Image from Wikimedia Commons

Thanks very much to Melisa Eraslan for submitting her MIMM 214 assignment to post on The Turret. This guest post will explain why older people are more vulnerable to COVID-19.

We are currently facing one of the biggest pandemics seen in history: coronavirus disease (COVID-19), an infectious disease caused by the coronavirus named SARS-CoV-2. Thus far, it has afflicted over 100 million people worldwide and taken the life of 2 million. (1) There is a vast heterogeneity in COVID-19 disease severity; the spectrum of infection ranges from mild to fatal outcomes. Amid various risk factors for severe infection, age is the largest one; older adults (aged above 60 years) are disproportionately afflicted, with the highest number of infections, complications, hospitalizations and deaths. (2) Although research is still underway, scientists have unveiled certain reasons why this age group is particularly vulnerable to COVID-19.

The heightened COVID-19 risk in the elderly is multifactorial. One contributing factor involves enhanced exposure to the coronavirus because of increased shedding from infected cells into the environment, atypical disease manifestation, and difficulty quarantining. (3) Moreover, increased frailty due to preexisting conditions (comorbidities) and the decline in organs’ physiological capabilities, also increase elders’ susceptibility to the virus. (4) Equally important, as age advances, the immune system weakens, which is called “immunosenescence.” (3)

The human immune system is composed of many cells, molecules, tissues and organs. Under normal circumstances, our immune system orchestrates a complex response, referred to as inflammation, which protects us of harm from small disease-causing infectious agents referred to as germs or pathogens. The immune system is separated into the innate immune system, our body’s first line of defense, and the adaptive immune system, our second-line force of acquired immunity against specific pathogens. Pathogens – namely, viruses – gain a foothold in humans by evading our built-in immune mechanisms to cause disease.

When encountered with a virus, innate immune cells secrete messenger molecules called type 1 interferons, which are warning signals prompting protective antiviral activity. (5) In older patients, SARS-CoV-2 is particularly stealthy in its strategy in bypassing our innate immune defenses, specifically, the triggering of these warning signals, which results in a delay in the innate immune response. (6) Furthermore, with aging comes chronic inflammation, referred to as “inflammaging.” (3) This is a baseline continual production of messenger molecules promoting inflammation (such as IL-6 and TNF-α). Although inflammation normally protects us, when triggered without appropriate stimulation from pathogens, or when overstimulated, it can be detrimental. Inflammaging compounded with the coronavirus can cause the aged innate immune response to flare out of control, exacerbating COVID-19’s impact on the elderly. (7)

On the other hand, the adaptive immune system surges into the battle field soon after the innate response. The adaptive system’s main fighters are T and B cells: immune cells specialized in defending against specific pathogens upon their activation. T and B cells are able to respond to new pathogens by directly and indirectly killing infected cells, and by secreting germ-neutralizing proteins called antibodies.  Prior to their activation, these cells exist as “naïve” cells, not yet programmed to fight, but eagerly waiting to. In a recent study, Moderbacher et al. shows that this quantity of “naïve” T cells in our body dwindles with age, leaving elders depleted of T cells able to fight against new pathogens. (8) Fewer soldier cells dealing with never-before seen attackers, such as the coronavirus, increases disease severity in older adults.

Research continues unabated as scientists scramble to elucidate the full story behind COVID-19’s lethality for the elderly. What we do know is that the weakened and dysfunctional immune system in elders is a key part of the story, since it responds to the virus inadequately. On the bright side, the advent of COVID-19 vaccines is encouraging news for populations at risk, as vaccination is able to boost the weakened aging immune system. Needless to say, it is vital to follow pandemic regulations to protect our vulnerable populations from this disastrous virus.

References

1. BBC News. Covid map: Coronavirus cases, deaths, vaccinations by country [Internet]. London ENG: BBC News; 2021 [updated 2021 Feb 6; cited 2021 Feb 7]. Available from:  www.bbc.com/news/world-51235105

2. Ottawa Public Health. Older Adults & COVID-19 [Internet]. Ottawa CAN: Ottawa Public Health; 2021 [updated 2021 Feb 5; cited 2021 Feb 7]. Available from: www.ottawapublichealth.ca/en/public-health-topics/Older_Adults_and_COVID-19.aspx

