BioQuakes

AP Biology class blog for discussing current research in Biology

Tag: T cells

Scientists can now ‘supercharge’ cancer-fighting T Cells

Scientists at Yale University have identified a way to “supercharge” tumor-attacking T Cells, a finding that may not only improve the effectiveness of a promising type of cell-based cancer immunotherapy, but also expand the number of cancers it can treat. Most people are familiar with cancer treatments such as surgery, radiation, and chemotherapy. But, a newer option called immunotherapy, is getting well-deserved recognition across the cancer community. These drugs teach the immune system how to recognize and kill cancer cells, equipping it to hone in on diseased cells while leaving healthy cells alone.

First, blood is drawn from the patient and sent to a lab. At the lab, the T cells are separated from the blood and ‘supercharged’ with a gene that generates chimeric antigen receptors (CAR), which allow the T cells to bind to cancer cells and destroy them. Hundreds of millions of these T cells are synthesized in the laboratory to create a personalized, well-armed immune defense. Finally, the patient’s newly modified T cells are returned to the clinic and reinfused into the patient, seeking and destroying cancer cells in the patient’s bloodstream. The discovery can advance CAR-T cell therapy, which harnesses the immune response of T cells to cancers by introducing tumor-detecting molecules into the cells. In the last decade, the U.S. Food and Drug Administration has approved six CAR-T cell therapies to treat B cell lymphomas and multiple myeloma. But despite early successes, the effectiveness of the treatment tends to diminish over time, which has launched a search for ways to boost function of T cells.

Researchers have devised an ingenious way to efficiently scan the genome of CD8 T cells for specific genes that might enhance the cells’ ability to attack cancer cells. They developed a new kind of genome-wide gain of function screen to find a molecular enzyme that acts like a foot on a gas pedal to increase metabolic activity in T cells.

They found high levels of activity in several genes, including PRODH2, a gene involved in cell metabolism, stimulate increased CAR-T cell activity in mouse models used to study three different types of cancers, including solid-tumor breast cancer. The findings show it is possible to produce hyper-metabolic CAR-T cells that outperform existing cell therapies. Using these systems and findings, I believe future studies can test the newly identified types of metabolically enhanced CAR-Ts in clinical settings, to identify other T cell super-chargers, and to extend cell-based immunotherapy to different cancer types, especially solid tumors.

Can eating less save your life????

Nutrition and calories have been a topic of much discussion over the past few years.  In a recent study by Yale University, results show that a diet with less calories than the recommended amount can increase longevity.

In this study, researchers at Yale asked participants to eat a diet with a certain amount of calories that is recommended to them based on their weight. They then asked a few people to lower their calorie intake by 14% . The results were extremely positive. The immune system is fueled by the thymus gland. In this gland  T-Cells are produced, which are an essential part of the immune system;  the body will die without them. One of the main issues that come with the human body with age is fat buildup in the thymus gland. This fat buildup happens fast, and the thymus becomes almost fully deactivated when filled up with fat. This means that less T-Cells will be produced.

T-Cells are vital to the body’s function. There are two types, Cytotoxic T-Cells and Helper T-Cells. The Cytotoxic T-Cells kill infected cells and certain types confer future immunity to antigens, and the Helper cells activate other immune system cells. When these pieces are removed, the whole system falls apart, and the body can get infected easier. This is why any change to one’s life that can increase the activity lifespan of the thymus is very important.

T-dependent B cell activation

This all is connected to the PLA2G7 protein in the body, which is created by macrophages, another important type of cell in the immune system. Inhibition of the protein targets inflammation that causes the fat buildup which stops the thymus from working. This is done through calorie restriction, which alters the gene for this protein.  Even now, inhibiting PLA2G7 is being talked about as a potential prostate cancer drug.

Overall, this study shows that there is hope. This protein’s effects may change the way people eat and live. While decreasing calories has positive effects, as long as one consumes a healthy diet, there will be plenty of health benefits. It is important to go at a dieting pace that fits every body differently.

