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The flu explainer Chicago didn’t know it needed

Health is a civic undertaking.

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BOBBY SIMS
  • Bobby sims

You're hopefully not going to die of the flu this year. But the truth is that you could.

During the 2017-2018 flu season, the Centers for Disease Control and Prevention (CDC) reported an estimated 80,000 deaths and 900,000 hospitalizations due to infection with the virus—a jump in severity over previous seasons. The last update the City of Chicago Department of Public Health released on May 25, 2018, reported 582 influenza-associated hospitalizations and 38 deaths for the entirety of the 2017-2018 flu season; this represents a 50 percent jump over the previous year's numbers, which had remained fairly consistent for about four years in a row. These numbers don't account for individuals who get the flu but don't require hospitalization, which go untallied. As of November 30, the Chicago Influenza Surveillance Activity Report shows hospitalizations are up this year: six for the current season in comparison to the four that had been reported by this time last year on December 1, 2017.

Health is easy to take for granted. The experience of a burning throat, stuffy nose, lack of appetite, clogged ears, fatigue, fever, aching body, and chills is so dissonant from the normal ease of existence (normal for some of us, anyway) that it quickly becomes clear that something is wrong. An illness of some kind has taken root in the body. Adding insult to the injury of physical misery is the frustration of feeling helpless, weakened, and unable to control the process of getting better. In most illnesses, symptoms fade after two to five days, but sometimes the severity of the illness and unresolved symptoms necessitate treatment from health care professionals. The influenza virus, commonly referred to as the flu, can cause symptoms that last anywhere from three to seven days, but fatigue and cough can linger for up to two weeks. Declarations such as "Bundle up. You don't want to catch a cold," or "You'll get sick if you leave the house with wet hair" are often heard as temperatures begin to drop, but illness isn't caused by exposure to cold weather. Cold, dry environments often lead to cracks in the skin, which is the body's primary protective barrier. Being indoors in closer proximity to others than during other times of the year simply allows for more opportunities for transmission. A recent paper published by Dr. Ishanu Chattopadhyay, a research scientist at the University of Chicago, compiled large datasets about the different factors that trigger flu outbreaks and a decade's worth of influenza data to show that multiple factors, including geospatial patterns, travel, weather, and adaptation of the influenza virus, all contribute to the spread. Flu activity tends to start in November and peaks between December and February.

And that means we're just entering flu season in Chicago. Season's greetings!

BOBBY SIMS
  • Bobby sims

The Virus and the City

Once the virus that causes the flu enters the body, it begins to multiply and cause damage to the respiratory system (nose, throat, and lungs). Children, pregnant women, adults over 65, and patients with compromised or weakened immune systems are all at risk of developing secondary complications from the flu, as damage done to the body by the flu virus can lead to increased risk of additional illness, and in severe cases death. Infectious agents, and others that cause damage to cells, are referred to as pathogens. Viruses are one of five classes of pathogens, along with bacteria, protozoa, fungi, and prions. It can be hard to believe that a pathogen isn't innately bad when it's causing physical discomfort and damage to your body, but pathogens are simply doing what living things do—looking for a nutrient-rich environment that will allow them to survive and reproduce. The human body is the home some of these pathogens like best.

In a way, the body can be thought of as a city like Chicago. Just as a body has organs and tissues, a city has distinct neighborhoods. Within the organs and tissues are cells, and within our neighborhoods are people. Cells are the individual citizens of our bodies, and they contribute to the economy and the daily function of our collective system. Microorganisms can be thought of as people not originally from here, perhaps from Appleton or New York, who have moved to Chicago and adapted to the icy cold winters, chosen a sports team, familiarized themselves with widespread segregation and inequitable distribution of resources, and know all about the repeated history of fiscal mismanagement. Microorganisms, like people, have preferences and specific areas they prefer to make their homes, although they prefer the skin, mouth, large intestine, or vagina over, say, Logan Square. Those that can establish residence without causing infection or harm are considered normal flora, or microbiota. These organisms become part of the community and contribute to the overall health of the body in the same way that people who move to and establish residence in Chicago do.

So-called normal flora exist peacefully within the body, but when placed under the right conditions or brought to the right location, some members of the flora—called "opportunistic pathogens" or "facultative pathogens"—are capable of causing disease. If there's a disruption to the normal flora by use of an antibiotic, if the body's response to warding off illness has been compromised, or if the microorganisms manage to enter a part of the body that's normally sterile via an accident, injury, or other illness, the pathogens continue to grow and replicate without immediately being discovered, causing harm along the way. A common example of this occurs when patients take antibiotics to treat an infection, which kills off much of the normal flora, allowing for overgrowth by the opportunistic pathogen Clostridum difficile, or C. diff, which can cause severe diarrhea, inflammation of the colon, organ failure, or death.

