Welcome among the ranks of the world’s largest and most efficient army, with millions of soldiers prepared to fight to the death in order to ensure order and safety. Welcome to the immune system, a highly-sophisticated defence apparatus that is the result of millions of years of evolution: accustomed to working under the radar in peacetime, in an emergency it can take to the streets with its tanks and unleash an all-out war.
Its ranks are made up of simple soldiers who are used to close combat, but also of special units and the finest intelligence experts who coordinate complex and targeted actions. All of them belong to the great family of white blood cells and receive the call to enlist in their "birthplace" – our bone marrow. Some are immediately sent out on patrol in our bloodstream and in our tissue, while others are sent to the thymus academy, the gland located in the thorax in front of the trachea, where the most qualified law enforcement officers undergo tough training. Here they mature and learn to recognise the body’s own cells and molecules, so that they can distinguish them with certainty from anything that is foreign and potentially harmful. This is a fundamental lesson which, if not learnt properly, can confuse the roles, triggering dangerous friendly fire with unpredictable consequences.
Having a good nose and quick reflexes is essential for all agents, especially those on patrol: both for granulocytes, which travel along the "highways" of the blood vessels, and for monocytes, which, once they have left the bloodstream, don the uniform of macrophages so that they can patrol the "districts" of our tissue with greater authority. They reach the most dangerous areas, namely the skin and mucous membranes, which are exposed to contact with the outside world, as is the case in the digestive and respiratory tracts. These are the borders that are most often encroached by viruses, bacteria, fungi, parasites and other enemies. All the patrol officers need is a fleeting glance to realise that it is time to act. Among the first to swing into action are the granulocytes - immune cells whose cytoplasm contains granules that are clearly visible under a microscope. As soon as they sense danger, they pounce on the enemy, even if they are not sure of its identity, and devour it on the spot. This mechanism is as fierce as it is established: it is so efficient that evolution has preserved it in invertebrate organisms all the way down to us. Macrophages in our tissue also do this as soon as they smell the traces of chemicals scattered by intruders. However, when it comes to dealing with an insidious virus that can take the cells hostage, much more is needed: the special units of NK (natural killer) cells come into play, recognising the infected cell and, without further ado, fill it with toxic substances that destroy it like explosives. This is also what happens when the cell is not prey to an external enemy but is a rebel itself, breaking the rules and turning into a dangerous tumour.
Up to now we have seen the actions of the sentries of so-called innate immunity, a type of aspecific immunity that is present and active from birth. It is our first line of defence and is very effective, but not always impassable. This is why it is backed up by the ranks of adaptive or specific immunity, whose actions are more targeted and acquired over time thanks to experience. These are true and proper reinforcements that can be summoned by those on the front line: such as, for example, by macrophages, which, after having ingested the enemy, tear it into pieces and then display it on their membranes like insignia on their chest. These molecules, better known as antigens, are a kind of identity card of the captured enemy that is presented to the special agents, called T lymphocytes. Trained in the thymus gland and resident in the "barracks" of the lymph nodes, T lymphocytes can recognise whether the cell presenting the antigen belongs to the immune system, and is therefore a sentry requesting reinforcements, or whether it is a cell of the organ itself that has been attacked or has become cancerous, and hence must be destroyed.
If the cell has to be eliminated, the killer T lymphocytes - snipers with an ultra-precise aim - intervene. If, on the other hand, the cell is a sentry searching for help, the helper T lymphocytes respond. These are the intelligence experts that orchestrate the complex intervention of encircling the enemy and are the ones who call in their specialised colleagues from our bone marrow - B lymphocytes – who, in turn, are the only ones that can transform themselves into plasma cells in order to produce specific weapons against each enemy: antibodies. The antibodies can block the proteins in viruses, by neutralising them, or they can attach themselves to the membranes of the invading bacteria and other micro-organisms so they are more visible to the devouring sentries. While the battle rages on, there are certain B lymphocytes that document every move for future reference: in this way, if the same enemy should reappear, they can recognise it more quickly and then multiply and turn into plasma cells more efficiently. This is exactly the same mechanism that is used by vaccinations in order to prevent infection.
In this sophisticated organisation of the immune system, however, something can go wrong. It may be the case, for example, that the guardians of our body get confused about the identity cards of the enemies and end up labelling substances that are completely harmless as dangerous, such as plant pollen or the proteins in certain foods. Hence, B lymphocytes start producing special antibodies (called IgE) that cause certain granulocytes (basophils) to release their histamine bombs, triggering vasodilation, swelling and inflammation, which form the basis of the typical symptoms of allergic reactions, such as itching and difficulty breathing. At other times, however, it may be the case that T lymphocytes misunderstand the lessons taught at the thymus academy and end up mistaking "honest" cells in the body for rogues to be destroyed: this is how autoimmune diseases develop, such as rheumatoid arthritis, which attacks the joints, or multiple sclerosis, which affects the nervous system. Sometimes it is the enemies themselves (such as the mononucleosis virus or streptococcus bacteria) that mislead the B lymphocytes, making them react to cells in the body.
In addition to getting confused and muddled, the guardians of the immune system can also become lazy and apathetic: this happens, for example, when T lymphocytes leave the thymus academy without having completed their training (primary immunodeficiency), or when they are weakened by malnutrition or the HIV virus that replicates within them (acquired immunodeficiency). In short, every day things happen in the human body that are worthy of an exciting thriller. Are you curious to find out more about them? Then don’t miss the episodes illustrated by Marino Neri, which you can find in this site.