Bulletproof Your Immune System

Lesson 1: How Your Immune System (Usually) Protects You

Lesson 1 Protocol 1

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To understand the basic, normal immune response to a pathogen, such as a virus, through activation of the innate and adaptive immune systems, and their respective immune cells and molecules

Lesson Summary

Our immune system consists of two different layers. The first layer is the innate immune system, which acts within minutes of infection to provide kind of a rapid response. This doesn't require any specificity; it is engaged after any kind of infection. 

But this innate activation is important to triggering the second layer of the immune system, which is the adaptive immune system. In the adaptive immune system, the key players are B cells and T cells; they eventually acquire specificity and memory, which are the basis of the vaccinations. 

Having those T- and B lymphocytes that are specific to a particular pathogen and provide a memory response in the long term is very important.

How Your Immune System Is Supposed To Protect You

The immune system is very complicated, perhaps the most complex part of the human body outside the brain. 

The purpose of the immune system is to protect us from viruses and other    pathogens. It protects us through an intricate, mind-boggling network of cells and molecules that summon, intensify, provoke, calm, and transform one another.

What’s Immunity?

The relationship between the many various elements of the immune system is truly complex… and confusing!

Even the word immunity creates confusion. To you the word might mean protection, as in you’re immune from some invading pathogen. But when immunologists refer to immunity, they’re talking about how the immune system works properly. For instance, by making antibodies or launching defensive cells, which may or not be protective.

Thus, not every immune response offers immunity in the way that most of us think of it, where we’re completely protected from pathogens. The question about whether or not your immunity is actually protective depends on how effective, numerous and durable those antibodies and cells are.

Immunity is not binary. It’s neither completely protective nor not protective at all. For most of us, the level of protection conferred by our immune system lies somewhere in between those extremes.

Nothing so well illustrates this as does the coronavirus pandemic, where many who get infected have no symptoms, while others get very sick, and some die.

But before we get into how this novel SARS-CoV-2 virus is messing with our immune response, it will be helpful to learn a bit about how our immune system typically responds to a virus.

The Immune System’s Response To A Virus

Viruses are pieces of genetic material surrounded by a protein coating. They can't reproduce without finding "host cells." This is why they seek out cells to infect.

When a virus enters our bodies, it finds a cell with a matching receptor on the surface of the cell, and injects its genetic material into it. This allows the virus to take control of the cell and multiply.

To battle this, the body's immune system must destroy infected cells. When the body first encounters a new viral infection, it deploys T cells, which find and kill infected cells. If the infection continues, the body then deploys B cells, which create antibodies that can better attack infected cells.

Even after the infection has passed, antibodies remain in the body to help the body fight off future infection. How long these antibodies last in the body varies, ranging from days to a lifetime. 

Basically, the immune system works within three phases: [1]

  1. Detecting a threat, 
  2. Summoning help, and 
  3. Launching a counterattack.

The threat detection happens when a virus enters your eyes, nose or mouth, and infiltrates the cells that line them.

In order for detection to occur, the immune system has to recognize that the virus is not self, and it doesn’t belong inside of your body. When immune cells sense molecules common to pathogens and uncommon to humans (detecting a threat), they produce proteins called cytokines (summoning help). 

The Role of Cytokines

Cytokines are proteins that are produced in response to an antigen, and function as chemical messengers for regulating the innate and adaptive immune systems. They are produced by virtually all cells involved in innate and adaptive immunity, but especially by T- helper (Th) lymphocytes.

Cytokines are a vitally important part of cell signalling within the immune system. They set off alarm bells or interfere with the virus reproducing itself and spreading, and in so doing they, in effect, are "summoning help", the second phase of how basically the immune system responds to an invading pathogen.

When cytokines sound the alarm, they activate a variety of white blood cells that can swallow and digest viral particles, as well as hit them with destructive chemicals. Cytokines that prevent or interfere with viral reproduction have an appropriate name, “Interferons”. 

Cytokines are inflammatory by design -- this is a sign that the immune system is working correctly, as long as the inflammation doesn’t get out of hand, which, as you’ll learn, is a big problem with COVID.

The Dance Between the Innate and Adaptive Systems

Immunity cell Definitions

Innate immune cells are the body's first line of defense. They quickly respond to foreign cells to fight infection, battle a virus or defend the body against bacteria.

