allergies and hypersensitivity

What is the most common food allergy in children?

Peanut

Symptoms of a peanut allergy

*gastrointestinal pain
• diarrhea
• nausea
• hives
• Itching or tingling sensation on or around your mouth or throat
• swelling of the lips, tongue, or throat
• respiratory problems, such as shortness of breath and wheezing
• drop in blood pressure
• racing pulse
• confusion
• dizziness
• loss of consciousness
• coronary artery spasms may lead to heart attack

Treatment for an allergic reaction

-Mild reactions can be treated with OTC antihistamines

-Severe reactions require administration of epinephrine (such as an Epi-pen)

What happens when the allergic reaction starts vs when the epinephrine is administered

When you start to have an allergic reaction your blood pressure drops significantly, however whenever the epinephrine is administered your blood pressure starts to increase

Allergen classes

-Prolamin superfamily

-Cupin superfamily

-Profilins

-bet v-1-related proteins

-oleosin

-defensin

when are allergens in food considered major?

Allergens in food are considered major if they are recognized by the serum IgE of greater than 50% of the allergic population

The cause of allergic reaction

• your immune system makes IgE antibodies to the peanut allergens
• these IgE molecules bind to the Fcε receptors on mast cells, sensitizing them
• upon the next exposure to antigen, the antigen binds to and crosslinks the IgE
molecules on the mast cells
• the mast cells degranulate and release histamine and other modulatory molecules

Hypersensitivity reaction 1: IgE mediated

Anaphylaxis

Allergies

Asthma (atopic)

Hypersensitivity reaction 2: antibodies

GPS, Graves disease

Erythroblastosis fetalis

Autoimmune hemolytic anemia

Rheumatic fever

Hypersensitivity reaction 3: Antigen- antibody complex

Glomerulonephritis

Arthus reaction

SLE Serum Sickness

Hypersensitivity reaction 4: T cell Mediated

Dermatitis (contact)

IBD

GVHD

M. Sclerosis

T1DM, TB

Rheumatoid Arthritis 

Th1

IgG production (pathogen coating)

Th2

IgE production → binds to mast cells → common allergy symptoms

Th2 vs Th1

If you have more Th2 youre more exposed to antigens, and vise versa

Hygiene hypothesis

This hypothesis proposes that early and frequent exposure to bacterial and other
antigens, such as is common in developing nations, leads to a normal Th1 response, but
that better public hygiene and less infections observed in industrialized nations may lead
to persistence of the Th2 phenotype and thereby increase our risk for developing
allergies

Allergy shots

regular injections over a period of time (generally around three to five years) to stop or reduce allergy attacks. Each shot contains a small amount of the allergens, just enough to stimulate your immune system. Overtime the allergen dose is increased to cause desensitization.

Etokimab

an antibody that inhibits the activity of IL33, which is critical in IgE mediated allergic responses

Hypersensitivity

Body’s response to a particular substance in an exaggerated way

4 types of hypersensitivity

• Type 1(allergy/anaphylaxis)

• Type 2 (cytotoxic)

• Type 3 (immune complex)

• Type 4 (Delayed type)

• ACID

Immediate vs delayed hypersensivity

• Type 1, 2, & 3 are immediate 

• Type 4 is delayed

• immediate is antibody mediated; Delayed is t cell mediated

• Immediate happens within 1-3 hours; Delayed happens in 24-72 hours

What is type 1 hypersensitivity triggered by

The interaction of allergens with allergen-specific IgE antibodies that are bound to mast cells, basophils, and eosinophils

When it binds to IgE antibodies, the cells degranulate and release a potent mixture of inflammatory mediators

Common type 1 hypersensitivity allergies

skin allergies

hay fever

allergic rhinitis

Asthma

food allergy

First step of hypersensitivity mechanism

first step is sensitization (asymptomatic)

• activation of B lymphocytes to produce IgE and sensitization of mast cells

Second step of type 1 hypersensitivity

Subsequent exposure (symptomatic)

-Includes the activation of mast cells, basophils, and degranulation 

-clinical manifestations of type 1 reactions result from mediators released during mast cells or basophil degranulation get an increased vascular permeability and inflammatory state

Effect of Mast cell degranulation

Localized reaction of type 1 hypersensitivity

Rashes or blisters in the skin

increased eye and nasal secretions, itching, and sneezing

oropharyngeal mucosal edema

abdominal pain

diarrhea

vomiting

bronchospasm

wheezing