Wednesday, August 14, 2013

Allergies

Figure 1: The immune system. Um, yeah... a little 
complicated. (Source)
The allergic response is caused by the immune system. You know what the immune system is? It’s freaking complicated, that’s what (Figure 1). There are B cells, T cells, natural killer cells (really!), dendritic cells, and mast cells. Some of these cells can morph into slightly different cell types that basically have super powers and do cool stuff to keep you healthy. Inhalant allergies are what happens when the immune system decides that normal particles from the environment are evil.

Symptoms of allergies:


Figure 2: Allergen, epitope, and 
antibody. Not to scale; antibodies 
and epitopes are about 1000 times 
smaller in comparison to the 
allergen than shown.
Allergy symptoms can range from mildly annoying to feeling like you were hit by a fatigue truck. The reason is that everyone’s immune system reacts differently to allergenic particles. In fact, only 10-30% of the world’s population suffers from allergies at all*. If you have a family history of allergies (your grandmother and father both had them, for example), your chances of developing them are increased. Once they begin, you immune system determines whether it’s going to adapt to the allergenic particles or gradually mount a full blown war against them. So why does the immune system decide random particles in the environment are evil?

First, some background. Pollen, animal dander, and mold spores are allergens (the random nice particles seen as evil). An allergen has a bunch of proteins and molecules on its surface which themselves have special little spots on them called epitopes. Antibodies are created by the immune system and the ones involved in allergies, IgE antibodies, look like this: Y. The stump of the antibody is called the constant region because it’s identical in every antibody of that type. Antibodies have specialized areas on the top of the Y arms, called the variable portion, which bind only to a specific epitope (Figure 2). IgG antibodies are involved at the beginning of the immune response, and they also look like a Y.
Figure 3: Hi, I'm ragweed pollen 
and I make some people feel like 
crap! (Source)

Let’s use ragweed as an example (Figure 3). When ragweed pollen (allergen) is inhaled (Figure 4A), it’s engulfed by antigen presenting cells (Figure 4B). It is also bound by IgG antibodies on B cells (Figure 4B, green Ys) that have a variable region matching the ragweed epitope. The antigen presenting cells, you guessed it, present the epitope to B cells and T cells, which graciously accept this lovely gift (Figure 4C).

If a T cell and a B cell near each other both recognize the same epitope, the T cell sends out activating signals to the B cell (Figure 4D, B cells ACTIVATE!). The B cells are normally little IgG factories, but the T cell makes them switch to making IgE instead (blue Ys). The B cell then makes a bunch** of IgE antibodies that have the ragweed epitope binding region (Figure 4E) in preparation for their next encounter. This massive troop of ragweed-specific IgE antibodies leave the B cell and bind to mast cells (Figure 4F) and just hang out there… waiting.

The next time the person breathes in ragweed pollen BAM! The pollen binds the IgE antibodies located on the mast cells (Figure 4G), which causes changes in the cell to make it EXPLODE. The mast cell spews histamine and other allergy mediators, called cytokines, everywhere (Figure 4H). These mediators are responsible for allergy symptoms.

Figure 4: The allergenic process.

Here’s the breakdown:

There are several types of histamine receptors** in the body located on different kinds of cells. They’re conveniently named H1, H2, H3, and H4 receptors but only H1 and H2 are involved in the allergic response. When histamine binds to H2 receptors on blood vessel cells in the nose it causes the vessels to get larger (dilate). When it binds to H1 receptors of the nasal blood vessels, it makes fluid (called lymph) leak out into the surrounding tissue causing swelling. The dilated vessels and swelling cause nasal congestion. When you’re congested, it’s not that your nose is plugged with snot, the tissue is actually swollen and partially blocking airflow. There may be a lot of snot running out of there too though because histamine increases mucus (snot) production as well.

The ever-present itchiness associated with allergies is due to the activation of H1 receptors on sensory neurons, again by histamine. Sensory neurons are specialized for different sensations: itch, pain, temperature, etc. The receptor part of the neuron is in the tissue but it has a looooong arm that reaches up into the brain connecting with other neurons along the way. When histamine binds the itch receptor, the neuron brings a signal to the parts of the brain responsible for recognizing itchiness (the anterior cingulate cortex and parietal lobe, if you’re interested).

And now we all hate histamine. Don’t hate too hard though, histamine does good things too like increasing acid release into your stomach to digest food!


Special thanks to Dr. Alex Taylor, aka @AntibodyBoy, for helping me get this blog post right.

*Though this percentage is rising and it is a major cause of concern. Read this nice dense “white book” if you’re interested.

**Relative to the normal amount, still not very many in the grand scheme of things. 
***Receptors are proteins on the outside of cells that recognize other proteins. The other proteins bind to the receptor and cause changes in the cell that lead to a response.

I am not a medical doctor, none of this is intended as medical advice, and I cannot diagnose you in the comments. If you are concerned about your health, please see your physician.

References
R. Pawankar, G.W. Canonica, S.T. Holgate, et al. (2012) WAO White Book on Allergy 2001-2012 Executive Summary, Milwaukee, WI.
K.D. Stone, C. Prussin, and D.D. Metcalfe (2010) IgE, mast cells, basophils, and eosinophils., The journal of allergy and clinical immunology. 125, S73–80.
R.M. Naclerio, C. Bachert, and J.N. Baraniuk (2010) Pathophysiology of nasal congestion., International journal of general medicine. 3, 47–57.
S.G. Leknes, S. Bantick, C.M. Willis, et al. (2007) Itch and motivation to scratch: an investigation of the central and peripheral correlates of allergen- and histamine-induced itch in humans, Journal of neurophysiology. 97, 415–22.

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