Tag Archives: Immune System

Intro to Immunology, 1/19/26

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The Immune System is a complex interplay between a dozen+ cell types, signaling molecules, anti-microbial systems and physical barriers that serves to protect our body from internal and external invaders in addition to leading clean up and repair of natural damage that occurs as part of daily life. The goal of this writing isn’t to outline every detail and nuance of the Immune System, but rather to provide a general overview of the major pieces and parts that contribute to protecting our bodies, allowing us to navigate life in a complex world full of dangers. In addition to providing a few relatable real-world examples of how our immune system protects us, I will also include some information on how it can become dysfunctional in its own right, leading to self-inflicted harm. This article will be a precursor to many more detailed and disease specific articles focused on creating comprehensible and digestible understanding of complex disease topics that affect life.

TERMS:
Innate Immune System = Non-specific pieces of the immune system.
Adaptive Immune System = Pathogen specific immune system.
Mucosa = Soft tissue that lines organs such as the airways, intestines and reproductive tract, allowing regulated entry/absorption from the surroundings to the rest of the body.
Pathogen = Agents such as viruses, bacteria and parasites that can infect a person.
Antigen = Any material foreign (from the outside world) or naturally occurring in the body that can cause an immune response.
Anti-microbial = Something that is known to stop the growth of or kill microorganisms such as bacteria, viruses, fungi or parasites.

The Immune System is divided up into two separate arms, the Innate Immune System which is made up of quick reacting non-pathogen specific protection mechanisms and the Adaptive Immune System, comprised of antigen specific responses that can be both short lived and very long lived (memory). The Innate Immune System is made up of three arms; natural barriers to entry (such as skin and airways), circulating molecules that destroy invaders and damaged cells and immune cells that wander the body looking for things to clean up. All of these mechanisms function in a pathogen agnostic manner, meaning it doesn’t matter if the invader is Bacteria A or B, Virus A or B. Meanwhile the Adaptive Immune Response exists for when these initial mechanisms get overwhelmed and our body needs to create a more specific response in order to eliminate the threat before it can cause too much ancillary damage to our own body. T-cells (Helpers and Killers) and B-cells (producing Antibodies) are the two main components of the Adaptive System that get amplified in response to a specific target. Once the threat is cleared, a portion of these cells can remain dormant in our body for years, just waiting for the same target to return (our Immune Memory). If that’s all you are interested in learning about the specific cells and pieces of the Immune System, feel free to skip down to the sections on “Health, Immune Function and Dysfunction” below, as the next section is a more detailed and denser explanation of the Immune System’s parts and pieces (for the nerds out there).

Components of the Innate and Adaptive Immune System
Immune exposure and development begins in utero, but really kicks into full swing after birth, when we are thrust into a dirty world full of new antigens and pathogens. While the process of exposure and reaction to our environment never stops after birth, the human Immune System is mostly formed by 3-4years of age. The first line of defense of the Innate Immune System are natural barriers like the skin and mucosal cells lining the airways, intestines and reproductive tract. These create physical barriers that provide limited and restricted access to the body, helping to prevent bacteria, viruses and allergens from regularly gaining entry. In addition, hair in the nostrils along with mucus in the airways and intestines help trap outside materials, allowing the cells that line these surfaces to produce natural anti-microbial molecules that are capable of destroying some pathogens. If these external barriers and systems are damaged or overcome, then the body has two additional sets of quick responding Innate mechanisms that serve to clean up and protect our organs and tissues. The first of these are a series of circulating molecules that include anti-microbial peptides (similar to natural antibiotics), proteins designed to tag and identify foreign molecules (eg CRP, lectins and ficolins) and complexes that help destroy infected or damaged cells (complement proteins). None of these are living, but all are capable of interacting with their targets to assist in protecting our body.

Innate Immune Overview. Anaya JM et al. Autoimmunity, From Bench to Bedside.

