Analysis: the second most complex biological system in the body, your immune system is ready to go into battle for you every day, but it can malfunction
We all have the ability develop immunity to every disease we encounter - yes, that is correct! From the Spanish influenza in 1918 to the current pandemic of Covid-19, to whatever the next troublesome microbe emerges, your body is immune-ready, pre-prepared with millions of immune cells with specific microbe-detecting sensors waiting to be launched in an attack against the new invader.
But how can our immune system know what pathogen is coming down the line? It is thanks to a system of cells and molecules that evolved millions of years ago to guard our bodies and work tirelessly to keep us safe from infectious microbes.
The immune system is the second most complex biological system in the body, second only to the brain. Research over the last 200 years has taught us a lot, and some say that we have only cracked the surface, but those of us that study our immune system - immunologists - feel we've made tremendous advances that have allowed us develop vaccines against major infections, such as COVID-19.
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From RTÉ Radio 1's Today with Claire Byrne, Professor Cliona O'Farrelly, Chair of Comparative Immunology at TCD on your immune system and sleep
The immediate immune response
So how do immunologists explain how we have immunity against a bacteria or virus that we have not yet faced? First, it is important to know that our immune defence system is divided into two battalions. The first is called the innate (immediate) immune response, which is a rapid-responder. The innate immune response consists of a group of immune cells and molecules that are present in our blood from the day we are born. It is constantly on the lookout for any infectious pathogens that might enter our body, and is primed to mount a 'generalised’ attack against them.
You may have heard of some of these general immune cells, often grouped together as white blood cells, consisting of neutrophils, macrophages, monocytes, basophils and eosinophils. These work as a team, each playing a different role to work together to recognise invaders. Immune cells can recognise friend from foe by ‘touching’ the pathogen in their environment and sensing foreign patterns or molecular shapes (called Pathogen Associated Molecular Patterns: PAMPs) common only to bacteria and viruses. Once alerted by PAMPs, the innate cells respond decisively, close in on the pathogen and activate a process of elimination which involves the production of lethal substances.
The adaptive immune response
The second important battalion of the immune system is the adaptive immune system. Unlike the innate immune system which acts like an infantry on the ground, the adaptive immune system is very specific and, as suggested by its name, can adapt to any pathogen to bring in the big guns, antibodies and cells that act like assassins.
From TED-Ed, how does your immune system work?
The adaptive immune system is an incredible defence mechanism that helps protect us from a vast array of pathogens. Unlike the non-specific innate immune system, the adaptive immune system is highly specific and tailor-made to recognise and attack individual pathogens, thanks to the genetic diversity of T and B cells. T and B cells are two types of white blood cells that play a crucial role in the adaptive immune system. Each of these cells has a unique receptor capable of recognising a specific antigen, which is found on the surface of bacteria or virus. Genetic recombination allows T and B cells to generate millions upon millions of different receptors, creating an adaptive immune system that can recognise and attack virtually any pathogen it encounters.
However, the genetic diversity of the adaptive immune system is not just limited to the present. Memory cells generated by the adaptive immune system can retain information about past infections, allowing for a more rapid and effective response in the future. Even if we encounter a pathogen we have never seen before, our adaptive immune system may already have a blueprint for attacking it.
Although highly effective, the adaptive immune response takes longer than the innate immune response. This is because each adaptive immune cell has a specific receptor for each type of invading microbe, requiring them to search the body to find the invading microbe, which can take time. Once activated, adaptive immune cells multiply and create memory cells, allowing for a faster response in the future. However, this process can take between three to seven days to see an effect against the invading pathogen.
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From RTÉ Radio 1's Today with Claire Byrne, Professor Cliona O'Farrelly, Chair of Comparative Immunology at TCD on your immune system and stress
The T and B cell diversity is constantly expanding and adapting to new threats, making the adaptive immune system one of the most sophisticated and powerful defence systems in existence. Although the adaptive immune response takes longer than the innate immune response, its ability to generate memory cells for a faster response in the future is vital for our immune defence.
Thymus
But this is where we run into a problem. If the adaptive immune system can rearrange its genetic code to form so many different receptors, what happens if it accidentally creates a receptor against our own bodies cells? That could be disastrously fatal, right?
Well in fact this happens all the time. However, once the immune cell has been created it undergoes an intense screening process in the specialised organ called the thymus. The thymus is located in the upper chest and it is the screening centre for all immune cells. The thymus puts them through an inspection to ensure they do not recognise their own body self-cells.
Read more: Why are viruses such challenging foes?
If any cells do recognise human self, these immune cells will be killed, and their parts recycled before they can cause any damage. The thymus is so thorough in its screening process that only 2% of cells make it out of the thymus and into circulation, all other cells are recycled. Interestingly, the thymus begins to continuously shrink once we hit puberty, and it is a suggested reason why immunity weakens as we age.
Can the immune system malfunction?
Unfortunately, the answer is yes. In autoimmune conditions, immune cells with receptors against our own body cells do make it out of the thymus. These adaptive immune cells will identify human self-cells as a threat and attack. Examples of autoimmune conditions include type 1 diabetes mellitus which attacks the cells that make insulin, multiple sclerosis which targets the myelin which protects nerve fibres, or Hashimoto's thyroiditis which aims at the cells that make thyroid hormones.
Furthermore, even if the immune system attacks the correct target - the microbes - sometimes this can be too aggressive, and the body becomes collateral damage. When this happens, it can lead to a deadly illness called sepsis. Sepsis is an over-reaction of the immune system, causing a storm of damage to the body. In an effort to kill the invading microbes, the immune system inflicts injury to its own tissues which then become harmed. This leads to inflammation that spirals out of control and once it begins it is very difficult to stop.
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From RTÉ Radio 1's Drivetime, Dr Martina Healy, National Clinical Lead with the HSE Sepsis Programme, talks about the importance of early recognition and treatment of sepsis
While autoimmunity and sepsis are over-reactions of the immune system, it can also under-react. This is known as immunodeficiency. Immunodeficiency can occur as a result of diseases such as common variable immunodeficiency (CVID), or a result of medical treatment such as steroids or chemotherapy. People who have an under-reactive immune system are very vulnerable to infections and may need to take extra precautions day-to-day.
Interestingly, the Molecular Parasitology Laboratory (MPL) at the University of Galway are working towards developing treatments to help people with over-reactive immune systems such as autoimmunity or sepsis. The MPL studies pathogens called parasites that have unique ways of manipulating the immune system. By understanding how parasites interact with the innate and adaptive immune cells we might discover new ways to prevent the immune system from over-reacting, and hence find new ways to treat autoimmune diseases!
International Day of Immunology is April 29th.
The views expressed here are those of the author and do not represent or reflect the views of RTÉ
