Like the nervous or the cardiovascular system, the immune system pervades the entire organism. It forms organs, including lymph nodes, thymus, spleen. Immune cells patrol the body through blood and lymph vessels and populate immune organs.
The immune system is involved in a variety of diseases:
- Protection against microorganisms & prevention via vaccination
- Allergies – pathological overreactions of the immune system increase continuously
- Autoimmune diseases such as rheumatoid arthritis, diabetes, or multiple sclerosis
- Immuno-oncology is the area of hope for cancer treatment
- Transplants require control of the immune system in order to prevent rejection
- Wound healing is an area in which the immune system makes important contributions
- Diseases of the cardiovascular system, in particular atherosclerosis, are influenced by the immune system
- Neurodegenerative diseases are influenced positively as well as negatively by immune cells in the brain
- Pregnancy – of course not a disease but of undeniably enormous importance
Without the immune system live is unthinkable! This becomes clear in congenital or acquired immunodeficiencies – AIDS, but also in cancer patients, whose immune system is destroyed by chemotherapy. Without a functioning immune system, patients often die from trivial infectious diseases despite intensive treatment with the most powerful antibiotics. Faulty regulation of immunological defense mechanisms, as is the case with autoimmune diseases, can lead to life-threatening diseases. Patients receiving immunosuppressive treatment after organ transplantation develop cancer significantly more often than the average healthy person – a key indicator that the immune system protects us from cancer.
In recent years, modern biomedical research has succeeded in increasingly understanding the function of the immune system. More and more often it is possible to manipulate the immune system for therapeutic purposes. Nevertheless, we are still far from having a complete picture of the functioning of the immune system.
Introduction
Every day battles rage in your body – a constant change of war and peace. Sometimes you perceive the effects of these hostilities – you are sick. In most cases, however, you do not notice anything of any military conflicts.
What are these battles fought for? To ward off threats by foreigners – microorganisms; or to contain the danger emanating from alienated cells – tumor cells; there are always civil wars – autoimmune diseases in which the immune system attacks one’s own organism; sometimes your immune army fires huge guns at harmless sparrows – allergies; it happens that suddenly a foreign organ emerges in the body that supposedly has to be eliminated – transplantation; cardiovascular and neurology diseases are modulated and maybe caused by the immune system; and in the body of women, a living being can grow, which bears half of its own identifying tissue features, but on the other half that of a second person, and thus half of it is foreign – pregnancy.
In the battles raging in your body the cells of your defensive army, the immune system, oppose the troops of foreign invaders, often hostile microbes or higher cells. Defenders and attackers cross their molecular blades.
In the early years of life, your immune system learns to distinguish friend from enemy and dangerous from harmless. The immune system has ground forces, navy, air force; it uses different types of weapons: infantry, cavalry, pioneers, etc. It engages in hand to hand combat but uses snipers as well; it conducts espionage and protects against counterintelligence. Strategic and weapon training is necessary throughout life. The immune system uses a sophisticated logistics and
communication system to ensure the supply of the troops and to maintain the chain of command from the general staff to officers to the fighting troops. In a huge database collected information and acquired knowledge about the microbial world is stored out there and the stored data can be retrieved at any time.
White blood cells – immune cells – leukocytes
We distinguish between innate and acquired/adaptive immune system. As these names suggest, we are born with the one whereas we acquire the other during the course of life by dealing with what is in us, on us, and all around us. The innate immune system is the evolutionary older part, which is also found in lower organisms. The mechanisms of defense consist primarily in eating up and as dangerous-classified material – phagocytosis. The acquired/adaptive immune system uses specific recognition structures, antigen receptors, in order to detect the causes of a threatening situation and render it harmless. Innate and acquired immune systems do not work independently in higher organisms, but assist each other in defending the body.
The leucocytes of the innate immune system include the dendritic cells, which are essential in triggering and controlling a defense reaction; you could call them the generals of the defense army of our body. They form the interface of communication between innate and acquired immune systems. Other representatives of the cells of the innate immune system are granulocytes, macrophages, and a few more, which will not be discussed here. An important task of the innate immune system’s defense cells is the uptake of all sorts of material from their environment. These cells are called phagocytes. The dendritic cells can distinguish between cells that died in a natural-physiological way (apoptosis) from cells that died under pathological conditions (necrosis). Necrotic cell death is interpreted by the dendritic cells as a danger signal and leads to the activation of defense reactions by the acquired immune system.
If the cause of cell death is a microbial infection – viruses, bacteria, fungi – the microorganisms or their fragments are eliminated by phagocytosis. In particular, the dendritic cells recognize special molecules of the microorganisms that do not occur in higher organisms, and categorize them as microbial danger signals. When encountering a danger signal, the dendritic cells activate T-lymphocytes, i.e. cells of the acquired immune system, in order – in addition to the non-specific defense mechanisms of the innate immune system – to mobilize the specific defense mechanisms of the acquired immune system just as in the case of necrotic cell death.
The innate immune system initiates the activity of the acquired immune system. The dendritic cells are at the interface of innate and acquired immunity; from this interface they orchestrate the immune response. I will continue to consider dendritic cells the generals of the immune system. In this capacity they communicate with mainly with T lymphocytes, the so-called helper T lymphocytes, which in this military style description represent the officers of the immune system. The helper T lymphocytes on the other hand, interact with other lymphocytes representing the two arms of the fighting force: cytotoxic T lymphocytes and antibody-producing B lymphocytes. The former can recognize and destroy target cells via their antigen-specific receptors; they are therefore also – not quite correctly – called killer cells or killer T cells. The B lymphocytes secrete their antigen-specific receptors as antibodies in large quantities. The released antibodies bind to microorganisms and other antigens to inactivate or mark them for uptake by phagocytes. One might consider the cytotoxic T lymphocytes as hand-to-hand combatants with sword or ax, while the B lymphocytes are the shooters who hurtle volleys of spears and arrows at the enemy. An interesting feature is that these defense weapons find their own target, perhaps more comparable to modern long-range weapons.
Antigen receptor
A characteristic of lymphocytes of the adaptive immune system is their antigen receptor. The antigen receptors of T and B cells are formed in unbelievably large numbers and varieties, but purely by chance. Amongst these multiple lymphocytes, each carrying a receptor of a different specificity, there are also those that can interact with autoantigens. To eliminate such autoreactive T cells, they are subjected to a selection mechanism in a not yet fully mature state before being released into the organism. The thymus assumes the task of sorting and of performing the basic training of the later officers and soldiers of the defense army of our body; we speak of central tolerance. T cells that interact with an autoantigen can not pass the thymus; they are phased out, which means that the programmed cell death is triggered in auto reactive T lymphocytes.
In addition to central thymic tolerance, dendritic cells provide a second protective mechanism against autoimmunity, peripheral tolerance. This may sound paradoxical at first, as I have previously described the dendritic cells as the generals of the immune army, sending their soldiers into battle. But a general must be able to lead his troops in retreat or use it for peacekeeping measures. Of particular importance is the peripheral tolerance in connection with the control of tumor cells – or with their failure and thus the uncontrolled proliferation of cells still have these alienated, so mutated, autoantigens that can be recognized by the immune system in principle. How it comes to this I will explain a little later.
The troops that are recruited by the Dendritic cells before a battle must be released after the end of the fight. In order to prevent marauding mercenaries whose war is over, murdering and pestaging through the organism – so trigger autoimmune reactions – is triggered in the no longer needed soldiers of the programmed cell death. At this point, the analogy between the immune system and the army ends: the victorious soldiers of a real army return to their homeland and are celebrated as heroes. Such sentimentality does not afford the immune system: all that remains of a winning battle is the memory – in the literal sense. From a small number of veterans of the won battle, helper T-cell officers, and soldiers of the arms B-cells and cytotoxic T-cells, memory cells are formed; in the other no longer needed lymphocytes the programmed cell death is triggered. The memory cells can remain part of the immune system for many years, possibly even entire life. If it comes to a renewed contact with the same intruder, the defense can be set up very quickly and effectively. Information on how a particular microorganism looks and can be most effectively fought retrieves the immune system from the memory of veterans of past battles. The vaccinations are based on this principle.
Memory
“To light a candle is to cast a shadow.” This is what Ursula K. Le Guin writes in her 1968 fantasy novel “A Wizard of Earthsea.” This also applies to the immune system. In addition to protecting us from threats in our environment, once unleashed the immune system can do a considerable collateral damage. One failed communication or a misunderstanding in the chain of command may cause the immune system to attack healthy tissue; we speak of autoimmune diseases. The security mechanisms available to terminate an immune response are designed to prevent this.