The second set of Innate mechanisms comprise a diverse group of cells that are both programmed to both dispose of garbage and to signal other more specialized cells to enhance the immune response. All of these cells have Pattern Recognition Receptors that are designed to identify common patterns found on bacteria, viruses, parasites, environmental allergens and damaged cells. These common antigens are things that our bodies are exposed to daily, and that we’ve evolved to recognize and clear out as part of our normal immune function. Granulocytes are some of the first cells to respond to issues, these include cells such as; neutrophils that help eat up foreign invaders and destroy damaged cells, eosinophils that help kill parasites and mast cells and basophils that are commonly involved in responses to allergens. The next class of cells collectively known as phagocytes (Monocytes, Macrophages and Dendritic Cells) serve two important functions, to eat up and destroy any garbage they find floating around and in more extreme cases to use this garbage to activate more specific Adaptive Immune responses (remember this in the next section). The last subset of Innate Immune cells are specially programmed killers, whose sole goal is to destroy foreign invaders and mutated cells (ie cancer cells). They are responsible for maintaining the balance between normal growth and dysfunction (parasites, mutations and cancers), preventing the latter from coopting our body.

Primary cells of the Adaptive Immune System. https://cellcartoons.net/lymphocytes/

While the Innate Immune System has some generic patterns it recognizes, it is NOT responding in a pathogen specific way. Meaning it would respond to most bacteria using similar mechanisms and the same goes for many similar viruses. If the first lines of defense fail to contain the pathogen/damage, cells known as Antigen Presenting Cells (often Phagocytes) are able to trigger activation of the pathogen specific Adaptive Immune Response. The two cells many people are familiar with that drive Adaptive responses are T-cells and B-cells. There are three major classes of T-cells, each serving a different role in enhancing specific immune responses; CD4+ T-helper cells, CD8+ Cytotoxic T-cells (specialize in killing) and gamma-delta T-cells (Immune surveillance). During normal development, each CD4+ and CD8+ T-cell is created with a unique random target, in fact there are millions of these unique cells just floating around the body. If by chance one of the Antigen Presenting Cells finds a new infection that matches the unique target on one of these T-cells, then that unique cell multiplies in response to the specific activation signals. The CD4+ Helper T-cells role is to identify the location of these unique infections and to signal other killer cells and B-cells to migrate to the site of infection/damage, thus specifically amplifying the immune response. There are Helper T-cell types that target infections hiding inside our cells, others that target free floating infections, some that participate specifically in allergic responses, others that help in tissue repair and even some that are specifically programmed to slow down inflammation if things get too wild and crazy. Meanwhile the CD8+ Cytotoxic (Killer) T-cells have overlapping specificity to the Helper T-cells, but instead of recruiting other cells and amplifying immune response, their sole job is to kill any cell that matches their unique target. This includes both infected cells and mutated/cancerous cells.

The last arm of the Adaptive Immune Response is the infamous B-cell and the Antibodies they produce. Just like the T-cell, during normal times our body creates an army of millions of B-cells, each with a unique random target, just hanging around, waiting for a Phagocyte or T-Helper cell to show them the right target. If they find the unique antigen that matches their Antibody, they go into action, multiplying and cranking out Antibodies against the target. These Antibodies are basically very sticky keys (though shaped more like a Y), that bind to the infection/target, both marking it to be destroyed by the killer cells (discussed above) and walling off the target to prevent it from doing further damage to the body. In cases where the body amplifies T-cells and B-cells against a very specific infection/target, some of those cells mature and turn into memory cells that go into a hibernation like state, hanging out for years (or even our entire life). These cells lie in wait for that same infection/target to return, ready to quickly respond and prevent us from getting sick (this is generally how vaccines work). In total, our Immune System is a complex web or responses and interactions, all tightly regulated with feedback loops to allow careful responses to invading pathogens, repair damaged tissues and prevent excessive collateral damage to our own body from within.

Health, Immune Function and Dysfunction
You might be asking, how do all these cells and pathways affect how my daily bodily function, or when I get sick with a bacteria/virus, how about when things become dysfunctional leading to self-inflicted disease? Even more than the details above describing the different parts of the Immune System, these questions are much more pertinent to life on a day-to-day basis. Though unfortunately in some ways these questions are far more complicated than the Immune System itself. My goal in this section is to introduce some general trends and concepts, rather than to address every health condition, supplement, disease, Autoimmune condition out there. In subsequent posts I’ll be addressing specific diseases, conditions and health topics that are either of specific interest to me or that have been requested by people in my life (feel free to reach out with your request).

