Author: adamedmonds19

Actemra, also known as tocilizumab, is a monoclonal antibody drug approved by the U.S. Food and Drug Administration (FDA) to treat patients with various forms of severe arthritis. Monoclonal antibodies are scientifically-made antibodies that are engineered to target infected self-cells in specific autoimmune diseases that regular antibodies generated by the infected individual would miss. These antibodies are made by first taking a specific antigen and introducing it to a non-human organism, such as a mouse, and then allowing the organism to generate B cells specific to the antigen. Ultimately, the scientists take these dead B cells and dead myeloma cells, and mix them to create cells called hybridoma cells that carry the antibodies for the specific antigen. Once the specific antibodies are isolated, the antibodies are then incorporated into medications that can ultimately target the antigens within human cells to fight against autoimmune disorders or specific cancers.

The FDA has approved Actemra to be used in the treatment of individuals with severe rheumatoid arthritis, as well as individuals with polyarticular juvenile idiopathic arthritis and systemic juvenile idiopathic arthritis over the age of 2 years old. This medication ultimately reduces inflammation within these individuals with arthritis, to prevent or reduce further damage or pain caused by the body’s inflammatory response to its infected self-cells. Actemra accomplishes this task by binding to interleukin-6, which is responsible for promoting the inflammatory response that is caused by arthritis. By blocking the effects of IL-6 within the body of the infected individual, the effects of inflammation are greatly diminished and reduced within the patient. Listed below are several possible side-effects of the drug Actemra, as described by the FDA:

• Neutropenia
• Thrombocytopenia
• Elevated Liver Enzymes
• Pneumonia
• Urinary Tract Infection
• Cellulitis
• Herpes Zoster
• Gastroenteritis
• Diverticulitis
• Sepsis
• Bacterial Arthritis
• Upper Respiratory Tract Infection
• Nasopharyngitis
• Headache
• Hypertension
• ATL Increased
• Dizziness
• Bronchitis
• Rash
• Mouth Ulceration
• Upper Abdominal Pain
• Gastritis
• Increased Transaminase
• Fatal anaphylaxis
• Stevens-Johnson Syndrome

Some of the above side-effects such as pneumonia and bacterial arthritis have a higher risk of occurring in patients who are taking Actemra, since it is an immunosuppressive agent. In addition, since this drug makes patients more susceptible to disease infections, it is highly discouraged for patients who have any risk factors or any form of Tuberculosis, to not take the medication. This is because since the medication targets interleukins, it impacts the immune system to where any inflammatory response is reduced or prevented and can allow certain opportunistic infections to occur. As a result of the actions of Actemra, it does negatively impact the innate immune response, as it directly alters the inflammatory response. Overall, I do believe this drug can be very useful in treating different types of arthritis, where inappropriate inflammation is a major concern; however, this drug does bring many possible adverse reactions that may impact an individual’s health in a less desired direction.

Scientists, researchers, and investigators alike all across the world are currently on the hunt for a test to identify signs of recovery from this novel coronavirus that is currently causing a pandemic. In order to identify individuals who have recovered from COVID-19, a test must be administrated that identifies certain antibodies of SARS-CoV-2 that are circulating in the blood stream of the recovered individual. A test to this liking has recently been created and approved by the US Food and Drug Administration, and its purpose is to not identify an active infection, but to identify individuals who have experienced this infection and have built up an immunity to it, through new antibodies. This blood test is also known as a serology test, in which it looks for specific components of an immune response to demonstrate that the individual has been infected by the virus and thus received immunity from it. The immunity built up from being infected from the virus is generally characterized by the presence of IgG and IgM antibodies that are specific to the virus in question.  

Immunoglobulin M is the first antibody to be generated from an infection of an unknown virus, and serves as the first line of defense among the adaptive immune system. If a person had a serology test performed and a titer was positive for only IgM antibodies, this would mean that the individual had a recent infection of COVID-19, as there wasn’t enough time for IgG antibodies to develop. Immunoglobulin G antibodies are the second antibody to develop from a novel infection, and are primarily sources for future immunity. This means if an individual has a titer positive for both IgM and IgG, this shows that have had a recent infection, but it has been a couple of weeks since there is IgG present in collaboration with IgM. If a titer results in IgG antibodies being present without IgM antibodies, a period that is later in regards to the course of infection would be portrayed.

A titer that presents positive results for the presence of IgG and not IgM, clearly portrays that the individual had an infection in the distant past and now has an immunity built up to that particular virus. This is because IgM has a shorter half-life than IgG, which allows IgG antibodies to make up the immune response and allow for a defense against future encounters with the particular virus. Ultimately, if a person results in a positive titer for IgG, this would mean that they have an immunity against the virus, and will be able to be exposed to the virus and not get a corresponding infection. By testing the public for IgG antibodies specific to SARS-CoV-2, public health officials will be able to identify what percentage of the general population has been infected with COVID-19 and the levels of corresponding immunity. By having a positive titer of IgG antibodies specific to SARS-CoV-2, the individual cannot necessarily become infected with the virus or spread it, thus allowing these specific individuals to ultimately return to “normal” life.

Dendritic cells and T cells are the upcoming front runners for immunity-based therapies used to treat a variety of conditions, such as breast cancer. Dendritic cells are antigen-presenting cells (APCs) that play a very important role in the activation of the active immune response, in which dendritic cells activate naïve T cells. These T cells further the immune response by dividing into cytotoxic T cells and helper T cells, which allows the immune response to be effective against foreign-antigens and dangerous self-cells. By increasing the amount of functional dendritic cells within an immunocompromised individual, it could potentially allow their body to build up enough immunity to fight off the disease that is limiting their immune response. I believe that these types of immunotherapies have great potential for fighting diseases that not only limit an individual’s immune response, but also eventually restore or supplement the affected individual’s natural response to fight of these infections.

This form of immunotherapy alters dendritic cells retrieved from immunocompromised patients and adjusts them in a way to redirect the cells towards the goal of tumor suppression or elimination. The dendritic cells are incorporated with antigens that are originally spawned from tumor-related proteins or cells. This allows the dendritic cells to have an improved response against the tumors within the affected individual’s body. The efficacy of DC therapy is still being improved upon, as it has the potential for success but not has demonstrated as such. Dendritic cell therapy has the capability to be applied to several different cancers and other immune-suppressing conditions, including breast cancer.

Breast cancer can take various forms that can defer from person to person, and is commonly identified by the tumor markers present on cancer cells. These receptors include estrogen receptors, progesterone receptors, and human epidermal growth factor receptor 2 (HER2). Dendritic cell vaccines can potentially be used to treat different types of breast cancers, with specific research concerning its efficacy against HER2 positive breast cancers. Since the immune response of these particular cancer patients have a decreased agility and efficacy against HER2 tumor cells, dendritic cell therapy has the capabilities to stimulate the immune response to initiate an active immune response against these tumors. This vaccine to aid in the progression of breast cancer can be extremely expensive, as some the cost for the vaccine itself can start at about $22,000 dollars and rise substantially depending on the dosage required and other factors. In addition, certain side effects can affect individuals receiving this vaccine, as the side effects of flu-like symptoms and injection site reactions have been seen with DC vaccines targeted for other conditions. Overall, there are pros and cons to every experimental treatment; however, I will say that I do believe that dendritic cell vaccines show great potential with the budding potential of modern-day science and knowledge concerning immunology.

Hello my fellow ImmuniTEA spillers! This week’s blog is going to be a tad different from my normal opinionated reporting on microbiology-centered current events, as I will be giving my perspective on how COVID-19 is impacting my personal life. As a student at a public university, I have not only been forced off of campus, but I have also loss my job as a Resident Advisor. Even though I had to move back home and figure out how to pay for personal expenses and my car payment due to the loss of my primary source of income, I am lucky enough to have a home to return to that is unaffected by COVID-19. Others in this world and even at UNC are not fortunate enough to return to a safe, stable, or welcoming home environment. I am grateful to attend a university, where students with these particular difficulties are able to stay on campus and are provided with extra resources to avoid being stranded in unsafe situations.

