30 Nov 2020
Issue #35: Sensing and responding
Setting it Straight - Issue #35
Written by Nobel Laureate Professor Peter Doherty
The higher vertebrates have two immensely complex (and still partly understood) internal networks that operate to recognise, and respond to, a seemingly limitless diversity of specific challenges to our health and wellbeing (#19). Only one, the nervous system (NS), functions at the level of consciousness, though rational decisions concerning, say, medical interventions, can affect the operation of the other, the immune system (IS). Simplistically, neurological input reflects that chemical/electrical signals travel along nerve fibres following the activation of various sensing receptors located in the eyes, the ears, the nose, the skin (for pain, pressure, heat, cold) and so forth to register in that central processing unit (CPU) we call the brain. The resultant perceptions of pleasure, pain, danger, safety, or some other familiar sensation or situation causes us to make choices expressed via outgoing signals that speed along other nerves to innervate the muscles of, for example, the mouth (smile, grimace) or the legs and arms (fight or flight), leading to a response that seems right for that time and place. Later, we may, as humans, reflect on, even agonise, about the choice we made. Do other animals ever do that? I’ll leave that question to the neuroscientists!
Immunity, the other great, and exquisitely specific detection/response system found in nature is, so far as we are aware, manifests in its most advanced form as the T and B lymphocytes (#22, #33) of the reptiles, the bony fish, the birds and the mammals. Any consciousness we have of an immune response is, of course, registered via the NS. While we may feel pain subsequent to the triggering of pressure receptors in a swollen (due to cell recruitment) lymph node, or may ‘be off’ as a consequence of some IS product (Interleukin-1 makes us sleepy) circulating in the blood, we have (other than taking it easy and seeking medical help) no conscious control over what our IS does as it strives to eliminate a novel pathogen like SARS-CoV-2. When it comes to immunity, the ‘power of positive thinking’ only operates when we have the capacity to make informed choices about eating a balanced diet and taking advantage of whatever therapies or vaccines are offered to us!
When it comes to finding the best available information, look for evidence presented by professionals who deal with the science and/or patients and dedicate their lives to solving problems by finding out how disease processes work. Tune out ‘gossip over the back fence’ and any plausible conspiracy theorist who ‘cherry picks’ information that supports some ‘brave’ theory or his/her commercial interests. If you don’t know how to go about that, read my book, The Knowledge Wars. And there are plenty of easily accessed, reliable sources of medical information, including from the Mayo Clinic and Harvard University. Combined with deliberate ignorance, ‘fake news’ kills.
President Trump no doubt benefited greatly from the option of ‘emergency use’ treatment with monoclonal antibodies (mAbs) that neutralised SARS-CoV-2 and stopped progression to what may, considering his age, have been a severe case of COVID-19. That therapy came too late to treat the much younger UK Prime Minister, Boris Johnson, who did become very ill, though recovered. As discussed early on (#5), the intravenously-injected mAb ‘cocktail’ given to Donald Trump provided instantaneous, passive immunity that cleared the virus out fast and ended the disease process.
On the other hand, Boris Johnson’s eventual recovery was due to the fact that attentive doctors, and nurses sitting by his bed to provide extra oxygen when needed, brought him through the severe clinical phase to the point where his own, emerging adaptive immune response eliminated the SARS-CoV-2 pathogen. The way we ‘jump start’ protective immunity is, of course, to be immunised. Most of us are eagerly anticipating the (hopefully) not too distant availability of vaccines to stop the development of significant symptoms of COVID-19. Though, at time of writing, we haven’t seen real data, preliminary results are looking good. Vaccines offer the best, and cheapest way of ending this.
Apart from the issue of consciousness, perhaps the greatest difference between the NS and the IS is that the NS is essentially ‘hard wired’ via the nerves, while the IS is dispersed and operates at the level of the individual cell and its clonal progeny. The brain, spinal cord, nerves, and sensory organs all stay in the same place. But, though mature members of a particular lymphocyte lineage may ‘settle’ in a predictable anatomical location (antibody-forming plasma cells in bone marrow), the lymphocytes are highly motile and circulate through the blood, tissue and lymph compartments as individual entities. At post-mortem, the mass and volume of the brain and spinal cord are easily measured, but we don’t really know where all the lymphocytes are or, in fact, how many there are. The simple question: ‘how big is the IS?’ is not easily answered. And, while the NS has distinct sensing (eyes, brain) and effector (muscles) arms, the same IS cell lineages (or their secreted products) are responsible for both detecting and eliminating an invader.
Focusing on the anatomy of any response the neuroscientists concentrate, of course, on the brain. But the IS has no CPU. Anatomically, the immunologists think in terms of primary and secondary lymphoid organs. The T cells are ‘trained’ as they differentiate in the ‘primary’ site of the thymus while, in birds at least, the B cells learn something of what they are supposed to do in the anatomically distinct, Bursa of Fabricius, with that function likely occurring in the mammalian bone marrow. In seeking to understand COVID-19, what interests us in, at least, the first 7-10 days after infection is the events and interactions occurring in the secondary lymphoid tissue, where the naïve T cells and B cells first recognise, then respond to an invading pathogen like SARS-CoV-2. That’s where we’ll go next, to the secondary lymphoid tissue concentrated in the mammalian lymph nodes, the spleen and at various localised tissue sites, especially in the gastrointestinal tract.