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High Yield Notes
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Anaphylaxis is characterized by a type I hypersensitivity reaction that results from free antigen cross-linking immunoglobulin E on the presensitized cells.


USMLE® Step 1 style questions USMLE

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USMLE® Step 2 style questions USMLE

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A 17-year-old girl comes to the clinic for a routine health maintenance examination. She has been well and reports no concerns. She has a history of atopy but requires no regular medication. Physical examination shows dermatographism. The type of hypersensitivity involved in dermatographism is the same as which of the following?  

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Anaphylaxis comes from the greek word “ana-“ which roughly means against and “phylaxis” which means protection, implying that someone’s immune system has reacted to something in such a way that ends up damaging them, instead of protecting them.

It’s basically a severe type of allergic reaction that affects multiple organ systems and it’s potentially life-threatening.

Normally, the immune system recognizes and acts against pathogens that can cause disease.

These pathogens have specific molecules on their surface, called antigens, and they help trigger an immune response.

In some individuals, though, the immune system overreacts and starts targeting harmless molecules that don’t cause any problems for most people.

These include molecules found in foods like peanuts and shellfish, medications like antibiotics, and in the venom of insect bites.

In most cases, there might be a mild to moderate allergy, but sometimes things get really serious, involving two or more organ systems, and at that point it’s called anaphylaxis.

Anaphylaxis, just like any allergic response, happens in two steps, a first exposure, or sensitization, and then a subsequent exposure, which is when it actually gets a lot worse.

So, let’s say a person is stung by a bee from a nearby beehive, for the first time in their life.

When the bee pierces the skin with its stinger, its venom gets into the skin.

Part of that venom molecule can get picked up by a dendritic cell, which is a type of immune cell.

The dendritic cell gobbles up the foreign particle and presents it to a nearby lymphocyte, called a T cell.

If the T cell is activated, it starts to produce cytokines, which stimulate B cells, another group of lymphocytes, which produce IgE antibodies.

These IgE antibodies get released into the bloodstream and bind to the surface of mast cells and basophils, which are immune cells that are full of granules that contain proinflammatory molecules.

Okay now, let’s say that that same person is stung by a bee again, maybe a few months later, then it’s probably time for this person to move away from this beehive, because they’re obviously lousy neighbors.

Nevertheless, with this second exposure, the mast cells and basophils which already have IgE antibodies on their surface, bind to the antigen and release their proinflammatory molecules.

In a simple allergic reaction, these molecules would cause some localized damage, like swelling around the sting site.

In anaphylaxis, these molecules leak into the bloodstream and reach multiple organ systems.

Now, one of the important molecules is histamine, which causes the smooth muscle that lines the bronchi and gastrointestinal tract to contract, making those passageways narrow and tougher for air and food to get through.

At the same time, histamine causes blood vessel dilation and increased permeability, meaning that while blood vessel diameter and blood flow to the affected area increase, fluid is also allowed to more easily leak out the blood vessel wall and get into the interstitium, the space between cells.

That causes the pressure in the vessels to fall, and causes swelling or edema, as well as urticaria or hives.

In addition to histamine, tryptase is also released by mast cells.

Tryptase is a type of protease that breaks down proteins, causing tissue injury.

In some cases, mast cells and basophils also start synthesizing small proteins, called cytokines, such as interleukin- 4 (IL-4) and interleukin-13 (IL-13) that signal the B-cells to make more IgE antibodies, and tumor necrosis factor-α (TNF-α), but also leukotrienes, which are smaller molecules made out of fatty acids, like leukotriene B4 (LTB4) and leukotriene C4 (LTC4), which can attract immune cells - like neutrophils, mast cells, and eosinophils to their location even after the allergen is long-gone.

Since all these signalling molecules take a while to be formed, though, their effects don’t get seen until hours later.

Now although most anaphylactic reactions involve IgE, sometimes anaphylactic reactions don’t.