The Immune System is something that’s constantly working, reacting, resting and repairing the body every single day. The surrounding environment is full of agents that have the potential to harm us, cause disease or coopt our cellular machinery, and the Immune System is one of the major factors that keeps a lot of these in check. This includes preventing allergens from entering the body, killing off bacteria/viruses that we’re exposed to on a daily basis to repairing damaged tissue from all the cuts and scrapes we accumulate, the Immune System does a little bit of everything. Our external environment is constantly challenging our body’s defenses, and for the most part it does a good job of blocking out many things, killing off small numbers of invading pathogens, clearing out cancerous/dead cells and repairing both internal and external tissue damage. There are many aspects of our daily lives that help keep things functioning well, including proper nutrition, a good supply of energy (aka calories), adequate sleep, low stress and exercise. Even if we did everything perfectly to keep the body functioning at 100% (basically impossible), our body’s defenses and repair mechanisms sometimes need a little extra help.

Overview of the Infection cycle and Immune Response. Kuby Immunology.

The most common challenge our Immune System faces is an overwhelm by too many pathogens. If a pathogen is either too numerous or has mechanisms to evade the immune system, then our body starts going into overdrive, manifesting in what most of us think of as ‘getting sick’. Our body temperature increases (fever) to both inhibit pathogen replication and increase immune activity, our vessels flood immune cells to the site of infection (causing inflammation), we have aches and pains (caused by stimulation of local nerves and the battle that’s being waged around them) and we become fatigued as our body reallocates energy to fighting off the infection. This infection can happen locally around a cut/wound, in a specific tissue (like a stomach bug or respiratory infection) or systemically (in your blood) affecting the whole body. There are varied degrees of severity of this process, at it’s best our body responds quickly to control the invading pathogen and we barely feel any symptoms (vaccines help prime these responses to be quicker), but at it’s worst the invading pathogen spreads throughout our body both infecting and killing cells directly but also hyper-activating our immune system so much so that it causes self-inflicted damage in its effort to clear the infection (collateral damage). So in general it is good to let the body go through the inflammation and healing process naturally, though if a fever gets too high or the immune response too severe, it can start to damage organs and cause more harm than good, and that’s when it’s a good idea to seek medical attention (especially for younger children). Unfortunately, sometimes it’s hard to know when our body crosses this line and what the best line of care is, because how each of us responds and how much each individual can tolerate is different.

The other challenge our immune system regularly faces is trying to keep the body from dysfunctionIng and directly attacking itself. This can occur in two main forms, Autoimmune disease (where the body mistakenly attacks itself) and Cancer (where mutations cause uncontrolled growth). Autoimmune diseases cover a wide-range of issues including Rheumatoid Arthritis, Type 1 Diabetes, Eczema and Psoriasis, Crohn’s disease, Multiple Sclerosis and Lupus among many others. In all of these diseases, some part of the Immune System becomes misdirected and hyperresponsive, leading to the body attacking itself and damaging a specific tissue or cell type. These diseases can be triggered by genetic factors, infections that cause a misfiring of the Immune System, random mutations causing auto-reactive cells, environmental triggers, chemical damage and other factors that we’ve yet to identify. Because of the varied causes of Autoimmune Diseases, we can’t always predict who or when they might occur. Even more challenging is that not all Autoimmune Diseases of a single classification are created equal, meaning one person with Eczema (skin disease) might have a different pattern of immune dysfunction than another person, so what treatments and interventions work best of each could be different (coming in the next blog). These are the types of discussions I’ll be trying to dive deeper into as part of future writings, discussing the more subtle nuance of a single disease or classes of diseases and what that means for those working through those challenges.

The other major classification of dysfunction is the diverse field of Cancer Biology. In over-simplified terms, Cancer is caused by a mutation that occurs somewhere in the body (really could be anywhere) that creates cells that divide, grow and spread in an uncontrolled manner. These cells can be in Immune Cells, epithelial cells, structural cells, nerve cells and so on. Regardless of the cell type, during normal maintenance processes, the Immune System is responsible for identifying these malfunctioning cells and destroying them before they can divide and spread, but when they are missed during the normal surveillance process is when disease can happen. These mutations can lead to the growth of either benign or malignant tumors, the former being a non-cancerous clump of cells (don’t spread and invade other tissues) and the latter growing rapidly and spreading throughout the body causing serious risk to normal tissue function. While there are some patterns in the mutations/cells that cause Cancer, there is also a lot of variability, which adds to the challenge of treating the disease, especially in the context of minimizing damage to non-cancerous tissue in the body, not always an easy feat. As such there is a wide range of therapeutic options, ranging from targeted radiation that kills the cancerous cells (and nearby cells), drugs that can interrupt cell division and growth, specialized therapies that can tag cancer cells for the immune system to identify (if they are unique enough) and the use of specially designed synthetic immune cells specially designed to attack the cancerous cells (one of the newer technologies). While the Oncology field has made great strides in understanding and treating Cancer, there are still many cancers that are hard to predict, identify and treat, meaning much more research is needed to improve the understanding of the what, how and why.

