BioQuakes

AP Biology class blog for discussing current research in Biology

Tag: #immunity

A New Step for Fighting Allergies Has Been Taken

Scientists are one step closer to resolving your allergies. New studies have found that certain immune cells are responsible for causing allergic reactions to harmless things such as pollen, peanuts, and dander. Understanding where these allergens come from allows scientists to dive deeper into cures for them.

Depiction of a person suffering from Allergic Rhinitis

How Do Allergies Develop?

Allergies occur when the antibody IgE is released on innocuous proteinsIgE is produced by memory B cells. It is designed to ward off bacterial infections and neutralize toxins. However, sometimes it triggers an immune response to harmless substances. When a person is first exposed to an allergen, they release a large amount of IgE. The next time they are exposed to the allergen, they may have an allergic reaction. Specific memory B cells called MBC2s are responsible for remembering the proteins that spark the allergic reactions. As we learned in AP Biology, when the immune system is triggered, large amounts of responses occur in the body. The body will physically respond with symptoms such as hives, fever, or even anaphylactic shock. These symptoms are in parallel to symptoms of allergic reactions. These symptoms are in an attempt to rid the body of the invader. Inside of the body, the response begins with proteins on macrophages displaying the invader antigen and releases cytokines. T helper cells recognize the antigen and trigger an attack response. T killer cells kill infected cells while B plasma cells secrete antibodies to bind and neutralize the invader. The macrophages then eat and destroy it. Finally, T memory cells prevent reinfection while B memory cells patrol the plasma to prevent reinfection. This entire response occurs to people with allergies when there is a non-threatening pathogen in the system. 

Primary immune response 1

The Studies

Immunologist Joshua Koenig studied 90,000 people with allergies and their B-memory cells. He used RNA sequencing to find the specific memory-B cells, MBC2s, making the antibodies responsible for immune responses against parasitic worms and allergies. In people with peanut allergies, Koenig found an increased amount of MBC2s and an enhanced amount of IgE antibodies. 

 

In immunologist Maria Curotto de Lafaille’s study, she sampled children with and without allergies. She also found that children with allergies have more MBC2 cells than children without allergies. She found that cells switch from making protective IgE antibodies to allergy causing ones. Before the switch, cells made IgE, but not the protein. The RNA enables the antibody to switch the type of antibody it makes when it encounters an allergen. The signal switch depends on a protein called JAK. Stopping JAK production could prevent memory cells from switching to IgE production in contact with allergens. 

 

The Future

If scientists can find a way to manage the production of IgEs when in contact with harmless allergens, we could be looking at a potential cure for allergies! Would you participate in a treatment for allergies if it was applicable to you?

COVID Always Spikes in the Winter!

Have you ever wondered why you always catch a virus when it’s cold outside? Perhaps why we have seen spikes in the disease, COVID-19 (caused by the virus SARS-Co-V-2) during the winter months compared to summer? Recent studies have been conducted on why viruses thrive in cold weather. Additionally, researchers have come up with ways to protect yourself during the cold season!

Novel Coronavirus SARS-CoV-2 (50047466123)

How We Catch Viruses

Viruses are caught by breathing in small droplets known as aerosols. As learned in AP Biology, when a virus is first detected, the innate immune system activates. The innate immune system is nonspecific and will attack anything. It consists of barrier defenses such as mucus and saliva to trap pathogens. Then, if a pathogen gets past these barriers, innate internal cellular defense is activated. The mast cells release histamine and macrophages secrete cytokines. Histamine dilated blood vessels to increase capillary permeability, causing the area to swell. The cytokines attract smaller phagocytes called neutrophils that digest pathogens and dead cell debris. The innate immunity response might induce a fever, for higher body temperatures enhance phagocytosis. However, if the virus (ex: SARS-Co-V-2) makes it past this, it will begin to infect the cells. The virus will latch onto the ACE2 receptors of a cell, allowing the viral genetic material to fuse with healthy human cells. The human host cells will then begin to replicate SARS-Co-V-2RNA to create the proteins that make up SARS-Co-V-2.

