Hypersensitivity I

This is a topic that I've spoken about before, notably here and here. But now we get to go over it again! Yay!

Hypersensitivity is basically when your immune system is oversensitive and freaks out at random shit that most would consider to be harmless. (Essentially me in a nutshell- my immune system is probably the only thing about me that generally isn't hypersensitive. At least, as far as I know, it isn't hypersensitive.)

In this post I'm going to talk about Type I hypersensitivity, which is analogous to type B immediate drug reactions. It is also known as IgE-mediated hypersensitivity, and you'll see why that is in a moment. Atopy is the tendency of an individual to develop this type of hypersensitivity.

Sensitisation and Activation

Believe it or not, people with allergies generally aren't born immediately allergic to stuff. They have to be sensitised first.

In the first exposure to an allergen, IgM is produced, just like in every other immune response. Over the course of the immune response, though, T_H2 cells are activated and produce IL-4 and IL-13. These cytokines stimulate the class switching of B cells to produce IgE. IgE can then bind to FcεRI (Fc-epsilon-receptor I) on mast cells, where they sit there and wait for the next exposure to the allergen.

In subsequent exposures to the allergen, IgE bound to mast cells cross-links, causing the mast cell to degranulate, or release its granules. The first wave of stuff to be released are granules containing vasoactive amines such as histamine, which cause vasodilation and itchiness. Chemotactic factors that attract neutrophils and eosinophils are also released at this stage. The next wave consists of lipid mediators such as prostaglandins and leukotrienes, which add to the vasodilation. The third wave consists of cytokines, such as IL-3 and IL-5, which induce more eosinophil activation, and IL-4 and IL-13, which induce greater activation of T_H2 cells. A chemokine called MIP-1α, which attracts neutrophils, is also released at this stage.

Fun fact of the day: some allergens (essentially antigens that cause allergic responses) are also enzymes. For example, phospholipase A2, which I've spoken about here and here, is found in bee venom. Cysteine protease, also known as the Der p 1 enzyme (herp derp!) is found in the faecal pellets of house dust mites. Der p 1/cysteine protease can cleave occludin, which is a protein found in tight junctions, allowing it to enter the mucosa. In the mucosa, it meets dendritic cells, which go off and do their whole antigen presenting thing, which ultimately leads to T-cell activation, B-cell activation and BOOM the poor person has now been sensitised to dust.

Allergic Rhinitis

Allergic rhinitis is an immune system disease in which the body responds to allergens in the upper respiratory tract. Some of the symptoms of this include excess mucus secretion, which leads to coughing, sneezing and difficulty breathing. There may also be some irritation due to histamine, which can be treated via antihistamines.

Bronchial Asthma

In contrast to allergic rhinitis, allergens in bronchial asthma tend to affect the lower respiratory tract. People with this condition essentially have chronic bronchial inflammation, causing repeated asthma attacks and possible tissue destruction in the alveoli further down the track. The culprits here are eosinophils, cytokines released by T_H2 cells and LTC4. LTC4 is a leukotriene released from mast cells which causes bronchoconstriction.

There are several medications that can help people with asthma. Cromolyn is a medication that can stabilise mast cells, preventing release of vasoconstrictive leukotrienes. Corticosteroids can halt production of inflammatory cytokines. Epinephrine/adrenaline can prevent bronchoconstriction.

Food Allergies

Food allergies are, well, allergies caused by food. They can cause vomiting, diarrhoea, skin conditions and, in really bad cases, anaphylaxis. Skin conditions that can be caused by food allergies include urticaria (hives), which is an acute condition that can be treated with antihistamines, and atopic eczema, which is a chronic condition that requires more aggressive treatment with corticosteroids. Anaphylaxis, as I've mentioned before, is basically when the histamine and other inflammatory mediators go overboard, causing blood pressure to drop and airways to constrict, ultimately leading to death if medical attention isn't sought quickly. This can be treated via epinephrine, which is often given via an automatic injector like the EpiPen.

Skin Prick Test

If type I hypersensitivity is suspected, a skin prick test can be done to make a more definitive diagnosis. In this test, a low dose of an antigen is delivered subcutaneously. If the patient is allergic, then around 20 minutes later they will develop a "wheal and flare." The "wheal" is a small swelling, and a "flare" is erythema (redness) surrounding the wheal.