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

Summary

The video script explains hypersensitivity, focusing on type one reactions mediated by IgE antibodies. It details how allergens trigger allergic responses through a two-step process involving sensitization and subsequent exposure. The script delves into the genetic predisposition to allergies, the role of T-helper cells and interleukins in the immune response, and the release of mediators like histamine causing symptoms. It also covers the treatment options for managing allergic reactions, including antihistamines, corticosteroids, and epinephrine, emphasizing the importance of medical attention in severe cases.

Takeaways

• 🛡️ Hypersensitivity is an immune system reaction that can damage the body instead of protecting it.
• 🔍 There are four types of hypersensitivities, with Type I being IgE-mediated and involving immediate reactions.
• 🌟 The term 'allergy' originates from Greek words meaning 'other' and 'reactivity', referring to reactions to external molecules.
• 👃 Allergic reactions can occur from various sources, including foods, animal dander, bee stings, and pollen.
• 🧬 Genetic predisposition plays a role in allergies, making them more common within families.
• 🔑 The process of an allergic reaction involves two steps: sensitization upon first exposure and a more serious reaction upon subsequent exposure.
• 🧬 T-helper cells, particularly the TH2 type, are crucial in the development of Type I hypersensitivity reactions.
• 💉 Interleukins such as IL-4, IL-5, and IL-10 influence the differentiation of T-helper cells into TH2 cells.
• 🚀 The production of IgE antibodies and the activation of eosinophils are key components of the allergic response.
• 🏥 During an allergic reaction, mast cells release mediators like histamine, causing symptoms such as bronchoconstriction and edema.
• 🚑 Severe allergic reactions can lead to anaphylactic shock, which requires immediate medical attention.
• 💊 Treatment for Type I hypersensitivity can include antihistamines, corticosteroids, and epinephrine to manage symptoms and prevent anaphylactic shock.

Q & A

What is hypersensitivity and how does it differ from a normal immune response?

Hypersensitivity is a condition where the immune system reacts to a substance in a way that ends up damaging the body instead of protecting it. Unlike a normal immune response that defends the body against harmful invaders, hypersensitivity involves an overreaction to typically harmless substances.

How many types of hypersensitivities are there and what are they classified based on?

There are four different types of hypersensitivities. They are classified based on the mechanisms of the immune system response, such as the type of antibodies involved, like Immunoglobulin E (IgE) in type one hypersensitivity.

What is the role of IgE in type one hypersensitivity reactions?

IgE antibodies play a crucial role in type one hypersensitivity reactions. They are involved in immediate hypersensitivity and are produced in response to allergens, leading to allergic reactions when the body encounters these substances again.

What is the origin of the term 'allergy' and what does it signify?

The term 'allergy' comes from the Greek words 'Allos' meaning 'other' and 'ergon' meaning 'reactivity'. It signifies a reaction to molecules from outside the body that most people do not react to, such as substances in food, animal dander, or pollen.

How does an allergic reaction occur in two steps as described in the script?

An allergic reaction occurs in two steps: first exposure or sensitization, where the immune system recognizes the allergen and prepares a response, and a subsequent exposure, where the immune system overreacts to the allergen, leading to symptoms of an allergic reaction.

Why do some people have a genetic predisposition to allergies?

Some people have a genetic predisposition to allergies because they possess certain genes that make their T-helper cells more sensitive to specific antigens. This genetic link is why allergies tend to run in families.

What are antigen-presenting cells and what is their function in an allergic reaction?

Antigen-presenting cells, such as dendritic cells and macrophages, are immune cells that capture antigens and present them to T-helper cells in the lymph nodes. They are essential in initiating an immune response, including the allergic reaction process.

What is the significance of TH2 cells in type I hypersensitivity?

TH2 cells, or type 2 T helper cells, are significant in type I hypersensitivity as they differentiate from naive T-helper cells upon exposure to an allergen. They release interleukins that stimulate B cells to produce IgE antibodies and eosinophils, contributing to the allergic response.

How do mast cells play a role in allergic reactions?

Mast cells play a critical role in allergic reactions by binding IgE antibodies on their surface. When the person is re-exposed to the allergen, the mast cells degranulate, releasing pro-inflammatory mediators like histamine, which cause the symptoms of an allergic reaction.

What are the 'early phase reactions' and 'late phase reactions' in an allergic response?

The 'early phase reactions' occur within minutes of the second exposure to an allergen and include symptoms like bronchoconstriction, blood vessel dilation, and edema due to the release of mediators from mast cells. 'Late phase reactions' happen 8-12 hours later and involve the recruitment of more immune cells to the site of allergen exposure, resulting in a prolonged inflammatory response.

What are some common treatments for type one hypersensitivity reactions?

Treatments for type one hypersensitivity reactions can include antihistamines to block histamine effects, corticosteroids to reduce inflammation, and epinephrine, which can be administered via an EpiPen or intravenous injection to constrict blood vessels and prevent anaphylactic shock.

Outlines

00:00

🌪️ Understanding Type I Hypersensitivity and Allergic Reactions

This paragraph delves into the concept of hypersensitivity, specifically focusing on Type I hypersensitivity reactions, which are mediated by Immunoglobulin E (IgE) antibodies. It explains how these reactions, often termed immediate hypersensitivities, occur rapidly and are commonly associated with allergies. The paragraph outlines the process of sensitization, where the immune system first encounters an antigen, and the subsequent reaction, which can be triggered by allergens such as ragweed pollen. It details the genetic predisposition to allergies and the role of T-helper cells in the immune response, particularly the differentiation into TH2 cells. The paragraph also describes the activation of B cells to produce IgE antibodies and the involvement of eosinophils and mast cells in the allergic response.

