Type I hypersensitivity Flashcards
Inhaled materials
- plant pollens
- dander of domesticated animals
- mold spores
- feces of very small animals - house dust mites
injected materials
- insect venoms
- vaccines
- drugs
- theraputic proteins
ingested matierals
- food
- orally administered drugs
contacted materials
- plant leaves
- industrial products made from plants
- synthetic chemicals in industrial products
- metals
Type I hypersensitivity locations
- skin
- resperatory tract
- gut
The four types of hyper sensitivity reactions are characterized by
the molecules and cell types involved
Antibody induced reactions
Type I-III
T cell induced reaction
Type IV
Type I main antibody
IgE
Type II and III main antibody
IgG
Type IV main cells
T cells and macrophages
Type I has a broad variety of severity
can be anything from seasonal allergies to life threatening anaphylaxis
Type I - IgE mediated Hypersensitivity
Results from antigen binding to antigen specific IgE which is bound to its FcR on mast cells.
Mast cells degranulate and release inflammatory mediators and histamine
- can be from runny nose to death by asphyxiation
- known as immediate hypersensitivity
- commonly caused by inhaled particulate antigens such as pollen
Type I hypersensitivity:
the mast cell is at the heart of the response
- IgE is already bound on the mast cell surface htorugh Fc receptor (epsilon).
allergic reactions develop
AFTER an individual is exposed and sensitized.
NOBODY is born allergic.
First exposure to pollen (example of an allergy)
mechanism induces Th2 type T helper response, producing IL4, stimualting B cell isotype switching to IgE (plasma cells), and then the IgE binds to surface of mast cells, which then can granulate upon a secondary encounter with the allergen.
systemic anaphylaxis
- drugs
- serum
- venoms
- peanuts
Respnse: systemic
- Edema
- Increased vascular permeability - causes vessels to become more permeable and low blood pressure - heart has to work harder to pump blood. and oxygen in tissue is way too low
- Tracheal occlusion
- circulatory response
- death
wheal and flare
skin localized
- insect bites
- allergy testing
Swelling and redness of skin
Response: local increase in blood flow and vascular permeablity
allergic rhinitis (hay fever)
Pollens, dust mite feces
Response: local, edema of nasal mucosa and irritation of nasal mucosa.
Bronchial asthma
Pollens, dust mite
Reponse: local
- bronchial constriction
- increased mucus production
- airway inflammation
Food allergy
shellfish
milk
eggs
fish
wheat
Response: systemic
- vomiting
- diarrhea
- pruritis (itching)
- Urticaria (hives)
- anaphylaxis
Allergic rhinitis case study
- among most common chronic dieases
- sneezing, drainage, nasal stuffiness
- 2004 study estimates that 25.3 million Americans, 6.7<18 years old
- seasonal or perennial (spring/summer/fall)
trees
highest in early spring
grass
highest in late spring
weeds
summer - fall
skin testing (diagnostic)
- must be off all antihistamines
- percutaneous
Serum specific IgE testing
- used when skin testing cannot be performed
wheal
swelling
flare
red color
allergic responses have..
early and late phase
early phase of an allergic response
Wheal (swelling) and flare (redness from spreading wheal)
- due to immediate mast cell degranulation
late phase of an allergic response
Generalized swelling spreading out from initial site of exposure
- due to leukotrienes, cytokines, and chemokines produced by mast cells after initial degranulation.
asthmatic reaction also have..
early and late phase
- resulting in decreased breathing capacity
Breathing capacity drops very fast initially, then goes back to normal
which of the following rxn’s requires mast cells to synthesize new immunomodulatory proteins?
