And so, as the race began to bulk up the industry and find new prophylaxes to provide to their public, the need grew to provide a rationale for their products. They had to justify the need. Clearly, initially, there were two participants in this. There were the medical fraternity, whose role in society could well have been diminishing in direct proportion to the improved standards of living. Kids just did not die like they used to, although much unpleasantness certainly did occur – the polios, for one. During World War One many, many medics were called off to help patch up the troops as they fought in that most pointless of conflicts – and are not most wars such! Meanwhile, back home, there was a great upsurge in health and far less loss of infants in childbirth some say due to the LACK of healthcare……
And then there was the nascent Pharmaceutical Industry. Apothecaries in their workshops could not handle the manufacture of these potions. These were not tinctures of rose blossom or any of the nasty Victorian chemical syntheses that I’d prefer to forget were ever even toyed with, let alone used as routine (eg Calomel, an early example of the mercury poisoning of kids). I have previously referred to this industry as being the direct descendents of the Medicine Men who sold their lotions and potions from their horse drawn wagons around the Wild West. That still stands for me but, of course, these days complaints have to be addressed – you can’t just ride off into the dusty blue yonder when your clients don’t get well or are harmed by your product.
Pasteur’s recognition of Bacteria as infective agents and his subsequent production of a “rabies vaccine” clearly put a technical shine to such efforts and others inevitably attempted to reproduce and advance the techniques. However, smallpox remained the major jab in town until after World War One when it was eventually joined by vaccination for Tuberculosis (TB). War became an issue as the idea of using bacteria as weaponry raised its ugly head – the UK, for example, used smallpox (Check) over Middle Eastern – yes, Iraq – regions, for example, in an early attempt to destabilise and massacre the region, and used a Scottish island to attempt to grow weapons grade anthrax spores. In this case the spores got out and contaminated the island which was then designated a no-go zone for decades. The talk, below, gives another example of weaponising disease.
After World War Two polio grew to being a mass problem and was very destructive in the United States, where the condition led to countless deaths and disability. So, whereas most illnesses had already declined sharply, the polio condition was going in the opposite direction. Understandably there was widespread unease and panic, even, as epidemics blew up frequently.
The reasons behind this state are so well discussed elsewhere, for example by Dr Suzanne Humphreys:
in a video of an excellent lecture she gave. As you will see the illness is far better named “The paralysis that was named Polio” and was an almighty stage-managed exercise which is best explained by referral to a range of contributory factors, rather than a sudden upsurge in virulence of an infectious virus (eg “provocation polio” due to previous jabs which, at this time, would have been smallpox jabs.)
The result was, of course, that polio vaccine became standard and was soon aimed to “rid the whole world” of the illness. Also used, at that time, were Diphtheria and TB, the latter being drawn from a culture first started in the early 1920s. It’s still in use today!
More recently, as we all know, there has been a great upsurge in the industry with far more vaccines against far more antigens introduced. This has required a large pool of manufacturing companies and this whole new career of Immunobiologist blossoming, providing the technical abilities to produce massive numbers of product to be distributed worldwide. Tens of thousands of such scientists as well as training for pharmacologists, medics and nursing staff.
So there are two areas of research. Firstly there is the description of how the body reacts to deal with the threats posed by micro-organisms gaining ingress into the inter or even intra cellular spaces. How does the body remove micro-organisms and their toxic products? What mechanisms are there to retain the integrity of the system and avoid illness and premature death? Naturally. And then, secondly, they ask, how can we improve matters? How can we continue to utilise Jenner’s discovery? What systems did Jenner find and what was the result of his input upon these systems?
The questions all run together and so do they in the teaching of the subject. Janesway et all – “Immunobiology – the immune system in health and disease” is the brand leader in text-books and conveys the spirit of the learning experience. After graduating through this tome and its accompanying course, you’ll be out there, developing a new vaccine against, well, any new illness you can come up with and sell as a threat to humanity.
Section one covers basic concepts. It opens with a homage to Jenner, although it does not describe his pasting puss into a freshly cut wound! On page 33 they go on:
“the deliberate stimulation of the immune response by immunisation has achieved many successes since Jenner’s pioneering experiment.
“Mass vaccination programmes have led to the virtual eradication of several diseases…….Immunisation is considered so safe and so important that most states in the USA require children to be immunised against up to seven common childhood illnesses…….The prospect of controlling [other] important diseases is tremendously exciting. The guarantee of good health is a critical step toward population control………At a cost of pennies per person, great suffering and hardship can be alleviated.”
Heady stuff indeed!
And then it gets profoundly technical. There has been so much deep science and analysis, great use of our impressive range of laboratory methodologies and machinery, huge reams of numbers crunched and brains taxed to bring forward the descriptions of the systems as they find them.
They describe the comprehensive innate immune system, fitted to all of us in fully functioning condition, ready to go on delivery. It is the external surfaces, of course with their “You shall not pass” message to all would be invaders but there’s plenty more fall back. “The understanding of how innate immune systems recognise pathogens is rapidly growing”. However, they admit, “the adaptive immune response…has been the focus of nearly all studies in immunology because it is much easier to follow and experiment by using reagents and responses that are specific for defined antigens.”
And you can use it to make money from by conjuring up new vaccine formulations of said antigens, of course. And so massive streams of research funding are made available.
OK, but they have built up a pretty sophisticated description of this “adaptive immune system” nonetheless, and it is illuminating to go there with them.
In the beginning, which is always the best place to start, in the beginning an antigen is circulating within the blood stream which didn’t ought to be there. Now I’ve defined antigen in a previous post but “didn’t ought to be there” just about hits it on the head. Whether it’s protein, little peptide, alien polysaccharide, bacterial cell or virus particle, stuff that DOTBT are antigenic and need to be removed. And yes the innate system has obviously fallen down for them to even be there but something must be done.
Well, we thought about that already. Oh, yes, we are very well prepared for we have T-cells and B-cells is vast variety such that, for every possible antigen we have a T and a B to meet up to it. Lurking in our circulation, at our lymphic regions, in our T –hymus and our B-one marrow and elsewhere, such as in the alimentary canal. I realise that my tone has gravitated towards near mirth. Shame on me! But no, really, the description of the system is very, very impressive. It has chromosomal rearrangement – somatic manipulation of the genetic grail is deeply impressive and an elegant solution to the impossibility of otherwise having the ability to generate a response to pretty much any antigen nature could put up against us. Incredibly there is then , additionally, hypermutation of some of these same sequences to increase further the adaptive capabilities. This is re-writing the DNA to order (and see later!)
So, how does it all fit together?
White blood cells, lymphocytes, come in various designations, of which B and T are two. Both originate in the bone marrow, but Ts migrate to the thymus. Differentiation for these cells takes on a whole new meaning as each develops its own, individual immuno-active protein to produce by doing a kind of mix and match with the component pieces. Think of those kids sectioned books with different people on each page – milkman, nurse, policeman, pope etc – which are divided into sections, so’s the pope’s head can be on the nurse’s shoulders in hilarious fashion. With 6 or 8 subunits each having 10 to 50 or so different codings the total quantity of potential assembled proteins is vast.
Concept is that each cell chooses its immune protein pretty much at random and, after checking that it is good not to be auto-immune, the cell is released to circulate. They sail round, essentially until they meet “their” antigen, at which time the cell becomes “chosen” as it “bears the code” for an important, battle winning antibody. If they do not have this crucial encounter then, sadly, they die, but this does not matter as there is a constant supply of new ones. Billions of them, like snowflakes, all different.
But, I hear you ask, why Bs AND Ts? Well, when it meets its antigen, a T must tell its corresponding B cell that that B cell must excrete its antibody and that it is one of the chosen cells that must not die, so that it can be rolled out to secrete this specific antibody whenever it might be needed in the future. Also so it can be multiplied up to produce as much product as may be required. In this teacher capacity the T cell is called a “helper-T-cell”, which, I feel, does not do the role enough justice as, to me, it seems rather a top job and not just a helper job. Still, that’s just me! Essentially all Ts have an equivalent B, both tailored for one particular antigenic form, should such ever be encountered. The B-cell decorates its external surface with said antibody in some recognisable manner.
Ts have to meet the antigen within the cell walls of an infected cell. This is made much easier for the T-cell by the infected cell sending out to its exterior cell surface a kind of SOS-cum-suicide note in the form of that piece of the infecting organism that the passing T-cell has long since been pre-programmed to recognise as “its” antigen. Are you still with me? Mm, well it gets better. Let me quote Janesway et Al, verbatim (from page 387):
“B-cell activation by many antigens, especially oligomeric proteins, requires both binding of the antigen by the B-cell surface immunoglobin – the B-cell receptor – and interaction of the B-cell with antigen-specific helper T-cells. Helper T-cells recognise peptide fragments derived from the antigen internalised by the B-cell and displayed by the B-cells as peptide:MHC class II complexes.Helper T-cells stimulate the B-cell through the interaction of other TNF-TNF-receptor family ligand pairs, and by the directed release of cytokines. Activated B-cells also provide signal to T-cells, for example via B7 family molecules, that promote their continued activation. The initial interaction occurs at the border of the T-cell and B-cell areas of secondary lymphoid tissue, where both antigen-specific helper T-cells and antigen-specific B-cells are trapped as a consequence of binding antigen. (Sounds like a punitive regime, here!). The initial interaction is closely followed by the migration of antigen specific B and T cells to the T-zone:red pulp border, where there are marginal sinus bridging channels in which further proliferation and plasmablast differentiation happens. Finally, further interaction between T-cells and B-cells continue after migration into the B-cell zone or follicle, and the formation of a germinal centre.
“Helper T-cells induce a phase of vigorous B-cell proliferation and direct the differentiation of the clonally expanded progeny of naive B-cells into either antibody secreting plasma cells or memory B-cells. During the differentiation of activated B-cells, the antibody isotype can change in response to cytokines released by helper T-cells, and the antigen-binding properties of the antibody can change by hypermutation of V-region genes. Somatic hypermutation and selection for high affinity binding occur in the germinal centres. Helper T-cells control these processes by selectively activating cells that have retained their specificity for the antigen and by inducing proliferation and differentiation into plasma cells and memory B-cells. Some non-protein antigens stimulate B-cells in the absence of linked recognition by peptide-specific helper T-cells. These thymus-independent antigens induce only limited isotype switching and do not induce memory B-cells. However, responses to these antigens have a crucial role in host defence against pathogens whose surface antigens cannot elicit peptide specific T-cell responses.”
Now I am aware that full/any understanding of the above two paragraphs require considerable vocabulary and background theory introduction and some will be good but my purpose is to illustrate the elaborate description that has been compiled and how it all used to justify the vaccination interaction and is not simply description of a natural system. It is not simply working as an astronomer and mapping the heavens or investigating a remote isolated ecology. Here they are creating a rationale for an existing process, two hundred years after it was first utilised. What they cannot do is come up with reasons to demonstrate the process to be both flawed and to be damaging. This comes through the very composition of their prose and the mechanistic, engineering, manner they describe systems they analyse. This is very apparent in the illustrations, showing deterministic flow charts and practically conscious protein molecules taking up their stations. No room for error – this is what you do, this is where you do it.
OK. Somatic Hypermutation. This is a good one, referred to above. Here we see a purported system for improving on the already achieved very specific B-cell and T-cell for each and every antigen. Once the marriage, described above, between T and B takes place, hypermutation describes a process of detailed extra moulding of the antibody product by allowing genetic changes (mutations) to occur at a far greater frequency during somatic cell division of the chosen B-cells. These are thus implied to be CONSCIOUS mutations, driven in a manner wholly contrary to all previous understanding of the process. This is practically “The Hand of God” re-writing the script. “No, no, I think we need a lysine molecule there, so maybe if we take out that tryptophan. Yes, I think I’ll try that. OK, now that means I’d better take out that TGG and put in, let’s say, AAG just here. Mm, yes, that’ll do. Now if you just make up that antibody for me we can test it out on the piece of antigen that T-cell over there is just holding for us. OK, OK, now does that fit better? No. Oh, Devil take me, what else can we try?………..”
[Wiki codons: http://en.wikipedia.org/wiki/DNA_codon_table]
I’ve only scratched the surface of this literary appreciation exercise and intend to pin it down further. This will take a “Part Three” but now I need a breather – doubtless you, too. When I come back, I’ll use some reinforcements. Here’s a taster, from the Ukrainian Canadian Immunologist Dr. Tetyana Obukhanych. She say:
“Without alum adjuvant or mercury etc, and without [the] damage that it creates, the immune system would simply disregard the injected foreign protein [in the vaccine]as innocuous and not make any antibodies against it”.