The process of healthy and normal immune function is a complex web of maintenance, reaction and regulation. Serving to protect our bodies, maintain normal growth and fix damage. All of the information above is just a small window into the complexities of disease and immune functionality. It’s also important to keep in mind that we’re all individuals and while I’ve outlined some general patterns that apply to most humans, we each have our own unique challenges, strengths and body types that need to be treated as such. This blog series is intended to be an ever-evolving work that serves to help those with Non-Scientific backgrounds further understand complex health related topics. As such I welcome all questions and any constructive comments and critiques from Scientist and Non-Scientist alike. Up next, “Skin Diseases, Disruption and Immune Dysregulation”…. If you’re a more visual learner, check out the University of California Televisions video on Immunology Basics, it’s about 1.5h long, so strap in.

This content is for educational and informational purposes only and is not a substitute for medical advice. It does not provide diagnosis, treatment recommendations, or guidance for any individual’s specific medical situation.

References

  • Abbas A et al. Cellular and Molecular Immunology. Elsevier Science, 2003.
  • Alberts B et al. The Cell. Garland Science, Taylor and Francis Group. March 2002.
  • Alotiby A. Immunology of Stress: A Review Article. Journal of Clinical Medicine, 2024; 13, pg6394.
  • Anaya JM et al. Autoimmunity, From Bench to Bedside. El Rosario University Press. September 2013.
  • Goldsby R et al. Kuby Immunology. WH Freeman & Company. January 2002.
  • Jain N. The Early Life Education of the Immune System; Moms, Microbes and (missed) Opportunities. Gut Microbes, Sept 2020.
  • Shishido SN et al. Humoral Innate Immune Response and Disease. Clinical Immunology, June 2012; 144, pg142-158.
  • Wrotek S et al. Let Fever do it Job. Evolution, Medicine and Public Health, Nov 2021; pg26-35.

COVID-19; Immunology and the Infection Cycle, 4/22/20

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Sorry for the delay, but this one has taken a lot of time and thought to put together (and reading some 80 odd Covid research papers). My goal in this edition of Covid Science Theater 2020 is to talk about what happens when the virus enters our body, infects our cells and subsequently leads to either mild disease or more severe infections. It’s going to be a fairly dense article, but I’ll do my best to keep the science and terminology to something generally understandable and hopefully educational.

For those who don’t want to delve too much into the specifics of all the virology, immunology and pathology I’ll provide a short 1 paragraph set of clifs notes here. The virus most commonly enters the host through mucus membranes (eyes, nose, mouth) and infects vascular endothelial cells and cells of the lungs, kidneys, GI tract and begins to replicate. The body initially responds to the virus through a host of Innate Immune mechanisms; these generic counter measures are deployed against all invading pathogens as a first line defense and are not specific to the invading pathogen. Unfortunately, these initial immune responses aren’t always adequate to contain the virus (the virus sometimes evades destruction, other times the virus just overpowers the immune response) so our body deploys a second type of response known as the Adaptive Immune response. In this phase, T-cells and B-cells are primed to respond to the specific infectious agent (here, SARS-CoV-2). Often this two-pronged approach works to contain the infection, eliminate the virus and build up lasting memory to subsequent infections. Unfortunately in some people the virus spreads too rapidly and the immune response doesn’t respond appropriately, leading to destruction of their organs (notably the lungs) and potentially death. Sometimes this more severe outcome is caused by the virus itself, but more often it seems to be caused by an overzealous immune system trying to play catch-up. So there’s the quick and dirty; in the following paragraphs I’ll go into more detail about Viral Entry/Binding/Replication, Early Cellular Responses, Clinical Symptoms, Adaptive Immune Response and What Happens and Why the Immune System Sometimes Fails.

The information in the following paragraphs comes from a combination of basic immunology principles (Kuby Immunology textbook), observations and early research released about Covid-19 and conclusions drawn from earlier studies of SARS-CoV-1 (a virus that is very similar to the current SARS-CoV-2, but with some caveats of course). As Covid-19 is still a new disease, we are constantly learning new things about the virus, infection cycle and pathology, so while what I outline here is based on a lot of research, there are definitely aspects of this virus that we don’t fully understand, and need further investigation.