Schematic-representation-of-an-immune-response-to-a-bacterial-infection

How Weather and Seasons Impact Viruses

To start, your location matters in regards to catching COVID. Researchers have found that being outside significantly decreases your odds of catching COVID from the SARS-Co-V-2 virus. The outdoors are well-ventilated. Viruses exhaled outside are diluted faster in the vast and clean outdoor air. This is relevant because we tend to be outside more in the summer than the winter. Inside (during cooler months), viruses can build up in the poorly ventilated space: such as schools and office buildings. 

Additionally, humidity plays a large role in the spread of SARS-Co-V-2 and other viruses. The droplets that the virus is in, such as saliva, dry slowly when it is humid. This could kill viruses like SARS-CoV-2 and influenza. However, the dry air of the winter is known to disarm people’s immune systems. Studies have found that dry air can trigger death of the cells lining the airways. These are the cells of the innate immune system. 

Evidence also suggests that the cold itself is a culprit for the spread of SARS-Co-V-2 and other viruses. When a virus is detected, sensor proteins signal the cell to produce bubble like structures called extracellular vesicles. These vesicles act as a sort of diversion for the virus. The virus will attempt to dock to the vesicle rather than the cell. The vesicle’s microRNA will then release in an attempt to kill the virus. Research states that compared to the standard 37° Celsius, cells in 32° Celsius released 42% less vesicles. They also packed 24% less microRNA than the vesicles in warmer temperatures. 

Face Mask used in Coronavirus pandemic COVID-19

How Can I Keep Healthy This Winter? 

While a humidifier may help, it can produce mold and rot. So, professionals are now leaning towards using exhaust fans, or even better, a HEPA filter to filter viruses in the air. Post Pandemic, we know a lot about mask wearing.. Did you notice that you did not contract as many illnesses while wearing a mask?  Well, masks act as shields to protect you from the aerosols an infected person may produce. Additionally, masks keep the nasal area warm and moist, boosting the immune system.

COVID-19 on the Genetic Level

Similar to any other virus, the symptoms of COVID-19 are amplified in patients who are of old age, have additional complications, or are unvaccinated. For instance, researchers found that unvaccinated individuals ages 50 and older are 12 times more likely to die from COVID-19 than individuals who are vaccinated with boosters (Hesman Saey). Additionally, cancer patients, especially those who are immunosuppressed, are at a higher risk of facing the serious impacts of COVID-19. Research suggests that baseline immunosuppression increases the risk of a cytokine storm. Cytokine storms result in extreme immune responses towards a pathogen which can result in harmful conditions for the body or inSARS-CoV-2 without background​​​ some cases death. 

These factors play an important role in the severity of COVID-19, however, there are still some severe cases that are unaccounted for. Throughout the COVID-19 pandemic, one question that has perplexed many scientists is: why do certain healthy patients contract severe cases of COVID-19 while others merely experience the symptoms of the common cold? Recent research has found that genetics may be the answer. Studies have revealed that genes passed down from our ancient ancestors can both help and hurt individuals infected with COVID-19. A global study that took DNA samples from 28,000 patients infected with Covid-19 and about 600,000 healthy patients confirms this theory.

The two main genes taken i3D Structure of Legumin Proteinnto account are toll-like receptor 7 (TLR7) and TYK2. Variants in these genes are what can control the severity of a COVID-19 case. TLR7 is a gene whose protein is responsible for initiating an immune response by sending signals to other cells that a pathogen has invaded the body. If this process is not operating correctly, it is more difficult for the body to defend against a virus. So, if SARS-CoV-2 enters the body, a variation in TLR7 can cause a more severe case of COVID-19. TYK2 is responsible for producing interferons. A variation in TYK2 can cause an overproduction of interferons. When there is a virus present, such as SARS-CoV-2, the production of interferons can be helpful in the body’s defense. 