An Antidepressant Is The Next “Weapon” Against COVID-19

Is the COVID-19 vaccine the only way to lower death rates and hospitalization rates? While more individuals are becoming vaccinated against COVID-19, researchers have looked at how a low-cost antidepressant prescription could potentially tackle the virus. Fluvoxamine (Luvox), an antidepressant medication, has the capacity to reduce hospitalization and morality rates after patients receive COVID-19 within a few days. Although fluvoxamine is licensed by the FDA for the treatment of obsessive-compulsive disorder (OCD) and other disorders such as depression, it is not approved for the treatment of COVID-19. In a study, conducted in Brazil, 1,500 newly diagnosed COVID-19 patients were assessed. 741 of the participants received a 100 mg pill of fluvoxamine twice a day for 10 days and the remaining 756 participants received a placebo twice a day. 16 percent of those who took the placebo twice a day got ill enough to necessitate a lengthy hospital stay compared to 11 percent of those who took fluvoxamine. Researchers discovered that participants who took at least 80% of the fluvoxamine administered to them had a two-thirds lower chance of hospitalization! Furthermore, there was only one fatality among individuals that took fluvoxamine, compared to 12 fatalities in the placebo group. According to The Lancet Global Health, this research has shown that the drug has reduced morality rates by roughly 91 percent. The antidepressant drug can be easily prescribed by doctors for COVID-19 using their clinical judgement.

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When the COVID-19 virus enters the body through the eyes, nose, or mouth and travels to the lungs, the immune system strives to protect itself from the invading pathogens by producing antibodies that, on occasion, eliminate invading infections. If the invading pathogen is unfamiliar to the body, B-memory cells will be unable to detect it, and B-plasma cells (antibody secreting cells) will be unable to manufacture antibodies, allowing the virus to enter the cell and flourish in the body.

Fluvoxamine

Fluvoxamine is a 2-aminoethyl oxime ether of aralkylketones. The antidepressant medication, if taken promptly after receiving COVID-19, may be an additional method of minimizing viral transmission and accompanying medical concerns. Fluvoxamine is easy to get and inexpensive to manufacture, particularly as a generic drug. COVID-19 treatments, in general, serve as both a cure for severe sickness and a treatment for the beginning of illness. Fluvoxamine, as an SSRI (selective serotonin reuptake inhibitor), attaches to a cell’s receptor that governs cellular stress response and the generation of cytokines, proteins that alert the body of a problem and lead to extreme inflammation. Nevertheless, fluvoxamine has been shown to minimize inflammation. When people get COVID-19, it’s theorized that the damaged cells produce a slew of cytokines that generate inflammation in the lungs, making it difficult to breathe. Patients would be able to breathe better and require fewer hospitalizations if fluvoxamine was taken to help decrease inflammation.

Fimmu-11-01648-g002

Who knew that an antidepressant that inhibits the serotonin reuptake pump at the presynaptic neuronal membrane might reduce inflammation and allow you to breathe? Because fluvoxamine works by boosting serotonin levels between nerve cells in the brain, it is impressive that the medicine might be used for purposes other than treating depression or OCD. The lingering question is whether someone with COVID-19 who has been taking these antidepressants for a previous disorder has an edge.

Are We One Step Closer To Eradicating Cancer?

Could you imagine if the scientists of today were able to produce a 100% percent effective treatment of all cancers? Researchers at the Children’s Hospital of Philadelphia (CHOP) have made a discovery that brings us one step closer. They had a breakthrough in the treatment of neuroblastoma, an aggressive solid cancer often found in children. When neuroblastoma is discovered in a patient’s nervous system, it is disguised so the immune system won’t attack it. The researchers have found that with the help of engineered CAR-T cells, treatment is possible for some leukemias and solid cancers, and hopefully every cancer in the future. T cells created in your body come from the thymus and have the sole purpose of floating around your body until they recognize a foreign antigen on the surface of a cell. They then get to work killing the host cells and activating other immune cells. Cytokines are released, creating a cell-mediated immunity. But because cancer cells do not appear as foreign to our immune systems, they are able to grow unchecked and can kill the patient. CAR-T cells are made from the patient’s own T cells and are “re-engineered” to see certain proteins on the surface of a cancer cell as foreign. When the CAR-T cells are searching for a cancer cell, they locate fragments of the proteins which are normally used as indicators through peptides on the major histocompatibility complex(MHC). The CAR-T cell then attacks cancer and hopefully kills the cancer cell. Neuroblastoma has proven difficult to cure with immunotherapy due to its low MHC levels. Neuroblastoma is a tumorous cancer that is most commonly found on the adrenal glands, but it is classified as an aggressive tumor due to its ability to metastasize. It is driven by modifications of gene expression that advance uncontrollable tumor growth.

