Introduction

5 Min Read

There's a lot to cover, here's what to expect:

As the second most complex biological system known, the human immune system is a hidden universe of intricate interactions. It contains a collection of specialised cells that move through the vast expanses of the body. They exchange information in finely choreographed ways and fight fiercely against the constant onslaught of invading micro‑organismsA micro-organism is any microscopic form of life - something that is too small to be seen by the naked eye. This can include bacteria, yeast and even mould.. In this article, we will cover the main defences of the innate immune system, explaining the methods and concepts with the aid of easy-to-follow illustrations. We will look at why the immune system exists and why it is so important for your survival. Then investigate the ways it has specialised to prevent entry, as well as the countermeasures to mitigate the ever-improving efforts of the invaders.

So where to start? How about…

What is the Immune System?

Whenever you’ve had a cold, a mild headache or a sore throat, you probably weren't thrilled about it, especially if it not sufficiently bad to skip work or school, but enough to make you feel groggy or sore. You may also think nothing more of it but there is likely more to it than you initially think. Your body is more than just a vessel of your conciousness, it contains continents worth of diverse terrains that, in comparison to a single cell trying to navigate it, are absolutely enormous. And within this space, there are many different structures and processes that all co-exist so that you can continue living. The immune system alone features hundreds of lymph nodesLymph nodes are the laboratories of the immune system where lymph - the clear fluid that circulates in the lymphatic system - is filtered for analysis. spread throughout, that are linked via a system of vessels and cell transport networks as part of the lymphatic systemThe lymphatic system is a complex system with multiple organs. Its functions include: managing excess fluids left in tissue, and fighting infection, whilst preventing cancer.. In addition, at any given time, there are billions of cells patrolling your body, prepared to engage when necessary. With each type of cell having its own specialisation and role in the collective. All of this, and more, in an effort to provide extensive protection to every corner and crevice of your body. But why? What is so important about the immune system that it requires so many resources and such extensive layers of defence?

For a pathogenPathogens are micro-organisms that can cause disease. This includes: certain viruses, bacteria, fungi, protozoans, worms and arthropods., you are a perfect environment full of dense forests and deep resource-filled oceans. You are the sanctuary in the chaos, full of useful resources, with plenty of space to inhabit and make the most out of. More formally, a pathogenPathogens are micro-organisms that can cause disease. This includes: certain viruses, bacteria, fungi, protozoans, worms and arthropods. has a decided preference for certain body tissue, and to infect it, it must gain access first. But your immune system, whist very powerful, is not perfect. To function efficiently, the response needs to be effective, without causing unwarranted collateral damage or excessively draining resources in the process. In cases, there are multiple stages of activation and interactions required before certain cells can attack with their full potential, as without them they could cause irreparable damage every time a minor issue is encountered. In addition, Autoimmune Diseases can cause your own cells (Self) to be detected as foreign substances (Other), resulting in your immune system attacking the cells and tissues they were meant to protect.

But first, we should first consider your own cells, and the micro‑organismsA micro-organism is any microscopic form of life - something that is too small to be seen by the naked eye. This can include bacteria, yeast and even mould. that are trying to invade them.

The Protein Factories: Cells in Context

To begin, it would help to reinforce the understanding of what cells actually are without going into the fine details of biochemistry. As the smallest unit of life, cells are autonomous protein factories that have mini organs; referred to as organelles. Neutrophil AnatomyThey follow their DNA programming that has been moulded through billions of years of natural selection. The two main feature of cells to discuss here are: metabolism and their response to their surroundings. The former links to the collection of chemical processes that take place in the cell, and their ability to absorb nutrients from the surroundings (endocytosis) and exhaust waste products back out (exocytosis). The latter, focusses on their response to stimuli. Cells are dumb in the sense that they have no conscience or feelings - they move and act entirely based on a myriad of biochemical reactions stimulated by external means. Put simply, when these signalling proteins and molecules bind to the complementary receptors on cells, they have the ability to trigger a chain of events within the cell that carry out the instructions, altering their activities. However, for this to be effective, the cells need to be coordinated. So how are these reactions controlled and distributed between a greater number of cells?

Recognition and Response

Looking at the collective system, your immune cells need to be able to identify danger and request reinforcements, otherwise the immune response won’t be very effective. So how do your cells know what to do and where to move?
Although it may sound obvious, the cells in your body can't see, especially as there should be no light reaching inside you - otherwise you will have bigger issues. Senses like hearing are also out of the question, as it requires large, specialised structures; so what about smell? The process of smelling, in humans, involves detecting and recognising tiny particles in the environment, where a greater concentration relates to a stronger smell. This can work, so how does it apply to cells? The cells in your body, and especially within the immune system, can exchange information and commands by releasing chemical messengers, or what are called cytokines.