The processes impacted by TRL7 and TYK2 directly relate to the body’s innate immune process. Innate immunity is the body’s first line of defense once a virus has passed through our innate immune system. The innate immune process involves mast cells which release histamines and macrophages which release cytokines. Interferons work in a similar way. All parts of innate immunity are focused on keeping the pathogen from advancing. Cell signaling is central to innate adaptive immunity, so any alterations in it would result in a less effective defense and therefore a more severe case of COVID-19. 

I found this COVID-19 study to be intriguing because this past January a few members of my household were infected with COVID-19. However, only one experienced extreme symptoms. Since all were vaccinated, it may be possible that the alterations in TLR7 and TYK2 are the reason for the differences in reactions among my family.

Is Covid-19 Becoming Immune to Us?

The Coronavirus has been a focal point for each individual in the past three years. Regardless of your age, gender, ethnicity, or even location, COVID-19 has been the one commonality for everyone. Because of COVID-19’s immense reach and detriment, scientists have worked tirelessly to source treatments and provide them to the people. Although the initial treatments worked in the beginning, as the virus grew and adapted, scientists, doctors, and Coronavirus professionals were forced to follow suit. To this day professionals are still trying to keep up with the ever-changing nature of the virus.

New research shows that initial Coronavirus treatments are slowly becoming more and more ineffective as the virus continues to mutate. The initial treatments for COVID-19 mainly consisted of monoclonal antibodies. Simply put, these are antibodies targeted to a specific illness, Coronavirus in this case. Because the antibody is targeted to one specific disease, as the disease mutates the antibody can no longer be applied to the newly altered disease. For example, recently the US Food and Drug Administration issued information regarding one Coronavirus antibody, Evusheld. They essentially stated that there is an increased risk of COVID-19 as certain variants cannot be neutralized or treated by Evusheld, the current monoclonal antibody. These new changes are critical for those with weakened immune systems who are reliant on strong antibodies to protect them.

To continue, scientists are exploring new ways and attempting to find new treatments for mutated viruses. They do this by seeking out vulnerable parts of the virus and creating an antibody for it. A former Harvard Medical School Professor, William Halestine, hopes that these new treatments will soon be in clinical trials for research.

One example of these clinical trials is currently being administered in Brazil and South Africa by Immune Biosolutions, a biotechnology company. Here they have created a new mix of antibodies and administered them to patients with both mild and high-severity cases of COVID-19. Two of the antibodies in the mix aim at a region of a spike protein where the virus would attach to the human cell. They want these antibodies to block this region and prevent the virus from attaching.

This process can connect to multiple concepts and ideas learned in our AP Biology Class. First, we learned about ligands and receptors, where each ligand is shaped specifically to its own receptor. In this scenario, the virus and antibody are both specific ligands for the spike protein and can only attach to specific spike proteins. This can be compared to our understanding of ligands docking with shape-specific receptors. Second, our understanding of antibodies can be paralleled with the company’s antibody mix. We learned that cells have a certain adaptive immunity to respond to new viruses. This can connect to the company creating new antibodies to adapt to the new virus. Furthermore, we learned that cells can have humoral or antibody-mediated responses, Immune Biosolutions antibody mix is exactly this, a humoral response.

I personally believe that there will be a point where the efforts of scientists and professionals surpass that of the virus. Where we can take control of the virus rather than working for it.  Hopefully, we as humans will eventually stop having to create newer and newer antibodies as the virus slows its mutations.

SARS-CoV-2 without background

 

Coronavirus and Natural Immunity…Are You Protected?

Since the start of the pandemic, scientists have vigorously worked around the clock, conducting research experiments and clinical trials to fully understand how this relatively new virus affects us. How long do our antibodies last? Should I get vaccinated? Can natural immunity protect me forever? The UTHealth School of Public Health, located in Houston Texas, conducted a research experiment on 57,000 volunteers (over the age of 20) across the state to grasp a better understanding of natural immunity and the presence of  SARS-CoV-2 antibodies in our system.

