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The Art of Immune Warfare - Lines of Defense

Updated: Jun 8, 2020

Now we have established the battlefield and the forces partaking in a possible attack, lets look into the measures they have in place to counter any such attacks.

Invaders – Pathogens

These are foreign bodies that can cause damage to the body in form of a disease. Just like any invaders they can attack from outside (exogenously) or from within (endogenously). These can include bacteria, fungus, virus, parasites, toxins, harmful chemicals etc.

The Renegades – Collateral Damage - Auto Immune

The primary function of the immune system is to protect us from an invasion by foreign organisms. But how does the immune system avoid mounting attacks against our own cells? In other words how does the immune system distinguish between our own cells and foreign cells not to mention against internal threats, such as cancer cells. Our immune system is pretty smart. It can distinguish self (own cells) from non-self (foreign cells) by using a sort of tagging system (think of it like a passport).

Own cells are tagged with something called Major Histocompatibility Complex molecules (MHC class I). You can think of MHC-I as a badge holder with the own cells identity, “This is me” Once the border patrol comes across cells with MHC-1 they tend to leave them alone.

Foreign cells are tagged using Antigens. These are recognized by our immune system and releases antibodies (lock) that bind to these antigens (key). Its like solving a puzzle, each antigen has a characteristic shape of an exposed portion (epitope), which the antibodies produced can fit into thereby recognizing a cell as a foreign cell and initiating an immune response.

Even proteins from food may be rejected unless they are first

broken down into amino acids by the digestive system.

Our immune system goes through selection processes early in the developmental pathways to kill or suppress those immune cells that react strongly with self-markers (imagine each cell wearing a hat so other cells can identify them).

Although our selection process is remarkably efficient in suppressing the immune response to self-antigens, failures do occur. Such failures results in autoimmune diseases, where the immune system starts attacking our own cells. These diseases include relatively common illnesses such as type 1 diabetes, multiple sclerosis, rheumatoid arthritis etc. In these illnesses, immune responses against self-antigens result in damage to selective tissues that express the antigen.

Lines of Defense

Our immune system can be divided into three basic lines of defense against any pathogenic attacks. These are:

1. Physical Barriers - Confronting the Invaders

This is our first line of defense. Physical barriers that prevent microbes from entering the body or that physically remove them from body surfaces. They job is to ensure whatever gets in is taken care off immediately. Different modes of barrier defenses are associated with the external surfaces of the body, where pathogens may try to enter. If pathogens cannot enter our body, then they cannot disrupt the normal physiological functions and cause disease. Our body has several ways of keeping out invaders, both living or otherwise. These include:


The primary barrier to the entrance of microorganisms into the body is the skin. Not only is the skin covered with a layer of dead, keratinized epithelium that is too dry for bacteria to grow, but as these cells are continuously sloughed off from the skin, they carry any bacteria and other pathogens with them. Additionally, sweat and other skin secretions may lower pH, contain toxic lipids, and physically wash microbes away.


These structures, which accumulate all sorts of materials taken into the body through eating and breathing, actually encourage pathogens to penetrate deep into the tonsillar tissues where they are acted upon by numerous lymphoid follicles and eliminated.

Eyes and Mouth

Another barrier is the saliva in the mouth, which is rich in lysozyme—an enzyme that destroys bacteria by digesting their cell walls. The flushing action of tears and saliva helps get rid of debris and prevent infection.


The acidic environment of the stomach, which is fatal to many pathogens, is also a barrier.

Mucus Layer

Additionally, the mucus layer of the gastrointestinal tract, respiratory tract, reproductive tract, eyes, ears, and nose traps both microbes and debris, and facilitates their removal. In the case of the upper respiratory tract, ciliated (imagine a mechanical brush constantly clearing away debris) epithelial cells move potentially contaminated mucus upwards to the mouth, where it is then swallowed into the digestive tract, ending up in the harsh acidic environment of the stomach.

Considering how often we breathe compared to how often we eat or perform other

activities that expose us to pathogens, it is not surprising that multiple barrier

mechanisms have evolved to work in concert to protect us.

2. Border Patrol – Innate Immune Response

This is our second line of defense. Some microbes penetrate the body’s protective barriers and enter the internal tissues. Anything which manages to breach our physical barriers will trigger the alarm and bring in the border patrol. These are non-specific cellular and molecular responses and just like guards/police who do not have special training they do not differentiate between different types of pathogens. In innate immunity, the body recognizes and destroys certain foreign substances, but the response to them is the same each time the body is exposed. Innate immunity includes body defenses that are present at birth (remember the thing about mother's gut biome?) and genetically determined.

3. Special Forces – Adaptive/Acquired Immune Response

The final line of defense are the special forces who have special training to deal with serious breaches. Although a bit slower to respond they do have a targeted approach and are capable of detecting distinct Antigens (remember the hat thingys). They also form memory cells, thereby ensuring long-term immunity to a particular pathogen so the response to them is faster and stronger each time the foreign substance is encountered. Memory is the ability of adaptive immunity to “remember” previous encounters with a particular substance. As a result, the response is faster, stronger, and longer-lasting.

Adaptive immunity includes body defenses that are acquired through a person’s lifetime, depending on exposure to different microorganisms. In adaptive immunity, the response during the second exposure is faster and stronger than the response to the first exposure because the immune system “remembers” the bacteria from the first exposure. For example, following the first exposure to a pathogen, the body can take many days to destroy them. During this time, the pathogen damages the tissues and the immune response produces the symptoms of an illness/disease. Following the second exposure to the same pathogen, the response is rapid and effective. Pathogens are destroyed before any symptoms develop, and the person is said to be immune.

Just like how police and special ops need to coordinate and work together, Innate

and adaptive immunity are intimately linked. Most importantly, mediators

of innate immunity are required to initiate and regulate adaptive immunity.

So who are the key players? and what are the different modes of attack? That's in Part 3

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