Type I hypersensitivity (IgE-mediated hypersensitivity) – causes, symptoms, pathology

By Adem Lewis / in , , , , , , , , , , /

Having a hypersensitivity means that someone’s
immune system has reacted to something in such a way that it ends up damaging them,
as opposed to protecting them. There are four different types of hypersensitivities,
and in the first type or type one, the reactions rely on Immunoglobulin E, or IgE antibody,
which is a specific type of antibody – the other major ones being IgG, IgA, IgM, and
IgD. So because IgE is involved with type one hypersensitivity
reactions they are also called IgE-mediated hypersensitivities. This type of reaction is also sometimes called
immediate hypersensitivities, because the reaction happens super fast—on the order
of minutes. So most allergic reactions are IgE-mediated,
and therefore most allergies are type I hypersensitivity reactions. “Allergy” comes from the Greek Allos which
roughly means “other” and ergon which means “reactivity”. Essentially, allergies are reactions to molecules
from outside your own body that most people don’t react to—and these are specific
molecules from things you might breathe or take in like foods, animal dander, bee stings,
mold, drugs or medications, and pollen. You can also mount an allergic reaction to
things you come in contact with on your skin like latex, lotions, and soaps. These specific molecules are also called antigens,
and when they cause an allergic reaction, they’re called allergens. An allergic reaction happens in two steps,
a first exposure, or sensitization, and then a subsequent exposure, which is when it gets
a lot more serious. People that react to these allergens usually
have a genetic predisposition to having over-reactions to unknown molecules or allergens. This means that these people have certain
genes that cause their T-helper cells to be more hypersensitive to certain antigens. Since the production of these T-helper cells
is genetically linked, allergies to things tend to run in families. So let’s say this person breathes in some
ragweed pollen, that person happens to have T-helper cells that can bind to a specific
molecule on the pollen, making that molecule an allergen. First off, that antigen gets picked up by
immune cells hanging out in the membranes along the airways, which then grab the molecule
and migrate to the lymph nodes, which happens regardless of if the person is allergic or
not. These cells are antigen-presenting cells,
since they carry the antigen to the lymph nodes and present it to the T-helper cells
living there. Dendritic cells and macrophages are examples
of antigen-presenting cells. When the person is allergic, the antigen presenting
cell will also express costimulatory molecules, which are needed to mount an effective immune
response. Before the T-helper cell sees the antigen
though, it’s called a naive T-helper, since, even though it’s built to recognize the
antigen, it hasn’t actually seen it before. When the T-helper gets its hands on the antigen
though, and also binds the costimulatory molecule, it’s now been primed, and the naive T-helper
changes into a different sort of T-helper cell. Usually in type I hypersensitivity it differentiates
into a type 2 T helper cell, or just TH2 cell, and this step happens in response to various
small proteins or interleukins that might be floating around at the time. Some interleukins that sway the T-helper cell
into turning into a TH2 cell are interleukin 4, interleukin 5, and interleukin 10, and
these are all cytokines – and they’re given numbers because it’s easier to keep track
of them that way. At any rate, the excited TH2 cells release
a bit of their own interleukin 4 and get the B cells to undergo antibody class-switching,
and so the B cell switches from making IgM antibodies to making IgE antibodies which
are specific to ragweed pollen in our example. TH2 cells also release some interleukin 5,
which stimulates production and activation of eosinophils, a granulocyte, which is a
type of white blood cell that degranulates or essentially releases a whole bunch of toxic
substances that can damage both invading cells and nearby host cells. These ragweed-specific IgE antibodies have
a high affinity for, or basically really like Fc epsilon receptors on mast cells, another
type of granulocyte, so they quickly attach themselves to the surface of mast cells. These antibodies are also called cytotropic
antibodies, since they can bind to cell surfaces. At this point it’s like the mast cell’s
been geared up for combat, and is ready for action, and therefore we’re finished with
the sensitization phase. Now let’s say that that same person breathes
in the ragweed pollen again, maybe a few months later – a second exposure. Well, the suped up mast cells, using their