3. Smorenberg AN, Peters ED, Daele PA, Nossent ES, Muller MA. How does SARS-CoV-2 target the elderly patients? A review on potential mechanisms increasing disease severity. Eur. J. Intern. Med. [Internet]. 2020 Nov 30 [cited 2021 Feb 6]; 83(1):1-2. Available from: doi.org/10.1016/j.ejim.2020.11.024

4. Begley SH. What explains Covid-19’s lethality for the elderly? Scientists look to ‘twilight’ of the immune system [Internet]. STAT News; 2020 Mar 30 [updated 2020 Apr 1; cited 2021 Feb 7]. Available from: www.statnews.com/2020/03/30/what-explains-coronavirus-lethality-for-elderly/

5. Murphy KE, Weaver, C. Janeway’s Immunobiology. 9th edition. Washington: WW Norton & Co; 2016 Jun 13.

6. Sette AL, Crotty SH. Adaptive immunity to SARS-CoV-2 and COVID-19. Cell [Internet]. 2021 [cited 2021 Feb 6];1(6):10-11. Available from: doi.org/10.1016/j.cell.2021.01.007

7. Nidadavolu LO, Walston JE. Underlying Vulnerabilities to the Cytokine Storm and Adverse COVID-19 Outcomes in the Aging Immune System. J. Gerontol. [Internet]. 2020 Aug 25 [cites 2021 Feb 5];1(209): 2-4. Available from: doi.org/10.1093/gerona/glaa209

8. Moderbacher CA, Ramirez SY, Dan JE, Grifoni AL, Hastie KA, Weiskopf, Belanger SI. Antigen-Specific Adaptive Immunity to SARS-CoV-2 in Acute COVID-19 and Associations with Age and Disease Severity. ScienceDirect [Internet]. 2020 Nov 12 [cited 2021 Feb 6];183(4):996-1012 Available from: doi.org/10.1016/j.cell.2020.09.038

Thank you very much to Cyril Kazan for letting us post his MIMM 214 assignment on The Turret. In this post, Cyril talks about an interesting aspect of our immune system.

Memory is an essential element of everyday life. Without it, learning would not be possible. Similarly, when it comes to your immune system, memory is priceless. Vaccines, for instance,would never work without your immunological memory. After being exposed to a pathogen, which is a term used to describe infectious agents like bacteria and viruses, your immune system will remember it. This way, the next time it encounters this same pathogen, it will eliminate it much faster. This concept, termed adaptive memory, has been well understood for decades. It is associated exclusively to a part of your immune system called adaptive immunity. The other part, innate immunity, has always been known to be non-specific and non-adaptive, meaning that it cannot remember a pathogen and will have the exact same response if it re-encounters it in the future.

Recently, a growing body of research is challenging what has always been thought of as true. Greater protection against re-infection has been reported in plants and invertebrates, which lack an adaptive immune system. Furthermore, certain infections and vaccinations can induce broad protection against other pathogens through innate immune mechanisms. This has led researchers to hypothesize the presence of an innate immune memory they coined “trained immunity”. In a review paper published in Nature, scientists explain what has recently been discovered about this intriguing mechanism.

How Trained Immunity Works
Unlike adaptive memory, which works by keeping a reserve of memory cells specific to the pathogen previously encountered; trained immunity is thought to function through epigenetic reprogramming, which is a change in the expression levels of genes. Adaptive memory and trained immunity are therefore fundamentally different mechanisms.

During a typical immune response, genes coding for proteins called cytokines are expressed. These proteins play a broad range of key roles in the immune response including inflammation and recruitment of immune cells. Research findings have shown that the expression of these genes leaves behind an “epigenetic scar”. This leads to an easier expression of these genes on the following infection, resulting in a greater and faster production of cytokines on the next contact with a pathogen, and to a more efficient immune response overall. Notice that it will lead to a more ample production of cytokines regardless of the identity of the pathogen. Trained immunity is therefore non-specific.

But it is not so simple. A reprogramming of the cell’s metabolism, the series of biochemical reactions occurring inside of it, also takes place and affects how efficiently cytokine genes will be expressed. It is also important to keep in mind that these are relatively recent discoveries and that the exact mechanism behind trained immunity is not yet fully understood.

Why It’s Important
Armed with this fair understanding of how trained immunity works, you may now be wondering why you should care. First of all, trained immunity plays a critical role in humans. Interestingly, more and more evidence is showing that live vaccines such as the smallpox vaccine, measles vaccine, and the BCG vaccine for tuberculosis, which normally provide specific immunity through adaptive immune cells actually have a broad beneficial effect against infection by other pathogens as well.

