Allergies

Chances are you either have allergies or know someone who has allergies. Maybe you get itchy watery eyes in the autumn. Maybe your sister is allergic to peanuts, or your mother gets an itchy mouth when she eats shrimp. Maybe when you were dating, your husband was afraid to tell you he was allergic to cats for fear you wouldn't go out with him again, knowing your love of cats (hey, that's me!). What's behind all these symptoms? How does it happen?

First, let's introduce the co-stars of this production: B cell and mast cell. You may remember meeting B cell in our previous post, "Meet Your Immune System".

Now let's meet the villain, The Allergen (the thing to which you are allergic).

It all starts when B cell is just going for a stroll through your body, on patrol making sure everything is ok.

When all of a sudden, the B Cell encounters The Allergen (dun, dun, dun). This sends the B Cell into high alert: he calls for his friends and starts whipping out boomerangs ("antibodies") to wrangle The Allergen.

Mast cell wanders by and grabs hold of some of these boomerangs ("antibodies"). You see, mast cells have special hands that are designed only to grab antibodies. These hands are called "Fc Receptors", because you really wanted to know that.

When mast cell's hands grab these antibodies, that sends him into high alert as well, and he begins producing tons of a chemical called "histamine".

"Histamine! I've heard of that: I take anti-histamines to block that! Bad, bad, bad!" you say. Well, actually, histamine has the very important job of making your blood vessels bigger so that other superhero immune cells can come to the site of the action and get rid of the villain, The Allergen.

This biggering and biggering makes you swell up or get itchy bumps, and this is pretty uncomfortable and you don't like it, so that's why you think histamines are bad. And actually, sometimes this swelling can get out of control and make your airway close up and blood pressure drop since there's more room for blood to pool elsewhere ("anaphylaxis")-- so, sometimes it is indeed dangerous and requires medication.

Wait! So many questions!

"Why does my body think an allergen is bad in the first place? Why does the immune system treat it like a bacteria or a virus?"

When you're infected with bacteria or a virus, there are conserved signals that your immune system sees. In other words, most pathogens have similar codes / elements that signal danger to the immune system-- codes that are conserved and haven't changed over time. So our bodies have evolved to see these as dangerous. All of us. But if we intake something that doesn't have the conserved "danger signal" (like food), then our immune systems don't react against it like an invader.

But some people's bodies see non-invaders as a threat. Why? That's an area that's under active study. One possibility is that some people have immune cells that were activated by a pathogen but also cross-react with the allergen. In other words, the allergen looks a little like an invader that the person's immune system once saw, so the immune cells see it as related and mount an attack. This would also explain why some allergies (like those to pollen) generally don't start until ages 5 years old and up. Another possibility is that allergic people have increased sensitivity to weaker stimuli. (Related follow-up posts to come: immune tolerance, and diversity).

"Do I have to worry about anaphylaxis with all allergies?"

Anaphylaxis is usually only associated with allergens that you eat or that are injected into you: foods, insect stings, and medicines. Allergens that you breathe in or that touch your skin (like pollen) don't usually trigger anaphylaxis (but inhaled allergens can trigger asthma attacks... for a future post!).

"How do the common treatments for allergies work?"

Exhibit A: Anti-histamines. These block the "histamine" secreted by mast cells, depicted above!

Exhibit B: Steroids (oral, topical, or inhaled). Picture yourself eating lots of little stop signs. They tell immune cells to stop, stop, stop.

Exhibit C: Allergy shots. Sometimes you don't even need a shot; you get it in a little tablet to dissolve under your tongue. The idea here is that you're giving your body a very low dose of the allergen, so low that it doesn't trigger a big response. Dendritic cells (introduced in Meet Your Immune System) gobble up the allergen and then send signals that help make Regulatory T cells (also introduced in Meet Your Immune System). The more you do this, the more Regulatory T cells you make. This might warrant a future in-depth post itself, because there are some other interest aspects of allergy shots, and you can read all about this in a scientific article if you want.

