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Our blog just had its first birthday! Yeah! And what would be a better way to celebrate than a new post? And not unlike the very first post, I am going to write about the basics of the immune system – but this time from an evolutionary point of view. Inspired by a recent review on the “Tissue biology perspective on macrophages” in Nature’s January 2016 issue, I got to think about how immune cells came to develop their highly specialised functions.
But that’s the thing: progressive specialisation of cell types is a main trend in evolution. While organisms grow more complex, cells within become more specialised and divide the labour of staying alive between them! So while the one cell of a single cell organism must fulfil all functions needed to survive, more advanced life-forms such as mammals split functions first between different organs but then also, within the different organs, between different cell types. Our brain and central nervous system is the main control centre over our body; our skin is a specialised layer to protect us from our environment; our muscles keep us moving and our intestine is specialised in the uptake of nutrition, that after distribution throughout our body powers each cell.
One example of shared labour within tissues is the brain where neurons carry out the primary function – the transmission of signals (called action potentials) from one cell to the next. Those signals allow us to respond to our environment as they first integrate signals from our eyes or other senses to then give signals to our muscles to respond. To enhance the speed of the signal transmission, so called Schwann cells form myelin sheet around the axons of neurons. Microglia (the macrophages of the brain) on the other hand manage the connections between neurons by a process called synaptic pruning. Both microglia and Schwann cells have supportive functions — neurons could insulate its axon itself but by giving the function to another cell it saves energy and can “concentrate” on its primary function. So as organisms becoming more complex during evolution their cells tend to become more specialised, starting to share functions and work together — leading to more highly specialised cells.
So how does the immune system fit into this system?
The immune system is a specialised support system — whereby all other cells leave the immunological defence from pathogens to the immune cells. This led to the development of two forms of immune defence: the innate and adaptive immune system. While innate immune cells such as macrophages and neutrophils developed mechanisms to recognise common structures on pathogens via so called pattern recognition receptors and became efficient and fast killers of the invaders, adaptive immune cells recognise peptides specific to one pathogens. This specificity makes adaptive immune cells such as T and B cells more effective but also slower compared to the innate immune system. The adaptive immune system developed late during evolution, it is only found in vertebrates. It could only develop after an efficient first defence system (the innate immune system) was in place — because without it organisms would die due to infections being able to spread before a response!
A down side of the highly specialised immune defence is that the body cannot function without immune cells, as no other cell type can effectively defend the body from pathogens. Examples therefore are immunodeficiencies such as SCID, where the patients lack T and (sometimes also) B cells. Untreated the condition is deadly, only transplantations of bone marrow can restore the immune function and help the patients.
Macrophages are special
Macrophages have a special place in the model, as besides their immunological function the cells also have tissue-specific function. Splenic macrophages for examples play a role in recycling heme and iron, while macrophages in bones (osteoclast) can remodel bones and a lack or dysfunction of the cells leads to osteoporosis. In both organs the macrophages play supportive functions, similar to what I described above for the brain. In the spleen, they help red blood cells with their role in the transport of oxygen to all cells of the body by recycling the iron-heme complexes after the red blood cells die. In the bones osteoclast keep the balance of bone formation and removal — with osteoblasts, the cells that build bones as the primary function cells.
In conclusion, macrophages do their part to allow a smooth function of different organs by helping the primary cells in those organs (e.g. neurons) with their functions. And while their role is crucial, they are a “side product” of evolution whereby primary function cells outsourced parts of their role to be more efficient at the main task at hand. This allows better and faster function as a whole organism but leaves the organism with highly specialised cells which cannot perform on their own anymore and where a loss of one cell type causes a disease.