This occurs through non-specific activation of innate immune mechanisms. In addition, although trained immunity has evolved as a beneficial mechanism that makes our response to pathogens more effective, studies are pointing out the potential harmful effects it can have. These effects have been especially observed in the context of sterile inflammation, inflammation that does not result from a pathogen, but from food for example. It is becoming increasingly evident that sterile inflammation, boosted by trained immunity, in response to diet and lifestyle changes, forms the basis on which chronic inflammatory diseases develop. These augmented immune functions can lead to tissue damage in some instances.

Last but certainly not least, trained immunity can be critically important in the context of the interplay between innate immune cells and tumour cells. It can be either beneficial or detrimental. A stronger and more efficient innate immune response is helpful in the fight against cancer cells. Nonetheless, excessive or prolonged inflammatory responses can also contribute to the progression of the tumour. For instance, an increased cytokine release by innate immune cells that infiltrated the micro-environment of the tumour is associated with an enhanced growth of the tumour and its spread to other parts of the body.

References
Mihai G. Netea et al.. Defining trained immunity and its role in health and disease. Nature Reviews Immunology [Internet]. 2020 March 04. Available from: https://www.nature.com/articles/s41577-020-0285-6

Janeway CA Jr, Travers P, Walport M, et al. Immunological Memory. Immunobiology: the immune system in health and disease, 5th edition. [Internet]. New York, 2001. 10-21;10-24. Available from: https://www.ncbi.nlm.nih.gov/books/NBK27158/

Molnar C, Gair J. Adaptive Immune Response. Concepts of Biology, 1st Canadian Edition [Internet]. 2012. 23.2. Available from: https://opentextbc.ca/biology/chapter/23-2-adaptive-immune-response/University of Pennsylvania.

By altering bone marrow, ‘training’ can prepare innate immune system for future challenges. Science Daily [Internet]. 2018 January 11. Available from:
https://www.sciencedaily.com/releases/2018/01/180111141646.htm

Namrata Rana. Trained immunity: the immunologic memory that humans have always had. The McGill Tribune [Internet]. 2021 January 26. Available from: http://www.mcgilltribune.com/sci-tech/trained-immunity-the-immunologic-memory-that-humans-have-always-had-01262021/

A big thank you to Reese Ladak for submitting their MIMM 214 assignment to post on The Turret. This guest post may give you new hope about the future of cancer treatments!

______________________________________________________________

CAR T-Cell Therapy: A New Era in Cancer Treatments

Reese Ladak

“I’m sorry, the test came back positive. You have cancer.” – are words that no patient ever wishes to hear. Characterized by rapid and uncontrollable proliferation of cells, cancer research has the most funding–and with good reason, given how cancer death rates have decreased only 32% in males and 17% in females in 30 years (Close, 2015). Although conventional treatments like chemotherapy and radiation are effective, more than 35% of cancer patients in the US alone died in 2018 (Siegel, et al., 2018). Oncology treatments thus far have been not as effective as they are mentally, physically, and financially taxing on a person. This, however, will not be the case for much longer. Due to extensive research by scientists and biomedical engineers, a new branch of cancer treatment, CAR T-cell therapy, is on the rise (Maus, et al., 2014). In the near future, patients sitting in a doctor’s office will no longer skip a heartbeat when they hear the word “cancer.”

What is it?

As the name suggests, CAR T-cell therapy involves T cells, which are soldiers of the body that protect it from harm. Each T cell has a specific pathogen (or “enemy”) of the body that it targets and subsequently destroys. In CAR T-cell therapy, the pathogens are solely cancer cells, courtesy of the chimeric antigen receptor (CAR) (Pagel, 2017). The science behind CAR is simple: only cancerous cells carry the specific molecule which CAR has strong affinity for, and hence all the T cells carrying CAR will be targeted towards just cancerous cells (Guthrie, 2019). With that said, CAR inducing a higher degree of selectivity in T cells is the reason behind CAR T-cell therapy’s increased effectiveness compared to chemotherapy. The more conventional treatments, such as chemotherapy, are untargeted forms of treatment, meaning both cancerous and healthy cells are victims. Hence, the undesirable side effects of conventional cancer treatments, including hair loss, are no longer a concern for patients. Not only is it safer than chemotherapy, CAR T-cell therapy is much more convenient. With chemotherapy, patients must receive daily treatments. Contrastingly, patients undergoing CAR T-cell therapy require only one treatment, since CAR T cells autonomously fight the cancer to eradication (Tripathy, 2017).