CAR T-Cell Therapy

This recent advances in CAR-T therapy have led to breakthroughs in the treatment of leukemia, but the CHOP researchers are focused on neuroblastoma. Neuroblastoma presents a tricky challenge of how to connect CAR-T cells to destroy the cancer cell. The reason for this problem is that most of the proteins that the cell requires for survival and the growth of the tumor are inside the nuclei or the cell itself. After much research, they discovered peptides on the surface of the cell that can be targeted by peptide-centric chimeric antigen receptors (PC-CARS), activating the immune response to destroy the tumor. This is very similar to the receptor-mediated endocytosis we have studied in class. Two cells come together by recognizing indicators on the outside of the cell. Pushing through all the obstacles presented by the difficulty of locating and connecting with a neuroblastoma cell, the researchers at CHOP wanted to ensure that the CAR-T cells they sent into a patient’s body did not attach to similar peptides that exist in normal tissue, to avoid cross-reactivity. To do this, the researchers got rid of the MHC molecules present on the neuroblastoma cell to determine which peptides were present and at what population levels. They used a genomic database to do this. To pinpoint a perfect CAR-T cell, they filtered the peptides against the database of MHC peptides on normal human tissues, thus destroying any CAR-T that targeted a peptide with a parent gene from normal tissues. The final peptide discovery was an unmutated peptide of neuroblastoma cells that comes from the PHOX2B, which is a neuroblastoma dependency gene. They created a PC-CAR that was targeted to attack cells with this peptide on its surface. They discovered that not only does it locate the cancer cell, but it is able to do so with patients of more diverse genetic lineages. After this discovery, the researchers decided to first test their theory on mice, to prove that the PC-CAR can completely destroy the neuroblastoma tumors while not attacking normal cells in the mouse.

This subject is very important to me, as I have had family members pass from cancer. My father’s work in biopharmaceuticals has imparted a deep understanding of cancer. Many long car rides to sports games listening in on conference calls has not only given me a grander understanding of the world of business but also how it can relate to science and beyond. This discovery is vital to the continuation of the world facing all the diseases and struggles that come with life.

 

Have We Discovered The Itchy Stitch?

A Brand New Poison Ivy Vaccine is in the Works; here is What We Know So Far.

Vaccine: The word spoken and heard by most Americans at least ten times daily this past year, yet not usually preceded by “Poison Ivy.” Working at Duke University, biochemist Sven- Eric Jordt heads a team of researchers investigating pain and itch mechanisms, studying the unpleasant sensations of Toxicodendron radicans, better known as poison ivy. Jordt reveals that contact dermatitis (the red rash received from poison ivy) is usually treated by local doctors and rarely shown attention or mass funding. Author of ‘A Vaccine Against Poison Ivy Misery Is In The Works,’ Claudia Wells states, “given the toll in suffering and dollars, you would think serious attention would be paid to this worsening public health issue, you’d be wrong.” When pharmaceutical companies recognized more money was to be made on drugs for chronic skin conditions like eczema, they felt no need to research effective treatments on a temporary rash.  

Toxicodendron radicans (poison ivy) 2 (49046043216)

Having never personally contracted poison ivy, I cannot describe the exact feelings of pain or irritation, but to quote a good friend, “it would be less painful for my skin to be set on fire.” Now I must state that this friend did have an extreme reaction to poison ivy, they pitched their tent in a field of the poisonous plant, yet severe reactions are more common than most might assume. Every year 10 – 50 million Americans contract poison ivy and suffer for an average of 2-3 weeks. Research obtained in a six-year study at Duke University found that an increase of carbon dioxide, i.e., climate change, causes the poison ivy plant to produce a more potent allergenic form of Urushiol, the resin responsible for the rash. With increased concerns regarding climate change, it appears odd that Jordt is one of few who take this rash seriously.

 Currently, the main treatment methods of antihistamines and cortisone cream do the rash very little justice. This is because our body’s reaction to Urushiol has no relationship to histamines, rendering antihistamines useless. In explaining this information to my dad, he agreed that all of the efforts recommended to him when he got poison ivy, a little less than two years ago, proved ineffective. To solve this, Sven Jordt and his colleagues began to analyze receptors that matched with proteins that showed inflammation from Urushiol.

In biology, receptors are proteins that receive signals by bonding with molecules known as ligands to send a specific message onward. A cell’s response depends on the types of receptors present, and each cell has its own number and type of receptor that allows them to act differently to various stimuli. Regarding poison ivy, Jordt and his team discovered that interleukin 33, an immune chemical in the body, is the main culprit behind the symptom of itchy skin. Jordt and his team of researchers are currently testing antibodies against IL-33, such as ST2, in primary sensory neurons. If ST2 could effectively block IL-33’s receptors, the necessity to scratch would virtually disappear. “This is all very new information,” Dermatologist Brain Kim, co-director of the Center for the Study of Itch & Sensory Disorders at Washington University in St. Louis, states. In the past, scientists believed that both the rash and itch from poison ivy were triggered by the immune system’s T cells. Further studies, however, have shown that the inflamed rash and itch sensation come from two different places entirely; It is believed “T cells do cause the inflamed rash of poison ivy but that these other pathways provoke the itch.” (Brian Kim)

 While human research has been challenging to complete due to a lack of study funding, a compound called PDC-APB, a small synthetic molecule derived from active urushiol components, is being developed into a vaccine to prevent painful contact dermatitis.