Graphic of the structure of a SARS virus, the S, M and E proteins are the most important in regards to host recognition, Li et al 2020.

Viral Entry and Replication

Coronaviruses get their name from the hallmark shape, a circular capsid (or shell) that is spiked with proteins on the outside and sheltering the virus genetic sequence on the inside. The Spike (S), Membrane (M) and Envelope (E) proteins make up the majority of the viruses outer shell, while the Nucleocapsid (N) protein found inside the virus assists in viral replication. This small assortment of proteins, plus a few others, make up the bulk of the very simple viral structure (Weiss 2005, Li 2020). The novel coronavirus 2019 (COVID-19) shares a lot of homology or similarity with the original SARS virus that was discovered in 2002, genetically 80% similar, while being 76-95% similar for the major proteins listed above (Xu 2020). This allows researchers to draw a lot of conclusions from previous research on SARS-CoV-1, though we must be careful when doing so, as there are some known (and unknown) differences between the two viruses. The infection cycle starts with the virus gaining entry to the host, usually through mucus membranes of the eyes, nose and mouth. Once inside the virus often begins it’s infectious cycle by infecting vascular endothelial cells that line vessels throughout the body. While different viruses have different mechanisms by which they enter host cells, SARS-CoV-2 binds to the ACE2 receptor using its spike protein (same as SARS-CoV-1), allowing it to enter the host cell (Jia 2005, Walls 2020). Like most viruses, SARS-CoV-2 then goes through a multi-stage process by which it hijacks some of machinery inside our own cells to in order to replicate, escape and subsequently infect more cells in a continual cycle (Frieman 2008).

Overview of the SARS viral life cycle inside the host, Frieman et al 2008.

Early Cellular Response

Thankfully our body has a whole host of immune mechanisms it utilizes to deal with infectious agents of all types. Almost as soon as an invading pathogen has infected our cells the immune system starts going to work. The Innate Immune response is our constantly active sentinel, whose cells are constantly circulating all over our body just looking for foreign invaders to attack and kill. These innate cells use Pathogen Associated Molecular Patterns (PAMPs), or markers of foreign invaders, as the initial signals something is wrong and that it’s time to go to work (Li 2020). Some cells go to work directly attacking the virus and infected cells in an attempt to destroy the virus, others release signaling molecules known as cytokines and chemokines that recruit other cells to help in the fight (Frieman 2008), and some cells just go ahead and sacrifice themselves in an effort to prevent the virus from hijacking them, a process known as apoptosis (Lim 2016).

Symptoms: What and How They Manifest

While this system works well for many invading pathogens (why we are not sick all the time), allowing our body to control the infection, many viruses (and bacteria) have evolved mechanisms by which to evade, subvert and co-opt the immune response to their advantage. For SARS-CoV-2 it seems to be able to prevent the host immune system from activating one of it’s key anti-viral signaling pathways, the Type 1 Interferon pathway (Lim 2016, Li 2020, Frieman 2008). While it is not known exactly how the virus subverts this system a few hypotheses involve the Nucleocapsid protein (Lim 2016), other non-structural proteins (Lim 2016), and some of the SARS enzymes (Chen 2014). So by reducing the host immune response the virus is able to more effectively replicate and spread, leading to a more systemic infection. This is when we start to experience more of the hallmark symptoms of the infection; fever, sore throat, coughing, fatigue, pulmonary inflammation leading to shortness of breath and possible pneumonia and lymphopenia (a decrease in lymphocytes, more on that later) (Huang 2020, Zhu 2020). Most of these symptoms are a physical outcome of the body’s ongoing fight with the virus, trying to delicately balance destroying the invader, while preserving the host organs and system. The fever is the immune system’s attempt to raise the core temperature enough to burn out the infection. The sore throat/cough is an outcome of our immune system attacking infected cells of the airways and trying to expel the invader (mmm mucus), same for the pulmonary issues (initially, more on this later too). While many of these symptoms may be scary and uncomfortable they are often a normal part of our body’s healing process when dealing with a foreign invader. So under normal circumstances, it’s best to rest and let your body do it’s thing, unfortunately this doesn’t always go as planned, as we’ll find out in the following sections….