Is it effective?

Based on a study done in 2016, where multiple CAR T-cell therapies were administered, it is! This study was trying to find the best way for CAR T-cell therapy to target cancerous cells, by evaluating different target molecules on cancerous cells that CAR may have high affinity towards. The study indicated that CAR T-cell therapy shows great potential. Based on the data based on more than 8,000 patients, it was apparent that blood cancers are much more treatable than solid tumours through CAR T-cell therapy. Furthermore, it was found that CD19 was the target molecule that was the most effective; a remarkable 80% of patients were completely cured of their cancer. The study also addressed a few flaws of CAR T-cell therapy, but, fortunately, they are quite manageable, and their severity is insignificant compared to that of cancer (Almåsbak, Aarvak, & Vemuri, 2016).

Should I care?

Yes, you definitely should – even if cancer is not a relevant part of your life. Cancer has been tormenting us for too long with requiring expensive, time-consuming and less than ideal treatments. Although current CAR T-cell treatments are far from perfect, such as being expensive and not 100% targeted towards cancerous cells, it is a major improvement from existing treatments–and it is only going to get better in the future. Current studies are trying to improve the selectivity of CAR T-cell therapy on blood cancers, as well as to introduce a way for the therapy to target solid tumours effectively (Sendra, 2018). Hence, a future where patients no longer have to worry about cancer is imminent.

References

• Almåsbak, H., Aarvak, T., & Vemuri, M. C. (2016). CAR T Cell Therapy: A Game Changer in Cancer Treatment. Journal of Immunology Research,2016, 1-10. doi:10.1155/2016/5474602
• Close, K. (2015, August 03). JAMA Paper Breaks Down Medical Research Funding in the US. Retrieved from https://diatribe.org/jama-paper-breaks-down-medical-research-funding-us
• Guthrie, G. (2019, January 24). CAR T-Cell Immunotherapy: The 2018 Advance of the Year. Retrieved from https://www.cancer.net/blog/2018-01/car-t-cell-immunotherapy-2018-advance-year
• Maus, M. V., Grupp, S. A., Porter, D. L., & June, C. H. (2014). Antibody-modified T cells: CARs take the front seat for hematologic malignancies. Blood,123(17), 2625-2635. doi:10.1182/blood-2013-11-492231
• Pagel, J. M. (2017, November 01). Chimeric Antigen Receptor (CAR) T-Cell Therapy. Retrieved from https://jamanetwork.com/journals/jamaoncology/fullarticle/2652907
• Sendra, J. W. (2018, May 23). What You Need to Know About CAR T-Cell Therapy for Cancer. Retrieved from https://healthblog.uofmhealth.org/cancer-care/what-you-need-to-know-about-car-t-cell-therapy-for-cancer
• Siegel, R. L., Miller, K. D., & Jemal, A. (2018). Cancer statistics, 2018. CA: A Cancer Journal for Clinicians,68(1), 7-30. doi:10.3322/caac.21442
• Tripathy, D. (2017, March 19). Weighing the Benefits and Risks of CAR T-Cell Therapy: The Stakes Are High. Retrieved from https://www.curetoday.com/publications/cure/2017/hematology-1-2017/weighing-the-benefits-and-risks-of-car-tcell-therapy-the-stakes-are-high

A big thank you to Steve Lee and Anthony Johansen for submitting their Engineering Professional Practice (FACC 400) blog post to The Turret. This guest post will have you thinking about a future society on Mars.

Benefits and risks of Mars Colonization

Steve Lee
Anthony Johansen

Mars, also known as the Red Planet, have caught many scientists’ and engineers’ attention after rovers sent by NASA have found evidence of water on the planet in 2012. The discovery of water was very important since it indicated possibility of life on Mars, and further implies that the Earth is not the only planet where living being exists. Since then, many space agencies around the globe have sent their probes and rovers to collect more information about Mars. Recently, Mars became a popular topic again due to success of SpaceX, a private aerospace company which aims to reduce cost of space transportation and colonize Mars. Elon Musk, the CEO of SpaceX, believes colonizing Mars “i​s potentially something that could be accomplished in about 10 years, maybe sooner, maybe 9 years.” ​But despite all the efforts to make Mars colonization true, how can this benefits our society?