coat of antibodies, binds to the antigen. Actually, it takes two or more bound antigens
to cross-link the IgE antibodies, which signals the mast cell to degranulate and release a
bunch of pro-inflammatory molecules called mediators that ultimately causes the effects
seen in an allergic reaction. One of the major mediators released in an
allergic reaction is histamine. Histamine binds to H1 receptors and causes
the smooth muscles around the bronchi to contract, which means the airways get smaller, making
it more difficult to breathe. It also causes blood vessel dilation and increased
permeability of the blood vessel walls, meaning that, while blood vessel diameter increases
and blood flow to the affected area increases, fluid is allowed to more easily leak out the
blood vessel walls and get into the interstitium, the spaces between cells, which causes edema
and swelling, and urticaria, or hives. In addition to histamine, mast cells release
other pro-inflammatory mediators including some that activate eosinophils and proteases
which chop up large proteins into small peptides. The effects of these molecules are called
“early phase reactions”, and they happen within minutes of the second exposure. There are also “late phase reactions”
though, which happen 8-12 hours after that second exposure, where even more immune cells
like TH2 cells, eosinophils, and basophils, yet another type of granulocyte, are recruited
to the site where the allergen is located because of the cytokines and pro-inflammatory
molecules produced during that early phase. These include some of those same interleukins
again, interleukin 4, interleukin 5, and interleukin 10, but also leukotrienes which are smaller
molecules made out of fatty acids and facilitate communication between a local group of cells. Two leukotrienes in particular, LTB4 and LTC4,
can not only cause smooth muscle contraction and damage to the epithelium like histamine,
but they can attract immune cells – like neutrophils, mast cells, and eosinophils to their location
even after the allergen is long-gone. A lot of people with allergic reactions experience
mild symptoms, like hives, eczema, allergic rhinitis—which is inflammation of the nose,
as well as asthma. Certain people though, when exposed to a large
load of specific allergens, like bee stings, seafood, or peanuts, can have a really severe
and potentially life threatening allergic reaction. The increased vascular permeability, along
with the constriction of airways can be severe enough such that the body can’t supply the
vital organs—like the brain, with enough oxygen-rich blood, a condition known as anaphylactic
shock. Treatment for type one hypersensitivity can
involve a variety of medications. Antihistamines, act to block the effects of
histamine, which reduces vascular permeability and bronchoconstriction. Also there’re corticosteroids, which can
be used to reduce the inflammatory response, as well as epinephrine, which is sometimes
given during severe reactions via intramuscular injections through an EpiPen or intravenous
injection. Epinephrine can help constrict blood vessels
and prevent anaphylactic shock. If there’s ever a serious type one hypersensitivity
reaction that requires something like steroids or Epinephrine, it’s super important to
get medical attention because type 1 hypersensitivity reactions can be serious and can sometimes
get slightly better before getting worse again.

45 thoughts on “Type I hypersensitivity (IgE-mediated hypersensitivity) – causes, symptoms, pathology

  1. Some nights I can’t sleep because I can suddenly feel how my toes and fingers are together and I feel the need to separate them. And I can feel blood going through my veins. I can almost hear it! I can see very small things. Like small tiny dots and it makes me not want to eat or drink out of dishes or bowls. I only like eating and drinking out of paper because I can see things all over anything else. I can feel things crawling on me all the time and it makes me feel really itchy. It makes me feel anxious and annoyed and I get zero sleep. It only happens rarely though. Is this hypersensitivity?

  2. My only wish in this life would be to know those people who dislike this kind of Videos and informations how they think. pleaaaase…

  3. Thank you Osmosis, you are the best! Too bad we don’t have e-payement here in Algeria so I can donate 🙁 You really deserve it… Thank you so much

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  5. wait…hang on, i could have sworn IL4 & 5 are B cell stimulators produced by Th2 cells not t cell stimulators… can anyone confirm this?

  6. Wow it's perfect perfect lecture. Thank you for uploading this perfect lecture. I immediately subscribed

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