One of my favorite places on the internet is r/askscience, a place on reddit where people come and ask questions, and a panel of scientists answer. People can ask follow-up questions, and there is often some great back-and forth (to be honest, part of the reason I haven't been writing as much here is because I'm using up all my time over there). Recently, an number of people have been asking questions about allergies - Can people grow out of allergies? Why is the incidence of allergies increasing? Can eating honey cure allergies?
You can check out those threads if you want answers to those specific questions (I'm commenting as "KeScoBo"), but I decided I wasn't done after my semen allergy posts, and thought it would be a good idea to go back to basics. From the perspective of the immune system, what are allergies, and how do they arise?
At its most basic level, an allergy is an inappropriate immune response to a non-harmful substance. But there are many ways the immune system can respond that wouldn't cause problems - they key to allergies is that your immune system thinks that pollen is a worm.
To back up a sec - as soon as a pathogen breaches the barriers of our skin or epithelial tissue, the immune system kicks into gear. Receptors on the surface of specialized immune cells or on the inside of normal cells fire off, indicating the presence of an infectious agent. Macrophages do their best to clear out the invades, dendritic cells run off and sound the alarm in nearby lymph nodes, and signaling molecules called cytokines and chemokines activate and recruit a massive influx of immune cells from the blood.
But not all infections are created equal. Depending on the type of pathogen, different receptors will be triggered, and the immune system will tailor its response appropriately. Broadly speaking, there are three major types of pathogens that the immune system needs to respond to:
1) Intracellular - these pathogens (all viruses and some bacteria like Listeria) live most or all of their life inside our own cells. In order to deal with them, the immune system needs to be able to identify and kill infected cells, while preventing new cells from becoming infected.
2) Small extracellular - These pathogens (mostly bacteria, some fungi) live outside of cells. They are small enough to be eaten by phagocytes, but often reproduce very quickly and produce toxins that can kill or manipulate healthy cells.
3) Large extracellular - Pathogens like worms can't be eaten by our own cells, and they can't be neutralized with antibodies. They only way to deal with them is to make their living environment terrible and try to flush them from the body.
One of the differences between these different immune responses is the selection of antibody isotypes. The binding sites of all antibodies are generated in the same way, but during an immune response, the B-cells that are participating are instructed to choose a particular butt depending on what type of pathogen their attacking. IgG is good at binding and neutralizing viruses and toxins, IgA can be shuttled across mucosal barriers, and IgE is good at making your life miserable.
Actually, IgE is the antibody isotype (butt) most associated with allergic reactions, and its "natural" job is to fight worms. Worms are mutlicellular, and often WAAAAAY bigger than our own immune cells. Because of this, the combat strategies that work well for viruses and bacteria are useless against worms - it'd be like trying to fight off a grizzly bear with a fly swatter. Instead, IgE arms the hand grenades - immune cells called granulocytes are filled with noxious chemicals, and chemical messengers like histamines. When the IgE coating the surface of these cells bind to something, the cell explodes - flinging poison and death at anything in the area.
Allergens trick your immune system into thinking they're a worm. Your immune system freaks out, and starts flinging hand grenades every time you inhale. As you might imagine, damage and misery result.
Up next: what makes your immune system think "worm."
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Another great thing about r/askscience and other science blogs: it's easy to forget that when most people look for information about a science topic they can't get past the journals' firewalls. Most journal articles aren't acessible unless you are attached to a university (or still have accommodating friends at one). If you need a pdf, ask nicely at reddit and someone will help you out.
It's been a long time ... ... ...on a personal note, when I was in lab school in the Navy, this is the sort of thing that really fired me up to want to learn more about hematology, immunology...I can't really be specific, but it was things like electrolyte balance in blood, clotting factors and clotting factor cascades, antigen-antibody response... ... ... at any rate, this is great to read and see again. I really find this stuff interesting and have never been able to find anything in libraries or on the internet that really delve into it like I would find in a good college/university education.
Hi Kevin, cool post - have you thought about uploading some of your stuff to December's MolBio carnival? I'm hosting it over at my blog, Ruleof6ix and thought this allergy stuff would be pretty interesting! Check out the link: http://molbiocarnival.blogspot.com/
"it's" does not equal "it is'; PLEEEASe use 'its'.
If IgE invokes more of an inflammatory response than other antibodies, is this possibly why an allergic condition can in some cases develop into an autoimmune response?
Thanks!
@ hibob - Yup. Paywalls are retarded. In fact, I think the entire science publishing model is broken, but that's a subject for another post.
@ Mike - Yeah, I've been kicking around the idea of writing a book that would explain the immune system for precisely that purpose.
@ Connor - No, I rarely think about carnivals. I'm thinking about it now though :-)
@ Snooty - Fixed, but I believe you mistyped: "It's" actually DOES equal "it is." You also used apostrophes when you meant to use quotes, and periods and semicolons go on the inside of quotation marks. But somehow I knew what you meant...
@ Megan - I'm not aware of allergies that turn into autoimmune disorders, though people who are prone to allergies are statistically more prone to autoimmune disorders. If the regulatory mechanisms that keep the immune system in check are weak, your immune will attack things that it's not supposed to, whether that's pollen or your beta islets.
So I take allergy shots, Xolair, Allegra, and whatnot because my stupid body thinks it's fighting worms??? Curse you, body!
@ Karen - Yup. And the irony is, if you were actually fighting worms, you probably wouldn't have allergies (more on that later).
Reminds me of case of autism and colitis that improved by taking pig whip worm eggs several times a week.
This is a great post that really exemplifies all the great sources on the web available that bolster's the public's understanding of immunology and disease! Also,as a fellow Immunology PhD student who has taught many immunology courses, I appreciate your spot-on easy-to-understand explanation of the inflammatory nature of IgE involved in allergy.
I've really enjoyed We Beasties since I stumbled across it months ago and I hope you (and your awesome readers) can help support a fellow science research blogger. I'm a finalist for a $10K scholarship for full-time students who blog, but I need the support of the online community to win! If you're interested to learn about the latest published research in the fields of immunology, human health and disease, I encourage you to checkout Escaping Anergy:The Immunology Research Blog!
Thanks in advance and keep on advocating science communication!!
@ http://www.collegescholarships.org/blog/2011/11/15/vote-for-the-winner-…
@ Megan - I'm not aware of allergies that turn into autoimmune disorders, though people who are prone to allergies are statistically more prone to autoimmune disorders. If the regulatory mechanisms that keep the immune system in check are weak, your immune will attack things that it's not supposed to, whether that's pollen or your beta islets.
Just today saw this:
http://onlinelibrary.wiley.com/doi/10.1111/j.1399-5448.2011.00758.x/abs…
Wahlberg, J et al (2011)
Asthma and allergic symptoms and type 1 diabetes-related autoantibodies in 2.5-yr-old children
Pediatric Diabetes
DOI: 10.1111/j.1399-5448.2011.00758.
Does that make the link any closer?
@ Megan - I know the study on colitis, but I've never seen a link between worms and autism, and a quick pubmed search didn't turn anything up. Do you have a reference by any chance? I know there was some (now discredited I believe) thought that colitis was associated with autism - it's possible that the two were conflated without any scientific study.
@ Neil - Thanks for the link! It looks like there's a pretty good statistical correlation, but again, I don't think that argues that having an allergy would directly lead to autoimmunity. Though honestly, I don't know how you could tease out the difference, at least in humans.
Evidence is now coming out of Africa where in some area,s they have been running a de worming program that for the first time allergy has reard it's ugly head.