Arguments for opposing vaccines truly do run the gamut but I find those relating to the efficacy of vaccines to be especially poorly founded. It is common practice when it comes to pseudoscience to co-opt the jargon of the pertinent field to attempt to create some semblance of credibility, and one form this takes when it comes to vaccine is the Th1-Th2 gambit. This claim goes as follows:

“What people don’t know about vaccines — what most doctors don’t know — but well demonstrated in medical literature, is that vaccines shift your immune system to an immune suppression type of state called the ‘TH2 shift.’ That’s what most vaccines do. They shift your immune system to a weaker, antibody type immune system… If you’re injecting people with so many vaccines that your keeping them in this constant state — that now your [sic] switching everyone to this TH2 immune suppression — then everyone becomes more susceptible [to infectious diseases]… and no one is talking about that. Now, a lot of scientists know that, but they are afraid to speak out because their careers would be ruined.”

Dr. Russell Blaylock M.D.

As far as I can tell, Blaylock is the original author of this claim, and in another life, he was a neurosurgeon. Then he decided that MSG was evil, Obamacare euthanized the elderly, water fluoridation causes ADHD and is part of a deep state plot, and somewhere along the way decided vaccines are… bad. Regardless, virtually no part of this claim is correct. And, regrettably, Brandolini’s law is true again.

Prepare for science.

You have a staggering number of different cell types within the immune system, all of which have distinct functions, some of which are shown above. While this might sound prejudicial, some of these are more important than others, which we know because deficits in certain cell types produce more serious disease than with others. Among the most important are the helper T cells, also called CD4+ T cells (because they express the protein CD4 on their surface). You can think of these as being, essentially, the brains of your immune system, and it is largely because HIV kills these cells that renders your body so vulnerable to any infection.

There are all sorts of different pathogens that your body might need to defend you against. In the broadest sense, we can group them as being intracellular or extracellular. For example, all viruses are intracellular pathogens. They are only able to cause damage if they can get inside your cells. Bacteria and parasites can be both intracellular and extracellular depending on the specific one you’re talking about. Fungi are extracellular pathogens.

T helper (Th) cells come in all sorts of subsets (I like to think of them as flavors, like ice cream or quarks) to help tell your other immunological cells what to do depending on the nature of the pathogen they have to respond to. Each flavor of T cell produces certain kinds of cytokines that activate certain other kinds of immune cells to give rise to effector responses (basically the specific mechanisms that give rise to infection clearance, like antibody production or cytotoxicity- killing cells). What’s more is that helper T cells of a certain flavor can induce naive T cells which lack flavor to become the same flavor of helper T cell as they are, which results in a positive feedback loop that amplifies itself. For example, in the early stages of infection, many innate immune cells may produce interferon-gamma, a cytokine that promotes inflammation. Interferon-gamma, along with IL-12, causes naive helper T cells to become Th1 cells. Th1 cells then go on to make more interferon-gamma, which leads to more Th1 cells.

The Th1-Th2 model comes from observing leprosy infection:

Leprosy is caused by the pathogen Mycobacterium leprae, which is an intracellular bacterial pathogen. In the process of immune surveillance (how your immune system patrols for signs of infection, cancer- basically makes sure everything is going as it should be) the bacterium ends up getting phagocytosed (eaten) by a cell, typically a macrophage, and then it lives inside the endomembrane system of that cell, stealing its energetic resources and thriving. But your immune system is far from helpless. It will still end up mounting an adaptive immune response against the bacteria, and this is controlled by- you guessed it- your helper T cells! The disease generally had either of 2 polar manifestations, but intermediate ones existed. The first was as follows: the infection causes the immune system to cause a lot of damage to the body’s own cells in attempting to clear it, with a great deal of inflammation in the skin and nerves. It was a very unpleasant experience, but patients who underwent this kind of response generally survived quite well and recovered. This kind of manifestation is known as tuberculoid leprosy, and the immune response it generates is what is known as a Th1 response. Th1 cells were the predominant type of helper T cell evoked, and they went on to activate cell-killing machinery like cytotoxic T cells, NK cells, and macrophages which wrought much havoc, but were typically successful at clearing the infection. The other kind of immune response people generated looked a lot milder: this is a response directed primarily by antibodies, but because the bacteria live inside the host’s own cells, antibodies don’t really reach them. This allows the bacteria to grow virtually uncontrollably and creates a disseminated infection all over the body. Those who had this kind of response had much poorer survival rates because the infection grew to uncontrolled levels that exceeded the ability of antibodies to control them. This manifestation of the disease is called lepromatous leprosy. It is caused by what we call a Th2 response, governed by Th2 cells. Th2 cells act to produce cytokines that drive the secretion of antibodies by B cells and promote their maturation into memory cells and plasma cells. So, essentially, Th1 responses are associated with immunity against intracellular pathogens. They work to stimulate phagocytes to eat and kill cells which have been infected, and stimulate killer T cells to kill infected cells. Th2 responses work to stimulate production of antibodies against the pathogen.

At first glance, this seems like a reasonable and robust model for describing immune responses, but there are problems. The truth is that there is no such thing as a Th1 response or a Th2 response in practice- not really. These responses are 2 extremes that belong to a spectrum of responses your immune system can produce, and, unfortunately, this model is WAY too simplistic to be useful in most contexts even if we view it as a spectrum if we set those things as the extremes.

If we are to take Blaylock at his word, one may wonder, are antibodies useless then?

Antibodies: Not Useless

The example with leprosy does make it seem as though antibodies are not useful for controlling an intracellular infection, but this isn’t always true. I am afraid that equating antibodies with extracellular protection against infection is also overly reductionist, thanks to the phenomenon of antibody-dependent cellular cytotoxicity (ADCC).

ADCC occurs when antibodies cross link an antigen on the surface of a cell that’s been infected with a virus, which is then detected by an NK cell (a cousin of the T cell). The NK cell then receives activating signals that cause it to degranulate (release the contents of its granules), releasing perforin and granzyme, which kill the infected target cell. It turns out, that this process is critical for the control of several viral infections, including HIV, influenza (a vaccine-preventable disease), and West Nile virus. In the case of these infections, viral proteins appear on the surface of the cell, and antibodies specific for those proteins bind them, which are then found by the NK cells (and macrophages and neutrophils), which ultimately ends in the demise of the infected cell.

Furthermore, antibodies can mediate protection against intracellular infections in other ways. Generally, intracellular pathogens have to be able to spread from cell to cell to cause infection. However, when they are exposed outside the cells in this fashion they are vulnerable to the neutralizing power of antibodies. This is most apparent with the measles virus. Antibodies against H and F proteins, the proteins it uses to invade cells, offer excellent protection.

A Shaky Framework

In leprosy, the major cytokines associated with Th1 and Th2 immunity are shown above. Take a look for a second at IL-4. Sure, you see a lot of it with a Th2 response (lepromatous leprosy), but you also make a lot in a Th1 response (tuberculoid leprosy) (the black dots reflect stained protein; the bigger and denser the dot the more protein there is). That doesn’t really make sense if these two things are supposed to be the opposite of each other, as one might want in establishing extreme values. As it happens IL-4 is one of the most important cytokines in making antibodies. But, we make a lot of it with Th1 responses too (in fact the cytokines produced by Th1 cells induce B cells to make IgG1 antibodies). So do Th1 responses not make any antibodies? This is a construct that isn’t tethered to reality. It’s meant as a framework to help us classify specific immune responses, a deliberate oversimplication, because the actual complexity is more than any one human mind can be expected to handle. We can have Th1-dominated or Th2-dominated responses, but as it turns out even this classification framework has problems.