 As stated earlier, I have thankfully never had poison ivy myself, and I would like to keep it that way. As someone who goes on Sunday hikes through the woods with my family, contracting poison ivy is a constant fear of mine and leaves me wearing pants while walking in the July heat. I think a vaccine would be a fantastic option for someone who spends much of their time in places of possible poison ivy. The only question would be, is this the solution to our itchy problem?

 

WP20Symbols vaccine

Don’t Kill Me Immune System! I’m a Friend.

Believe it or not, but not all bacteria is out to get you, especially some of your gut bacteria. These helpful bacteria can aid in digestion and overall healthy, but the question is, why doesn’t your immune system kill them just like harmful bacteria? In other words, how does the immune system differentiate between good and bad bacteria? For now, we are not really sure, but a study from March of this year by Immunologist Ivaylo Ivanov and his team at Columbia University could bring us closer to understanding this form of cell signaling.

The study focuses particularly on the interaction between T cells and segmented filamentous bacteria in the gut. Normally, the immune system would produce antibodies that would bind to antigens on the foreign cell’s surface. As a result, the cell would be marked for destruction by the immune system. However, through an experiment on mice, the researchers found that although the T cells were activated by the segmented filamentous bacteria, the T cells did not destroy the bacteria.

These gut bacteria located in human, mouse, and fish intestines cling themselves to the gut wall and have antigens. So why aren’t they killed? Well, the antigens are packaged in tiny vesicles located near the tip of the hook-like appendage that the bacteria uses to cling to the gut wall: the holdfast. Sorry, that’s about all I can give you. The rest is speculation at this point.

Nonetheless, Ivanov and his team discovered something previously unnoticed by finding these vesicles that hold antigens in segmented filamentous bacteria. They speculate that the T cells read antigens in different ways based on whether or not it’s exposed on the outside of the cell or packaged in a vesicle. In the end, this a big discovery that peaks my interest, especially for its implications on the study of cell signaling. What’s your hypothesis as to why the T cells don’t attack the gut bacteria?

CRISPR: The Next Step for Cancer Treatment

CRISPR is a gene editing technique that is currently still being researched and expanded upon, however, upon recent discoveries, one can note the great advantages this technology brings to the table to enhance cancer immunotherapy .  More specifically, according to the Washington University School of Medicine, “these T cell immunotherapies can’t be used if the T cells themselves are cancerous.” However, there is more to this discovery. Let’s backtrack.

What exactly is CRISPR? “CRISPR technology is a simple yet powerful tool for editing genomes. It allows researchers to easily alter DNA sequences and modify gene function. Its many potential applications include correcting genetic defects, treating and preventing the spread of diseases and improving crops. However, its promise also raises ethical concerns.” For the sake of this article, we are just focusing on the benefits it has on cancer treatment solely. Also, what exactly are T cells? They are “a type of white blood cell that is of key importance to the immune system and is at the core of adaptive immunity, the system that tailors the body’s immune response to specific pathogens. The T cells are like soldiers who search out and destroy the targeted invaders.” On the other hand, T cells can become cancerous therefore not being able to accomplish their task of destroying invaders.

How does CRISPR enhance cancer immunotherapy? Scientists at the Washington University School of Medicine engineered human T cells that can attack cancerous human T cells. Additionally, they engineered the T cells to eliminate a harmful side effect known as graft-versus-host disease. This was all thanks to CRISPR. But, how exactly did they figure this out? Were there any flaws or bumps in the road?

Well, this type of treatment cannot work if the T cells they use are cancerous. Supercharged T cells can alternatively be used to kill cancerous T cells, but the cells can also kill each other because they resemble each other closely. This is where CRISPR came in, preventing the human T cells and cancerous human T cells from killing each other. Another benefit of this is that the scientists engineered the T cells so any donors T cells can be used without the fear of not matching the person in need of the T cells.

Overall, anything to better the prevention of cancer is a scientific win in most’s book. But, CRISPR is a controversial tool. Some think it should be put to use and some do not. However, will this technology alter other aspects of the human genome besides diseases and deadly occurrences? How will this affect our ethics as a community? Will our genetics continue to increasingly become more altered? Time will only tell.

