BioQuakes

AP Biology class blog for discussing current research in Biology

Tag: immune response

How HLA-B*15:01 Gives the Immune System a Head Start Against SARS-CoV-2

By

On December 11, 2023

In Student Post

In the article I came across, it discusses how researchers have come across an ally within our immune system’s genetic coding. Human leukocyte antigen (HLA), otherwise known as the protein markers that signal the immune system, has been discovered to hold a secret that may revolutionize our approach to combating COVID-19. A specific mutation in the antigen, HLA-B*15:01, has emerged as a key player in asymptomatic infection of SARS-CoV-2. How did scientists stumble upon this discovery, and how does this mutation in the antigen actually allow infection without the presence of sickness?

Research conducted at the University of California, San Francisco (UCSF), led by Dr. Jill Hollenbach, didn’t hesitate to dive right into the genetic phenomenon, finding the very answers to those questions outlined above. Using a national marrow donor database and the COVID-19 Citizen Science Study (CSS) app, they tracked nearly 30,000 individuals through the first year of the pandemic, providing insights into genetic factors influencing COVID-19 infection and immune system-related reactions. In the end, the researchers revealed that a staggering 20% of asymptomatic individuals carried at least one copy of the mutated antigen HLA-B*15:01. Moreover, it was found that those with two copies were over eight times more likely to avoid falling ill.

SARS-CoV-2 (CDC-23312)

The secret of these genetic guardians is actually quite simple, and, through collaboration with researchers from La Trobe University in Australia, the UCSF team focused on the memory T-cell – a key element of the immune system’s ability to remember previous infections. Through their exploration, the researchers found that individuals with HLA-B*15:01, even without previous exposure to SARS-CoV-2, demonstrated T-cell responses to a specific viral peptide (the NQK-Q8 peptide). The researchers then concluded that exposure to a kind of seasonal coronavirus, which carries a strikingly similar peptide to SARS-CoV-2 called NQK-A8, enabled T cells in these individuals to quickly recognize Coronavirus and mount a faster, and, overall, more effective immune response. This led to minimal – if any – presence of symptoms within the study.  

Let’s link this research to what we’re currently delving into in our AP Biology class. In this unit in particular, we’ve been discussing and exploring the functions of cell signaling, as well as the ins and outs of the immune system. Thus, there are obvious associations between bodily response, antigens, and the immune system with SARS-CoV-2 to what we are currently uncovering in class. We learned how Helper-T cells kickstart the immune system by releasing cytokines that trigger mitosis in B – plasma B cells (which produce antigens) and memory B cells – and T cells – cytotoxic and memory. Knowing that this mutation in the antigen appears similar to SARS-CoV-2 NQK-A8 peptide, we can understand how this may have triggered an immune response in the past, and that a secondary infections would have been easier to take care of considering the memory B and T cells were already present in the body.

Can you see how it connects to what we’ve been learning in our AP Bio class? Isn’t our immune system fascinating? Let me know how you feel about this discovery!



 

 

The “Most Complicated” Cancer Treatment EVER

By

On April 23, 2023

In Student Post

There are many approaches to treating cancer, ranging from invasive surgeries to extremely damaging radiation and chemotherapy.  The teeny-tiniest clinical trial ever began at UCLA in yet another attempt to find another way to eradicate cancer.  With only 16 participants, this trial combined two areas of research: gene editing and T-cell engineering.   The reason for the miniscule sample size is the intensely customized nature of the treatment.  Each patient’s tumor had completely unique mutations, so each patient needed equally unique T-cell engineering through gene editing.  

One reason cancer is so hard to treat is because they have adapted to be resistant to the body’s own immune response.  The patients that have cancers, especially ones in the later stages, have lost the battle against their cancer with their own immune system, so a new super-immune system must now be built.  This army of new T-cells (white blood cells, which identify and kill bad cells, seen below) will need “training” for its difficult battle ahead.  First, however, the researchers must determine how to train these cells so they will actually be successful.  They used algorithms to find identifiable mutations in the tumor, something that the T-cell can seek out to differentiate the cancerous cells from the normal cells.  Healthy Human T Cell

After testing to make sure that the T-cells can actually identify these mutations, T-cell receptors are designed specifically to their tumor.  Then, each patient’s blood is taken so that the DNA code for the new receptors can be inserted using CRISPR,  a genome editing technology at the cutting edge of genetic medical research.  The DNA code is transcribed to mRNA, which is then used in the ribosome to build polypeptides, in this case, the receptor proteins for the T-cells.  In order to ensure that these new T-cells (with the special receptors) are received, the patients had to take medication that suppressed the number of immune cells, so that the ones they are given can take hold.  