When you look at a map of the world, you’re examining everything in 2 dimensions. That’s nice and it’s useful but you miss out on a lot of information, like for instance the topography of the land. Plus it’s a spherical object that you’re representing in a plane so you naturally distort the picture to make things neater, which not only results in a loss of information, but actually some misrepresentation. So that’s when you get a globe so you can see it in 3 dimensions. But the Th1-Th2 model is kind of like trying to look at helper T cells as a 2-dimensional thing, when the reality is that they have too many dimensions for us (well me anyway) to even visualize (I can only think in up to 3 dimensions- sorry to disappoint).

As it turns out, T cells, in particular helper T cells, are so shockingly diverse that we are reaching a point where we literally have to profile each cell individually. Originally we said 2 flavors. But then we decided to add a third one: the Th17 cell (so named because it makes IL-17).

One of the most popular applications of the Th1-Th2 model is to describe autoimmune diseases, for instance, like is done here and more recently, here. Some autoimmune diseases are regarded as being more Th1-like while others are Th2-like based on which kinds of immune responses drive those diseases. Turns out, this is not nearly good enough even with an oversimpifications, because the Th17 cells are actually incredibly important for driving a huge number of autoimmune diseases and are critical for responses against extracellular bacteria and fungi. But this upsets the neat framework we had where Th1 corresponded to intracellular pathogens and Th2 was extracellular pathogens. Th17 cells have a distinct cytokine profile that makes them especially well suited for defenses at the mucosal surfaces. Agents that block IL-17, the major cytokine made by Th17 cells (like those sometimes given in Crohn’s disease) can allow for the development of some very unpleasant fungal infections as well as extracellular bacteria . Furthermore, hyper IgE syndrome, a condition in which individuals make disproportionately high quantities of IgE, frequently suffer from debilitating fungal infections, largely because this disorder also prevents them from having any functional Th17 cells.

The revised framework for this model looks something like this:

Hence in this framework, Th2 cells are recognized as the key cells in responding to helminths (worms) and other parasites, Th1 cells are critical for intracellular pathogens, and Th17 cells are critical for extracellular bacteria. It’s worth discussing the other two T helper cell types mentioned in that figure. TFH cells (T follicular helper cells) are critical cells for making antibodies. Within the lymph node, they help to make B cells differentiate and produce the right antibody. Tregs (T regulatory cells) are actually among the most important subsets of T cells that you make. They are responsible for dampening your immune responses to minimize tissue damage and maintain self-tolerance (the state where your immune system does not attack your own body as it does in autoimmune disease). These are the true immunosuppressive cells of your body.

Recently Th9 and Th22 cells are getting some attention. Th9 cells are useful for immunity to parasites, but can have pathological roles in autoimmunity. Th22 cells are important for extracellular defenses in the skin but can also cause inflammatory skin diseases.

So, this gives us 7 flavors of T cells. Delicious.

The Connection to Vaccines

From the example with leprosy, it is tempting to infer that Th2-dominated patterns of immune responses are weaker than Th1-dominated ones. That is entirely incorrect, however. The proper immune response is dependent on the context of the pathogen and the disease. Consider for instance, DTP vaccines (which include DTaP, Tdap, and DTwP). These vaccines provide protection against 3 pathogens: Corynebacterium diphtheriae, Clostridium tetani, and Bordetella pertussis. What is the best mechanism to protect against disease from these 3 deadly pathogens? It’s actually surprisingly simple (in theory): all 3 of these pathogens secrete toxins which are responsible for causing the feared pathologies they are associated with. How would a Th1-dominated response protect you against, say, diphtheria? Th1 cells can promote the mechanisms of cytotoxicity that other effector cells use, but how might that help you? Diphtheria’s principal virulence factor, diphtheria toxin, acts by halting protein synthesis in target cells, killing them. The toxin is secreted into the extracellular space and taken up by target cells. Pertussis toxin and tetanospasmin operate based on similar principles (but have different mechanisms of action). If an individual infected with any of these were to mount a Th1-dominant response, it would be certain to end quite poorly, to say the least. Why would a Th2 response help?

Antibodies are amazing proteins with numerous functions that depend on the class of antibody, but as applies to this example, the one most germane is their capacity to neutralize antigens, like bacterial toxins. In short, the antibody binds toxins and prevents them from ever reaching their target cells. Eventually the antibody and the antigen together are taken up by a cell, typically a macrophage, and degraded, with the toxin never having harmed anyone. Hence the Th2 response that promotes the development of mature antibodies against these toxins is, in fact, the ideal way to deal with toxin-mediated infections.

For pertussis, the picture is more complicated because a Th1-Th17 response seems to be especially important for clearing infection, should it occur, and in general, even with a pertussis infection, the immunity gained does not last very long. Still, antibodies against key pertussis virulence factors, like pertussis toxin, filamentous hemagglutinin, pertactin, and adenylate cyclase toxin, which are present in the acellular pertussis vaccine, are overall quite important for preventing the clinical syndrome caused by the bacterium. The vaccine even seems to do quite well for pertactin-deficient strains- though the protection does not last very long (which is why Cherry proposes here to do Tdap immunization every 3 years). Nonetheless, we do need a better pertussis vaccine, and efforts are actively underway to get us one. I should offer caution though regarding those who extol infection-acquired immunity by pointing out that even a pertussis infection does not provide lifelong immunity (estimates typically say between 10 and 20 years on average).

I’ll also highlight that aluminum salt adjuvants are extremely useful for inducing protective antibodies because they have a tendency to bias towards a Th2 response. While this is often pointed to as a deficiency in the use of such adjuvants, it does not mean that they are not without their uses. Prior to the addition of aluminum salts, DP vaccines (the precursor to our modern DTP vaccines) did not offer very much protection at all. Indeed, antibodies to tetanospasmin are essential for protection against tetanus but nothing has been able to induce them quite as well as aluminum salts (in some European countries, calcium phosphate was once used as an adjuvant but failed to induce anti-tetanus antibodies).

There’s another key point to Blaylock’s insinuation though- do vaccines only produce Th2 immunity? While it’s true that aluminum salt adjuvants do favor Th2 immunity, it is not true that vaccines can only lead to a Th2 response. Subunit vaccines, like the DTaP vaccine, do require adjuvants to provide the necessary “DANGER” signals to the immune system for it to be able to mount a response, and of the adjuvants, the most commonly employed ones are aluminum adjuvants as they have an extensive track record of safety and efficacy. However, live vaccines, as well as whole killed vaccines, come pre-made with their own danger signals.

Measles-containing vaccines, like MMR for instance, do induce a strong Th1 response, as do other live viral vaccines. For instance, varicella, mumps, and rubella. This is in part why having negative titers does not necessarily indicate an absence of immunity. Titers can only measure antibodies, but some vaccines produce other correlates of protection. Hence even if your antibodies wane below protective levels, you might still be protected.

So, as one of my Immunologist pals, Dr. Jen Totonchy PhD, says regarding these things:

“Repeat after me: immunology is hard and we don’t understand it.”

Key References

1. Murphy K, Weaver C, Mowat A, Janeway C. Janeway’s Immunobiology. 9th ed. New York, N.Y.: Garland Science; 2017.

2. Punt J, Kuby J, Stranford S, Jones P, Owen J. Kuby Immunology. 8th ed. New York, N.Y: Macmillan Education; 2019.

3. Lu L, Suscovich T, Fortune S, Alter G. Beyond binding: antibody effector functions in infectious diseases. Nature Reviews Immunology. 2017;18(1):46–61.

4. Raphael I, Nalawade S, Eagar T, Forsthuber T. T cell subsets and their signature cytokines in autoimmune and inflammatory diseases. Cytokine. 2015;74(1):5–17.

5. Annunziato F, Romagnani C, Romagnani S. The 3 major types of innate and adaptive cell-mediated effector immunity. Journal of Allergy and Clinical Immunology. 2015;135(3):626–635.