The immune system is not sentimental if heavily armed uncontrolled immune cells become a threat to healthy tissue. The general staff orchestrating and directing the defensive battles ensures that everyone adheres to the rules; improvisation is not permitted. After a battle against an invading force of microbes, marauding groups of retired immune cells could do a lot of mischief. The human veterans of a won battle are celebrated as rescuers and protectors after returning to their barracks. The veterans of a won immune battle do not return! Soldiers who are no longer involved in a combat trigger their self-destruction, programmed cell death, apoptosis.
Only a small group of immune cells are excluded from programmed cell death. These immune cells differentiate into memory cells that can be mobilized very quickly upon renewed contact with the same invader. Since the memory cells know the enemy and its weak points, an effective defense is built up in a very short time. An immune reaction that is led by memory cells can be so fast that you do not perceive it as an illness at all; at most you might recognize mild symptoms. The memory cells destroy the first invading pathogens immediately not even permitting them a chance to multiply sufficiently in your organism to cause damage.
Immunity – a tensed bow
Your immune system is a constantly tensed bow, on whose bowstring the arrows are ready for firing. Not any arrows! Compared to the immune system, the almost infallible bow and arrow skills of Jeremy Renner’s superhero Clint Barton, aka Hawkeye, from the Avenger comics and films seem downright amateurish. In the face of the various types of arrows available to the immune system, Hawkeye would be envious.
At the slightest hint of danger, the immune soldiers release the string of their bow. The arrows with which the immune system defends your organism, rush away. However, the immune system’s constant defensive vigilance causes risks as well. If an army of archers with their arrows readily waiting on the taut bowstring waiting for the command to launch the attack, it can sometimes come to misunderstandings: False alarm leads to overreaching reactions; a banal communication error in the chain of command and the arrows fly through your body; a shooter with sweaty fingers lets the string slip out of his hand; rheumatism relieves an older veteran of the strength to hold the bowstring. Even a superhero like Hawkeye would at some point lose strength if he had to keep his bow taut all the time. In contrast to the immune system, Hawkeye usually wears his bow over his shoulder and his collection of special arrows is in the quiver.
The immune system must be constantly ready to respond to attacks as quickly as possible before intruders can do damage; hence the continuously tensed bow. But the immune system also has to make sure that the proverbial red button is not pressed at the wrong time and place. For this reason, the immune system is constantly using troops for maintaining peace and order. Peacekeepers ensure that the bowstrings remain taut and the arrows are not launched without an external occasion. This may well be surprising: The main task of the immune system is to prevent fighting – immune reactions. That’s why the immune system puts a lot of its resources into peacekeeping.
Sixth sense immune system
The known five senses of our body are part of the nervous system. Some of our senses deal with the physical environment, light – seeing, sound – hearing, mass and structure – touch. Two other sensory organs observe chemical events around us, tasting and smelling – sensory organs, which also serve as quality controls for food and the air we breathe.
In addition to the five senses of the nervous system, you may consider the immune system as our sixth sense. Between the area of tiny chemical and biochemical molecules and the visible, audible or palpable things of our daily lives lies the incredibly complex and diverse world of microorganisms. The inhabitants of this world are too small to hear, see, or touch, but too big to be recognized as chemical events by tasting or smelling. This world of microbes is the domain of the immune system.
Immune system and nervous system are not unlike each other: both communicate with the environment, gather information, make decisions, have memory, and both are integral parts of every tissue in the entire organism. Just like the nervous system, the immune system builds up its own organs: spleen, bone marrow, thymus, lymph nodes.
Irun R. Cohen writes in his book “Tending Adam’s Garden” that the immune system has perceptive skills that – in an emergent process – arise from its complexity. A principle that neuroscientists also attribute to human consciousness. But that does not mean that there is an immunological consciousness; at least nobody has ever claimed to have found one.
Another similarity between the immune system and the nervous system: both work on the principle of the tensed bow. For conducting a signal in a nerve cell, electrically charged particles – ions – are first pumped through the cell membrane of nerve cells, which requires energy. An electrical potential develops at the cell membrane of the nerve cell due to the uneven distribution of electrical charges – an electrical state of tension.
A nerve stimulus is generated and transmitted by opening channels in the outer membrane of a nerve cell. Through these channels, the unequally distributed ions inside and outside the nerve cell flow to the other side of the cell membrane. In this way, the electrical voltage on the membrane discharges. This braking down of charges at the membrane is the signal that is relayed in a nerve cell. Whereas no engird is needed to transmit the signal, the organism uses energy to rebuild the polarized state to be ready for the next signal.