Cytokines are very small, short-lived proteins that come in many different types for conveying different information. Cells can produce them when needed and they can be used to regulate and coordinate a variety of cell activities. Cytokine release by Immune CellsThis could vary from triggering inflammationInflammation is your body's natural first response to danger. It is induced via inflammatory mediators such as histamine and causes vasodilation (widening blood vessels) in the area. to stimulating active immune cells or even instructing cells when to die. Every cell of the body has an array of receptors to react to different molecules and can secrete at least a few cytokines, where different receptors are specific for different chemical messages. So how does this work? Well, these receptors are the 'noses' in our analogy and by detecting these particles, through biochemistry, the cells can be coerced into particular actions. If only a few receptors are activated, there will be negligible effects, but if most receptors are triggered, then the cell will be highly motivated to take part in the action. In addition, these receptors are spread out around the membrane of the cell providing directionality to the signal. This becomes very important for knowing which direction to travel in.

Speaking of which, chemokines are a subset of cytokines Cytokines are small, short-lived proteins that come in many different types for conveying different information and modulating cell behaviour. that induce what are known as chemotaxis. When chemokines are released, certain cells in close proximity will be attracted along the concentration gradient, making them move towards the source of the emission where the concentration will be the highest. Therefore, when a cell such as a macrophage encounters some bacteria, for example, 'recruitment' chemokinesChemokines are a subset of cytokines that induce chemotaxis. This results in certain cells in proximity being attracted to the source of the emission, thereby 'recruiting' immune cells. can be released to attract nearby Neutrophils to the site so they can aid in eradication.

In terms of cytokinesCytokines are small, short-lived proteins that come in many different types for conveying different information and modulating cell behaviour., they are split into six major 'families', with the main ones that modulate the immune response including Interleukins and Interferons. Interleukins were identified in the 1970s and were named because they were believed to be produced by leukocytesLeukocytes (another name for white blood cells) refers broadly to "the cells of the immune system". to interact with other leukocytesLeukocytes (another name for white blood cells) refers broadly to "the cells of the immune system". - making them inter (between) leukocyte chemicals. In the modern day, interleukins represent a group of naturally occurring proteins that mediate cell communication. These are notably used for activation of your immune cells, allowing them to be more aggressive, and can cause the onset of inflammationInflammation is your body's natural first response to danger. It is induced via inflammatory mediators such as histamine and causes vasodilation (widening blood vessels) in the area. and fever. Interferons, following a similar naming style, interfere with the invading bodies. These are proteins that are produced in response to viral activity within cells, in an attempt to interfere with their proliferation. However, the interferons do not directly inhibit the multiplication of the virus, instead the proteins signal to nearby cells to produce proteins that can then prevent the virus replicating and infecting more cells. This is the quickest, and arguably most important defence against viral activity.

Innate Immunity

10 Min Read

Blocking the Path: Physical Defences

Enveloping most of the body, one of the most notable physical barriers is the skin. A flexible outer cover that, whilst at its thickest is only a few millimetres thick, is the largest and heaviest ‘organ’ of the body, accounting for approximately 1/7th of your weight. It is a living barrier that protects against environmental factors, such as moisture and radiation from the sun, but equally important, it guards from other. It produces a dry and undesirable environment that is designed to be difficult to tunnel through and can kill certain types of micro‑organismsA micro-organism is any microscopic form of life - something that is too small to be seen by the naked eye. This can include bacteria, yeast and even mould. without any active involvement of your immune cells.

As skin is constantly under threat and can get easily damaged or torn, it needs to able to deal with this daily wear and tear, as well as any potential breaches. For this, its main strategy is constant regeneration – your skin works like a conveyor belt of dying cells. In this case, it is a keratinocyte conveyor belt.

Looking at the outermost section of skin, known as the epidermis, near the bottom, we can find the basal layer (or stratum basale if you prefer). Here, around a millimetre deep, is where the conveyor belt starts. A single layer of stem cells is constantly multiplying, churning out identical cells via mitosis, that begin to push upwards as they are produced. This pressure provides the power to our metaphorical conveyor belt. These daughter cells differentiate and become keratinised, making them "keratinocytes". In this process, the cytoplasm they contain gets gradually replaced with keratinFound in hair and nails as well as skin, keratin is a fibrous structural protein that makes substances harden and provides a waterproof layer. and they harden. In addition, the cells squash, getting noticeably flatter. This results in them being packed closely together with neighbouring cells, forming a dense outer wall at the surface. In the process of maturing, the cells depart from the nutrient-supplying blood vessels and begin to die. They then shed from the surface of the skin, through exfoliation, mechanically removing any pathogensPathogens are micro-organisms that can cause disease. This includes: certain viruses, bacteria, fungi, protozoans, worms and arthropods. in the process. These cells are then replaced with even more dying keratinocytes on the conveyor belt at the stratum corneum (surface layer of skin).

In addition to the constant renewal of cell, there are chemical defences that come into play on the surface of the skin. Glands in the skin can secrete oily substances with the ability to kill certain bacteria with an acidic pH. Furthermore, a special enzyme called lysozyme is secreted in the skin, as well as in tears and saliva. It has the ability to break down the outer wall of some bacteria and is used in phagocytosisPhagocytosis is the process in which cells, known as phagocytes, engulf and dismantle foreign bodies. for digestion.

