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The Art of Immune Warfare - The Key Players

Updated: Jun 8, 2020

Now we know about our defenses, lets look into the key players who facilitate and engage in an attack, but prior to that lets take a small detour and look into the evolution of our immune system to better understand the workings of it.

Evolution of the Immune system

Our immune system has been moulded by evolution to respond to acute infections and attacks by foreign bodies. Our protective system evolved from simpler defense mechanisms and it appears that the most primitive devices for producing specific, acquired immunity gradually diversified to meet the new environmental hazards as we evolved and moved out of the sea onto the land. Given the absence of a major selective pressure on humans beyond reproductive age, we had to seek out and develop genetic traits to ensure early life fitness.

To respond effectively to a vast array of pathogens (more than a quadrillion quadrillion individual viruses alone exist on earth let alone other microorganisms like bacteria, parasites, fungus etc), the immune system must be tremendously adaptable. Adaptation by the immune system follows the principles of evolution: an enormously diverse set of potentially useful proteins is generated; these proteins are then subjected to intense selection so that only cells that express useful proteins flourish and continue development, until an effective immune response to a specific invader is generated. Critical to the development of our immune response is the selection process, which determines which cells will reproduce.

This adaptive system operates through the principles of evolution, including reproduction with variation followed by selection of the most well suited members of a population.

The process comprises several stages. In the early stages of the development of an immune response, cells expressing molecules that bind tightly to self-molecules are destroyed or silenced (for obvious reasons. We don't want our cells attacking each other), whereas cells expressing molecules that do not bind strongly to self-molecules and that have the potential for binding strongly to foreign molecules are preserved. The appearance of an immunogenic invader at a later time will stimulate cells antibodies (more on this in a bit) that bind specifically to elements of that pathogen to reproduce in evolutionary terms, such cells are selected for. Thus, the immune response is based on the selection of cells expressing molecules that are specifically effective against a particular invader. This response evolved from a population with wide-ranging specificities to a more focused collection of cells and molecules that are well suited to defend the host when confronted with that particular challenge.

We can synthesize large amounts of specific antibody against virtually any foreign determinant within a matter of days of being exposed to it so our immune system is pretty bad ass!!

After birth, the sudden exposure to environmental pathogens, calls for a rapid change to make distinct immune responses appropriate for life. The key players that facilitate this response are as follows:

The Key Players

The Arsenal

Bone Marrow

In the embryo, blood cells are made in the yolk sac. As development proceeds, this function is taken over by the spleen, lymph nodes, and liver. Later, the bone marrow takes over most hematopoietic functions, although the final stages of the differentiation of some cells may take place in other organs. The red bone marrow is a loose collection of cells where hematopoiesis (making of blood cells) occurs, and the yellow bone marrow is a site of energy storage, which consists largely of fat cells. Red bone marrow is the place where the key players of our adaptive immune response take shape. The B cell undergoes nearly all of its development in the red bone marrow, whereas the immature T cell, called a thymocyte, leaves the bone marrow and matures largely in the thymus gland. More on these cells further down!


The thymus gland is a bi-lobed organ found in the space between the sternum and the aorta of the heart. Connective tissue holds the lobes closely together but also separates them and forms a capsule. The outer region of the organ is known as the cortex and contains large numbers of thymocytes with some epithelial cells, macrophages, and dendritic cells (more on these below). The medulla, where thymocytes migrate before leaving the thymus, contains a less dense collection of thymocytes, epithelial cells, and dendritic cells. Thymus produces thymosin, a hormone that stimulates the differentiation and maturation of T cells.

One major cause of age-related immune deficiencies is thymic involution, the shrinking of the thymus gland that begins at birth, at a rate of about three percent tissue loss per year, and continues until middle age, when the rate declines to about one percent loss per year for the rest of one’s life. At that pace, the total loss of thymic epithelial tissue and thymocytes would occur at about 120 years of age. Thus, this age is a theoretical limit to a healthy human lifespan.

This process appears to be genetically programmed.

Lymph Nodes

Lymph nodes function to remove debris and pathogens from the lymph, and are thus sometimes referred to as the “filters of the lymph”. Any bacteria that infect the interstitial fluid are taken up by the lymphatic capillaries and transported to a regional lymph node. Dendritic cells and macrophages within this organ internalize and kill many of the pathogens that pass through, thereby removing them from the body. The lymph node is also the site of adaptive immune responses mediated by T cells, B cells, and accessory cells of the adaptive immune system.


In addition to the lymph nodes, the spleen is a major secondary lymphoid organ. It is located to the left of and slightly posterior (behind) to the stomach. It’s roughly oval in shape, normally measuring about 3 by 8 by 13 centimeters and weighing about 23 grams. The spleen is a fragile organ without a strong capsule, and is dark red due to its extensive vascularization (blood vessels). The spleen is sometimes called the “filter of the blood”. Essentially, its structure is that of a really large lymph node, and it filters blood in much the same way the lymph nodes filter lymph, removing pathogen cells along with exhausted RBCs and many kinds of foreign matter. The spleen also functions as the location of immune responses to blood-borne pathogens. Note that the spleen has no role in filtering lymph (only blood).


