So, this week was apparently proclaimed ‘Vaccine Awareness Week’ by the authority of fringe medicine practitioner Joseph Mercola and Barbara Loe Fisher (co-founder of the infamous National Vaccine Information Center).
This seems to be but a stunt from two rather prominent anti-vaccine activists, but, it gives us at She Thought, a nice opportunity to delve into the subject of vaccination, a subject dear to skeptical hearts and one made topical by both this year record pertussis epidemic (the highest incidence rate in 50 years) and the looming flu season… So, let me open what could become a week of vaccine frenzy with a short (maybe) run-down focusing for today on the mechanisms behind generating the humoral component of the specific immune response that vaccines target.
F*cking acquired humoral immunity –part 1, origin of the immunoglobulin.
Vaccines work by taking advantage of the natural mechanisms for acquired humoral immunity. Basically, our genome contains three loci of genes (two of these loci codes for what is called the light chain of the immunoglobulin while the third one codes for the heavy chain).
This heavy chain is composed of three main regions of interest: the V, the D and the J region (V stands for ‘variable’, D for ‘diverse’ and J for ‘joining’). Interestingly, each region contains multiple slightly different of the same segment (a bit like ACDC discography). For example, we have a bunch of ‘V’ segments following each others, and then a bunch of ‘D’ segments and finally a handful of J segments (in total, we have 65 copies of the V segment, 27 of the D and 6 of the J segment).
The light chains are pretty similarly organized but lack the D segment.
Now, there is a group of immune cells referred to as ‘lymphocytes’. During their maturation process they undergo what is called ‘somatic recombination’ and, simply put it consists of the elimination of all but one segment of each kind, hence generating a random sequences of this segments. In addition, random nucleotides are added in the process at the VDJ joint, thereby, increasing the diversity even further.
Thankfully, Wikipedia provided us with a nice little diagram of the process (cf. figure 1):
Figure 1: Somatic recombination, thanks to gustavocarra for Wikipedia common.
The immunoglobulin molecule is then assembled using two light and two heavy chains, assembled together by disulfide bonds (cf. figure 2) in such a way that the highly variable region created by the somatic recombination in each chain stick together in two regions called, quite unsurprisingly, ‘variable region’.
Figure 2: The structure of the immunoglobulin molecule.
This process is a veritable machine to create diversity. The recombination of random version of the multiple segments, itself, will produce about 3 million different possible combinations; introduce the additional layer of random nucleotide insertion and the number of possible variable regions jump to an astonishing estimated 1016…
Each cell will only produce one type of antibody with its own particular sequence, but, taken together, this amazing diversity insure that, whatever molecules are expressed by the pathogen entering the body at any given time, there will be a lymphocyte expressing just the right antibody to match it…
By the way, these molecules, that the pathogen expresses and the immune system ‘recognize’ are called ‘antigens’. Because pathogens express more than one type of antigen, the various antigens expressed, taken together, is referred to as the ‘antigenic profile’.
F*cking acquired humoral immunity –part 2, enter the antigen.
At this stage, the immunoglobulin produce stay stuck on the surface of the cell that produces them. That way it ‘recognizes’ the antigens it corresponds to. However, because these molecules are so specific, the odds of a circulating leukocyte to encounter its corresponding antigen are very low (it is estimated that, for one specific antigen, less than one in 10,000 or one in 100,000 lymphocyte will recognize it).
However, these lymphocytes also re-circulate between secondary lymphoid organs (spleen, lymph nodes and discrete location around the gut and respiratory track (GALT and BALT, respectively). When a cell of the non-specific immune system (which is not as picky and is quite likely to identify any given antigen) capture one such antigen, it migrates to the secondary lymphoid organ to present it to the lymphocytes. Because, as mentioned, lymphocytes congregate in these organs, the odds of finding one matching any given antigen are drastically increased.
Upon presentation of a matching antigen, B-cells are activated, they will maturate into plasma cells and some of them will start producing a first wave of antibodies, called IgM (cf. figure 3).
Other will form what is called ‘germinal center’ in which there will undergo somatic hypermutation, essentially, one more step of point mutations. This can either increase or decrease the strength of the binding to the presented antigen, the ones in which the strength of the binding is decreased enter programmed cell death, so this process allows for the production of cells with yet even more specificity to the antigen. Then, they will switch to a different class of antibody, called IgG (cf. figure 3). These are both smaller and more specific and constitute the main thrust of the specific immune response.
Another thing that takes place in the germinal center is a clonal expansion of the plasma cells. There the cells that, as we have said, had already been selected to be highly reactive to the infection taking place, greatly multiply in number. Among the cells produced are memory B-cells. These will then move in the bone marrow when they will where they will survive for several years (estimates for the duration of circulating plasma range from only a few days to a few weeks)…
Figure 3: The two main types of antibodies.
Memory cells:
As we have seen, mounting the adaptive immune is a complex process and it is also quite slow. Generally, it takes between ten days and a few weeks (a couple of weeks in average) for the body to mount an effective specific immune response.
But after this, the body will have a stock of highly specific memory cells remaining so that, if the same antigen is encountered a second time, the immune response will be able to by-pass these steps and will start chucking out antibodies much faster…
This is particularly important as the first days of the infection are the most critical: the pathogen’s numbers are at their lowest but, because the body immune’s response is as it’s weakest; they are also increasing at their fastest rate.
By cutting this response time, the body is therefore able to counter the pathogen before it was able to establish an infectious beachhead…
What about vaccines?
You’ll notice that, when describing the mounting of the immune response in part two, I used the term antigen but never mentioned the actual pathogens it is normally attached to… That’s not an accident, because any molecules that trigger the immune system will be processed through this process. Whereas an actual pathogen or not, active or not, virulent or not, the basic mechanism behind the immune response will be the same.
There are subtleties, of course, as I mentioned, this is for what is called the ‘humoral’ response, there is whole other arm to the immune response (but it is simpler and we will go over that in later and hopefully shorter post) and I completely avoid mentioning the different compartments of the immune response (again, next post). But right now, it seems about enough information so, my friends, that’s all for today…
Simon Mentanteau is a microbiologist and fish pathologist from Mississippi (by way of France), which explains his fancy dress :)
Simon, this is fantastic! You do a much nicer job of explaining this bit than I have (repeatedly) attempted to do in my layperson’s way:
“But after this, the body will have a stock of highly specific memory cells remaining so that, if the same antigen is encountered a second time, the immune response will be able to by-pass these steps and will start chucking out antibodies much faster…
This is particularly important as the first days of the infection are the most critical: the pathogen’s numbers are at their lowest but, because the body immune’s response is as it’s weakest; they are also increasing at their fastest rate.
By cutting this response time, the body is therefore able to counter the pathogen before it was able to establish an infectious beachhead…”
I might lift this as my gmail signature!
Love-love the fancy dress!
This is a wonderfully helpful post! Thank you.
Thanks Simon. That helped make things a little easier for me to understand.
I got my flu shot. My daughter got her flu shot AND a DPT booster. She got tricked into going to the health department with a co-worker and before she knew it, she had two little holes in her arm.
I have an appointment with my allergist next month. I will be asking about a booster. I had a tetanus booster two years ago, but no the D or the P part.
But then there is the question. If one has had Pertussus, do I need a booster? Probably wouldn’t hurt.
Very well explained, nice work.
One little point: The antibody diagram is incorrect. The hinge region connecting the Fc and Fab of the heavy chain is not a disulphide bond, it’s one long polypeptide, and the inter-heavy chain disulphide bonds are apparently absent. And technically everything south (or ‘C-terminal’, I guess) of the hinge is the Fc region. Fc receptors don’t just grab onto the very C-terminus, case in point being IgA receptors which bind surprisingly close to the hinge.
This is a very good explanation for those truly unfamiliar with the concepts. It is a shame that not mentioning CMI or mucosal antibody isotypes will makes this an instant dismissal for anti-vaxxers. It seems the concept of yet-unmentioned nuance makes anything that disputes their nuttery instantly wrong.
I look forward to future installments!
Hello Tom!
Thanks for pointing that out, you are right, I got confused when drawing my little stick figure… I corrected it now… Thanks a lot.
You are right about the CMI and the mucosal immunity, these are interesting concept, especially considering I’d like to go on to mention the various types of vaccines and these are important factors when comparing bacterin and deactivated vaccines to live attenuated ones…
In fact, these are the very subject of my post for today…
@Sylvie.
Yes, it is now recommended that you get a booster for your pertussis vaccine (the disease is not too bad in adult but you can still act as a carrier in the transmission of the disease).
In the last few years, there has been a new accelular version of the vaccine (included in the Tdap vaccine) that has been developed and does not carry some of the side-effects that were sometime associated with the DPT. I got my shot back in September (thanks to a clinic organized as part of the wonderful “Hug me I’m vaccinated” campaign and I did not feel any side effects at all…)
Hi Simon.
Thanks for the mention in the latest post. If you’d like any clarification on these points my major is (that is, is about to be :P) in immunology, I’m more than happy to help.
I didn’t mean to be ‘that guy’, sorry if the correction was a little abrupt or jerk-y.
i love the writing, it’s very readable, and explains the concepts in a very accessible way. Please keep it up!
Don’t worry, I love being corrected, it is the best way to learn! (plus there is the added plus that, that way, I don’t mislead the reader, that’s good too ;) ).
Nice theory – only, it’s pseudo-science at its best (or worst). Junk science, Mickey Mouse science and tobacco science are other appropriate descriptions.
Vaccines have never protected anyone, or saved anyone’s life, let alone the lives of millions.
Vaccines have never prevented anything – apart from health, sanity and common sense.
Vaccines are an organised criminal enterprise dressed up as disease prevention.
They are the establishment’s way of circulating its latest biowarfare agents.
“Belief in immunization is a form of delusional insanity.”
Dr Herbert Shelton, USA
“I was shocked to find that this whole vaccine business was indeed a gigantic hoax. Most doctors believe that vaccines are useful, but if you look at the proper statistics you will find that this is not so…It was obvious that I and every other doctor had been grossly milsed.”
Dr A Kalokerinos MD, Australia
“Vaccines contain substances which are so noxious they should not ever be injected into a human body.”
Dr Viera Scheibner PhD, Australia
“We are slowly but surely destroying the intelligence of our future generations with vaccines… Vaccination is child abuse and a crime against humankind.”
Dr med G Buchwald, Germany
The sooner everyone wakes up to the fact that vaccination is an ugly and brutal money-making racket and exits the Cult of Vaccinology, the better.
Hi Erwin- the argument from authority is a poor one. However if you’re going to use 4 quotes from ‘Dr.s” as some kind of justification for your position, then they invite some dissection.
Dr Herbert Shelton – was not a medical doctor, repeatedly jailed for practising without a license. He starved a patient under his “care” to death. His “school” of health was bankrupted after he – without qualification – was charged with negligence for the death of another patient.
Dr Viera Scheibner PhD a palaeontologist.Not a medical doctor.
Doesn’t mean they are wrong, of course- they could be spot on.A medical doctor might be wrong. But don’t be so enamoured of a PhD – particularly one in an unrelated field. I’ve got one, for goodness sake, and you don’t (and you shouldn’t) assume I’m right for that reason.
We should get closer to the truth by the weight of evidence.
All your post does is this:
1) make unsubstantiated claims
2) Attempt to make an argument from authority (with half of your presumed authority being unimpressive)
If you want to make the argument from authority then you’re faced with explaining away the 10s of 1000s of doctors and researchers who are experts in the relevant field who have come to the conclusion that vaccines are effective and worthwhile, against your 2. But it shouldn’t be about that sort of argument (fortunately for you) . It should be about the weight of evidence.
So put more substance to your claims (I’ve not seen any yet despite the months I’ve been reading your posts – but I await patiently), otherwise you’ll come across as someone who just doesn’t know what they are talking about, and just making empty claims.
I’ll just add that Archie Kalokerinos has stated that 50% of the deaths of Aboriginal children in Australia are caused by vaccines. Unfortunately reality is terrible and embarrassing for Australia. The most common cause of death for Aboriginal children is ‘external causes’, including car accidents and domestic violence. Even better, indigenous children die from infectious diseases, many of which we have vaccines for, at a rate 4.5 times higher than non-indigenous children. Of course these figures come from the Australian Bureau of Statistics, so they are just part of the conspiracy.
I notice you have attracted the attention of one of the worlds most psychotic anti-vaxxers, Erwin Alber..
Given the heat I received for “being rude”, I expect to see you deal with this dangerous loon with a great deal of enthusiasm.
The likes of Erwin are our common enemy.
Milton has done a fine job, but it would be fitting that the hosts deal with this appalling menace to public health, swiftly and decisively, less other maniacs get the impression you are a soft target for trolling.
Hi Marius, yes unfortunately I do know of Erwin ‘chemtrails’ Alber.
Defining anyone as an ‘enemy’ makes a lot of assumptions about goals and means, don’t you think? In a broad sense perhaps.
I agree with you that Milton has done a fine job and I added some relevant information that touches my personal interests, I don’t really see that Erwin deserves much more time or attention. So far he’s made wild statements backed by nothing, which Milton clearly showed. He obviously didn’t read the post beyond the fact that it had vaccine in the title but has just copied and pasted his standard response to everyone who doesn’t share his delusions. He isn’t going to read anything said in reply to him, just use it as an opportunity to rant. And if other readers can get through the entire post and comments and then be swayed by his conspiracy rant, especially when it’s been pointed out that it’s only a very bad argument from authority, what more can be said? He’s wrong? Very well, he’s wrong and I have lots of doctors to back me up.
@Erwin – if you want a response, read the post and comment on it rather than repeating the same irrelevant rubbish. Oh, and you’re wrong and I have lots of doctors to back me up.
Hello Erwin; welcome to SheThought.
I am afraid I will have to disagree quite firmly with you, starting with your disparaging use of the term “theory”, a personal pet peeve of mine, which, in science, means “a comprehensive and testable explanation that includes all currently known facts. This constitute the highest level of explanation science can offer”. Hardly something to be ashamed of.
As for the science behind immunology, that was introduced in this post, I fear you are mistaken as this science is on very solid ground and tested many times and at many levels.
For example, the VDJ recombination has been pretty thoroughly investigated. I actually happen to have a colleague a few labs over that is working with deficient zebrafish whose genes do not undergo such recombination and part of her dissertation thesis was to confirm that these organism did not indeed produce specific immune cells.
Similarly, the migration of activated leukocytes to germinal centers is also well grounded (another colleague spend his own PhD confirming that this phenomenon also happened in catfish, using microscopic phosphorescent beads).
The amplification of the immune response upon reexposure is actually even older and better confirmed.
Calling all this ‘pseudo-science’, in my opinion, reflect a clear and severe lack of understanding of the subject.
Here is the thing, for any field, you will find some people on the fringe, maybe just plain deluded. In fact this is quite telling that you could find so little relevant authorities that you had to included references that are decades out of date (Shelton) or from people with no authority in the relevant fields).
It is not the fancy letters after one’s name but if he has science that can back his assertion. There are literally million of articles out there that agree on the mechanism behind vaccination and their general efficiency. I have yet to see any credible evidence to support your, rather outlandish, claims.
The overall contribution of vaccines at the population level is, of course, more difficult to evaluate as other factors did, most certainly, contribute to the sharp decrease in infectious disease that followed the introduction of vaccines.
Still, it is difficult to argue that vaccines did play a central role in this decline. Indeed, such proposition is actually testable using the scientific method as it is possible, knowing the average of level of contagion of a given organism, to calculate what level of protection is required to stop an epidemic. If vaccine are protective, a vaccination rate above this level will prevent an epidemic to take root. On the other hand, if such an epidemic fails to take place even after vaccination falls under this threshold, the hypothesis about the protective role of vaccines at the population level will be falsified.
In these conditions, deplorable as it is, the current pertussis epidemic is a pretty stark test of this hypothesis as the level of vaccination is currently slightly under the calculated level for herd immunity.
Indeed, mankind, in all its history, as only been able to totally eradicate two diseases. Not surprisingly, both of these happened following a prolonged, vaccination effort.
Of course, all this research and work, including the vast vaccination campaigns such as the one that lead to the eradication of the dreaded smallpox, were decades long effort involving tenth of thousands of personal all over the world.
The amplitude of the conspiracy that you hint at to make up all these evidences for the efficiency of vaccine would be quite astronomical and certainly, the cost of putting all this witnesses on the payroll for such a prolonged amount of time would dwarf any potential profits resulting of the vaccinations.
Speaking of the profits, do you realize how cheap vaccination actually are? When compared to the cost of even a single course of antibiotics? And that’s not even counting the cases avoided by cutting the infection short…
As a rule, pharmaceutical companies would make significantly more profit by foregoing prophylactic and selling multiple palliative treatment instead. The reason they are still selling the vaccines, of course, is that a competitive company would fill up the niche for them.
Anyway, nice to have your visit and please, keep on reading on the subject, especially from places that would challenge your beliefs.
SORY I Didn’t found ANY INFORMATION ABOUT HOW DTAP VACCINE ARE CREATE Dthrough recombination of dna techinique .please inform me in that regard.
and truly i liked all the articles wriiten by all above visitors and truly i too agry with them………………!
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