Establishing a colony on Mars would benefit our society in a number of ways. The first, and most notable way, is that a colony on Mars would mark the first interplanetary settlement in human history. This would be the most monumental achievement in our history to date and would likely be a point in history we would never forget. A settlement on Mars would also prove that such an endeavor is possible and pave the way for future colonizations of other planets and moons, inside our solar system as well as out.

Additionally, the world’s population growth have exponentially increased over the last centuries. United Nations projects that the world’s population will reach 9.8 billion in year 2050 and 11.2 billion in year 2100. At this fast growing rate, there is no doubt that the society will suffer due to limited resources available on Earth. However, colonization of Mars would leverage the problem by distributing the population of the Earth to Mars, and as well as improve the chances for mankind to survive in case the Earth is no longer sustainable.

Another important impact of a Mars colonization would be scientific research. As humans attempt to reach further and further into space, new and innovative advances in technology and science are required in order for us to reach these new heights. For example, since 1976 NASA has published a report every year called ​Spinoff which features new technologies based on research done by NASA. As of 2016, there are over 1,920 products in the ​Spinoff database which can be attributed to advances made by NASA researchers. A well known example is the Infrared Ear Thermometer, initially this technology was designed to measure the temperature of stars and planets across large distances, however it was eventually adapted to be used as a way to record human body temperature without direct contact with the body.

Unfortunately, as with any kind of undertaking of this magnitude, there exists risks. And while we do our best to plan for and minimize those risks, there is always a possibility of something going wrong. Some of the main risks in regard to the colonization itself lie in the environment of Mars. As Mars does not have a very substantial atmosphere, the mars colonists would need to be protected not only from the extreme weather and temperatures that can occur on Mars but also from the radiation that penetrates the atmosphere. Mars’ gravity is only 38 percent of that of the Earth and the difference affects greatly on human body. As a side effect, it causes weakness of bone and muscle, motion sickness, fluid redistribution and more.

Another element that creates risk is the human factor. Many engineers and scientists, try to make fault tolerant equipments, but sometimes a tiny little mistakes could result a great disaster. For example, on Jan 28, 1986, crews of the NASA’s space shuttle Challenger were killed during the launch due to failure of O-rings that seals the booster. It was mainly due to lack of experience launching the space shuttle in a specific environment, and lack of tests. Therefore, if the system designed for the Mars exploration have flaws, then it could lead to disasters.

Although there are risks associated to Mars colonization, there are many things that people can benefit from. As Neil Armstrong once said, the beginning of the mission will be “one small step for a man, one giant leap for mankind.”

References

Dunbar, Brian. “NASA Rover Finds Conditions Once Suited for Ancient Life on Mars.” ​NASA​, NASA, 19 Nov. 2015, ​www.nasa.gov/mission_pages/msl/news/msl20130312.html​.

Kelechava, Brad. “The Benefits of Colonizing Mars (Other Than Getting to Live There) – ANSI Blog.” ​The ANSI Blog,​ 4 Feb. 2019, www.blog.ansi.org/2016/10/the-benefits-of-colonizing-mars/​.

“World Population Projected to Reach 9.8 Billion in 2050, and 11.2 Billion in 2100 | UN DESA Department of Economic and Social Affairs.” ​United Nations​, United Nations, www.un.org/development/desa/en/news/population/world-population-prospects-2017.html​.

Patel, Neel V. “SpaceX CEO Elon Musk Says His Company Could Have a Mars Colony by 2026.” ​Inverse​, www.inverse.com/article/21156-elon-musk-says-spacex-could-start-a-mars-colony-by-2026​.

Mars, Kelli. “The Human Body in Space.” ​NASA​, NASA, 30 Mar. 2016, www.nasa.gov/hrp/bodyinspace​.

Tate, Karl. “The Space Shuttle Challenger Disaster: What Happened? (Infographic).” ​Space.com​, Space Created with Sketch. Space, 28 Jan. 2016, www.space.com/31732-space-shuttle-challenger-disaster-explained-infographic.html​.

Steve Lee – U3 Computer Engineering student
Anthony Johansen – U2 Software Engineering student