Dornbirn-COVID-19 antibody testing-02ASD

In October 2020, these volunteers enrolled in the Texas CARES survey to provide resources to understand antibody quantities over time. Researchers used blood-drawn samples from Oct. 1, 2020, to Sept. 17, 2021, to analyze the data around levels of antibody presence. Some of the variables identified from the data analysis are age, body mass index (BMI), use of smoking and vaping products, and the severity of the previous infection. Suppose you are exposed to Covid-19 for a greater period of time. In that case, you are much more likely to have a more severe infection which would drastically increase the number of antibodies you will eventually produce. The opposite goes for someone who is very briefly exposed to the virus. However, even with these indicated variables, all volunteers showed a similar rate of decreasing antibodies over time. “Our research shows that the level of antibodies in those previously infected increases for the first 100 days post-infection and then gradually declines over the next 500 days and beyond” (Michael Swartz, Ph.D., associate professor and vice chair of biostatistics at UTHealth School of Public Health). The findings were published in The Journal of Infectious Diseases.

Concluding this experiment, it is safe to say that you are most naturally protected from Covid-19 at 100 days after infection. After that period of time, your protection will gradually wane, slowly making you more vulnerable to severe symptoms again (similar to the covid-19 vaccine).  However, the data suggests that you will have some quantity of antibodies for well over a year after infection. As we learned in class this year, antibodies are a naturally formed secondary response from your immune system. The B-plasma cells secrete antibodies and can send them off to surround and immobilize the pathogen, allowing a macrophage to come and digest/destroy the cell. The B-memory cells are there to help prevent reinfection later down the road. This immune response is a way for our body to naturally protect us while storing information from previous infections for long periods of time. This is what keeps us safe!Antibody Opsonization

 

Can Cancer Cell’s Medication Immunity Be Stripped?

Cancer is one of the hardest diseased to fight. If a tumor begins to grow inside of a patient, they may be given drugs to fight off the corrupt cells. The problem with this is that the cancer cells could become immune to these drugs. Through the use of CRISPR. In Novel Crispr imaging technology reveals genes controlling tumor immunity, a new way of fighting cancer is revealed. Instead of targeting the whole tumor, Perturb-map marks cancer cells and the cells around cancer cells. Once this is completed, it is able to identify genes controlling cancer’s ability to become immune to certain drugs.

Mitosis appearances in breast cancer

To fight cancer cells, scientists use thousands of CRISPRs at the same time. This identifies every gene in a sequence and allows them to be studied. Through Perturb-map, scientists can now dive deeper and find where the cell immunity to drugs originates. A certain pathway in the cell is controlled by the cytokine interferon gamma or IFNg, and a second is by the tumor growth factor-beta receptor or TGFbR. When the cell had a gene with TGFbR2 or SOCS1, the latter of which regulates IFNg, tumor cells grew. When the cell lacked one of these, it shrunk. Moreover, it was discovered that tumors with SOCS1 were susceptible to attacks by T cells, but TGFbR cells had immunity against them. This stayed true even when both types of cells lived in the same environment. With findings like these emerging more and more, the future of cancer treatment is looking brighter than ever.

Chromosome DNA Gene unannotated

Needle in a Haystack

Immunization is defined as the action of making a person immune to infection by the process of inoculation. While the COVID-19 vaccine may be new, vaccines have actually been around for a lot longer than you may think. We’re used to getting vaccines through needles when we go to the doctors office, but what if I told you that that’s not the only way to receive one. Hundreds of years ago, Buddhist monks actually used to drink snake venom in order to build immunity to it. Though more formally, Edward Jenner is considered the founder of vaccinology after successfully inoculating a 13 year old boy in 1796 with a smallpox vaccine. The 13 year old actually demonstrated immunity and the first small pox vaccine was officially developed in 1798. While that may be just a brief recount of the history of vaccines, the significance of their revolutionary effects will follow humanity to the end of time. Through vaccines we’ve immunized viruses such as Chicken Pox, Polio, Influenza, Hepatitis A, Hepatitis B, HPV, Measles and many more. These viruses plagued the world in the past, but many of them are now obsolete.