In contrast to normal flora, pathogens consistently cause responses within the body that can lead to infection, illness, or disease. Pathogens can be compared to anything that causes harm to the city or the citizens that live here, whether that be other individuals, politicians, real estate developers, or gentrifiers. Dedicated pathogens (as opposed to opportunistic pathogens) don't require a compromised host and can cause disease in a healthy individual. Dedicated pathogens, like viruses, don't have their own cell replication machinery, so the only way they can replicate is by hijacking the cell replication machinery in the body's cells. Since these obligate pathogens can't multiply any other way than by infecting new hosts, most of them need to cause disease symptoms that help them move to a new host. For example, coughing, sneezing, and respiratory droplets carry the flu virus to people and exposed surfaces within a six-foot radius, enabling the virus to spread. Urban renewal projects like the elevated running and biking trail known as the 606, which cuts through Humboldt Park, or the planned Obama Presidential Center in Jackson Park are meant to revitalize neighborhoods but often displace residents and contribute to gentrification. Increased spread and transmission can occur when real estate developers looking to profit quickly come into gentrifying neighborhoods, build luxury condos, and then move on to the next profitable neighborhood.

Opportunistic pathogens, on the other hand, can live outside the human body and normally replicate in environmental reservoirs like water or soil, but they can cause disease if they encounter a host. For a pathogen to cause disease and then spread, it first has to get into or on the body, find the site that is most compatible to its growth, avoid elimination by the body, replicate using host cells, and then exit and get to a new host. These pathogens may simply be trying to live, but the body is too and it works hard to prevent pathogens from gaining ground. Similarly, the residents of the city can fight back against gentrification. On October 11, 2017, Chicago's Affordable Requirements Ordinance was amended to include pilot programs in two rapidly gentrifying areas of the city—the Milwaukee corridor and the near north/near west area, which includes several neighborhoods. Previously, developments that included 10 or more units were required to price 10 percent of them at affordable rates; alternatively, developers could pay an "in-lieu fee" to the city's Affordable Housing Opportunity Fund. The new pilot programs require 20percent of units to be priced to accommodate low-to-moderate income residents and there is no "in-lieu fee" alternative. This disrupted plans by Onni Group, a Canadian development company, to build 1,000 residential units on Goose Island.

BOBBY SIMS
  • Bobby Sims

The Community Organizations of the Body

The word "immune" can be traced back to Latin and French roots meaning exempt from and privileged from attack. The immune system, and the protection it confers, offers exactly that. There are two branches of the immune system: innate immunity, comprising nonspecific responses, and adaptive immunity, which can learn to recognize and respond to a specific pathogen. Upon infection, these two branches work in conjunction with one another to clear pathogens. Overall there are three lines of defense, the first two by the innate response, and the third by the adaptive response.

One of the most important ways the body can protect itself is by initially preventing a pathogen from entering the body. Within the innate immune system, there are two levels of nonspecific responses that work to prevent entry of anything unrecognized, neutralize anything that may get in, and alert the adaptive immune system to mount a defense. The first line of defense of the innate immune response is a combination of both physical and chemical barriers that block pathogens from establishing residence. Pathogens need to get in the body, and different types of surfaces provide different routes of entry for different organisms. Some pathogens can gain entry by physical contact with the body's external surfaces, or through wounds or insect bites. Similar challenges confront drivers around the city who are faced with potholes, poorly marked lanes, bridge closures, and seemingly endless construction. These add detours and frustration to the ease with which we navigate. We may not be pathogens, but the city doesn't always make it easy for us to get around in it.

The body's internal surfaces can be harder to reach, but they can be exposed to pathogens when air is inhaled into the respiratory system, when food or drink enters the gastrointestinal tract, and when sex partners make physical contact, exposing the reproductive tract. Recent contamination of Romaine lettuce with a pathogenic strain of E. coli is an example of how foods can contain pathogens that can be introduced into the gastrointestinal tract where they can cause illness.