Late phase
Inflammatory mediators produced by mast cells
Present in PreFormed granules
- Tryptase, chymase, cathepsin G, carboxypeptidase
- histamine, heparin
- TFN-alpha
biological effects of histamine and heparin
- Toxic to parasites
- Increase vascular permeability
- cause smooth muscle contraction
TNF-alphs promotes
inflammation, stimulates cytokine production by many cell types, activates endothelium
Enzymes: Tryptase, chymase, catepsin G, carboxypeptidase
remodeling of connective tissue matrix
Inflammatory mediators produced by mast cells
Produced in response to mast cell activation
- IL4, IL13
- IL3, IL5, GM-CSF
- CCL3
- Leukotrinenes
- PLT activating factor
IL4 and IL13
stimulate and amplify Th2 cell response
IL3, IL5, GM-CSF
promote eosinophil production and activation
CCL3 (chemokine)
chemotactic for monocytes, macrophages and neutrophils
Leukotrienes
- Cause smooth muscle contraction
- Increase vascular permeability
- Cause mucus secretion
PLT activating factor
- Chemotactic for leukocytes
- Amplifies production of lipid mediators
- Activates neutrophils, eosinophils, platelets
How do we treat allergic rhinitis?
- Avoidance
- antihistamines
- nasal steroids
- immunotherapy
1. Give increasing concentration of allergens to induce tolerance
2. IgE = initial increase in specific IgE levels but long term decrease in specific IgE
3. IgG = allergen specific IgG1, IgG4, IgA increase with immunotherapy
4. other lymphocyte markers - IL10,TGFbeta prod. from (CD4+, CD25+ Tregg cells)
5. Shift in Th1/Th2 balance (want to favor Th1)
Effects of IgE mediated allergic reactions vary with the site of mast cell activation
- Gastrointestinal tract
- Airways
- Blood vessel
GI tract (mast cell activation and granule release)
Increase fluid secretion, increased peristalsis
- expulsion of GI tract contents: diarrhea and vomitting
Airways (mast cell activation and granule release)
Decreased diameter, increased mucus secretion
- expulsion of airway contents (phlegm, coughing)
blood vessel (mast cell activation and granule release)
Increased blood flow, increased permeability
- edema
- inflammation
- increased lymph flow and carriage of antigen to lymph nodes
Systemic anaphylaxis secondary to food ingestion
symptoms:
Cardiovascular (most threatening)
- hypotension, tachyardia, bradycardia, shock, MI
Respiratory
- laryngeal/pharyngeal edema, rhinitis, wheezing, cough, shortness of breath
Cutaneous
- pruruitis, urticaria, angioedema, flushing
GI
- nausea, vomiting, diarrhea, abdominal cramping
Ocular (least threatening)
- pruritis, tearing, redness
How does epinephrine work against a systematic anaphylaxis reaction
- contricts blood vessels - decreases swelling and increase BP
- Increases contraction and heart rate
- relaxes muscles around airways in the lungs
- prevents release of additional allergic chemicals
food allergy
incidence of food allergy in the US ranges from 4-6% in children, 1-3% in adults
Incidence is rising, especially peanuts allergies (doubled last few years)
major allergenic foods in children
milk, egg, soy, wheat, peanut, tree nut
major allergenic foods in adults
peanut, tree nut, shellfish
<0.35 kU/L
indicates a negative test
Allergies may be lifelong
peanut tend to be lifelong, although studies show that abt 20% of children with peanut allergt do eventually outgrow their allergy
Children that are allergic to milk, egg or soy, were most likely to outgrow their allergies
The likelihood of outgrowing shellfish, tree nut, and peanut allergies was significantly lower.
systematic anaphylaxis :
caused by allergens that reach the bloodstream and activate mast cells systematically
Heart and vascular system
(anaphylaxis)
- increased capilarry permability and entre of fluid into tissues
- swelling of tissues
- including tongue
- loss of BP
- Reduced oxygen to tissues
- irregylar heartbeat
- anaphylactic shock
- loss of conciousness
Respiratory tract
(anaphylaxis)
- contraction of smooth muscle and constriction of throat and airways
- difficulty breathing and swallowing
- wheezing
GI (anaphylaxis)
- contraction of smooth muscle
- stomach cramps
- vomiting
- fluid outlflow into gut
- diarrhea
prevention
minimize exposure
- remove allergen from diet or environment
pharmalogical treatment
minimize impact of exposure
- antihistamines
- corticosteroids
- epinephrine
desensitization treatment
- give allergy in controlled escalating doses in an attempt to shift antibody isotype from IgE to IgG4
- or induce anergy in T cells using MHC peptide complexes
if you coulld engineer a T cell response to inhibit tyep I hypersensitivity, which type of Th susbset would you enlist?
Th1, Treg
