Thursday, February 27, 2014

Antivax doesn’t see the forest for the trees

Introduction:
Welcome to my anti-antivax blog. My pseudonym is Honey badger and I come from Slovakia (the small white spot on the map in the middle of Europe).
Believe or not, there are antivaxers in Slovakia, too. Slovakia is a small country, but it has a strong antivaccination movement. I cannot tell if it is because they are so good or because of a lot of stupid people who believe them here. Anyway, I couldn’t watch the amount of fail in this area, so I started writing this blog. At the top of this blog, there is a logo which is a parody of the logo on a Slovak antivaccination movement website (1). The motto there is a good one and it says: “Bullshit sticks to the people extremely quickly and adhesively, but scraping it off by facts is very hard if not impossible”.


Antivax doesn’t see the forest for the trees 

Have you ever heard about the Th1/Th2 model of immunity? I guess the answer is yes. Slovak and Czech antivax chiefs misuse it like you can see in this video (there are English subtitles, too). It goes like this:
“Immunity is like a Th1/Th2 see-saw. Immunization enhances the Th2 part and suppresses the Th1 part of immunity and that’s why it causes immunosuppression, allergies, autoimmune disorders and cancer.”
Pretty tricky, isn’t it? Let’s see what the science says.

The Th1/Th2 model (2) emerged in 1980s from experiments on murine CD4+ cell clones. From that time, a lot of new research has been done on mice and in humans, complicating this initially simple hypothesis so much that it is nowadays often called a paradigm (3, 4, 5, 6). One Czech homeopath and antivaxer, first named Ludmila (the second person in the initial video) has explained to antivaxers what the word “paradigm” means. She says that all doctors are living in old paradigmas because they don’t use alternative “medicine”. That’s funny because she herself lives in a 30 years old Th1/Th2 paradigm and misuses it to manipulate the masses (see in the video).

According to Th1/Th2 paradigm, one is healthy when there is a Th1/Th2 balance. If it skews to the Th1, it can cause autoimmune diseases, if it skews to the Th2, it can cause allergies (71 - scroll down for this reference).
However, there have been a lot of other quite important T-lymphocytes discovered since 1980s, e. g. Th9, Th17, Th22, Tfh and many others, which we know or even don’t know yet – so I am sorry, but the picture at the top on the right is also misleading, but less than the antivax model of immunity. It is even more complicated because these individual lymphocyte subpopulations can change their profile (s. c. plasticity, 8). Other very important T-cell type include regulatory T-lymphocytes (s. c. Tregs, 7) which regulate the immune response (22).

An antigen is recognized by a small amount of lymphocytes out of a number of total body lymphocytes. This small amount of them is activated thereafter (s. c. clonal selection, 9) and so there is no Th1/Th2 see-saw in the body as a whole. Similarly, there is no such a thing like aluminium adjuvants shocking the immune system and totally disbalancing it as the antivaxer Bert Ehgartner says (10, 72).


“Vaccination stimulates Th2 immunity one-sidedly and weakens the Th1 immunity”:

According to Th1/Th2 paradigm, Th1 suppresses Th2 via interferon gama (IFNgama) and on the contrary, Th2 suppresses Th1 via interleukin 4 and 10 (IL4, IL10). However, this antagonism is not absolute because Th1 produces IL2 which stimulates a lot of lymphocyte subtypes (including both Th1 and Th2 lymphocytes) (11 – scroll down for this reference). There are also other mechanisms of co-operation of these T-cell subsets (12).

Also Th2 does not solely mean only antibodies. Th2 type response enhances production of IgG4, IgA and IgE antibodies, Th1 supports the production of IgG1 (13). Antibodies connected to an antigen (s.c. opsonization) can be connected with their Fc part to Fc-gama receptors of fagocytes which helps the Th1 immunity fight encapsulated bacteria, e. g. hemophilus, pneumococcus or meningococcus. That means, serological studies (antibody level) tell us not only about the Th2 immunity but also about Th1. Serological studies are made because they are simpler and cheaper than Th1 immunity tests. Of course, there are studies on Th1 immunity response and they say that vaccination strengthens not only Th2 but also Th1 immunity (14).


Allergies:

Besides the Th2 cells, there are also other T-lymphocytes subtypes which contribute to the pathogenesis of allergies, e. g. Th1, Th9, Th17, Th22, ILCs, etc (15, 16, 17, 18, 19).  Tregs are very important, too (20, 21). So asthma can be divided to Th2 mediated (the majority) which is usually mild or moderate and responses well to the treatment, and non-Th2 asthma which is severe and does not response well to standard treatment (17, 18). On one hand, in acute atopic eczema, Th2 response is characteristic, on the other hand, in the development of chronic atopic eczema, Th1 response plays an important role (19).

Most quality studies have not found a link between vaccination and increased risk of allergies (23), also homeopaths following the results of epidemiological studies dissociate themselves from this link (24) and moreover, there are studies suggesting a protective impact of childhood vaccination on atopic disorders (25, 26). I think that antivaxers, reading these sentences, are being pissed off, but it is really not a cherry-pick because antigens-allergens with aluminium adjuvants can be used as a causal treatment (while Ludmila’s homeopathy is not causal and even not a treatment) of allergies in certain indications. It is called allergen immunotherapy (27, 28). There are a lot of studies, including randomized double blind placebo controlled ones, which show its effectiveness (e. g. 29, 28) and safety (e. g. 31). The most serious side effect is anaphylactic reaction which can occur more common than in “classic” vaccination because of the principle of allergen immunotherapy. In spite of that, this reaction is rare when the procedure is done lege artis (32, 33). Because the antivaxers are uneducated, they often confuse vaccination and allergen immunotherapy (34) and so, e. g. Slovak antivaxers use allergen immunotherapy side effects as a proof that vaccination does harm. That’s so gross… The biggest difference is that in allergen immunotherapy, an allergen is applied at low doses at the beginning, then the dose is escalating gradually. The schedule is different from immunization schedule (35). Allergen immunotherapy is a tertiary prevention, immunization is a primary prevention (34). There are several possible mechanisms how it works but the most important is an influence on the activity of Tregs and modulating the activity of T-helpers (36, 37). Aluminium can be used as an adjuvant and it has a depot function (38, 39).


Autoimmunity:

One would probably say that autoimmunity is nothing but bad. To tell the truth, autoimmunity at low level is useful, e. g. to eliminate old and damaged cells or cancer cells (40). An autoimmune disease develops when the autoimmune reaction leads to tissue damage. Our body has some tolerance mechanisms as well, which prevent autoimmunity, and these mechanisms fail, when an autoimmunity disorder occurs. 

According to Th1/Th2 paradigm, an excessive Th1 response leads to autoimmune diseases (41, table 1). Now, it is funny to watch the antivax steps. One of the Slovak antivax chiefs, Marian, sticks to the paradigm and says that vaccination causes Th2 mediated autoimmune disorders (minority) such as SLE. However, even SLE is not caused purely by the Th2 part of immunity (42, 43). Ludmila says that vaccination causes autoimmunity in general, Th1, Th2, whatever, it must be the vaccines.
  
The mechanism will be made somehow. And it was, by who else than chronically famous duo Lucija Tomljenovic and Chris Shaw (44). They suggest an LPS contamination of vaccines as a factor which skews the immune response to Th1 and thus causing autoimmune disorders (41). Is such a thing even possible? Yeas, it is…

Vaccination can cause autoimmune diseases rarely, possibly via molecular mimicry mechanism (47) or bystander effect (48, 73). E. g. GBS after swine influenza vaccine in 1976 or ITP after MMR vaccine (45, 46). However, infectious diseases themselves are a bigger risk factor for autoimmune disorders, e. g. GBS (49) and e. g. viruses like morbillivirus or mumps virus can be a risk factor for the development of DM1 (50, 51, 52). Most of studies haven’t found a link between vaccines and DM1, multiple sclerosis or IBD (23, 46).

I would like to mention as well, that autoantibodies is not the same as autoimmune diseases (AD). Autoantibodies can be found in healthy subjects as well as autoantibodies need not be present in individuals with AD. Autoantibodies support the diagnosis of an AD, but they need not be involved in the pathogenesis of that disease. E. g. in Hashimoto’s thyroiditis, autoantibodies against thyroid peroxidase can be detected, but in the pathogenesis of this disease, autoreactive T-lymphocytes and not the autoantibodies themselves are mainly important (53 – scroll down for this reference, 54).


Cancer:

Th1 immunity is very important in fighting cancer, Th2 is also not useless (55, 58 – scroll down for this reference). Th2 acts e. g. via ADCC (56) or complement activation (57). Weak Th1 immunity can be a risk factor for the cancer development and so some cancer treatment approaches on the base of this hypothesis has been tested, e. g. IFNalpha or BCG vaccine. IFNalpha can be used, e. g. in the treatment of hairy-cell leukemia or AIDS-related Kaposi’s sarcoma, but IFNgama is not used because of its side effects (59). BCG vaccine is partly useful in the treatment of bladder cancer (60, 11 – scroll down for this reference).

Saying that vaccines cause cancer is an unconfirmed hypothesis till now, but when we look at the other side, we can see the studies supporting the hypothesis that vaccines prevents cancer so much that it is not a hypothesis any more. It is the matter of HPV and HBV vaccine.

HPV vaccine is effective in protection against infection with the most frequent and pathogenic types of HPV virus, genital warts and precanceroses CIN, VIN, VaIN and others (61, 62, 63, 64, 65, 66). Since the CIN is a precancerose of cervical carcinoma, the incidence of this cancer is expected to decrease in the next few years, studies are on the way.

Approximately 5% of HBV infections in adults progress to chronic infection. This percentage is much higher, when the infection is contracted by children under 5 (30-50%) and even higher in children under 1 year of age (90%). About 20% of people with chronic HBV infection die prematurely because of cirrhosis or hepatocellular carcinoma. Vaccination against HBV in some countries with higher incidence of hepatitis B reduced significantly not only the incidence of this disease but also its complications – including hepatocellular carcinoma (67, 68, 69, 70). 


Conclusion:
In spite of criticizing the Th1/Th2 paradigm on the base of new studies, the aim of this article is not to discredit this hypothesis totally. The aim of this article is to point out that antivax chiefs “abuse” and fudge this hypothesis as they prefer and want regardless the new studies, thus manipulating antivax members and blinding them, so they cannot see the forest for the trees.  

References: 


11. Horejsi et al.: Immunology basics, 4th edition. 2009
53. Litzman et al.: Diagnostic basics in clinical immunology. 2007
58. Robins et al.: Cancer immunology. 2001
59. http://en.wikipedia.org/wiki/Cancer_immunotherapy#Interferon
71. Jesenak et al.: Vaccination in special situations. 2013

February 27 2014, Honey badger

7 comments:

  1. Careful about using all that science and so many references. Anti-vaxers will say you're part of the vast government-led conspiracy to keep the populace sick so big pharma and the medical establishment can make more money.

    Keep fighting the good fight.

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  2. It is indeed interesting that even though the Th1/Th2 discovery is 30 years old and that immunologists are constantly discovering things they didn't know in the past, that governments and doctors have been happy to inject vaccines into healthy people for 200 years. And tell you the benefit outweighs the risk. Based on what you explain here, they could not possibly be telling the truth because they know very little about the inner workings of the immune system.

    As for your theory on the many T cell types, immunologists seem to still be working in the Th1/Th2 paradigm. Zaghouani 2010 describes well how infants are indeed capable of mounting both arms, BUT they pay a price later. Zaghouani 2009 showed using the so-called antiquated Th1/Th2 paradigm that there is an age where the immune system changes. Before that age, there is a Zaghouani showed that neonates can mount a primary Th1 and Th2 response. Neonatal exposure to antigen by injection ( and the kicker is that her didn't use aluminium- imagine if he did), leads to secondary responses that are biased toward Th2 upon rechallenge with Ag later. So... yes infants are fully competent immunologically but they pay a price when that Th1 is activated strongly by injection. Someone better tell Dr Zaghouani. As for Th9 they are derived and similar to Th2. As for Th22 and Th17 little it known about them except they are possibly involved in autoimmunity. As for Treg and dentritic cells they regulate the initial immune response and have little to do with the Th1 and Th2 paradigm being limited or not. Your so-called information is lacking, sarcastic and actually not very helpful to the provaccine or as you call anti-anti vaccine. I suggest you review the available literature.

    As for your comment on vaccines helping the cell mediated response, let me remind you that all vaccines are different. Some use adjuvants, which BTW create DAMPS (have a read on that topic), some are more stimulative of Th1 like the BCG vaccine but the rest are not the same that way.

    Also read Galic 2009, "Transient immunological perturbation to a developing animal may program the organism for subsequent health complications as an adult." And Mandal 2013 that Immune stimulation in pregnant mother leads to offspring with a pro-inflammatory phenotype.

    In 2013 a scientist named Elahi showed a most interesting thing: Infants are fully capable of responding immunologically. When you take infant cells and put them in an adult they work normally. When you take adult cells and put them in an infant they don't. There is a program in infants, for a purpose, telling those cells to keep quiet while the immune system is being educated. But immunologists and vaccine manufacturers can't seem to keep out of that system and before knowing anything about it were willing and happy to throw cluster bombs into it. Which has mounted to a giant cluster F%$K to children world wide.

    And a final word is that we have some evidence that vaccines and their timing makes a difference in the allergic/asthmatic response. http://www.ncbi.nlm.nih.gov/pubmed/18207561

    Also your reference 22 and your other ones seem to also be living in the dinosaur Th1/Th2 paradigm. Have you even read your own references. Th1/Th2 is still a valid paradigm used in your references. Cheers.

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  3. This is a recent article I pulled up in full text. You can only get the abstract unless you have medical article access somewhere. http://www.nature.com/pr/journal/v75/n1-2/abs/pr2013214a.html

    This gem of an article, which funny enough is about finding new vaccines, tells us how the innate immune system actually has memory. Another discovery. " Moreover, in addition to
    providing early defense against infections, the innate immune
    response plays an essential role in triggering and driving the
    acquired immune system to respond effectively to infection
    (3,4). Moreover, the dogma of innate immunity lacking memory
    has also started to be questioned" So what does it mean that the innate immune system can actually function like the 'acquired' one when it comes to needing vaccines? Funny how the literature seems to always be slanted towards finding more vaccines rather than seeing how the body actually has its own means to deal with and recall infection, possibly leading scientists to investigate WHY it doesn't always work properly rather than just looking for more vaccines with aluminum to thwart the immune system. But who would fund that?

    In this same article they authors IN 2014, say "Vaccines vary in their ability to engage the innate immune
    system. For example, Alum, the most commonly used vaccine
    adjuvant, may exert its adjuvant activity via a range
    of mechanisms, including activation of the inflammasome
    and release of danger-associated molecular pattern molecules Of note, a birth dose of Alum-adjuvanted
    pneumococcal conjugate vaccine was associated with subsequent
    Th2-polarization of TLRA-induced mononuclear
    cell cytokine responses in vitro (46), suggesting that Alum
    adjuvant may trigger long-term (i.e., at least several months
    long) Th2-polarized immunity." AND "with age (42) such
    that trained immunity effects may be age specific. The recent
    recognition of trained immunity may inform future studies of
    TLRAs to boost host defense in vulnerable populations and
    potentially also reduce the risks of allergy and asthma, for
    example, via balancing Th2/Th1 polarization in accordance
    with the hygiene hypothesis" Someone better tell them how antiquated they are!

    It is all over the immunology literature that aluminium enhances Th2/allergic responses.Tomljenovic and Shaw did not make it up. They reference their work extensively with papers like this in 2014 that are talking all about Th1/Th2.

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  4. DocBastard,
    Funny, no science from you, but plenty of science from a vaccine critic.

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  5. Oh and I could not resist bringing you one more article showing how those who say Lupus and autoimmunity is 'idiopathic' and they can't figure it all out. Well, it turns out you are right that it is more complicated than th1/th2. See if you can wrap your brain around this. This Japanese scientist basically created Lupus by vaccinating animals, and when he transferred their CD4 and other cells to other animals produced autoimmunity... because of hyper immune stimulation with injected antigen. He didn't even use aluminium. Imagine if he did... http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0008382

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  6. Hi Suzanne,
    Thank You for Your comments.

    First of all, as I said in the conclusion, I am not denying the Th1/Th2 hypothesis. I am just against the way how antivax misuses it. They use the hypothesis without the new findings which I have showed in my article. And that is the dinosaur as You said, not the hypothesis itself.

    A lot of antivaxers (not only) in Slovakia say that vaccination causes the atopic disorders like asthma, meaning all of it. That is a lie, there is no evidence for such a claim. The right interpretation is that it could be the cause. There have been a lot of studies examining this cause and most of the quality ones have not found a link. You may like also the response from Spycher to Your “timing DTaP asthma study”. Another example being against the link is also in the article – the subcutaneous allergen immunotherapy using aluminium adjuvants. This method is totally opposing the link. Moreover, I am not sure about other countries, but in Slovakia, there used to be vaccines with twice more aluminium than now. Despite of that, now, we have more atopic disorders than before.

    When the antivaxers are losing words, they start with the Th1/Th2 hypothesis like it were the only thing in the immunology universe saying it must be the vaccines because of this hypothesis. No, it needn’t because there is the forest of new important findings. And because of it, the sequence vaccines – Th2 – allergy is not ultimate.

    I agree that at the beginning, when the aluminium was introduced as a vaccine adjuvant, scientists knew little in comparison with these days. However, they did not introduce it just for fun. There were kids dying and having serious complications of infectious diseases and the vaccines with aluminium worked well. Would You not have used them to save the kids? Anyway, till now, there is no clear evidence that vaccines are the cause of the atopic disorders and so I think that it was a very good job to introduce vaccines and that the benefits still far outweigh the risk.

    Tomljenovic and Shaw made up hypothesis how vaccines cause autoimmune diseases. Th1 or Th2, it must be the vaccines! Because they have always been, are now and ever shall be…

    My article was primary about Th1/Th2 paradigm. I know that antivax suggests a lot of other mechanisms but I focused mainly on the paradigm. Anyway, thank You for the Plos one study, antivaxers in Slovakia are using it as an argument, too. Over-stimulation? Allright. Infectious diseases can over-stimulate Your immune system more than the childhood vaccines as I wrote in my article. Also the authors do not suggest vaccines as an example, but rather an infectious disease – measles. Measles in unvaccinated.

    Lastly, when I look at Your comments, You are actually defending the Th1/Th2 immunity. You may not understand the point of my article which is written in the conclusion. I was not attacking the hypothesis itself, I was attacking the way how antivax “abuses” it.

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  7. http://thesciencebehindthephoto.blogspot.com

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