INTRODUCING THE IMMUNE SYSTEM

Medically Reviewed and Updated by Dr. Sony Sherpa (MBBS) - September 23, 2024

The immune system is one of the most sophisticated biological networks in the entire human body. In spite of decades of investigation, new insights about immune function are being discovered each and every day.

Understanding how the immune system works is an often overlooked part of a healthy lifestyle and optimal well-being. This article highlights the known components of a healthy immune system and how all the parts fit together at the cellular level to protect the body from illness.

Immune System Function: What Does the Immune System Do?

The immune system strives to protect the body from any threat, including pathogens, toxins, and any other environmental stressors.

The functions of the immune system can be summed up as follows:

1. Threat Detection
2. Threat Prevention
3. Cellular Preservation
4. Cellular Regeneration

Threat Detection - Separating Self from Non-Self

Protection from the external environment is essential for our survival. Without it, contact with the outside world can pose threats to our well-being. To ensure this protection, the immune system is expertly designed to detect and respond to potential threats.

Many people don't realize that the immune system serves as a barrier between the body and the external environment. Without it, the body would struggle to distinguish between itself and foreign substances.

Threat Prevention - Finding the Winning Strategy

Once a threat has been detected, the immune system quickly proceeds to understand the nature of the threat and eradicate it.

Threats are typically contained and chemically broken down before being eliminated from the body. Each threat poses different challenges for the immune system to overcome, with some being easier to handle than others. After working at it, the immune system is eventually successful and is able to store the winning strategy for next time.

Through continuous immune surveillance, all areas of the body are kept free of dangerous matter, and safety is maintained at all times.

Cellular Preservation - Keeping Calm Through Conservation

A healthy immune system preserves nearby cells by maintaining a balanced response to a threat. It also attempts to isolate the threat, keeping the overall damage to a minimum.

Nutrients help the immune system to function optimally and maintain the balance between preservation and destruction.

During an immune response, supporting immune components help to regulate and conserve cellular nutrients and essential by-products. Nutrients serve as the foundational building blocks for many compounds produced by the immune system and are also utilized directly in various defensive functions.

Cellular Regeneration – New Growth After the Storm

The immune system is more than just a security system – it’s also vital for cellular regeneration and the recovery of an organism.

In addition to its well-known role in defending against pathogens, the immune system performs several crucial but lesser-known functions. It aids in wound healing, helps remove various toxins from the body, and supports healthy cell maintenance by eliminating damaged or malfunctioning cells. These activities are essential for promoting new cell growth, tissue regeneration, and overall health.

Much emphasis is placed on either enhancing or suppressing the defensive aspects of the immune system. However, neglecting the regenerative aspects of immunity can be likened to having a gun without a safety switch—both dangerous and incomplete.

There Are Two Sides to the Immune System

The immune system is usually classified into two main branches: the innate and adaptive immune systems. Each branch has macro and micro components that work in unison to protect the body. [1]

Innate Immunity

As the name suggests, innate immunity is the innate or in-built part of the immune system that is native to every organism from birth. The innate immune system is our first line of defense, acting first and throughout the entirety of every threatening situation. [2]

Each cell harbors its own innate immunity, being created with in-built safety mechanisms that help to keep trouble at bay. An example includes raising the temperature inside the cell in order to neutralize a pathogen, creating a fever in the process. Furthermore, the innate immune system is home to a few specialized white blood cells that patrol outside of the lymphatic system in all other bodily tissues. The skin and the gut microbiome are also a part of innate immunity, serving as frontline barriers of defense between the body and the environment.

The innate immune system deals with threats before they enter the deeper compartments of the body. However, if the innate response proves to be inadequate, then the innate immune system activates the adaptive immune system.

Components of the Innate Immune System

Below is a discussion of the main innate immune system components aligned with its four fundamental functions.

1. Detection

Cells are experts when it comes to sorting through all the microscopic particles they are exposed to every day.

The innate immune system allows for all cells, including immune cells, to pick up on abnormal activity in or around the cell. Once something abnormal is detected, the cell takes an action appropriate to the nature of the abnormality. If it closely resembles a previous threat on a molecular level, the cell will start to initiate mild prevention and preservation measures, such as raising the temperature and signaling to immune cells that there is a danger.