"Well, my mouth just gets a little itchy when I eat [thing to which you're allergic]. It's ok for me to keep eating it, right?"

Nooooo, don't do it! Just because anaphylaxis didn't happen to you the first time, or the first 10 times, or the first 30 times doesn't mean that it won't happen. I've heard a lot of stories from folks who were surprised on their 10th or 30th exposure by anaphylaxis. Heed the warning signs.

"Are allergies more common these days than they used to be?"

We don't know for sure. What we know is that some medical institutions are reporting seeing more cases of allergies. Several possible explanations have been proposed:

Possible explanations, where there aren't actually higher rates of allergies (it just seems like it):

1. We're just detecting and reporting allergy cases better
2. Hospital closures funneling more people to fewer hospitals

Possible explanations, where there are more cases of allergies:

3. Environmental changes are skewing the immune system (stay tuned for a post related to the topic of environment influencing the immune system!)
4. Delays or increases in exposing children to nuts from an early age (this is a controversial topic, but there is no conclusive evidence either way right now-- only correlations)

"Why are some people more prone to allergies than others?"

The short answer here is: 1) Different people have different immunological "environments" or "balances" that favor or disfavor certain diseases, and 2) Different people have different sensitivity and responsiveness of their immune cells based on their genes (and this is why the "allergic phenotype" runs in families). Stay tuned for a whooooole other illustrate post on this with some really interest historical anecdotes.

If you've learned from this and want to share with others, consider my new illustrated immunology book!

Meet Your Immune System

A very basic overview of a very complex system: the human immune system. If you learn from this and want to teach others, consider my new illustrated immunology book. :)

When I tell people I'm an immunologist, the most common responses I get are questions about vaccines or cold viruses. But did you know that your immune system is involved in nearly every disease and health maintenance process? Asthma, cancer, diabetes, eczema, multiple sclerosis, wound healing.... you name it. (Personally, I studied T cells in cancer and autoimmunity). Your immune cells are in nearly every little part of your body (except two "immune privileged" sites: the eyes and testes).

So what exactly is your immune system?

Your immune system is amazing army of "cells" that zoom around your body, waging attacks on suspected invaders and cleaning up the damage. It helps you get rid of invading viruses, bacteria, and parasites. It strives to eliminate cancerous cells. It helps you heal from cuts and scrapes.

Sometimes it gets a little too eager and attacks yourself ("autoimmunity" - a future post).

Let's back up for a second and talk about what a cell is. Cells are little building blocks that do a lot of listening, talking, and acting. Cells work together to achieve a larger goal. For example, the cells of your skin bind together to form a barrier to the outside world. Likewise, the cells of your immune system work together to keep you safe from invaders, cancer, and damage.

Let's introduce a few of these immune cell superheroes, as they are bound to pop up in stories to come...

B cells have little feelers ("receptors") on their surface. Each B cell has its own unique receptor, and there are millions of unique B cells in your body. Your body basically makes every possible variety of B cell so that there are little feelers looking out for any possible invader. Your body deletes any B cells that recognize your own personal body's building blocks (but sometimes this goes awry, resulting in autoimmune diseases... for another blog post).

When a B cell's receptor comes into contact with an invader (e.g., bacteria), the B cell becomes activated and starts telling the rest of the immune system superheroes that there's an emergency and it's time to spring to action. The B cell will make tons of copies of itself, and will unleash a ton of boomerangs ("antibodies") to surround the invader and facilitate cleanup by other immune system players. These antibodies are basically identical to the receptor, so they can bind the more of the same invader that was originally detected.

There are a few different types of T cells. Okay, there are like 20 different type of T cells. The running joke is that a new T cell type is discovered every year. But we'll be simple here and I'll tell you about three of them: 1) Helper T cells, 2) Cytotoxic T cells, and 3) Regulatory T cells.

Helper T cells are like members of a phone tree: they have a lot of messages to spread around when something's wrong. They don't attack or eat anything -- rather, they can sense when something's wrong and then tell others folks and help them do their thing.

Cytotoxic T cells are members of the frontline warriors. They throw toxic pellets at invaders.

Regulatory T cells tell everyone to stop. They help calm down the immune response, helping it to wind down.

Natural Killer cells go around checking to make sure you're still you. They have little feelers that shake hands with other feelers on your other cells all day. And should any of your cells be missing feelers, then they attack. Why would any of your cells be missing their feelers? Well, for example, cancer is sneaky and likes to try to hide from the immune system - it hides feelers that would give away its identity (for a future post!). Viruses also do this sometimes too. If a Natural Killer cell can't complete the handshake, it destroys the target cell.

Dendritic Cells go around eating everything in their environment, digesting them, and presenting them out on their cell surface for everyone else to see. Kind of like a toddler who shows you what they've just chewed up. But this is actually good manners, you see, because then other immune cells can come have a look and detect if there's an invader.

There are so many more superhero immune players, and we will meet them in upcoming posts. I showed this to my 2 year old and she said "Where are the monocytes??" So, for any other toddler critics out there, stay tuned!

How did all these immune cells come about?

They started out IN YOUR BONES! Ever hear of bone marrow? (Perhaps you've ordered it at a restaurant? Not me...) You have stem cells in your bone marrow and these give rise to all of your immune cells which then travel and take up residence all over your body, poised for action.

So, there's your brief introduction to the immune system. Upcoming topics include:

- How the immune system remembers (memory)
- Why you sometimes overcome an allergy, or develop a new one (tolerance)
- When the immune system mistakenly thinks you're an invader yourself (autoimmunity)
- How exactly the immune cell superheroes communicate
- Where do all the immune cells live? Where do they hang out?

Leave a comment if you have special topics / questions you'd like me to write up, simplify, and illustrate!

Angela

Pass the Peanuts

Pass the peanuts! Well, check the expiration date first because if they're old, you'll want to pass on eating them. Moldy peanuts (and peanut products) produce a substance called "aflatoxin" - no, not the quirky insurance duck, but rather a very carcinogenic DNA intercalator that inserts itself in your DNA and sets the stage for DNA replication errors and cancer. Wait, what? Let's simplify this...

This was one of the first chemical reactions we studied in my "Organic Chemistry of Life" class in college because the chemical reaction is well known, and the concept relates well to practical reality. Being that we're trying to keep things simple, let's invoke a diagram:

Basically, when peanuts get moldy, aflatoxin is produced. Aflatoxin wedges itself into your DNA.

As a normal part of your life, your cells (the building blocks of YOU!) make copies of themselves as you grow and change. There's machinery inside each of your cells that makes copies of your DNA. Your DNA is your internal guidebook for everything about you - your hair color, your metabolism, and every piece of communication and cooperation that happens within you.

If a DNA intercalator wedges itself into your DNA, the DNA copy machine trips over it and messes up. It changes your code. Sometimes a harmless error is made. Sometimes an important error is made and your code changes in a way that throws off all future communications that cell will engage in. We'll call these code changes "DNA mutations". DNA mutations can make your cells grow faster, stop listening, and hide from your internal army of immune cells that constantly patrol and keep a lookout cancerous cells, among other things. Liver cancer is a common outcome, as your liver ends up interacting with aflatoxin as a byproduct of processing what you eat.

Is it just peanuts we have to worry about here? 

Peanuts seem to be the most commonly associated food, but cooking oils, corn, major cereal crops / grains, tree nuts, and cotton seed can all be affected. 

Just by eating it? 

Eating it, and sometimes even touching it - some types of aflatoxin permeate the skin. Also, meat can contain aflatoxin if the animals were fed moldy grains. 

Uh, so what do I do with this newfound trove of information?

The United States FDA has set thresholds for safe levels of aflatoxins in food products, and commercial food products are routinely screened, so the first thing to do is breathe a sigh of relief. Next, throw out any nut or grain products that are past their expiration date or have visible signs of mold... or have just been sitting in your pantry for way too long. 

Questions? Leave a comment!

- Angela