While these vaccines may be different in nature, they all have one similarity… They are administered through needles. The “proper” term inoculation, however it is not specified how the virus needs to be administered. Monks used to drink snake venom and that was considered inoculation. So that begs the question… Does a needle really need to inject a vaccine? The answer is no.

The sterility of each batch of vaccine is tested before it leaves the laboratory. USPHS (United States Public Health Service) Rocky Mountain Laboratory, Hamilton, Montana 

Title and other information from caption card.Transfer; United States. Office of War Information. Overseas Picture Division. Washington Division; 1944.More information about the FSA/OWI Collection is available at http://hdl.loc.gov/loc.pnp/pp.fsaowiTemp. note: owibatch1Film copy on SIS roll 1, frame 1090. 01/01/1942

How does the COVID-19 vaccine work?

The COVID-19 vaccine is considered an mRNA vaccine. Normal vaccines would put an inactivated germ into our bodies in order to build immunity. An mRNA vaccine uses mRNA that is created in a laboratory in order to instruct our cells on how to make a protein. The COVID-19 is administered through the upper arm muscle and it enters muscle cells. Inside these cells, the mRNA is assembled in the Endoplasmic Reticulum to form spike proteins. The mRNA that is injected is coded to constantly recreate the spike protein and it is displayed on the surface of the cell and our immune system will respond with antibody production.

What are other Methods of Vaccination?

According to Victoria University, there is more than one way to administer a vaccine. While they’re usually administered with a needle, you could also administer one using Jet Injectors. These Jet Injectors date back to the mid 1860s. They penetrated the skin and administered the vaccine without a needle. The method included a spring-loaded injector where a spring is released to deliver the vaccine. Another method of administering the vaccine is a liquid jet injector that uses very small volumes of liquid that is forced through very tiny microscopic holes in your skin, also not requiring a needle. This method was used during clinical trials against HIV and it is also utilized in some influenza vaccinations. A third method of vaccination is a band-aid-like patch that contains 400 tiny needles. It is said that if the vaccine were administered through antigen-presenting cells in the skin than into muscle cells the chances of the DNA (A DNA based vaccine) entering the nucleus would increase. The researchers created a delivery system by attaching DNA sequences encoding SARS-CoV-2 spike protein on the surface of nano-particles. The tiny needles were then coated with the nano-particles. After this, the patch would then be applied onto the skin, painlessly penetrating it.

Jet injector gun.jpg

 

LONG COVID

After the long sufferable weeks from catching COVID-19, you would think you are in the clear; until, that is, you feel some extra “health-issues”. The term for these health issues, specifically after COVID-19, are called Long Covid (post-covid). Generally “one in two [covid recovered people] experienced long-term COVID manifestations” and the symptoms included are a diverse field of sickness. Penn State investigators mentioned the trend of symptoms from 250,351 unvaccinated adults and children:

Loss of General Well Being (weight loss, fevers, fatigue)

Decreased Mobility (1 in 5 experienced a decrease in mobility)

Concentration Issues

Lung abnormalities (6 in 10 survivors tight chests and a quarter of patients had difficulty breathing)

Digestive Issues

What could be the reason that COVID-19 is still lurking around in our bodies when the sickness is gone? Researchers at Yale University studying long-COVID have found a pattern of patients having an “unusual level of cytokines” also known as a cytokine storm. Cytokines are a secreted chemical proteins released by cells for communication. In the Immune System process, after a Macrophage, large phagocytic cells, ingests an antigen it releases cytokines, signaling for a t-helper cell to come. After the helper t-cell recognizes the antigen, more cytokines are released and trigger the Cell-Mediated and Humoral Responses (B and T cells). I mention all this because researchers are saying that post-covid patients tend to have patterns of irregular, more-than average cytokines being produced as well as an “unusual pattern of activity by…t cells. The greater than average amount of cytokines suggests a “state of chronic inflammation” and “kill tissues and damage organs.” The unusual activity of t-cells suggests that COVID-19 could still be lurking in the body.

