"Imitation is not just the sincerest form of flattery - it's the sincerest form of learning." - George Bernard Shaw
Generally speaking, knowledge is the pursuit of all living things. As part of the animal kingdom we educate ourselves for our survival, as do birds learning to fly or lions learning to hunt. Learning even has implications on the molecular level, with increasing evidence pointing to long-term potentiation via the regulation of AMPA and NMDA channels in the synapse. The idea here is that post-synaptic neurons in the brain physically change in response to use over time, correlating use with channel up regulation. Perhaps this is why cramming before a test is less effective than reviewing the material on a regular basis leading up to an exam.
It is clear that how we understand learning is becoming increasingly more and more physical as we learn about physical factors on both the macro and the micro level; and most would agree that that this is good. Learning must of course be a positive experience, and many people nobly spend their lives in the pursuit of knowledge. However, Zheng and Zhang of the Beijing Tiantan Hospital’s department of neurology may warn you that molecular “learning” may not always be as positive as it seems.
One important part of your physiology that clearly learns over time is your immune system. Dendritic cells, macrophages and b-cells circulating in your blood are on the look out for pathogens and intruders. Once one of these cells, known as an antigen presenting cell, comes in contact with a pathogen via specialized and unique receptors on its membrane, the pathogen is rapidly phagocytized and pieces are presented to t-cells, which patrol your blood looking to destroy or mark for destruction any pathogen or pathogen infected cell. In the process of an immune response, b-cells will create b-memory cells that can survive for years or even decades in our system. This is the basis of immunization – your body is exposed to a small amount of pathogen, which elicits an immune response so that in the future if you come in contact with the antigen your body will recognized the problem via these memory cells, initiate an immune attack, and prevent the disease or infection from taking hold.
In theory and in practice this makes a lot of sense, the immune system is able to learn and protect you from the pathogens you are frequently exposed to in your environment, enabling continued survival a reproduction to pass along the genes encoding for this system. The only caveat is that the body needs to ensure it is only responding to harmful pathogens and not harmless molecules we have ingested or worse molecules endogenous to our physiology. Immune cells that learn to respond to molecules endogenous to our pathology is the basis of debilitating autoimmune diseases such as multiple sclerosis, where auto reactive antibodies attack myelin native to the nervous system, wreaking havoc on the present neurons.
The question in MS is often not just how do these auto reactive cells pass the blood brain barrier, but also why do these auto reactive cells stay in the barrier once inside? Zheng and Zhang flush out an idea for how this occurs known as “molecular mimicry”. The idea is that in the process of responding to a pathogen – be it viral or bacterial – the antibodies created may mistake an endogenous molecule for an invading one. Specifically, they look at the interactions between t-cells primed with various viruses, most of which the majority of the population is immunized against, and myelin basic protein or myelin oligodendrocyte glycoprotein, two of the essential proteins involved in the creation and maintenance of integrity within the myelin sheath. As you can imagine, an immune response against either protein in the brain would result in catastrophic effects for the host of the immune system. But how plausible is this idea?
As it turns out, in vitro experiments leading up to this point have shown this idea to be very plausible. A b-cell antibody will only present an amino acid sequence on the order or 10-15 amino acids, making this idea not only appealing but also plausible mathematically. What is so interesting about what Zheng and Zhang are researching is they have produced results of molecular mimicry in vivo using Lewis rats. For those studying molecular mimicry, these results have been illusive, but indicate that molecular mimicry may really underlie the pathology behind autoimmune multiple sclerosis. While the idea of molecular mimicry has been around for a decade or so, scientists are just now beginning to understand the processes a little more in depth. In fact, the solid evidence for molecular mimicry has been so difficult to obtain that the first person to finally crack the code on this maladaptation of learning will almost certainly be in the running for a nobel prize – for molecular biologists and immunologists, the race is on.
Zheng, M. M., & Zhang, X. H. (2014). Cross-reactivity between human cytomegalovirus peptide 981-1003 and myelin oligodendroglia glycoprotein peptide 35-55 in experimental autoimmune encephalomyelitis in lewis rats. Biochemical and Biophysical Research Communications, 443(3), 1118-1123. doi:10.1016/j.bbrc.2013.12.122 [doi]