Adaptive Immune Response; Stage 2

In the previous two sections you’ve seen how our well intentioned Innate Immune system can sometimes fail leading to illness, thankfully the body has a backup, the Adaptive Immune response. This secondary wave of the immune response goes into action very soon after the initial infection (several hours to few days, infection dependent) and is mostly comprised of two cell types; T-cells and B-cells. When the levels of virus in the body start to rise, several of the innate immune cells can act as activators of the adaptive immune response, taking pieces of the virus to specialized activation centers know as lymphoid organs. These centers of immune activation are spread all over our body and are the primary site of pathogen specific antigen (virus pieces) presentation. The antigen presenting cells (Dendritic cells are most prominent) present the virus to the T-cells and B-cells as if locks in a door, allowing the T-cells and B-cells to go to work making specific keys (receptors and antibodies) that can attack and destroy the pathogen in a very focused manner. The outer proteins that make up the viral capid (proteins S, M, E) tend to be the most effective as this is what is visible to our body when intact virion are released (Liu 2017). So the body makes a whole army of these specific cells that traffic to the sites of infection; T-cells directly attack the virus and infected cells, while B-cells make antibodies that bind to parts of the virus, preventing them from entering new cells and marking them for destruction (Liu 2017).

These two arms of the Adaptive Immune response are also what comprise our immunological memory. Virus specific T-cells and antibody producing B-cells remain dormant in specialized lymphoid organs (sometimes they also remain in circulation), just waiting for the virus to turn up a second time. This time since they are already primed and ready to go, memory T-cells and B-cells start attacking the virus almost immediately, usually preventing the virus from spreading and preventing us from getting sick. Studies of SARS-CoV-1 have found both memory T-cells and memory B-cells (producing neutralizing antibodies) that are capable of rapidly responding to viral reinfection (Li 2020, Liu 2017, Channappanavar 2014). In human patients who recovered from SARS-CoV-1 infection anti-SARS antibodies and memory T-cells were found in most patients up to 24 months after infection (Liu 2006, Ka fai 2008, Liu 2017). While antibody responses did decline over time in SARS-CoV-1 patients (many undetectable at 6 years), memory T-cell responses were conserved for up to 11 years after infection (Tang 2011, Ng 2016, Liu 2017). Similar high quality neutralizing antibodies have been found in COVID-19 patients, but since the disease is so new the longevity of memory responses to this new virus aren’t exactly known. Encouragingly, since SARS-CoV-2 is so similar to the original SARS virus, and lab testing has even shown that their be might cross-reactive protection between the two diseases (Walls 2020), there is much hope that the long lasting memory responses seen for SARS-CoV-1 would also apply to those who have recovered from COVID-19. All of this evidence, both old and new, does inspire a lot of hope that a functional vaccine would both be likely and very effective in providing some duration of immunity from COVID-19, but how long remains to be seen.

Graphical overview of the many cells and pathways involved in the host immune response to SARS. It’s a complex set of feedback loops and interactions with a lot of variables. Li et al 2020.

When the Immune System Fails, Severe Disease

The reason COVID-19 is such a scary disease, isn’t because our immune system has no problem fighting it off, but because in some percentage of the cases (uncertain, but estimates are as high as 10-20%) patients need to be hospitalized due to severe complications. If our immune system is so complex and so strong, why do patients with COVID-19 get so sick that they need hospital care? It comes down to numerous very subtle things this virus does that are different than coronaviruses that cause the common cold. One is the effect SARS-CoV-2 has on Type 1 Interferons mentioned earlier, reducing the body’s initial response to infection. Another early symptom seen in many severe cases is lymphopenia, or a loss of lymphocytes (notably T-cells) early on in disease (Huang 2020, Schmidt 2005, Weiss 2005). While the exact cause of this loss of T-cells is not known, it is hypothesized that the viral proteins may lead directly to T-cell death as a mechanism of immune evasion (Lim 2016, Li 2020). These mechanisms of avoiding immune detection along with the efficiency of viral replication can lead to an out of control infection very quickly.

