It is perhaps the most remarkable security system known to man; an intricate, ingenious and extraordinarily efficient series of defence mechanisms to fight off an extreme number of hostile threats, each with their own shape, size, composition and subversive character. It is the immune system and its remarkable defence mechanisms that ensure the vast majority of us resist and fight off infectious agents, allowing most of us to remain disease-free throughout our lives.
At the heart of this system is a multi-layered defence mechanism and a conglomerate of cells, each playing its own special role within a series of highly effective systems to deal with anything deemed to be an unwelcome intruder. Indeed the ability to recognise what is foreign is central to the function of the immune system, for that is what the 24 hour surveillance system within us does, monitoring the integrity of our tissues. It has two basic roles: Firstly to recognise all foreign substances and organisms that have penetrated through our first layer of defence – our natural physical firewalls (e.g. the skin and mucosal surfaces) and secondly to act in concert to eliminate and neutralise the threats.
Our firewall does more than simply act as a physical barrier to the external world replete with threats. Lactic and fatty acids in sweat generate a low pH which acts as a bactericidal solution. Other open paths of entry also create a hostile bactericidal environment, such as the acid in gastric juice. The bacterial flora of the body can also suppress the growth of potentially pathogenic bacteria through competition for essential nutrients and the use of inhibitory substances.
Our second layer of defence – the innate immune system – are the sentinels such as macrophages and neutrophils, standing guard as our intrusion detection system, looking out for the detection of particular molecular patterns that are associated with infectious agents. Pattern recognition receptors provide intelligence on the threat, revealing the precise nature and location of infection, fingerprinting the pathogen. The innate immune system stands guard, ready to destroy infectious agents from the moment they enter our bodies.
The most sophisticated threat defence mechanism lies within the third layer of our defence: our adaptive immune system. This layer, comprised of cell types such as cytotoxic T-cells and natural killer (NK) cells, excels in what is termed immunological memory: the ability to remember previous infectious threats in order to maintain a reserve of cells capable of swiftly responding to and eliminating a threat by the same type of microbe. It also acts as a more powerful targeted weapon in situations where the innate response fails to deal with infectious threats. Responding to a more advanced threat with a highly tailored solution requires time, which is why it may typically take 4-5 days for the innate immune system to respond to such intruders. Both the innate and adaptive immune systems work in concert to effectively deal with infectious agents through their actions and the exchange of information.
Responding to threats can also be metabolically costly (to make new proteins and cells), which is precisely why proportionality must play a critical role. Too eager a response, and not only is energy unnecessarily wasted, but healthy tissue of the self may also be destroyed. As a result, the immune system must carefully assess the threat at the initial stages of infection and use the most appropriate response from the wide variety of weapons at its disposal. There is no one size fits all response; Different types of infection (viral, bacterial, parasite) require different tailored responses in order to effectively deal with a threat. Moreover, each of these threats have evolved to use different strategies against us and evade detection. Some aim to steal nutrients to nourish their own tissues. Others, like viruses, invade our cells. Responding to a virus inside a cell requires a significantly different weapon to a bacterial infection outside of a cell. In the latter case the infected cell has to be killed and engulfed or contained in a way that minimises the escape of the pathogen hiding within. For these more advanced viral threats, our immune system uses the special cell types in its armoury: cytotoxic T-cells and NK cells, which are able to detect and kill infected cells. Engaged in an arms race with our immune systems, viruses and bacteria can mutate at exceptional rates, leaving us vulnerable if the genes responsible for our defence fail to rapidly mutate in response.
Even if a pathogen evades our surveillance mechanism, a growing body of evidence suggests that our immune system looks out for other unusual secondary signs of danger, such as any unnatural tissue damage leading to cell death. This too can trigger and activate the immune system. This type of damage results in the creation of molecular patterns that act as danger signals. In this way if a pathogen initially evades direct detection, its presence will eventually be betrayed if it provokes such cell death.
Among the most critical features of this astounding system is the ability of the cells to communicate with one another and this is done through protein signals (cytokines) released by cells in response to the detection of molecular patterns deemed as threats. Like a bugle call, this alerts other cells into joining the fight. Identified threats are also tagged for removal by molecules called opsonins.
All of this is an incredibly vast operation, with the average human requiring a daily production of four hundred billion of these cell types (leukocytes) involved in securing us from a wide array of external threats. Much of this prodigious production rate is a result of the short half-lives of these cells, but without these noble microscopic warriors protecting us within an ingenious security structure, our world would be a great deal less secure and indeed impossible to exist in.
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