The skin is composed of epithelial cells covered by an outer thick layer of epidermis cells, which both shed—themselves and pathogens—and repair quickly to maintain this physical barrier. The cells sit tightly next to one another, making it hard for pathogens to penetrate past into deeper tissues of the body. Imagine an incredibly packed CTA train whose occupants collectively sigh when the conductor asks everyone to make a little bit more room. Internal surfaces are also composed of epithelial cells, but these secrete mucus that can trap microorganisms. Fine hairs called cilia work to move trapped organisms out of the body in the same way city street sweepers clean up accumulated garbage and debris. Wounds and burns are interruptions in the skin's physical barrier that often allow pathogens to enter. When pathogens do enter the mucosal internal surfaces, however, there are still defense mechanisms. Hairs within the nose, vomiting, defecation, and urination are all methods the body uses to clear and expel pathogens. Hand washing is one of the most valuable tools we have to prevent pathogens from entering the body, and the CDC reports reduction of respiratory illness by 16 to 21 percent if hand washing is done correctly.

The body also uses chemical barriers that keep pathogens from growing. These include enzymes in tears and saliva that kill bacteria, stomach acid that inhibits bacterial growth, sebum on the skin that acts as a barrier, and the normal flora that can starve out pathogens by competing for nutrients.

But pathogens do often gain entry, and a main component of our immune system's ability to clear harmful microorganisms comes from the ability to discern between self and nonself. The immune system can recognize cells, proteins, and other molecules that our body has made as "self," and it also can recognize foreign proteins, particles, DNA, toxins, and chemicals from pathogens as "nonself" and can then target and induce an immune response against them. In Chicago, a city of 2.7 million, we don't all agree on what's harmful or nonself, but crimes, car accidents, and mass shootings are things we all recognize as harmful. Sometimes the body loses the ability to discern between self and nonself, which results in autoimmune diseases: the body attacks itself instead of protecting it. Similarly, the Chicago Police Department is supposed to serve and keep the residents of the city safe, but improper police training and consistent lack of accountability around conduct have resulted in repeated violations of justice and abuse through illegal searches, excessive force, and racial profiling and biases, leading to harm and even death of the city's residents.

If the first line of defense fails to keep the pathogen out of the body and the pathogen gets in, the second line of defense responds. At this stage, the body's cells work to clear and neutralize an infection while recruiting help. The second line of defense can be compared to an ordinary person's general awareness and social training instilled within us since childhood. If you're at North Avenue beach on a hot summer day and you see a child who looks lost and is crying, most people would try and find the adult the child came with or alert an authority who has more capacity and training to deal with the situation. Now imagine an organization devoted to ensuring the overall health of a community—No Cop Academy, for example, or Black Lives Matter Chicago—keeping a watchful eye on incursions into community vitality with no central command unit and no established funding sources, and you're beginning to have a sense of how the innate immune system works.

Let's get more detailed. Cells within both the innate and adaptive immune system use molecules called cytokines to talk and signal to one another. Where we would use phone calls or text messages to communicate across a distance, immune cells use cytokines. For example, an infected host cell will send out a chemokine—one type of cytokine—to alert the immune system that something's wrong, to let the neighboring cells know, and to call, or text, for help. This type of signaling occurs frequently in the second and third lines of the immune response and results in quick response to threat or injury. For example, inflammation and fever can be quickly activated by the second line of defense to protect the body.

Similarly, Chicago is divided into wards that are represented by aldermen who are elected to represent the interests of the ward's residents. During ward meetings, residents voice complaints and learn about benefits and city functions that exist within the ward. The Chicago City Council is made up of the aldermen, who have legislative powers and the ability to enact change. Cellular responses can be thought of as acts of legislation that are coming from certain types of white blood cells, or aldermen, that have the ability to respond to pathogens. Phagocytes are a class of white blood cell that circulate in the blood and can recognize, ingest, and destroy pathogens. Monocytes first circulate in the blood and then move into tissues of the body, like the lungs, gut, and connective tissues, where they mature into cells called macrophages. Macrophages and monocytes work similarly to phagocytes, but they can also activate cells that help get the adaptive immune response going. Community groups within wards like the Pilsen Land Use Committee (PLUC), composed of neighborhood representatives, use specific knowledge of their neighborhood to help combat gentrification. With the help of their current alderman Daniel Solis, who abides by an unwritten mandate that 21 percent of units in new developments meet affordable housing requirements, PLUC also has a say in zoning developments, which require their approval before Alderman Solis will move forward. (This might be a good moment to point out that aldermanic elections are coming up on February 26, 2019.)

Inflammation increases blood flow to areas of infection, which allows more white blood cells to arrive and respond to the signals sent by the macrophages. The Pride Parade, Air and Water Show, Bears games, and other large city events cause an influx of people to one area that stresses the area's capacity. Increased police presence, street closures, and additional buses or trains help the city respond to the crowd. In addition to fighting pathogens, the swelling and heat caused by inflammation can cause discomfort, and overwhelming responses in the case of infection or autoimmune disorders can lead to chronic pain.

Previously, it's been thought that children are more susceptible to the flu and other viral infections because they are not yet able to mount the thorough innate immune response that healthy adults are capable of. A paper published in April by researchers at Lurie Children's Hospital and Northwestern University's Feinberg School of Medicine reported findings that overwhelming inflammatory and monocyte responses were responsible for increased lung damage in juvenile mice infected with the flu in comparison to adult mice. These components of the innate immune system help fight infection, but they also cause a lot of the symptoms experienced during infection and sometimes the response harms the body.

I was fascinated with these findings and reached out to lead author, Dr. Bria Coates, via email. "Our bodies do this very well with most pathogens," she wrote, "but in certain circumstances, being in the wrong place at the wrong time can lead to a dysregulated inflammatory response that is much more harmful than the infection itself." While further studies will need to check whether the same thing happens in humans, the data here indicates that adult immune systems are better equipped to respond to flu infections in a healthy manner.

As uncomfortable as symptoms of illness are, they are a sign that the body's immune system is working. In flu infections, it's often the overwhelming, unhealthy response of the body to the infection that causes intensity of symptoms in children and adults. I was impressed by Dr. Coates's ability to explain complicated concepts, which likely comes in handy in her work at the Pediatric Intensive Care Unit at Lurie Children's Hospital. I asked her why she loves studying the flu and the immune system, and she responded, "One of the most interesting and challenging things about studying influenza and the immune system is finding the balance that will control infection but not harm the host."

The general response that the innate immune system provides is not enough to clear most infections—sometimes the city's snow removal efforts don't actually let you get to work or school—and this is where the adaptive immune system comes in. The third line of defense works to mount a targeted response to a specific pathogen, which helps the innate immune system clear the infection and prevent disease. At the same time, the adaptive immune system develops a long-lasting memory of that specific pathogen, so the next time it shows up, it can be quickly targeted and blocked. This process is called natural active immunity. The third line of defense can be thought of as trained first responders—the police and fire departments, paramedics, social workers, crisis therapists, and doctors. These people have developed the skills to identify and deal with a variety of accidents, conflicts, or emergency situations through training, certification, and licensure programs. The ability to recognize erratic behavior or respond to alerts from the community helps first responders know where they need to be and what to anticipate. The two main first responders within the adaptive immune system are the T lymphocytes, or T cells, and B lymphocytes, or B cells.

The ability to recognize and respond to specific pathogens builds on the immune system's ability to distinguish between self and nonself. Cells within the adaptive immune system can recognize specific portions of the foreign cells, proteins, molecules, and DNA called antigens. If a B cell has a receptor on its surface that fits with the shape of an antigen on the surface of a pathogen, it will recognize the pathogen as nonself. After identifying nonself components, certain cell types within the adaptive and innate immune system, called antigen-presenting cells (APCs), process the nonself components down and separate the antigenic portion unique to the organism or virus encountered. Think of this as a nurse triaging a patient and identifying what's wrong, determining the course of action, and notifying the doctor who is able to resolve the situation. The antigen is the piece of information that the APCs present to the T cells, and this alerts the T cells to respond.

Once activated, T cells send signals that call for backup: the body clones many identical T cells that are made to specifically recognize, target, and destroy that unique antigen. This process can be compared to using X-rays and laboratory tests to confirm the presence of a malignant tumor, and the establishment of a multidisciplinary cancer team to collectively plan the best course of action, for example, surgery followed by chemotherapy. These T cells have been given the description of the pathogen and are only able to bind to antigens or pathogens whose fingerprint is an exact match for the one they're trying to find. This process is called cell-mediated immunity. Separately, that same signal that gets sent out by the T cell once it's activated stimulates and activates B cells to respond if they haven't already been activated by directly encountering the pathogen. B cells can be considered another component of the T-cell/cancer treatment team. In addition to the doctors and specialized care team, a supportive care team composed of counselors, nutritionists, and rehabilitation therapists works with patients to support long-term health. Activation of B cells results in the production of clone B cells, called plasma cells, that produce antibodies that will specifically bind to the antigen of the encountered pathogen and clear them from the body. Analogously, your therapist may recognize certain patterns they guide you to focus on to help you respond to them in a different way so that those issues no longer affect you. It takes a few days for this response to occur, which is why the innate immune system's quicker initial response is so important. Additionally, after the infection has cleared, some of these activated B cells remain in circulation. If they encounter the antigen again in the future, the circulating B cells can produce antibodies and a specific response in one to two days. If you get emotionally triggered, you draw on the skills learned in therapy or reach back out to your therapist to get more help, and over time your capacity to handle hard issues increases as you heal. Similarly, the adaptive immune response and its encounter with pathogens leads to memory and immune protection.