But in the end, it’s only partially about the virus, and largely about an overexuberate immune response. In an attempt to catch-up to the wide-spread infection the immune response goes into overdrive, ramping up a lot of the inflammatory cells and signaling molecules that tell the body to attack the infection (Li 2020). This response does in fact kill the infected cells, but it also destroys lung tissue (primary target), vascular tissue, liver tissue and other infected tissues (Tian 2020, Schmidt 2005). This is often when the more obvious signs of pneumonia set in; the lungs fill with fluid, the efficiency of aveoli decreases (oxygen absorption) and breathing becomes very labored and difficult. This is the tricky thing about COVID-19, making our immune response more efficient would help prevent early infection, but later on would lead to increased tissue damage. But if we reduce the immune function of the body to prevent self-inflicted tissue destruction, we run the risk of allowing the virus to run rampant throughout our body. COVID-19 is a tricky disease to treat for these reasons, and because the disease severity has a wide range of outcomes for different people. In some, infection is very mild and asymptomatic, in others, their entire body shuts down as the virus (and immune system) destroys the host from the inside. The reason many comorbidities are important as risk factors for severe disease is that most of them either affect the immune system or lung function. Obesity, diabetes, auto-immune diseases all alter the immune system’s ability to function, making it harder to fight off the virus. COPD and asthma (though less prominent then thought) make the host pulmonary system more sensitive to damage caused by the virus and immune system.

But not all hope is lost! Because of the large body of evidence suggesting that SARS viruses create robust lasting immunity, this means a vaccine might be very effective at protecting most of the population. Also, now that there are many patients who have recovered from COVID-19, tests are underway to examine if using their plasma (containing antibodies) can help patients who are suffering from more severe cases of the disease (works for other viruses like Ebola). We also have several promising anti-viral agents that are already in clinical trials being tested against COVID-19, with hopes that one or more of them will help improve patient outcomes and be ready for use later this year. Unfortunately all of this does take time, meaning we won’t have a cure next month, but by slowing the spread of the virus, not only do we allow hospitals to manage the patient load, but we allow all the scientist out there to catch-up and produce much needed data, therapies and vaccines.

Thanks for reading. If you see any mistakes please bring them to my attention and I will correct them ASAP. If you have additional questions or want to discuss the immune response in more detail (this is a very high level overview) I’d be happy to do so via text or email. Stay safe and stay healthy.

Literature Citations:
Chan et al, Serological Responses in Patients with Severe Acute Respiratory Syndrome Coronavirus Infection and Cross Reactivity with Human Coronaviruses 229E, OC43, NL63. Nov 2005, Clinical and Diagnostic Laboratory Immunology.
Channappanavar et al, T cell-mediated immune response to respiratory coronaviruses. May 2014, Immunology Res.
Chen et al, SARS coronavirus papain-like protease inhibits the type 1 interferon signalling pathway through interaction with the STING-TRAF-3 TBK1 complex. Jan 2014, Protein Cell.
Frieman et al, SARS Coronavirus and innate immunity. 2008, Virus Research.
Huang et al, Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Jan 2020, Lancet.
Jia et al, ACE2 Receptor Expression and Severe Acute Respiratory Syndrome Coronavirus Infection Depend on Different Human Airway Epithelia. Dec 2005, Journal of Virology.
Ka-fai Li et al. T cell responses to Whole SARS Coronavirus in Humans. Oct 2008, Journal Immunology.
Li et al. Coronavirus infections and immune responses. Jan 2020, Journal of Medical Virology.
Lim et al. Human Coronaviruses: A Review of Virus-Host Interactions. 2016, Diseases.
Lu et al. Immune responses against severe acute respiratory syndrome coronavirus induced by virus-like particles in mice. June 2007, Immunology.
Ng et al, Memory T cell responses targeting the SARS Coronavirus persist up to 11 years post-infection. March 2016, Vaccine.
Schmidt et al. Coronaviruses with a special emphasis on First Insights Concerning SARS. 2005, Birkhauser Advances in Infectious Diseases.
Tang et al, Lack of Peripheral Memory B cell responses in Recovered Patients with Severe Acute Respiratory Syndrome: A Six-year Follow-up Study. May 2011, Journal of Immunology.
Tian et al, Pulmonary Pathology of Early-Phase 2019 Novel Coronavirus (COVID-19) Pneumonia in Two Patients with Lung Cancer. Feb 2020, Journal of Thoracic Oncology.
Walls et al, Structure, Function and Antigenicity of SARS-CoV-2 Spike Glycoprotein. Apr 2020, Cell.
Weiss et al, Coronavirus Pathogensis and the Emerging Pathogen Severe Acute Respiratory Syndrome Coronavirus. Dec 2005, Microbiology and Molecular Biology Reviews.
Xu et al, Systematic Comparison of Two Animal-to-Human Transmitted Human Coronaviruses: SARS-CoV-2 and SARS-CoV. Feb 2020, Viruses.
Zhou et al, Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. March 2020, Lancet.