05:05

🚨 The Allergic Reaction Process and Treatment Options

The second paragraph continues the discussion on allergic reactions, focusing on the mediators released during an allergic response, such as histamine, which causes various symptoms including bronchoconstriction, blood vessel dilation, and edema. It describes the 'early phase reactions' that occur minutes after allergen exposure and the 'late phase reactions' that follow hours later, involving additional immune cells. The paragraph also touches on the severity of allergic reactions, from mild symptoms like hives and allergic rhinitis to severe conditions like anaphylactic shock. It concludes with an overview of treatment options for Type I hypersensitivity, including antihistamines, corticosteroids, and epinephrine, emphasizing the importance of medical attention in severe cases.

Keywords

💡Hypersensitivity

Hypersensitivity refers to an overreaction of the immune system to a substance that is typically harmless to others. In the script, it is the overarching theme that explains how the immune system can damage the body instead of protecting it. The video discusses four types of hypersensitivities, with type one being the focus, which is mediated by the IgE antibody.

💡Immunoglobulin E (IgE)

Immunoglobulin E, or IgE, is a type of antibody that plays a central role in type one hypersensitivity reactions. The script explains that IgE antibodies are involved in allergic reactions, making them key to understanding the immediate hypersensitivity response, which is rapid and can cause harm to the individual.

💡Immediate Hypersensitivity

Immediate hypersensitivity is a term used to describe the rapid response of the immune system to an allergen, as mentioned in the script. This type of reaction is characterized by its swift onset, usually within minutes, and is typically associated with allergies that are IgE-mediated.

💡Allergens

Allergens are specific molecules from external sources that cause an allergic reaction in certain individuals. The script provides examples of allergens such as ragweed pollen, foods, animal dander, and latex. These substances are harmless to most people but trigger allergic reactions in others due to their unique immune response.

💡Sensitization

Sensitization is the first step in an allergic reaction, where the immune system is exposed to an allergen and begins to develop a response. The script describes this process as the initial exposure to an antigen, which primes the immune system for a more severe reaction upon subsequent exposure.

💡T-helper Cells

T-helper cells are a type of white blood cell that play a critical role in the immune response. In the context of the script, T-helper cells, particularly the TH2 subset, are involved in the allergic response by recognizing allergens and stimulating the production of IgE antibodies, which is central to type one hypersensitivity.

💡Interleukins

Interleukins are small proteins that are part of the cytokine family and are crucial in the immune response. The script mentions interleukin 4, 5, and 10 as examples that influence the differentiation of T-helper cells into TH2 cells, which is integral to the allergic reaction process.

💡Mast Cells

Mast cells are granulocytes that contain histamine and other inflammatory mediators. The script explains that these cells bind IgE antibodies, which, upon re-exposure to an allergen, trigger the release of these mediators, causing the symptoms of an allergic reaction.

💡Histamine

Histamine is a pro-inflammatory molecule released by mast cells during an allergic reaction. The script describes histamine's role in causing symptoms such as bronchoconstriction, increased blood vessel permeability, and edema, which are characteristic of allergic responses.

💡Anaphylactic Shock

Anaphylactic shock is a severe, life-threatening allergic reaction that can occur when the body's immune system overreacts to an allergen. The script mentions this condition as a possible outcome of type one hypersensitivity reactions, where the combined effects of increased vascular permeability and airway constriction can deprive vital organs of oxygen-rich blood.

💡Epinephrine

Epinephrine is a medication used to treat severe allergic reactions. The script discusses its use in anaphylactic shock to constrict blood vessels and prevent the severe drop in blood pressure that can lead to shock. It is often administered via an EpiPen during emergencies.

Highlights

Hypersensitivity is an immune system reaction that damages the body instead of protecting it.

There are four types of hypersensitivities, with type one relying on Immunoglobulin E (IgE) antibodies.

Type one hypersensitivity reactions are also called IgE-mediated hypersensitivities.

Immediate hypersensitivity occurs rapidly, within minutes, and is often associated with allergies.

Allergies are reactions to external molecules, or antigens, that most people do not react to.

Allergic reactions involve a two-step process: sensitization followed by a more serious subsequent exposure.

Genetic predisposition causes some people to have over-reactions to unknown molecules or allergens.

Allergies tend to run in families due to the genetic link in T-helper cell production.

In type I hypersensitivity, T-helper cells differentiate into type 2 T helper cells, or TH2 cells.

Interleukins 4, 5, and 10 influence the differentiation of T-helper cells into TH2 cells.

TH2 cells stimulate B cells to undergo antibody class-switching from IgM to IgE antibodies.

IgE antibodies bind to Fc epsilon receptors on mast cells, preparing them for an allergic reaction.

Mast cell degranulation releases pro-inflammatory mediators, including histamine, causing allergic symptoms.

Histamine causes bronchoconstriction, blood vessel dilation, and increased vascular permeability.

Late phase reactions involve the recruitment of more immune cells 8-12 hours after allergen exposure.

Severe allergic reactions can lead to anaphylactic shock, a life-threatening condition.

Treatment for type one hypersensitivity includes antihistamines, corticosteroids, and epinephrine.

Epinephrine helps prevent anaphylactic shock by constricting blood vessels.

Serious type one hypersensitivity reactions require immediate medical attention.

Transcripts

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.