Also known as white blood cells (WBCs), are present everywhere and functioning at all times. You notice their presence in the acute phase of certain diseases. Its the immune response and not the invader, which produces the well-known symptoms of flu. They function not only in the blood (plasma to be precise), but also in the interstitial fluid and the lymph. They’re never far off from a site of injury or infection because they’re everywhere. When a splinter pierces your finger, a contingent of local WBCs arrives at the site instantaneously. These cells of the blood, including all those involved in the immune response, arise in the bone marrow via various differentiation pathways from hematopoietic (anything that is involved in the formation of blood) stem cells.

The Soldiers

Innate Immune Response

Our immune cells are constantly patrolling our bodies, floating in the bloodstream, hanging out in the interstitial fluid, moving through the lymph, and some post up in the lymph nodes acting like guards keeping vigilance and checking everyone coming through a security gate. Most often, our bodies are able to destroy the pathogen before they can unpack their bags and cause any damage to us. This is the strategy of the innate immune system. If a pathogen makes it past our first line of defense (physical barriers), we have a barrage of cells ready to defend and put an end to these pathogens.

These WBC’s utilize phagocytosis as part of their strategy, engulfing and digesting (pakman anyone?) any foreign material. A phagocyte is a cell that is able to surround and engulf a particle or cell, through a process called phagocytosis. The phagocytes of the immune system engulf other particles or cells, either to clean an area of debris, old cells, or to kill pathogenic organisms such as bacteria. The phagocytes are the body’s fast acting, first line of immunological defense against organisms that have breached barrier defenses and have entered the vulnerable tissues of the body.

Natural Killer Cells are a type of cells that have the ability to induce apoptosis, that is, programmed cell death (in which a cascade of events inside the cell causes its own death), in cells infected with intracellular pathogens such as bacteria and viruses.

B, T and Plasma Cells – Adaptive Immune Response

If the pathogens are sneaky and somehow manage to get past the innate immune response, this is when we start to feel the characteristic symptoms of an infection. The battle is not lost though, our body has something else up its sleeve. Its secret weapon, the adaptive immune system. These cells are specialists in sniffing out the sneaky suckers and destroying them. We enlist the assistance of our B and T cells to mount a targeted attack on the pathogen, minimizing the collateral damage to our own cells that the innate strategies inevitably cause.

When the mechanisms of our innate immunity do not eliminate the pathogen, our adaptive mechanisms join in the battle. The trigger for this requires an antigen-presenting cell (APC); usually a macrophage or dendritic cell. When an APC comes across an unrecognized pathogen (meaning it has not been affected by any sort of immune response) it engulfs and digests it. However, it preserves the antigens (remember the hats) and displays them on its own cell membrane. It then flows around our fluids hunting for a T cell that has a matching receptor, thus activating the adaptive immune response.

B Cells

B cells are immune cells that function primarily by producing antibodies. An antibody (also known as immunoglobulins) is any of the group of proteins that binds specifically to pathogen-associated molecules known as antigens. An antigen is a chemical structure on the surface of a pathogen that binds to T or B lymphocyte (type of WBC) antigen receptors. You can think of the interplay between an antibody and an antigen as a lock and key mechanism. An antibody as a kind of molecular lock that needs to be unlocked if the white blood cell it's riding on is to take action. Now think of the antigen as the key. If the key fits the antibody lock, white blood cells start rapidly multiplying in an attempt to overwhelm and beat the crap out of the invader. Once activated by binding to antigen, B cells differentiate into cells that secrete a soluble form of their surface antibodies. These activated B cells are known as plasma cells.

B cells are manufactured with random receptor shapes in hopes that any pathogen we may encounter will have a matching B cell. Statisticians argue that the chances of us having a

match are so astronomically high that it’s safe to say there’s one in our body somewhere.

The problem is finding it before the pathogen does irreversible damage.

T Cells

The T cell, on the other hand, do not secrete antibody but performs a variety of functions in the adaptive immune response. Different T cell types have the ability to either secrete soluble factors that communicate with other cells of the adaptive immune response or destroy cells infected with intracellular pathogens.

Our immune system keep tabs on every microbe it has ever defeated through types of T and B cells, which can from memory cells for quick response if the pathogen returns. B cells secrete

antibodies to antigens in blood and other body fluids before they can strike the cell.

Once the pathogens manage to latch onto the cells then they are pretty much out of

reach of the B cells and that is when T Cells come into play.

Now that the stage is set for the battle, what's left is the weapons at disposal and the act of war itself. That's coming up next!

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