A crisis such as this current pandemic has the ability of always putting things that we may take granted, into perspective. For example, some of my senior friends will now not be able to experience things such as their Sorority Formal, Bar Golf, or even graduation on Mother’s Day. I may not be experiencing the same loss as these students; however, I do empathize for their loss of these traditions that they may never be able to experience. Thankfully, I am still in contact with all of my friends from college even though we are separated by miles and time zones. As I have talked to many of my friends, our individual adjustments have all varied as some were excited to be back home, while others dreaded reliving their living situations that they experienced in High School.

Personally, I was excited to return home to see all of my pets and even my family… and then I shortly realized why I loved college so much. I loved working around my own schedule, having the privacy of a room that my parents had no control over, and be able to engage in discussions that weren’t one sided. Not that my parents are strict whatsoever, they do have a tendency to spark political discussions that I rather not engage in. Having different political views sometimes may drive a wedge within a family, which doesn’t affect how I love my family, but may alter when I show that affection. Having a separate living space out of my parents’ house allowed me to experience my own opinions and thoughts, without defending them within my own living space. The repercussions caused by COVID-19 have been a humbling experience so far, as I’ve been able to understand what I have taken for granted on many levels.

Gonorrhea, also known as “the clap” in pop culture, is a sexually transmitted disease that is caused by a gram-negative diplococcus. This bacteria is known as Neisseria gonorrhoeae and can cause infections in men and women that may appear to be asymptomatic or symptomatic. The main symptoms caused by N. gonorrhoeae among both sexes includes abnormal penile/vaginal discharge and painful urination. Symptomatic men may particularly experience swollen testicles or pain in their gonads, while symptomatic women may experience abnormal periods of bleeding between menstrual cycles. Gonorrhea is one of the most common sexually transmitted diseases in the United State, and receives this title for multiple reasons, including increasing antibiotic resistance and ease of transmission.

In my opinion, N. gonorrhoeae is one of the most intriguing sexually transmitted diseases as a result of its growing resistance to antibiotic treatments. According to Rubin et al. this bacterium quickly became resistant to both sulfonamide antibiotics and penicillin during the mid to late-1900s. The current recommended antibiotic treatment within the United States is an injection of ceftriaxone (a third-generation cephalosporin) with the combination of azithromycin (macrolide) in oral form. The long term efficacy of this regimen is not completely known, as in 2016 there were patients with multi-drug resistant N. gonorrhoeae infections that had low susceptibility to both of the antibiotics in the recommended treatment. The occurrence of these specific infections showcase the ability of N. gonorrhoeae to gain antibiotic-resistance through conjugation.

Another important aspect about Gonorrhea is that its transmittance cannot only just infect others who engage within sexual activities. In addition to this horizontal transmission between sexual partners, gonorrhea can also be spread through vertical transmission, which is the transmission of the disease from a pregnant mother to a newborn child during birth. The specific disease caused by this transmission between mother and child is called gonococcal neonatal opthalmia. Since this bacterium can be spread horizontally and vertically, prevention through the use of condoms, abstinence, and/or monogamous sexual relationships is vital for limiting the spread of an infection. Overall, I do believe that with proper resources and education about gonorrhea, and STDs in general, infections can be minimized through these proper measures.

Antibiotic resistance is defined by the Center for Disease Control and Prevention (CDC) as the ability of a bacteria or other microbe to become resistant to antibiotic medications as the result of innate and acquired resistance. These microbes become increasingly resistant to these medications as selection pressures allow the most resistant to replicate throughout a specific environment to allow the most resistant microbe to become the main microbe infecting susceptible individuals. Certain antibiotic-resistant microorganisms can become resistant to multiple antibiotics, which makes them almost untreatable by most approved antibiotics in most cases. These particular microbes are commonly known as superbugs, as they cannot be treated by even the most complex antibiotics in most cases and have caused a plethora deaths. According to data reported from CNN, which was collected by the CDC, there is approximately 35,000 deaths that are caused each year due to an infection involving a “superbug”.