The following two mechanisms outline the way basic cellular absorption and metabolism form part of our innate immune system:

• Cell Receptors. Receptors are like harbors that wait for cargo ships to dock. When a molecule can fit into the receptor, it is taken up into the cell. If a molecule jams a receptor or struggles to make it through, the cell will likely signal for further immune investigation and damage control. Receptors are also able to detect any molecular configuration or pattern that resembles a previous threat. Once a threat has been detected, the cell’s innate responses will act in accordance with the situation.[3]
• Sensing Molecules. If something unknown managed to slip through the cell’s membrane via a receptor or otherwise, the cell has a few tricks left in order to detect a threat. Each cell has innate sensing molecules that line the interior. Similar to receptors, these molecules are waiting for the right molecule to bind with them and carry out a process in the cell. When a molecular pattern associated with damage or pathogenic activity binds to a sensing molecule, it triggers a chain reaction that initiates an appropriate innate and/or adaptive immune response.[4]
• Innate Immune Cells on Patrol. Macrophages, phagocytes, and dendritic cells patrol tissues outside of the lymphatic system for anything irregular. All three of these cells are known as antigen-presenting cells. They have the ability to collect samples of foreign proteins (antigens) and present them to adaptive immune cells to make them aware of the threat. Macrophages and phagocytes like to engulf antigens, while dendritic cells have long arms that they use to reach into places and collect them. Dendritic cells are mostly found investigating the gut microbiome, testing frequently to make sure all is in order. The other two can be seen patrolling all tissues of the body.

2. Prevention

One of the first ports of call for preventing pathogenic invasion or some other threat is signaling the adaptive immune system. Here are some of the main ways that the innate immune system does this:

• Inflammation. Inflammation is actually a rather broad term that refers to groups of molecules that act as cell signals within the immune system to perpetuate the inflammatory response[5]. When the innate immune system encounters a threat, the cell will generate the appropriate inflammatory molecules that alert to the type of danger and the action required.
• Oxidative stress, free radicals, and the remains of dead or damaged cells also act as immune cell signals that help to coordinate an appropriate response. Too much inflammation without immune moderation can lead to extreme responses and excessive damage. Chronic excessive inflammation tends to refer to an under or overactive immune profile and is often an indication of chronic disease[6].
• Oxidative Stress and Free Radicals. If the cell is under serious attack, it will begin to generate lots of oxidative stress via the mitochondria[7], which in turn creates free radical levels and increases the toxicity of the cell.[8] Free radicals are rogue ionic particles that require more electrons to complete their outer valence shell in order to neutralize their charge.
• When let loose, they wreak havoc, ripping out electrons from any viable source. Both the cell and the threat are punctured in the process. In the event of free radical overload, the cell becomes so damaged that it is forced to die off. Some pathogens take advantage of this and interfere with the cell’s innate immune defenses in order to promote their agenda. Reactive oxygen species and reactive nitrogen species are the main forms of free radicals released as a result of oxidative stress.
• The Complement System. This is an intricate innate mechanism that comprises more than 30 unique proteins that are found freely in the bloodstream or on cell membranes. These proteins can give rise to multiple unique protection mechanisms when activated in response to danger. Common functions of this system include alerting and activating phagocytic cells, such as macrophages, and giving all cells the innate ability to generate their own antimicrobial toxins.[9]
• Raising Temperature. Cells may start to use energy to generate heat in order to stifle a detected threat. Raising the temperature inside the cell starts to denature (cook) proteins and enzymes, which serve to break down foreign matter. This is essentially what is happening during a fever or when an inflamed area feels hot.
• In the case of a fever, the whole body is alerted to a threat and many of the cells work in unison to raise and lower the temperature. Heat shock proteins are also generated when the temperature is increased, which further aids the immune in handling an infection.[10]
• Apoptosis. Apoptosis is the term for programmed cell death. There are other types of cell death; however, apoptosis is the form in which the cell willingly self-destructs. When a cell initiates cell death, it is usually either for protection or regeneration. In the former case, apoptosis contains and destroys a serious threat for clearance from the body when all else fails[11]. Large amounts of oxidative stress can get the cell to initiate apoptosis, as can immune cells[12], certain cellular triggers, or any well-known threat that is capable of inducing dangerously high levels of inflammation.
• Natural Killer Cells. Some viruses have developed the ability to stifle the innate responses of their host cells, including the cell’s ability to initiate apoptosis. Furthermore, many viruses “write” their genetic material into the DNA code of host cells. Every cell that divides thereafter will be contaminated with viral material that allows for more of the same immune suppression.
• Natural killer cells are innate immune sentinels committed to removing these types of infected cells and are constantly surveying the body for opportunities to do so. In this way, optimal tissue growth and regeneration can take place, free from viral tampering and faulty cell progeny.[13]
• Phagocytosis. Macrophages and other phagocytes attempt to engulf threats whole and “digest” them through powerful chemical means.

3. Preservation

This part of innate immune function strives to keep the overall immune response stable and sustained. The cells, with their innate abilities, work together with specialized adaptive immune cells to keep inflammatory damage brief, contained, and to a minimum. Here are three ways in which immune preservation is achieved:

• Channeling Cellular Energy into Immune Function. When dealing with a threat, the cell stops any cellular functions that are irrelevant to the situation and channels all excess energy reserves toward helping the immune system. The mitochondria are responsible for producing the energy that powers everything a cell does in the form of ATP. Mitochondria are able to move around inside cells and are shuttled off along with extra ATP to the part of the cell that is experiencing a safety breach.[14]
• Antioxidant Production and Conservation. If there are enough nutrients available, the innate part of each cell will start to up the production of cellular antioxidants, such as glutathione, catalase, and superoxide dismutase. Antioxidants counter the damage done by free radicals by binding to and neutralizing them, rendering them non-reactive. Some dietary antioxidants, like Vitamin E and C, are stored by cells in order to protect and conserve the ones they make. In this way, energy, nutrients, and damage to the cells are greatly spared, and the immune system’s effectiveness is enhanced.[15]
• Nourishing Adaptive Immune Cells. The innate immune system also helps to fast-track immune responses by keeping adaptive immune cells well-nourished. With some support in the form of growth factors and other sustaining nutrients, immune cells multiply at much higher speeds and function at optimum capacity.

4. Regeneration

 The immune system is highly involved in the process of regeneration.[16] After receiving an immune offense such as a wound or an infection, the affected area is left vulnerable and needs to be restored to ensure the body remains protected.[17]

The following are ways in which the innate immune system facilitates regeneration:

• Apoptosis. Cell death or apoptosis is a natural innate immune process in which a cell initiates its own demise. This is essential for the growth of new cells in a tissue and for weeding out any deformed or malfunctioning cells[18]. If a cell is too damaged after an immune event, the cell can choose to initiate apoptosis in order to make way for healthy, viable cells.
• If a damaged or dysfunctional cell refuses to commit apoptosis, surrounding cells and/or the afflicted cell will release chemical signals that alert the appropriate immune cells to irregular activity. Adaptive immune cells will then get involved, ensuring that the cell dies off. In the event that the innate responses of the cell are silenced due to viral interference, natural killer cells will intervene to cause the cell to die off.
• Removal of Debris. Immune cells work responsively to clean up during and after an immune offense has taken place. Cell debris and toxins are engulfed by immune cells before being broken down for convenient removal from the body. This makes way for new growth and minimizes further damage.
• Stem cell Activation. Stem cells are one of the main driving forces behind all bodily regeneration, and research has revealed that they recruit relevant immune cells to areas that are in dire need of repair. Once the immune cells arrive, they activate and regulate the stem cells through the release of growth factors. These growth factors are vital for the activation, growth, differentiation, and survival of the stem cells, which eventually replenish the wounded area. In this way, tissue is repaired, and homeostasis is re-established.[19]

5. Gut Microbiome

The gut, skin, and lungs are the first points of contact that the body has with the external environment, and as a result, they display the highest levels of immune activity on average.

To cope with the large assortment of foreign matter that these sites are exposed to on a daily basis, the body has evolved to work symbiotically with beneficial microbes. Trillions of probiotic bacteria line the gut, skin, and lungs, forming an innate “firewall” that blocks the intrusion of pathogens and other problematic particles. [20]

The gut microbiome is the most extensively researched out of all of these microbial ecosystems. Being home to the largest amount of bacteria in the body, it serves more complex functions than any other bodily microbiome, contributing heavily to all basic immune functions, cellular energy metabolism, and nutrient absorption. Here are some of the ways the gut microbiome forms part of the innate immune system:

• Immune Cross-Talk. The bacteria in the gut let the immune system know when something threatens their survival via emitting their own distress signals. This causes the immune system to jump into action, defending any vulnerable areas and helping the gut to deal with foreign invasion. [21]
• Microbial Competition. One of the most important aspects of innate immunity is the passive protection provided by inter-microbial competition. A healthy gut is teeming with beneficial microbes that leave no space or resources for pathogenic competitors to find a home or make their way further into the body. [22]
• Passive Shielding. The cells in the gut secrete mucins to maintain a double layer of mucous in which probiotic bacteria are happily housed. This double mucous layer protects the sensitive skin cells that compose the digestive tract, acting as an additional passive barrier of defense. The mucous layer also serves to trap toxins and helps to keep things moving.
• Probiotic Defenses. Good bacteria have their own innate defense systems and come equipped with unique strategies for dealing with pathogenic intrusion. Some of these systems allow them to release toxins that either harm pathogens or make the environment inhospitable toward them. [23]
• Nutrient Production. The gut microbiome is actively involved in breaking down all matter that passes through the digestive tract. They secrete enzymes our human cells do not possess and break down food into basic building blocks so that gut cells can absorb the nutrients. A lot of the nutrients secreted by the gut microbiome act to fuel, nourish, and replenish all cells of the body, including immune cells. [24]
• Antioxidant Storage. Vitamin A and other antioxidant nutrients prove to be important ingredients in successful immunity. Immune cells can be found taking these nutrients and storing them away in various tissues, such as in the liver and the lining of the colon. Good gut bacteria take dietary vitamin A and convert it into the right forms for optimal absorption and storage.[25] The bacteria themselves also act as nutrient reservoirs, releasing their nutritious contents when they die off during an immune offense. 
• Toxin Conversion and Removal. The gut microbiome plays a big role in neutralizing and removing toxins from the body. Differing strategies exist amongst different populations. Some bacteria engulf the toxins and keep them contained until they themselves are excreted with fecal matter. Other strains process toxins, converting them into a safer or even non-toxic form for easy elimination.[26] These mechanisms help the immune system to keep the body clean during and after a security breach.

Adaptive Immunity

Adaptive immunity is our second line of defense and tends to only get involved when activated by the innate immune system. This usually occurs only if the innate response fails to contain a threat the first time.[27]

Other names for adaptive immunity are specific immunity and acquired immunity. The body is not inherently born with this type of immunity. Instead, we acquire it as we mature. The adaptive immune systems of infants and young children are still developing, which is why they are usually at a higher risk for infection mortality than the general population. Unlike the innate immune system, the adaptive immune response is highly specific.[28]

Adaptive immunity is responsible for the creation and maturation of adaptive immune cells, surveying the body for threats via the lymphatic system and bloodstream, learning from previous threats to enhance immune responses, and obliterating any threats it comes across.

T and B lymphocytes make up the majority of cells that form part of the adaptive immune system, also known as T cells and B cells. The lymphatic system is also a part of our adaptive immunity, constituting lymph glands, the thymus, the spleen, and the appendix.

Components of the Adaptive Immune System

The below points describe the main aspects of adaptive immunity in line with base immune function.

1. Detection

The adaptive immune system can detect threats just like the innate immune system; however, it is often activated as a result of innate detection. Here are some of the ways that the adaptive immune system detects specific threats before dealing with them:

• Cell Receptors. Just like all cells, adaptive immune cells have cell receptors that can sense molecular patterns associated with recognized pathogens or past damage. The difference is that adaptive immune cells are specifically primed for unique threats, whereas innate sensing mechanisms are more generalized.
• Antigen Presenting Cells. B cells belong to a group of cells known as antigen-presenting cells.[29] An antigen is another word for a foreign, threatening protein. When the innate immune system picks up foreign material, it usually delivers it to a B cell. When a B cell recognizes a threat, it changes form and starts to make antibodies for that antigen, which counteracts the threat.
• Major Histocompatibility Complexes (MHC). This is a term used to describe a set of genes that encode the surface proteins of nearly all cells. The surface proteins describe to the immune system if the cell is self or non-self, as well as if a threat has been detected. MHCs accept foreign proteins from innate immune cells and can be read by adaptive immune cells, thereafter activating the adaptive immune in response to pathogens, allergens, or faulty cell activity.[30]
• Systemic Patrol. B cells and T cells patrol the lymphatic system and the bloodstream for threats. These two systems connect the entire body, also allowing easy access to the innate immune system of any bodily compartment. When an antigen is recognized as threatening, a primary adaptive response is initiated.