Cytokine Release

Cytokine release and the numerous amounts of it

The treatment for these conditions are mostly to take the vaccine but there are still many unknowns to this Long-Covid problem. These problems are mostly lying in the Immune System rather than other parts of the body that can be tested with machines; which is why solving this problem is very difficult. This problem can only be solved by a matter of time and hope the scientists can figure this out.

 

Antibody Concoctions: Possible COVID-19 Prevention and Treatment?

We all have heard the exciting news about Pfizer’s COVID-19 vaccine: a possible savior and source of hope for years to come. According to a LiveScience article by Nicoletta Lanese, “an antibody cocktail designed to prevent and treat COVID-19” entered late-stage trials over the summer. Scientists have been working to find an effective treatment that doesn’t have as many limitations as current findings. A treatment known as convalescent plasma therapy has been circulating clinical trials. It is not FDA-approved and therefore not available to the public. Antibodies are extracted from recovered COVID-19 patients and injected into sick patients in order to boost their immune systems. This method is too unreliable and unpredictable.  The plasma donors all have a variety of antibodies. Some have proven to be effective against the virus by not letting it enter cells in the first place. On the other hand, nothing is guaranteed and a patient could be injected with antibodies that have no effect against the virus. To reduce this risk, drug developers have noted the effective antibodies against SARS-CoV-2 and mass produced them in a lab.

This is a representation of what a spike protein would be under a microscope. The clinical trials are testing to see which antibodies can bind to the spike proteins and prevent them from entering/infecting healthy cells.

Another possible therapy called REGN-COV2 has also entered a late phase in its clinical trial. It supposedly has two antibodies that can prevent the virus from infecting healthy cells by binding to the spike protein. Hopefully the FDA approves the drug at the end of its current phase (phase 3), so short and long-term effects can be monitored. The Co-Founder, President, and Chief Scientific Officer of Regeneron, Dr. George Yancopoulos, released this statement: “We are running simultaneous adaptive trials in order to move as quickly as possible to provide a potential solution to prevent and treat COVID-19 infections, even in the midst of an ongoing global pandemic.” Many other pharmaceutical companies continue with their trials to search for antibody treatments against the SARS-CoV-2 virus. The universal goal is to find a longer-term solution and stop the rising mortality count.

I originally chose the topic of prevention, because I thought it was only going to include mask-wearing and social distancing. It’s incredibly interesting that this article is another scientific take on preventative measures. The article shows how hard scientists and companies are working on developing a treatment. My main intention for this topic was to show how important it is for everyone to partake in the effort to stunt the spread of the pandemic. With recommended safety procedures as well as current trials, I’m optimistic that there will be great progress in our near future. I was able to link this to our AP Biology class, because we recently covered the immune system! The article refers to antibodies, and I know that they are the humoral defenses that go for pathogens. These antibodies are originally secreted from B-Plasma cells in order to bind to and neutralize the pathogens. By using plasma from recovered patients, I assume they are relying on the B-Memory cells to prevent infection/re-infection in other patients.

Please let me know what your thoughts are in the comments! How much longer do you think we’ll have to wait? Do these new updates give you hope about returning to a state of normalcy? I’d love to know.

UPDATE

Since the summer of 2020 (when this article was released), a lot has changed. Regeneron’s antibody cocktail was granted an Emergency Use Authorization in November. While this seemed to be heading the trials towards an optimistic future, that was not the case. Presently, only the Moderna and Pfizer mRNA vaccines are FDA-approved for public use. What happened to REGN-COV2? According to this Washington Post article, 80% of the allocated dosage supply is remaining unused in overcrowded hospitals. There is a common sentiment that resources should not be going towards an “unproven treatment”. The only FDA-approved antibody in the Regeneron cocktail is bamlanivimab. Although we are all eager to return to normalcy, we must be conscious of what is the best for our health.

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