulates or suppresses another antibody and recognizes an antigen. Based on the principles of the human immune system and Jerne’s idiotypic network theory this paper presents a method for cooperation among robots in a multi-robot system. The developed cooperative multi-robot system is fully autonomous and distributed. In the present paper, cooperation is not assumed a priori. If a robot is unable to complete a task alone, the system autonomously chooses the appropriate number of suitable and most capable robots in the fleet to cooperate with each other in carrying out a global task. The approach developed in the paper incorporates robustness and fault tolerance in immune system–based multi-robot cooperation.


2021 ◽  
Author(s):  
Saeed Sepehrnia

Approximately 80% of the pathogens that lead to deadly infections in humans choose mucosal tissue as the first site of infection. The mucosal surfaces of the body include the gastrointestinal tract, airways, oral cavity, and urogenital mucosa, which provide a large area conducive to the invasion and accumulation of many microorganisms and are of great importance in this regard. The large extent of mucus, as well as the accumulation of bacteria and countless foreign antigens in these areas, are the most important reasons for the importance of mucosal tissues. In addition to the myriad of symbiotic bacteria, large amounts of oral antigens (both pathogenic and non-pathogenic) enter a person’s body daily and human mucosal tissues are exposed to these antigens. The function of the mucosal immune system is to distinguish pathogenic antigens from non-pathogenic ones. In this way, against a large number of oral antigens or co-tolerant microorganisms, and pathogenic antigens, a favorable (and even non-inflammatory, possible) immune response is produced. Mucosal tissue, as the largest lymphatic organ in the body, is home to 75% of the lymphocyte population and produces the highest amount of immunoglobulin. The amount of secreted IgA (slgA) produced daily by mucosal surfaces is much higher than the IgG produced in the bloodstream. A 70 kg person produces more than 3 grams of IgA per day, which is about 70–60% of the total antibodies produced in the body. The first embryonic organ in which immune system cells are located in the intestine. Some researchers consider this organ (and specifically mucosal lymph nodes) to be the source of the human immune system.


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