2. Adaptive Immune Cell Maturation and Memory

All adaptive immune cells undergo different transformations in order to perform specialized protective functions. T cells and B cells start off as naïve cells and become effector cells upon immune activation. A small subset of effector T cells will live on indefinitely as memory T cells.

• Naïve cells are immature or non-specialized B and T cells that mature into effector cells once the immune has identified a threat. A small number of naive cells are in constant circulation, as are memory T cells.
• Memory T cells each hold a memory bank that instructs the cell on how to deal with a specific threat that it previously encountered. If a memory T cell encounters the specific antigen to which it is primed, it alerts the naïve cells to the danger and causes them to mature into copies.
• Effector cells are mature adaptive immune cells that are primed for dealing with one specific threat. The majority of effector cells die off after an immune offense has taken place. Some effector T cells remain behind and add to the pool of memory T cells, holding the precise configuration for how to best respond to the specific threat to which they were primed.

If the immune system has never encountered the threat before, the naïve cells mature into effector cells that best match the scenario. More cells are produced and matured until a winning strategy is achieved and the threat is contained. 

3. Prevention

The adaptive immune system has two main responses to any given scenario: the humoral immune response and the cell-mediated immune response.[31]

Humoral immunity revolves around the activity of B cells and antibody production:

• Antibodies. Antibodies are proteins produced by the immune system to recognize and bind to antigens—foreign substances that can be harmful, such as pathogens (bacteria, viruses), their toxins, food allergens, or other potentially dangerous molecules. When an antibody encounters an antigen, it binds to it, which helps neutralize the antigen and facilitates its removal or destruction by other immune system components.

Cell-mediated immunity accounts for T cell activity and includes[32]:

• Clonal Selection and Expansion. As described above, T cells mature from naïve cells into effector cells thanks to encountering an antigen or in response to T memory cells that have encountered their niche antigen. Effector T cells can become helper T cells or cytotoxic T cells – the former balances immune responses while the latter destroys target threats.
• Immunotoxins. Cytotoxic T cells have the ability to emit toxins that can break down infectious or hazardous material as well as infected or faulty cells.

4. Preservation

The adaptive immune system preserves cells by isolating threats and sustaining swift immune activity. Here are a few ways in which it does this:

• Growth Factors. Some of the products released by T and B cells act as growth factors, speeding up their proliferation and enhancing the swiftness of the response.
• Keeping Threats Contained. The adaptive immune system tries to keep threats contained to their main areas of activity to avoid unnecessary destruction. Helper T cells are particularly geared for this type of activity. If the body is experiencing a toxin overload, the adaptive immune system may initiate an allergic reaction in which the toxins are stored in nearby tissues for later processing.
• Growth Inhibiting Factors. Adaptive immune cells can release growth-inhibiting factors to limit the proliferation of normal cells in areas affected by immune response. This mechanism helps prevent the unnecessary use of resources on tissue regeneration in regions where it is likely to be damaged by the immune reaction. These growth-inhibiting factors act temporarily and specifically, without causing damage to normal cells or interfering with the growth factors necessary for immune cell proliferation.
• Adaptive Immune Memory. The healthy immune system recognizes and remembers previous threats, theoretically acting swifter each time to correct an issue, as described above. This memory is what allows for the adaptive immune system to learn from past mistakes, be evermore threat-specific, and better its protective strategies.[33] While the innate immune system also has its own memory[34], it’s not nearly as specific as adaptive memory.

5. Regeneration

During a full-blown adaptive immune response, regeneration is not possible. As the immune system makes progress on lifting the danger, the adaptive immune system slowly shifts its response from offense to defense, allowing for regeneration to occur. Most regenerative processes are carried out by the innate immune system as a result, with a few exceptions:

• Lymphatic Collection and Drainage. All areas of the body are either connected to the bloodstream or lymphatic system. When a threat is contained to an area, the immune system starts to demolish it and clear it from the area into the nearest blood vessel or lymph node. Ultimately, the blood supply and lymphatic system connect, allowing for optimal elimination to be achieved. This helps to make way for future regeneration.
• Ensuring Safe Wound Healing and Repair. The adaptive immune system plays a crucial role in protecting cells at the site of an open wound and aiding in the healing process. However, excessive inflammatory activity can interfere with wound healing.[35] Certain helper T cells suppress inflammation and help to activate stem cells, promoting the healing process.[36]

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