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Your immune system is the only thing that stands between your body and the billions of microscopic pathogens that make up our environment. On the other hand, commensal bacteria in the gut are also a crucial part of the body. Sometimes an overblown immune reaction can end up doing more harm than its use.
A common example is sepsis that is mostly a result of a bacterial infection. It can be lethal for people with weakened immune system and was certainly deadly before the time of antibiotics. Curiously, it is not the harm done by bacteria that causes death, but the extensive inflammation of the whole body: in septic shock blood pressure drops, major organs including the kidneys, liver, lungs, and central nervous system stop working and, finally, the host dies.
So clearly, the immune system should assess the threat first and then adjust the strength and length of its reaction proportionally to the danger: bacteria from the body should not be attacked, and a common cold needs to be handled differently than an infection with a deadly virus.
But then how will that decision be made?
The immune system is often compared to the military defending the body – and for good reasons. There are many, many different types of immune cells involved in a complicated network – very much like a chain of command in the army.
Sentinels scout for any signs of foreign invaders among the civil population. If the sentinels find something, they will analyse it and derive intelligence about the invaders. Furthermore, they will also look for circumstances and get alerted if they find any evidence of threat. In such a case they take the gathered intelligence back to headquarters and present it to their commanders. They will also report about the threat. The commanders will evaluate all the information and issue orders to the army to defend the civil population.
Unfortunately, in ‘immunology speak’ all of this sounds a lot more cryptic, but let’s try it:
Antigen Presenting Cells (APCs) scout the tissues for any signs of pathogens among the cells of the body. Pathogens can be viruses, bacteria, protozoa, fungi and worms, but they can also be the body’s own cells in case of cancer. If the APCs find something, they will digest it, and present the antigen derived from the pathogen on the outer surface of the cell. Furthermore, the APCs also engage their sensors searching for Danger Signals, which are unique molecular fragments that are only present in pathogens or cancerous cells, but otherwise absent from the host. If Danger Signals are recognised by their receptors, signalling pathways are triggered, leading to maturation of the APCs (that is the red glow around our cloudy friend). In this process, transcription factors are activated in the nucleus, which will initiate transcription of cytokine molecules that are used for communication between immune cells. The APCs deliver the antigens to the lymph nodes, where they come into contact with T cells specifically recognising that antigen epitope. The cytokines will trigger proliferation of the type of T cells most suitable for dealing with the type of threat. The T cells will coordinate the action of other immune cells. This sounds a lot more complicated, but it is essentially the same.
If you remember a little your high school biology lessons, then there is a fair chance that the antigen/intel bit sounds familiar to you. On the hand, the role of Danger Signals/evidence of threat have only started getting recognised since the turn of the millennium. In fact, they will make all the difference between war and peace! In my next post I’ll write more about the Danger Signals.