Mid 1.10 Hypersensitivity Reactions Type I, Amsflashcards16

Front 1

What causes hypersensitivity reactions?

Back 1

Abnormal immune reaction to an antigen in a previously sensitized host, leading to tissue damage in the host

Front 2

Four major types (Gell Coombs categories) of Hypersensitivity reactions, and prototype examples of each?

Back 2

1. Type I: Immediate Hypersensitivity (ex. hayfever, allergic asthma, hives, wheal and flare skin reaction)
2. Type II: Antibody-Mediated (ex. hemolytic anemia, goodpasture syndrome, graves disease, myasthenia gravis)
3. Type III: Immune Complex (ex. Lupus, serum sickness, post-streptococcal glomerulonephritis)
4. Type IV. Delayed Hypersensitivity (ex. poison ivy, host reaction to TB)

Front 3

Which of the four Hypersensitivity reaction types is the only one that is NOT antibody-mediated?

Back 3

Type IV (Delayed Hypersensitivity) is cell-mediated..it does NOT involve antibodies!

Front 4

Three "key players" in Hypersensitivity Type I reactions

Back 4

TH2 cells, IgE, Mast cells

Front 5

Key event in Type I reactions?

Back 5

MAST CELLS play an important role: Ag binds to IgE already on mast cells --> cross linking of IgE receptors --> degranulation of mast cells --> release of chemical mediators --> clinical effects

Front 6

What event causes the major clinical symptoms in Type I reactions?

Back 6

Degranulation of mast cells and release of chemical mediators

Front 7

What are the two major steps of Type I reactions?

Back 7

Sensitization and Re-Exposure

Front 8

What happens in the Sensitization phase of Type I reactions?

Back 8

Sensitization: host is first exposed to the antigen and produces specific IgE to that allergen

Steps:
1. Dendritic cell picks up allergen and presents it to CD4 cells, which differentiate and activate to TH2 cells
2. TH2 cells produce a variety of cytokines with different functions (mainly IL4 and IL14 to turn on IgE-producing B cells, and IL3 IL5 and GM-CSF to promote survival of eosinophils)
3. TH2 and B cells "dance" in peripheral lymphoid tissues.
4.There, under the influence of the IL-4 produced by the TH2 cells, activated B cells undergo class switching, and mature into IgE-producing plasma cells

Front 9

What happens in the Re-exposure phase of Type I reactions?

Back 9

On re-exposure to the same allergen, the allergen binds to the mast-cell bound IgE --> cross linking of adjacent IgE receptors --> mast cell degranulation --> clinical symptoms

Front 10

What are the vascular symptoms of Type I reactions?

Back 10

Increased: blood flow, vascular permeability, fluid, cells, and proteins in tissues (--> edema)

Vasodilation leads to hypotension

Front 11

What happens to airways, nasal passages, and GI tract in Type I reactions?

Back 11

Airways: bronchoconstrion (smooth muscle spasm), mucous secretion leads to congestion, wheezing, coughing, and eventually asphyxiation

Nasal passages: congestion, sneezing

GI tract: increased fluid secretion and peristalsis lead to nausea, vomiting, and diarrhea

Front 12

What are the two phases of Type I reactions?

Back 12

Immediate/Early reaction: Onset in 5-30 minutes, subsides in 60 minutes, due to mast cell degranulation

Late-Phase reaction: Begins 2-24 hours later (WITHOUT additional exposure to antigen), due to CELLULAR infiltrate, NOT mast cell degranulation

Front 13

What are some of the pre-formed (primary) mediators released in Type I reactions?

Back 13

Histamine: increases vascular permeability, vasodilation, bronchoconstriction, and mucous secretion (responsible for the edema, runny nose, and runny eyes symptoms)

Also, proteases, chemotactic factors, and lipid mediators. Most important Lipid mediators are Leukotriene CD4 and D4, which lead to bronchial smooth muscle contraction

Front 14

Which mediators of Type I reactions need to be synthesized?

Back 14

Cytokines:
TNF: promotes influx of inflammatory cells
IL3, IL5, GM-CSF: activates eosinophil and promotes their survival (most important in late-phase reactions)
IL4: promotes TH2 differentiation, helps make IgE
Chemokines: recruit inflammatory cells to sites of injury

Front 15

Why are eosinophils so important in Type I reactions?

Back 15

They amplify the inflammatory response in the late-phase reaction, and don't require the continued presence of an antigen.

These are the major cause of symptoms in many Type I reactions, like asthma. Treatment with steroids will inhibit this inflammatory response

Front 16

Why can't you treat allergic asthma with antihistamine alone?

Back 16

Though histamines do cause some bronchoconstriction, the majority of the bronchoconstriction that causes allergic asthma is due to Leukotriene CD4 and D4: this is the most vasoactive and spasmogenic agent released in this response.
Treatment with steroids inhibits this inflammatory response

Front 17

What is the most potent eosinophil-activating cytokine?

Back 17

IL-5

Front 18

What substances do eosinophils secrete, and why are they important?

Back 18

Highly toxic granule proteins (like major basic protein) are toxic to parasites. They are also toxic to epithelial cells, which is why host tissue can be damaged in Type I responses as well.

Eosinophils also secrete enzymes and lipid mediators

Front 19

What are the four routes of allergen administration? Prototypes for each?

Back 19

Intravenous: can lead to anaphylaxis (ie. bee sting, IV penicillin)
Ingestion: also has a risk of anaphylaxis (ie. food allergy)
Inhalation: upper airway (ie. hayfever), lower airway (ie. allergic asthma--anaphylaxis risk)
Subcutaneous: wheal and flare (anaphylaxis risk)

Front 20

What do the local and systemic reactions of a Food Allergy look like?

Back 20

Local reaction: ingest allergen --> mucosal IgE-coated mast cell degranulation --> contraction of intestinal smooth muscle (vomiting), outflow of fluid into gut (diarrhea)

Systemic reaction: if Ag diffuses in the blood instead of remaining localized in the GI tract, patient can have urticaria (hives), laryngeal edema, bronchospasm, and anaphylaxis

Front 21

What are angioedema and urticaria?

Back 21

Part of the systemic food allergy reaction

Angioedema: localized swelling of deeper layers of skin and subcutaneous tissue (on this boy's lips)
Urticaria: hives (on this boy's chest)

Front 22

What is an Epi-pen used for, and how does it work?

Back 22

Patients who know they are allergic to common food items or insect venom often carry an Epi-pen containing epinephrine in an easy to administer spring-loaded syringe.

Epinephrine is a bronchodilator, which can be lifesaving for someone having a Type I reaction

Front 23

Are all Type I reactions IgE mediated?

Back 23

YES! If it is not IgE mediated, it is NOT a Type I reaction!

Front 24

Classic symptoms of Hayfever? Which mediators are responsible?

Back 24

"Allergic rhinitis and conjunctivitis"

Affects the uppe airway: itchy eyes, runny nose, sneezing

Histamine is the responsible mediator (so, treat with anti-histamines)

Front 25

What would the histology of chronic allergic asthma look like?

Back 25

Look for chronic changes: thickening of basement membrane of bronchial mucosa, bronchial smooth muscle hypertrophy, chronic inflammatory cells in bronchial wall, edema, increased numbers of mast cells, eosinophil-containing mucous in bronchi

Front 26

What are the classic symptoms, medators, treatment, and triggers for allergic asthma?

Back 26

Symptoms: lower airways: wheezing, coughing, shortness of breath

Mediators: influx of inflammatory cells and activated mast cells

Treatment:
Mast cell “stabilizers”: Cromolyn
Bronchodilators: Epinephrine, Theophyline
Blocking inflammation: Corticosteroids
Leukotriene Inhibitors: Montelukast (Singulair)

Triggers: usually small, highly soluble proteins

Front 27

What are the main causes of asthma?

Back 27

70% of asthma is “allergic" (IgE mediated), 30% is triggered by non-immune stimuli (cold, exercise)

Front 28

What is the classic clinical symptom of a subcutaneous Type I reaction?

Back 28

Wheal and Flare reaction: can appear within 5-10 minutes after administration of antigen and usually subsides in less than an hour. Due to local release of histamine

Front 29

How do you determine allergies?

Back 29

History (consider possibility of cross-reactivity)
Skin testing (relies on the “wheal and flare” reaction)
Radioallergosorbent (RAST) Test: measures specific serum IgE antibodies

Front 30

How does skin testing work?

Back 30

Subcutaneous injection of the allergen in question --> look for a wheal and flare response

Be sure to do this in a controlled environment (ie. a doctor's office) due to risk of anapyhlaxis!

Front 31

What are the most common allergies?

Back 31

Food: milk, egg, peanut, tree nut, fish, shellfish, soy, wheat
Airborne: dust mites, pollen, molds, pet dander, cockroaches
Other: insect venom, medications, chemicals

Front 32

What is Atopy?

Back 32

Atopic individuals are prone to produce IgE antibodies in response to various antigens, and have strong, immediate hypersensitivity reactions. Genetic.

Front 33

What is the Atopic triad?

Back 33

1. Allergic rhinitis (hayfever)
2. Asthma
3. Atopic dermatitis (chronic eczema) or urticaria

Front 34

What is the hygiene hypothesis?

Back 34

Basically states that our lifestyle and decreased early exposure to antigens can lead to the expression of the allergic diseases such as asthma. Suggests that we "eat dirt" to gain more exposure to antigens early on.

Front 35

What are allergy shots? How do they work? What are the risks?

Back 35

Small but increasing quantities of antigen are administered subcutaneously 1-2x weekly for several months followed by monthly injections (typically for 3-5 years). Good for preventing acute anaphylaxis to bee venom, or treating seasonal allergies.

Mechanism is unknown, but possibilities include:
A change in predominant phenotype from TH2 → TH1, or induction of T cell tolerance

Risks are the same as with skin testing: anaphylactic reaction

Front 36

What is the link between immunotherapy and allergy?

Back 36

Normally, the binding of IgE to mast cells triggers the release or synthesis of histamine, leukotrienes, and other mediators of anaphylaxis.
Anti-IgE antibodies suppress mediator release by forming complexes with free IgE, thus preventing it from binding to mast cells and decreasing the allergic reaction.

Omalizumab (Xolair): is an FDA-approved human monoclonal antibody used for severe allergic asthma treatment