In the absence of skin, other defences are required at main points of entry to the body. Secretions such as mucus, saliva and tears can wash away potential invaders with their antibacterial and antiviral properties. Whilst found at other entry points, a mucous membrane can be located in the respiratory tract, where it traps small particles with its sticky properties. Then ciliaCilia are small hair-like organelles that can move in a coordination manor to provide locomotion that can carry substances such as debris, food or oxygen (depending on the animal). move in a sweeping movement to propel these trapped particles out of the body through the throat and nose.

First Response: Inflammation

Inflammation is the typical first response of your immune system that is activated when tissue is breached, or pathogens are detected; or on a broader scale: when you cut your finger or have an allergic reaction. If your immune system detects danger or damage, whether it is real or perceived, it will cause inflammation. This is the red, hot, swelling found in the area of the wounded or infected tissue, which will feel tender and sensitive. While it may be annoying, it is a critical part of the immune response as its purpose is to restrict the infection and stop it from spreading. In the process it can remove dead or damaged tissue and hasten the arrival of your immune cells.

One way this can be triggered is through certain cytokinesCytokines are small, short-lived proteins that come in many different types for conveying different information and modulating cell behaviour.. So when certain cells, such as Neutrophils or Macrophages, encounter a major issue, they can release their "alert" cytokines to notify nearby immune cells - in this case: Mast Cells. They are large, bloated cells that exist in areas such as the skin and the connective tissue of organs. They produce and store histamine, which is the main cause of inflammation as it is a chemical mediator. When secreted, it can cause the local blood vessels to dilate (or widen). This is referred to as Vasodilation, and has two main consequences: blood flow is increased, and the local blood vessels become more permeable.

More blood flow enhances the delivery of oxygen and nutrients to the affected area, which can hasten the healing of tissue in addition to supplying the cells in battle. The process also creates a build-up of heat in the area, which can speed up the metabolism of your cells, further contributing to healing the wound, and can weaken the infectious micro-organisms as they don't typically like hot environments. On the other hand, with a higher permeability, the vessels leak blood plasmaPlasma is the liquid part of blood that does not contain red and white blood cells, but consists of mostly water, as well as some proteins and other substances. into the affected area. This can also be referred to as exudate, extracellular fluids or tissue fluid, which causes the skin appear reddened and bloated. Additionally, it brings a group of small deadly proteins known as complementComplement are the proteins that make up the complement system. There are over 50 different types, that contribute to a range of functions including: lysis, phagocytosis and inflammation..

Side Note: The Silent Killers of the Complement System

The complement system is comprised of a over 50 different types of proteins that assist in the eradication of unwanted micro‑organismsA micro-organism is any microscopic form of life - something that is too small to be seen by the naked eye. This can include bacteria, yeast and even mould. in complex ways. Most of these proteins are produced in the liver and circulate in the blood as well as bodily fluids that exist outside of cells; referred to as extracellular fluids. Whilst a side note is vastly insufficient to cover the intricacies of complement, there are three main activities worth mentioning: lysis, phagocytosisPhagocytosis is the process in which cells, known as phagocytes, engulf and dismantle foreign bodies. and as an alternative trigger of inflammationInflammation is your body's natural first response to danger. It is induced via inflammatory mediators such as histamine and causes vasodilation (widening blood vessels) in the area.. Lysis, in effect, is the act of punching holes in the membrane of cells. This results in the cytoplasmic content of the micro‑organismA micro-organism is any microscopic form of life - something that is too small to be seen by the naked eye. This can include bacteria, yeast and even mould. being leaked out such that the cell disintegrates. In phagocytosisPhagocytosis is the process in which cells, known as phagocytes, engulf and dismantle foreign bodies., the complement proteins act as opsoninsOpsonins are antibodies or products of the complement system that make foreign cells more susceptible to the process of phagocytosis., where their binding to pathogens can make it easier for phagocytic cells to grab hold of them. Finally, acting as inflammatory mediators, the complement fragments can bind to the lining of small blood vessels and increase their diameter to enhance blood flow.

Leading back to inflammation, immune cells are directed towards the threat with the help of chemotaxisChemotaxis create a chemical concentration gradient that causes nearby immune cells to move towards the source emission., including those caused by certain complement proteins. And with the higher permeability of the blood vessels, immune cells can more easily migrate from the bloodstream to the site of injury.

In the case of an injury to a blood vessel, blood clotting can occur to patch the hole and prevent excessive bleeding. Through the use of coagulation factors, a sequential process can occur that, put simply, creates a protein mesh that traps platelets, blood cells and plasmaPlasma is the liquid part of blood that does not contain red and white blood cells, but consists of mostly water, as well as some proteins and other substances.. As the final stage of coagulation, the mesh contracts, pulling the sides of the hole together and squeezing out any fluid. This makes the wound easier to repair and produces a strong, insoluble barrier. After the repairs have been completed, this structure is degraded and the vessel is restored.

For a more detailed view of the clotting process, in the case of vascular damage, view the following video: