I’ll give Dr Tetyana’s comment some context by reference back to my father’s research, and that of numerous colleagues at university research labs around the world. They all found dietary proteins and their peptide derivatives circulating in the blood stream. Further, they could immunise a subject by oral dose of the antigen so later blood samples from these animals would show antibodies to this antigen. [“Antigen Absorption by the Gut”, edited by Dr W.A.Hemmings, MTP Press, 1978]
So this gives meal times a new twist – “let me immunise you with some roast beef and Yorkshire Pudding, with mashed potatoes , peas and carrots” the host might say. Does this mean that the next time you eat this meal you somehow react against it? Again, I have previously used this quotation but it’s apposite here, Janeway et al concede the same point eg on P684:
“Small, soluble proteins are unable to produce a response unless they are made to aggregate in some way. Most vaccines, for example, are aggregated protein antigens to potentiate the immune response”
Aggregate = denatured, no longer in their natural state
Potentiate = from potent “tending to produce violent effect” and Google say : “increase the power, effect, or likelihood of something, especially a drug or physiological reaction.
So they have described a complicated framework of physiological interactions which have no function in the real World and do not address commonplace, everyday events. It can so very well be argued that, in fact, their descriptors show why so many food allergies all of a sudden plague the population. It is not, as many anti-vaccinators quite reasonably suggest, because of extra, food derived antigens within the vaccine. No, it is probably because already circulating food proteins, peptides and the like are rendered antigenic by the carrier adjuvanting chemicals within the jabs. “Collateral damage”.
But we are all happy with the ideas of immune memory of disease, and that those without the appropriate memory are open to going down with said ailment, each with its own particular, distinctive range of symptoms. It is somehow felt that the germs, the infection, create these symptoms but it is very worth bearing in mind that, actually, what you see in the patient are the workings of his/her body to clear up the mess, to overcome the infection. Many, myself included, are persuaded that the only way to achieve such immunity is by going through the natural reactions – coming out in spots, collapsing in a heap for 5 days etc – and then emerging, fully recovered and no longer susceptible. Do Janesway et al describe the changes that your body then goes through or are they simply creating sagas from in vitro experimentation to justify the Jenner in all of them?
I love that life is so complicated and so evolved and that there are myriad flows providing maximal performance within the environments, the ecologies we are part of. We cannot comprehend the hows and the whys of these multitudinous subtleties, many of which have their origins in times we can get little or no record of at all. Yet this book reads like a Haynes Manual for car maintenance – and reads rather like one as well. In fact, I think they lifted some of the diagrams directly from the latest edition of onesuch!
I left Janesway playing God with hypermutation. They actually don’t use a God figure, although profoundly fall into determinist thought patterns. This is an ongoing scenario, real life event. The Chosen B-cell, with its selected antibody code, is hypermutating. When it divides, the progeny have altered antibody codes, so shapes and binding activity/potency. Some are good, some neutral, some silent and some bad. Thus;
“Those B-cells whose variable regions have acquired mutations that result in improved antigen binding are able to compete effectively for binding to the antigen”
“ receive signals that drive their proliferation and expansion, along with continued mutation” – well, who says you can never get better, eh?
Over the following two or three weeks, then:
“The antigen binding efficiency of the antibody response is improved”. Can’t have been much good to start with, really. I’m puzzled it was ever chosen!
The sad neutral, silent and bad mutanted B-cells are, of course, left to wither away. The infection? Oh that was long since over but the idea is that the T-cells operate a system of exhibition of battle trophies.
Yeah! OK, let’s do it:
Page 193 -The Major Histocompatability Complex, MHC, of genes can generate MHC glycoproteins. In an infected cell it is described that this protein coolly recognises the problem, captures a sample of the invading antigen, deposits it in a handy vesicle where it is split into handy fragments one of which is fitted to a second MHCg by a TAP (don’t ask!) and both then migrate – bravely – to the cell surface where the MHCg displays its antigen fragment – a mixture of trophy and SOS signal. It then patiently waits for THAT T-cell to come along which will recognise the antigenic shard as its destiny, at which point this butch T will become MC , kill off the infected cell and forward the indicative antigen to the appropriate B-cell by the cunning process of waiting on the corner for it to come along.
But look. This antigenic fragment is now the Holy Grail as it’s become the Reference Material for the process. Hypermutate a bit, compare back to antigen? Better? No? Hypermutate a bit more. “Hey, where’d you put that antigen – I need another look.” “Thought I left it with you” “Come on, I was busy hypermutating”.
To be fair, there’s quite a lot they write about chemical signalling, to carry around messages of intent and desire – “cytokines” and the like – in an attempt to draw together these interactions so’s the odds against their ever happening are not infinite. But the gaps in the description require a faith as devout as that for any fundamentalist religion.
Always they are driven by their Jenners and by the fear factor:
P193 – “Superantigens are produced by many different pathogens, including bacteria, mycoplasmas and viruses and the responses they provoke are helpful to the pathogen rather than the host”. I’ll resist my inclination to listen in to bacterial HQ, where they’re having a strategy meeting….
P327 The initial interaction of T-cells with antigen presenting cells, APCs, is mediated by cell adhesion molecules:
“As they migrate through the cortical region of the lymph node, naive T-cells bind transiently to each APC that they encounter. APCs, and dendritic cells in particular, bind naive T-cells very efficiently through [then a long string of coded names eg ICAM1] [Then a bit about redundancy in provision/supply].
“The transient binding of naive T-cells to APCs is crucial in providing time for T-cells to sample large numbers of MHC molecules on each APC for the presence of a specific peptide. (Sort of like a wild singles party!)
Anyway, if pair bonding is achieved, mating ensues. The association:
“is stabilised between the antigen-specific T-cell and the APC. This association [get this] can last several days during which time the naive T-cell [grows up and] proliferates, and its progeny, which also adhere to the APC differentiate into armed effector T-cells.” Ah, domestic bliss! But remember, it’s not always like this, because:
“Most T-cell encounters with APCs don’t, however, result in the recognition of an antigen; instead they deliver a survival signal.” Get me out of here!
And he carries on meeting, embracing, looking for that one special antigen on that one special APC. Then he’s whisked away in the lymphic flow, waiting for that next party, that next time when, maybe, just maybe IT might just happen. ‘Til then, he must remain frustratingly naive.
This is a review and not a text book. I’ve not expanded on innate immunity, that which works from day one, that which seems still to carry out the major duties of disease prevention and clear up when incidents do occur from time to time, as these things must, I’m sure, for many good physiological reasons. There are not really “two systems” at all, it seems to me and I would see the memory B and T cells as adjuncts to the whole complete physical surveillance and maintenance system. Certainly “naive” B-cells have great utility in producing generic antibodies for housekeeping activities, keeping the blood-system tidy, putting the dinner away. We do not want to be immune to Roast Beef, do we?
As the child grows up his/her thymus gland reduces in import so, as adults, we are barely aware we even have them. And, yes, we stop producing new T-cells although surviving post-naive T-cells are retained, circulating and dividing as and when they will. But they surely no longer have the ability to recognise any new antigens and so the capacity to instruct any naive B-cells in anything but the same old songs. Yes, these are maybe a memory of earlier infection – or at least some random antigenic elements thereof – but they preclude the establishment of any new immune memory. Why even think of vaccinating adults?
OK, that’s part three. And you now have the crux of my critique. I don’t like to “dish” a whole science but in the kingdom of the blind the one eyed man is king. This discipline has, consciously or unconsciously, adopted an institutional blindness because it was born Jennered. So it’s like telling Monsanto to switch to Organic Growing Systems – it’s not, as they say, in their DNA. I do not believe the discipline of Immunobiology can be reformed from its current mindset. Instead, I feel, elements can be adapted and adopted into the new field of Bio-Medical Ecology, where the whole field can be viewed without the profoundly distorting lens of Jennerism.
Part Four, to round this series up, will be to tie in a few remaining leads and project ahead to opportunities in Bio-Medical Ecology!