Taking care of your gut might be a pain now, but is definitely worth it!

Brain with Alzheimer’s

The contributions of microbes to multiple aspects of human physiology and neurobiology in health and disease have up until now not been fully appreciated.
Many people have said the human gut is like a “second brain.” With trillions of microbes, the digestive tract of the human gut can influence many things such as your metabolism, nutrition, immune function, and even your happiness. New research continues to show links between the brain and the health of the gut.

For example, a study from Lund University found that “unhealthy intestinal flora can accelerate the development of Alzheimer’s disease.” Alzheimer’s disease is an extremely common form of dementia or memory loss. It is caused by the death of many brain cells, which progressively decreases the size of the brain and the number nerve cells and connections. This study showed that mice with Alzheimer’s have a different bacterial profile in their guts than mice without this disease. Dr. Frida Fak Hallenius said that “Alzheimer’s is a preventable disease and in the near future we will likely be able to give advice on what to eat to prevent it. Take care of your gut bacteria, by eating lots of whole-grains, fruits and vegetables.”

 

After these discoveries, researchers are looking deeper into how bacteria can affect brain pathology. One of their ideas is that the bacteria may affect T-cells in the gut, which controls inflammatory processes both in the gut and brain. Therefore, if we can find a way to increase the health of the gut, we can reduce inflammation and brain damage. Alzheimer’s, while it is one of the most feared diseases, is preventable to in extent and if not preventable, there are several ways to delay it. The human gut microbiome has a huge impact on your health and your brain’s health. If scientists can continue to discover how to make your gut as healthy as possible, Alzheimer’s could soon be a thing of the past.

http://www.huffingtonpost.com/entry/gut-bacteria-alzheimers_us_589e0e09e4b03df370d628be

http://www.nature.com/news/the-tantalizing-links-between-gut-microbes-and-the-brain-1.18557

A Baby’s Immune System Might Be Stronger Than We Think

Lymphocyte_activation_simple

Mothers are often extremely protective of their newborn. Most moms are fearful that everything could potentially make their baby sick. Unfortunately though, there is no absolutely sure way to keep a child from getting sick. The immune system plays a huge role in keeping humans well. Two important parts of the immune system are antibodies and memory cells. Antibodies help kill harmful germs while memory cells help the immune system respond quickly to an infection and prevent disease. In fact, recent studies prove that the Immune system of newborn babies are stronger than people previously believed.

Scientists involved in a study led by King’s College London, are reporting that newborn immune T cells can trigger an inflammatory response to bacteria. Originally, it was believed that babies immune systems were immature and therefore couldn’t trigger the same inflammatory response adults normally demonstrate. The team discovered that whilst T cells in newborn babies manufacture a potent anti-bacterial molecule known as IL8. It activates neutrophils to attack the body’s foreign invaders.

In addition, Dr. Deena Gibbons, Lead author in the Department of Immunobiology at King’s College London believes that this “mechanism by which the baby protects itself in the womb from infections of the mother.” Next, she plans to better understand the reasons that there are many differences between the immune cells in newborns and those in adults.

The T Cell activity demonstrated by newborns could be used for future treatments to boost the immune system or neonates in intensive care (place with major risk of infection).

This article is very interesting and important because it is vital to keep newborn babies as healthy and safe as we possibly can. Sometimes it can be as simple as following common measures such as hand washing, avoiding people who are most likely to be sick, snotty noses or hacking coughs. A mother should try to do anything she can to limit the demands placed and a baby’s immune system in the early months to keep her baby healthy.

I chose this article because I know what it is like to be a patient in a Hospital and the precautions that doctors take to prevent further sickness when the immune system is not fully developed or strong.

Image links: 

Häggström, Mikael. “Medical gallery of Mikael Häggström 2014“. Wikiversity Journal of Medicine 1 (2). DOI:10.15347/wjm/2014.008ISSN 20018762. – Image:Lymphocyte_activation.png

http://en.wikipedia.org/wiki/Immune_system

Article: King’s College London. “Immune system of newborn babies stronger than previously thought.” ScienceDaily. ScienceDaily, 21 September 2014. <www.sciencedaily.com/releases/2014/09/140921145104.htm>.

http://www.sciencedaily.com/releases/2014/09/140921145104.htm

Other Sources:

http://en.wikipedia.org/wiki/Immune_system

http://www.wellness.com/reference/allergies/newborn-immune-system

http://www.nobelprize.org/educational/medicine/immunity/immune-detail.html

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