There are multiple antibiotic resistant superbugs that currently running rampant within the United States, of which they are classified by three different categories. These categories include concerning, serious, and urgent microorganisms; with urgent being the most dangerous superbugs with maximum resistance. There are currently five urgent superbugs that are pressing concerns within the United States, which includes Clostridioides difficile (C. difficile) that has the most estimated annual deaths of 12,800 per year. I believe that these superbugs are a major public health concern, not only within the United States, but also throughout the world for multiple reasons. One reason would include the overuse of antibiotics within the general population, which allows for the natural selection of the strongest and most-resistant microbes. By limiting the use of antibiotics for necessary infections only and improving upon microorganism identification will not only slow down the evolving of antibiotic resistance among microbes, but also will hopefully allow our current antibiotics to stay effective for longer periods of time. Another problem that superbugs present, is that they can affect anybody of any level of immunity, age, gender, etc. This causes concern as a solution cannot be targeted to specific subgroup of individuals, and any possible solution to antibiotic-resistance would need to have a wide range of affects.

According to USA Today, regarding the CDC report on antibiotic resistance, there are some superbugs that are relatively new that have emerged in the recent years that are now urgent threats. An example of a newly emerging superbug would be Drug-resistant Candida auris, which is a yeast that is known to be resistant to multiple drugs. This specific microorganism, along with the other urgent threats, tend to develop and spread between hospitalized patients. This commonality can be related to the generally low immunity level among these specific patients that make them susceptible to these infections.  In addition, the incorrect use of antibiotics among this population can lead to the dysbiosis of the normal microbiota and allow these superbugs to flourish, which is commonly seen among cases of Clostridioides difficile. Overall, I believe that the emergence of these superbugs should be taken as a warning sign to physicians and patients all over the world, that if we continue to use antibiotics improperly, there will be one day that antibiotics will no longer be effective and superbugs will run rampant all over the Earth.

Poliomyelitis is a disease that has the capability of having disastrous consequences upon infected individuals, as a result of the contraction of the poliovirus from another infected individual. According to the Center of Disease Control and Prevention (CDC), only 1 out of four individuals with polio will present flu-like symptoms, while a smaller group of infected individuals will present life threatening symptoms like paralysis and meningitis. To combat this life-threating virus, two vaccines have been made in order to prevent an infection of the poliovirus. The first polio vaccine was created in 1955, which was the inactivated polio vaccine (IPV), with the oral polio vaccine (OPV) following very short after. With the combination of these two vaccines, the United States has been polio free since 1979, while other nations have not been so fortunate.

The IPV and OPV immunizations have a similar goal of preventing the spread of poliovirus within a susceptible population. OPV has some advantages over IPV, including the ability of it to eradicate polio virus within the environment. IPV cannot eliminate the virus from the environment, as OPV has the ability to induce immunity within the mucosal and intestinal tracts to disrupt the transmission of the virus from person-to-person. However, OPV has not been used within the United States since 2000 as the vaccine has the risk of regaining its virulence due to the mutation of the live vaccine. I believe OPV is still used in other countries around the world, as the rare risk of the mutation of the vaccine is worth taking, as OPV is easier to obtain because it is more cost effective than IPV, and is easier to administer because it is given orally instead of intramuscularly. IPV is administered within the United States, and other countries were polio is not an active threat, in four doses starting at the age of 6 weeks old.

According to the United Nations, the World Health Organization has reported that all three stereotypes of the poliovirus have almost been eradicated from the face of this Earth. There are only two nations that have active cases of the poliovirus, which would include Afghanistan and Pakistan, while Nigeria has only been three years free from any instances of poliomyelitis. For comparison, there were 350,000 cases of polio in 1988, affecting over 125 countries. The efforts of the IPV and OPV has had a tremendous impact on the reach of this disease over the last 65 years, since the original IPV was created. Even though, the cases of polio of dramatically decreased since 1955, the dangers of the disease are still ever present in today’s society. In early January of this year, the World Health Organization announced that the poliovirus is still a Public Health Emergency of International Concern, as there 28 cases of polio in 2018, but 113 cases in 2019. This increase in the prevalence of polio is due to the dismissal of the IPV/OPV in Pakistan and Afghanistan due to the cultural beliefs of the populations. The presence of these active cases still present a danger to society as a whole, as it only takes one individual to contract polio asymptomatically and to spread it to an unvaccinated individual in the United States to initiate a pandemic of an almost eradicated disease.

The human microbiome is a wonderland of microbiology that is filled with interactions between many microbes, including bacteria and even archaea, to aid the body in many processes or in some cases, to hurt it. The human microbiota consists of these interactions between the plethora of microorganisms and their corresponding genes within the human body, which is specifically known as the human microbiome. The manifestation of the human microbiome does not begin until the birth of an individual; however, the microbiome is not completely established until approximately three years of age. In addition, everyone’s microbiome is unique to themselves as individuals, as we are all exposed to different environmental factors and genetic predispositions. In fact, an individual who was delivered vaginally or even breastfed as an infant will have a vastly different microbiome than an individual who was delivered by caesarian section or formula fed. This is because the vaginal canal and breast milk exposes the newborn to bacteria and other microbes that are beneficial in establishing their own microbiome, of which an infant who wasn’t exposed to these microorganisms would lack.

There is plenty of information regarding the microbiome that is still unknown today, even though the Human Microbiome Project was established over thirteen years ago in 2007. However, this research escapade and further research on the interactions between these microbes and our bodies have allowed medical advances to solidify a new era of medicine. A prime example of a treatment resulting from research on the human microbiome would be fecal microbiome transplantation (FMT) procedure. FMT has been experimentally shown to cure an infection caused by Clostridioides difficile (C. diff) through the transplantation of fecal matter from a donor to the patient. This procedure works by using the microbes within the fecal matter of the donor to introduce new microorganisms to stabilize the microbiome of the patient who is facing an infection that has destabilized their own microbiome. This procedure was only first introduced in 2013, so there is still much research to be improved upon in understanding how this transplantation of microorganisms can readily treat a patient so effectively.

An additional way that the human microbiome is enhancing the health of individuals, would be the use of the microbiome in the identification of early signs of cancer. It has been studied and evidence has been provided to support the claim that alterations in the gut and oral microbiomes can indicate an early signs of specific cancers. For example, hepatocellular carcinoma is third on the list of cancers that has caused the most deaths, and it can be caught early in its progression through the observation of changes among the microorganisms within the individual.  Microbial dysbiosis, or the dysfunction of the microbiome, among the gut and oral cavity specifically, can indicate that a change in the body has occurred that has caused the destruction of important microorganisms. This deterioration of the microbiome allows medical providers to assess possible causes of the dysbiosis, which can allow an early case of diseases, such as hepatocellular carcinoma, to be detected in enough time for possible medical intervention. Overall, I believe that future research can be done with the focus upon the microbiome and possible disease treatment and prevention that can results from the manipulation and observation of the plethora of interactions between microbes within our own bodies.

Influenza is a virus that comes in various flavors, as it is ever changing due to its genetic makeup and corresponding virulence factors. According to the Center for Disease Control and Prevention (CDC), each type of the influenza virus has a specific set of viral spikes on its surface. Hemagglutinin (HA) and neuraminidase (NA) are these specific proteins that trigger an immune response of the infected host, and each has their specific role in the infection process. HA viral spikes are used to attach the virus to a specific type of tissue (avian, human, etc.) and then the NA spikes spread the infection to the host by destroying receptors on the host cell’s surface. The combination of viral spikes upon the surface of an influenza virus is important in identifying and treating the virus; as well this is how the specific “flavor” of the flu gets its name. This is because there are 18 types of HA spikes and 11 NA spikes, so for example; H1N1 is the influenza with the first subtypes of the HA and NA proteins, respectively. New strains of influenza emerge through the processes of antigenic drift and antigenic shift. Antigenic drift occurs when mutations are caused among the viral spikes, which lead to the antibodies that were stored from a previous influenza infection to be ineffective against the new composition of HA and NA proteins. Antigenic shift on the other hand, is when new HA and NA proteins are created and lead to a total new strain of the flu. These changes in the genetic code can be synonymous to the changes in the seasonal flu (antigenic drift) and the generation of a flu pandemic (antigenic shift).