To protect the body, a fully functioning immune system needs both the innate and adaptive immune systems. The immune system can be weakened or damaged by malnutrition, genetic inheritance, drugs, radiation exposure, infection with a number of viruses, cancer, and old age. This can result in more frequent infections, inability to clear infection, inability to respond to bacterial or viral infection, inability to make an immune memory response and deliver long-lasting protection, and death.

The immune responses described above show the natural process of how the body fights an infection and gains long-term protection in the process. Active immunity can also be induced artificially with vaccines. Vaccines can generate long-term protection without exposure to dangerous forms of the pathogen that can cause illness or disease. Vaccines are developed and delivered in a number of ways, but two common examples are live attenuated vaccines and inactivated vaccines. Live attenuated vaccines contain weakened versions of the pathogen. The weakened pathogen cannot replicate or cause disease, but it still has the same nonself components as the full-strength version of that pathogen, so the immune system can learn to recognize it and form a response before it comes into contact with the full-strength pathogen. This gives the body a jump start, saving the time the immune system would need to learn to recognize the pathogen. Inactivated vaccines, on the other hand, contain antigenic components of completely destroyed pathogens. There is no chance of getting sick from the pathogen delivered in an inactivated vaccine, but you still develop an immunity.

Both artificial and natural active immunity require the immune system to function correctly in order for an immune response to develop because even with a vaccine, the components of the innate and adaptive immune systems need to respond to the antigenic components being delivered. For people who are immunodeficient or whose immune systems are still developing, passive forms of natural and artificial immunity exist, but they are short lasting, providing immediate protection only. The most common form of natural passive immunity is the delivery of maternal antibodies to a newborn through breast milk. Preformed antibodies can also be transfused to patients to work proactively to prevent illness when risk of infection is high. If you're immunocompromised or have never received a tetanus vaccine and you step on a rusty nail, there's a high risk of developing the life-threatening illness. Because of the time it takes for an immune response to develop, there's no immediate benefit to being given the tetanus vaccine at this moment. Instead, tetanus immune globulin (TIg), preformed antibodies to tetanus, are collected from people who have developed antibody protection and can be pooled together, and after transfusion provide immediate protection. There is also herd immunity. Those who are immunodeficient and unable to take vaccines can benefit from others getting vaccinated. The more people have artificial active immunity from the flu vaccine, the fewer hosts are available for the virus; this means fewer people coughing and sneezing—fewer opportunities for transmission. When enough people are vaccinated within a community, a pathogen has no chance of establishing infection and this prevents members of the community who are immunocompromised or whose immune systems may be underdeveloped from getting sick. Herd immunity is essential to protecting the vulnerable members of our society, who are in danger when others do not get vaccinated against preventable diseases.

One challenge to the logic of flu vaccination stems from the fact that viruses frequently mutate to avoid recognition, to increase their ability to cause disease and transmission, or in response to selective pressures. A virus, for example, can pick up new pathogenic elements by exchanging genetic material with other strains it encounters. Most vaccines contain multiple strains of the flu for the body to respond to, but delivery of too many antigens at a time can cause weaker immune memory responses. Alternatively, you could develop a robust immune response but by the time the flu gets to you the antigens of the virus no longer match the antigens your body is prepared to fight. Evidence shows, however, that even partial and weakened responses, in addition to cross-protective responses from previous years' flu immunizations, can provide protection that weakens the severity of infection. This means vaccinations tend to keep you healthier even when they "don't work"; they also keep your fellow Chicagoans healthier. Remember, hand washing is also an option!

The Chicago Department of Public Health offers walk-in immunization clinics to residents, as well as a mobile immunization CareVan that provides immunizations at no out-of-pocket cost to uninsured, underinsured children and those on Medicaid or CHIP up to 18 years of age. The locations of the clinics and the schedule of the CareVan can be found at the Chicago Department of Public Health website. The Department can also be reached at 312-747-9884, and for information about mobile services you can call the CareVan coordinator at 312-746-6181. To search for other locations offering walk-in flu shots through the city, visit https://chicagoflushots.org, where you'll find an interactive map that provides addresses, hours, and details for sites offering the shot.

We don't have control over the influenza virus, but we can control how we prepare for it. Why don't we all do what we can to keep ourselves and each other healthy?   v

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