Our acquired immunity—also called adaptive immunity—uses T-cells and B-cells, among others, when invading organisms slip through that first line.

Innate Immune System Cells

Macrophages (Greek: large eaters) are a type of white blood cell of the immune system that engulfs and digests cellular debris, foreign substances, microbes, cancer cells, and anything else that does not have the type of proteins specific to healthy body cells on its surface in a process called phagocytosis.

Natural killer cells (NK) are a type of lymphocytes (white blood cells) associated with innate immunity. Their production occurs in the bone marrows. They are mainly present in blood and spleen. Unlike other phagocytic cells, NK cells do not attack pathogens or invade microbes directly; instead, they destroy infected body cells.

Dentritic cells (DCs) are antigen-presenting cells (also known as accessory cells. Their main function is to process antigen material and present it on the cell surface to the T cells of the immune system; when that happens they act as messengers between the innate and the adaptive immune systems.

Neutrophils, also known as neurocytes, are a type of white blood cell that are central to our immune system. As part of our innate immune defense, neutrophils act as the first-line responders to infection, attacking bacteria, viruses, and other pathogens.

Eosinophils are specialized pro-inflammatory white blood cells. The two important functions they have is to destroy invading pathogens (like viruses, bacteria, or parasites such as hookworms), and to ignite an inflammatory response to pathogens, especially if an allergy is involved.

Basophils are a type of white blood cell helps fight infections, most commonly those caused by parasites. Basophils are also involved in producing some of the symptoms caused by allergic reactions, such as watery eyes, sneezing, and runny nose.

The Bridge Between the Innate and Adaptive Immune Systems

Natural Killer T cells and T cells can act as a bridge between the innate and adaptive systems by producing several cytokines with the capacity to jump-start and modulate an adaptive immune response.

T cells (also called T lymphocytes) are a heterogeneous type of lymphocyte or white blood cell formed in the thymus gland that that share properties of both T cells and natural killer cells. They can bind to various cells in the body to kill off infected cells and attack antigens.

Natural killer T cells (NKT) are a subgroup of lymphocytes associated with the innate immune actions of the body. NKT cells share certain features with both conventional T cells and NK cells. They are present mainly in the thymus, liver, spleen, and bone marrow, and are mainly responsible for producing an immune response against pathogens and auto-antigens. Also, they also participate in tumor rejection, control of autoimmune diseases, and immune surveillance. Based on the nature of the immune signal, NKT cells may produce either pro- or anti-inflammatory cytokines.

Note: The key difference between Natural killer (NK) cells and Natural killer T cells (NKC) is that NK cells are not antigen-specific receptors, while NKT cells are antigen-specific receptors. An antigen is the immune response initiator. It can either be bound by a specific antibody present in secretions or the blood, or by a B cell antigen receptor. Antibodies in the immune system are proteins produced by lymphocytes, and are specifically programmed to attack and kill invading viruses, bacteria or other foreign microbes, as identified by antigens.

Adaptive Immune Cells

Various kinds of B and T cells are among the most important cells of the adaptive immune system.

T cells produce cell-mediated responses, distinguishing them from antibody responses by B cells. T cells are different from B cells in that they are activated by only when the foreign antigen is displayed on the surface of antigen-presenting cells. T cells have two main categories: T helper cells and cytotoxic T cells.  Due to the presence of two different types of glycoproteins (CD4 and CD8) on the cell surface of T helper cells and cytotoxic T cells, they are referred to as CD4+ T cells and CD8+ T cells, respectively. (See below.)

B cells (also called B-lymphocyte) synthesize antibodies, which are the basis of the adaptive immune response. B cells produce billions of different antibodies, each having a unique amino acid sequence and a different binding site for antigens. Every individual B cell makes a single type of antibody with the same antigen-binding site. recognize intact antigens, whereas T cells recognize fragments of protein antigens that have already been partly degraded inside a cell. Another difference is that once activated, T cells have only a short-range effect, within a lymph node or at the site of the infection. T cells interact with other cells to either kill it or emit a signal.

CD4+ cells are a subset of T cells known as T helper cells that are responsible for the antigen presentation to B cells, and alert other immune cells to the presence of infections such as bacteria and other viruses in the body.

CD8+ cells are known as cytotoxic T cells.CD8 cells are responsible for indirect phagocytosis.