One month into treatment, 5 of the patients’ tumors stopped growing, and only 2 of the participants had associated side effects.  Although only 5 patients had the desired results, Dr. Ribas, one of the researchers, says that they “need to hit it stronger the next time” because they were limited to a small dosage of T-cells to start in order to establish safety.  Additionally, the technology will only get better and better as the research progresses and the T-cells can have more and more mutation targets to look for in a tumor.  

We’ve Been Programmed to Fight Coronaviruses since 6 Years Old

By

On December 20, 2021

In Student Post

It was previously thought that after initial infection your body creates antibodies tohelp your immune system in the future. But did you know that a common cold you had at a young age can affect how your react to covid today? Depending on the specific spike protein, your body may have a positive or negative response to future variants. An article by Rachel Brazil describes this as “original antigenic sin”(OAS) and has been linked to the differing immune responses to COVID-19.

THE HISTORY BEHIND OAS.

In 1960, Thomas Francis Jr, a US epidemiologist, noted that the immune system seemed to be ‘permanently programmed’ to produce specific antibodies against the first strain of flu it encountered. These antibodies would then reactivate when a flu virus shared similar epitopes to that of the first strain. Relating to SARS-CoV-2, the varying coronaviruses cause different immune responses from person to person. Similar to this, we learned about memory cells in AP Bio. Once the adaptive immune response takes place memory B, helper T, and cytotoxic cell are created to support future immunity to that specific virus.

child sick

Microbiologist at the University of Pennsylvania in Philadelphia, Scott Hensley, spoke with the author of the original article about his team’s work with OAS. “Much like flu, most of us are infected with these common coronaviruses by the age of five or six,” says Hensley. It’s surprising to learn that a coronaviruses have been around for many years before the pandemic. What’s even more surprising is that a simple cold we had as a kid can affectus even today. Hensley and his group analysed blood serum samples taken before the pandemic. Their findings were that the samples had antibodies that defended against a ‘common cold’ coronavirus called OC43. These antibodies could also bind to the SARS-Cov-2 spike protein. Hesley’s group then took samples from before and after SARS-Cov-2 infection for testing. Results showed that infection boosted the production of the antibodies that bind to OC43. They also found that these OC43-binding antibodies bound to the S2 subunit of the SARS-CoV-2 spike protein(due to its similar structure to that in OC43). On the other hand, the antibodies did not bind to the S1 region of the SARS-CoV-2 spike and were unable to stop the virus entering cells.

IS THIS A GOOD OR BAD THING?

Hensly’s group once again were studying OAS, but focused on its effects during the 2009 H1N1 pandemic. Their study showed that past infection to other historical flu strains provided protection against the H1N1 virus. While this may seem good, OAS also has drawbacks. The body may produce antibodies that could be used for other virus strains, but they may not be the best fit for the specific virus. As a result of this the ill equipped antibodies bind to the antigens preventing the body from creating more protective response. 

In her article Brazil mentions Aldolfo García-Sastre, director of the Global Health and Emerging Pathogens Institute at the Icahn School of Medicine at Mount Sinai in New York City. García-Sastre observed the levels of the OC43 binding antibodies in patients hospitalized with COVID-19 in Spain. He found an increase in levels of OC43 binding antibodies along with antibodies for HKU1(another betacoronavirus). García-Sastre claimed that, “We looked for a correlation between people mounting higher [levels of] antibodies against these conserved epitopes versus having less protective immunity against SARS-COV-2, and there was a slight correlation”.

THE VERDICT: THERE ISN’T ONE…YET

Because of the varying reactions that follow OAS, the debate on whether or not it is to be seen as beneficial is polarizing. Though th, scientists are still working to find ways to use it in potential vaccines. Comment below to let us know your opinion on the matter!

 

Vitamin D Points to Potential Life-saving Therapeutics for Severe Cases of SARS-CoV-2

By

On December 17, 2021

In Student Post

A promising new joint study by Purdue University and the National Institutes of Health (NIH) suggests that active metabolites of vitamin D are linked to reducing lung inflammation after SARS-COV2 infection. And no, before you break out your vitamin D pills, the vitamins inside your capsules are quite different from the active metabolites studied. Because of this, these researchers are warning those infected with COVID-19 against taking excessive supplements of vitamin D in hopes of reducing lung inflammation.

The researchers identified an autocrine loop involving vitamin D which allows T-helper (Type 1) cells to activate and respond to the active metabolites of Vitamin D which represses the signaling protein, Interferon Gamma. Distinguishing features of Interferon Gamma is the central role it plays in promoting inflammation. 

Interferon Gamma

Structure of interferon gamma. The two chains are colored in red (chain A) and green (chain B).

Although interferon gamma sounds wildly unrecognizable at first, we have actually learned about these proteins more broadly in our AP Biology class. Interferon Gamma is actually a type of cytokine! Regarding this cytokine’s structure, the proteins that compose interferon gamma are dimerized (sounds familiar? This is because we have also previously learned about dimerization through the tyrosine kinase receptor pathway in class!). 

Along with the suppression of Interferon Gamma, Interleukin 10, a cytokine with potent anti-inflammatory properties, is amplified. This is significant because this cytokine prevents damage to the host and maintains normal tissue homeostasis by reducing inflammation.

IL10 Crystal Structure.rsh

Structure of interleukin 10 as published in the Protein Data Bank.

In the near future, these pathways could be exploited therapeutically to accelerate the shutdown program of hyper-inflammatory lung cells in patients with severe SARS-CoV-2 infections. But for now, before vitamin D is adopted to treat COVID-19, clinical trials are still needed. However, research findings like these are critical to creating effective treatment not just for those infected with SARS-CoV-2, but also other respiratory diseases as well.

What do you think about this new discovery? Do you think this could lead to scientific progress regarding the treatment of inflammation?

Chemical Changes Triggering Allergic Reactions

By

On October 4, 2014

In Student Post

A research team at Oxford University recently conducted a study to determine what conditions are more likely to trigger an allergic reaction to nuts in mice. The team used roasted peanuts and raw (regular) peanuts, purifying the proteins from both and then introducing the 2 types of peanut proteins multiple ways.

The response was shocking: the mice who were exposed to dry roasted peanut proteins had many more immune responses than the mice exposed to raw peanut proteins. This “immune response” closely resembles a human allergic reaction.

8483070167_1a90af12df_zThe actual act of roasting peanuts seems like it wouldn’t change much other than taste, but the science of the act shows that with heat, the proteins are chemically modified. The common concept of enzyme performance being altered by changing the temperature or pH applied in this experience. Peanuts contain the enzyme Cyp11a1,  a recurring link in allergic reactions. When heat was applied to the protein of a peanut, the enzyme’s shape changed and therefore the active site was altered and the enzyme was unable to perform its function. Therefore, an allergic reaction to the heat-modified (roasted) nuts was more easily triggered.

Being someone who suffers from a nut allergy (I know, I’m missing out on Nutella), I found this article very interesting because I’ve experienced certain situation with inconsistent reaction triggers, and I’m curious as to what they might be. I also found the geographical link regarding the allergy outstanding – the Western population of nut allergies is reportedly much higher than that of the Eastern population, but in the article, the distinction is made that as Westerners, we tend to eat our peanuts roasted/dry-roasted, whereas the Eastern population is likely to eat their food raw.

Photo by: Daniella Segura ; Some Rights Reserved https://creativecommons.org/licenses/by/2.0/

Source: http://www.sciencedaily.com/releases/2014/09/140921223617.htm

Archives

Powered by WordPress & Theme by Anders Norén

Skip to toolbar