The seasonal flu is categorized as influenza B, while influenza A is the pandemic strain of the virus that can adapt rapidly and mutate from infecting only animals to infecting humans as well. In other words, antigenic drift is most commonly associated with influenza B, while antigenic shift is associated with influenza A. According to epidemiologist Lynnette Brammer of the CDC, the strain that has affected the most individuals is of the Victoria lineage of the influenza B virus. So far during the 2019-2020 flu season, over 87,000 individuals have been hospitalized due to an influenza infection. These statistics are were reported in early January 2020, so they may have changed as I am writing this blog post. I believe that the cases of influenza within the United States that have caused hospitalization or death will continue to increase significantly, as the influenza vaccine this year can only give protection from specific strains and antigenic drift and shift are one of the powerful allies of the influenza, besides anti-vaxxers.

The 2019-2020 flu season’s vaccine that was approved by the US Food and Drug Administration (FDA) is a quadrivalent vaccination that cover four strains of the influenza virus. Two of these strains are for the prevention of the influenza B virus, in which they producers of the vaccination used the same components to combat the Influenza B Victoria and Yamagata viruses from the 2018-2019 vaccination in this year’s vaccine. This was because, due to antigenic drift, these strains only mutate a little each year, which allows for the majority of the virulence factors (viral spikes) to be affected by the same vaccination. However, the two strains of the vaccination that were updated, were specifically focused upon two different strains of influenza A to increase the prevention of an outbreak of a new influenza pandemic. According to Brammer, the efficacy of the flu vaccine for this specific year is hard to determine in the middle of the flu season. However, she also stated that the efficacy of the flu vaccine against influenza B Yamagata and H1N1 (influenza A subtype) is pretty high. In contrast, as a result from influenza B Victoria having the highest level of diagnosis among individuals with influenza, the vaccine can be seen to be not as effective against this strain. Overall, even though the flu vaccine is not all encompassing, more lives are saved through the use of this prevention measure than the use of no vaccine.

Dr. Andrew Wakefield; a prime example of the impact that bad and misdirected science can have upon not only the scientific community, but the world as a whole. This British gastroenterologist published a paper in The Lancet along with 12 other co-authors in 1998, basically claiming a strong correlation between children who have received the MMR (Measles, Mumps, and Rubella) vaccine and the resulting development of Autism Spectrum Disorder. Following the publishing of “Ileal-lymphoid-nodular hyperplasia, non-specific colitis, and pervasive developmental disorder in children”, the scientific community reacted with speculation and the world reacted with amazement. The scientific community immediately went to work on verifying and replicating the results explained by Wakefield, in which they fell short. Over 11 studies with various designs (controlled observational studies, ecological studies, etc.) and various global cohorts all neglected to find substantial evidence to support the claims of Wakefield. The differences between these studies and the original Wakefield study began with the faults within Wakefield’s experimental design.

Wakefield only had a cohort of 12 individuals, of which were all selected by Wakefield, which defies the fundamental necessity of a double-blind experiment. This experiment was manufactured for the sole purpose of establishing a non-existent correlation between a life-saving vaccine and a developmental disorder that has a limited known etiology. The motive behind the fraudulent paper has been partially attributed to the conflict of interest that Wakefield held with research regarding the effects of the MMR vaccine. According to Dennis K Flaherty, Wakefield received over half a million dollars in monetary compensation from the legal team that was suing on the behalf of individuals who were “negatively effected” by the MMR vaccine. This a blatant conflict of interest, as his research may have been constructed for the sole purpose of winning the legal cases for these individuals.

Wakefield’s “research” is still having a cascading impact on the world. Through his manipulation of the facts and scientific data and with the combination of the exploitation of false data by the media, a large proportion of the population has started to decline the vaccination of their children. As a result of a decline in vaccination rates in first-world countries, such as the United Kingdom, diseases that have almost been eradicated, have re-emerged within modern society. The idea of herd immunity is only successful if the majority of society is vaccinate, and if a large number of individuals become unvaccinated, those that are immunocompromised become more susceptible to these deadly diseases that could have been avoided. There was a recent outbreak in 2014 in the United States, in which about 125 people contracted measles, which could have ultimately been avoided through the use of the MMR vaccine. Through the fear of vaccines established within modern society among individuals who are not aware of accurate scientific data, our society is declining in the efficacy of herd immunity and increasing in occurrences of preventable epidemics.