Identifying that the virus is not you, and the subsequent cytokine response is part of what’s called the innate immune system. It’s called innate because it’s generic. We’re born with it, and it works the same way in all of us. It’s also a blunt instrument that tries to knock out anything deemed foreign to the body without much regard to which specific pathogen is the enemy.

Though imprecise, and short-term (typically lasting no longer than 96 hours) the innate immune system is speedy, and does not depend on the pathogen being identified by an antigen. It quickly seeks to do its job to eliminate the infection (launching a counterattack), which it may or may not be able to do. If it does, great, the job’s done. If it can’t finish the job, it’s time for the second wave of the immune response, and the surfers on that wave are weaponized specialists called T cells. This is the beggining of a precise counterattack.

T cells, also known as T lymphocytes, are highly specialized white blood cells. The “T” stands for "thymus" -- the organ where these cells mature and learn to distinguish between self and non-self.

T cells are also found in lymph nodes, and that’s where they first encounter fragments of virus, carried there by various messenger cells. The messenger cells job is to find which T cell is pre-programmed to kill the particular virus it reveals.

For any new virus, you probably have a T cell somewhere that could theoretically fight it, but that T cell has to be found and mobilized. When a match between a particular T cell and virus is found, the T cell clones itself into an entire battalion and heads off to the infection site to do battle.

Some T cells are killers, which blow up the infected respiratory cells in which viruses are hiding. Others are helpers, called T helper cells, which boost the rest of the immune system. These helper T cells activate the B-cells that produce antibodies.

Like T cells, B-cells are lymphocytes, a specialized white blood cell. B-cells are as important as T cells. They make important molecules called antibodies that can trap specific invading pathogens. 

These antibodies neutralize viruses by gumming up the structures they use to latch on to their hosts. Roughly speaking—and this will be important later—antibodies mop up the viruses that are floating around outside our cells, while T cells kill the ones that have already worked their way inside. T cells do demolition; antibodies do cleanup.

But in order to make these antibodies, the B-cells need to recognize the specific pathogen, and they do this by recognizing the antigens on a virus. 

An antigen is a toxin or other foreign substance produced by a pathogen which stimulates an immune response in the body. Certain immune cells are able to present antigens on their cells' surface that identify it as a foreign invader that needs to be dealt with. This  promotes B- cell activation.  When activated, the B-cells produce and release specific antibodies to specific antigens. 

Both T cells and antibodies are part of the adaptive immune system. Remember that the adaptive system is more precise than the innate system, but much slower to react to a pathogen. Finding and activating the right cells to battle a specific pathogen can take several days. 

Though the adaptive system is slower to respond to a pathogen than the innate system, it’s remarkable in two excellent and necessary ways:

  1. It’s long lasting -- it battles with pathogens longer than does the native immune system; and  
  2. It remembers what it fought so that if infected again, it’s arsenal is ready.

While it’s true that the battle with the virus does deplete most of the mobilized T and B-cells, a small fraction remain on patrol throughout your bloodstream. This is the third and final phase of the immune system response, which is to be ready for launching a counter attack if needed.

If the same virus attacks again, these “memory cells” can spring into action and launch the adaptive branch of the immune system without the usual days-long delay that occurred the first time around. 

Memory is what’s needed for immunity to be what we want it to be, which is to completely protect us from a pathogen. Those memory cells have the potential to provide a lasting defense against whatever has previously harmed us.

The following table summarizes what you just read. In the following lessons, many of the immune cells mentioned in the table will be addressed. [2]

The Timeline and Antigen Dependency of the 

Innate and Adaptive System Immune Cells

So, now you know what should happen when a virus, or some other pathogen, enters the body, based on general knowledge about the immune system, and how it reacts to other respiratory viruses. 

But what actually happens when the new coronavirus SARS-CoV-2 enters the body? That’s the topic of Lesson 2.

Your Takeaway

Our immune system consists of two different layers. The first layer is the innate immune system, which acts within minutes of infection to provide kind of a rapid response. This doesn't require any specificity; it is engaged after any kind of infection. 

But this innate activation is important to triggering the second layer of the immune system, which is the adaptive immune system. In the adaptive immune system, the key players are B cells and T cells; they eventually acquire specificity and memory, which are the basis of the vaccinations. 

Having those T- and B lymphocytes that are specific to a particular pathogen and provide a memory response in the long term is very important.

Now that you know some of the basics about your immune system, this immune system animation may provide a helpful visual guide: