Hypersensitivites Flashcards
Hypersensitivity
Excessive adaptive immune response due to innocuous antigens (allergens)
Symptoms are due to response NOT allergens
4 types
1) immediate hypersensitivity
- mast cells and IgE are responsible
2) antibody mediated
- IgM and IgG antibodies are responsible
3) immune simplex-mediated
- antigen-antibody complexes are responsible
4) T-cell mediated (delayed)
- CD4/* T cells are responsible
Sensitization phase vs effector phase
Sensitization phase
- initial exposure w/ NO tissue pathology or clinical signs
Effector phase
- clinical signs as a response to subsequent exposures after initial exposure
Type 1 hypersensativites
Immediate hypersensitivity
- Most COMMON form
Mast cells bind allergen antigens via Fc receptors
- eventually cross link w/ IgE and cause degranulation of histamine and allergy mediate cytokines
Specific steps in the sensitization phase
1) dendritic cells migrate to lymph nodes w/ allergen antigen to prime T-cells for future exposure
2) differentiation into TH2 and class switching to IgE occurs in lymph nodes
3) antigen-specific IgE binds to high affinity IgE Fc receptors on mast cells
* waits for subsequent exposure*
Mast cell degranulation
Requires at least 2 molecules of IgE must bind to an allergen
When degranulation occurs, the following are released
- histamine and enzymes (causes vascular permeability)
- cytokines (IL3/4 and TNF-a)
- chemokines (CCL3)
- lipid mediators (prostaglandins and leukotrienes)
IL-3, IL-4, TNF-a, prostaglandins and leukotrienes specific effects
IL-3: works to promotes eosinophil production and activation
IL-4: stimulates and amplifies TH2 cell response
TNF-a: promotes inflammation and stimulates stroking production
Prostaglandins and leukotrienes: smooth muscle contraction, chemotaxis of eosinophils and increases vascular permeability
- also bronchoconstriction
What is the primary mover in type 1 hypersensitivity?
Histamine
- is stored in mast cells
- binds to H2 receptors and causes the following
1) vasodialation and increased vascular permeability
2) smooth muscle contraction
3) increased mucus production
What is the secondary mediator in type 1 hypersensitivity?
Prostaglandins and leukotrienes
- not stored and is produced de novo from histamine reactions
- Prostaglandin effects:
- vasodilation
- bronchoconstriction
- chemotaxis for neutrophils and eosinophils
Leukotrienes
- vasodilation
- increases vascular permeability
- smooth muscle contraction
- increases mucus production
act as positive feedback loops
What molecules dominate the early and late phase reactions?
Early phase (IgE mediated activation of mast cells):
- histamine
- neutrophils
Late phase (Accumulation of inflammatory cells):
- neutrophils
- ICAM-1
- eosinophils
long term exposure causes mediated chronic allergic inflammation
Exposure an doseage of allergen with respect to the symptoms
Intravenous high dosage = systemic/anaphylaxis shock
Subcutaneous low dosage = wheel and flare symptoms
Inhalation low dosage = asthma and rhinitis
Ingestion = diarrhea and vomiting w/ hives
this can lead to blood borne as secondary
Inhaled allergens and how it causes localized anaphylaxis in upper respiratory responses
Mast cells in nasal mucosa and conjunctiva react
- usually seasonal and year-round
Symptoms
- inflammation of nasal airway causes stuffy nose and rhinitis
- increased mucus production
- itchy eyes
Inhaled allergens and how it causes localized anaphylaxis in lower respiratory responses
Causes allergic asthm a
- mast cells in lower airways are reactive
Treated w/ SABA
Skin allergies
Mast cells in dermis are activated
- also is associated with filaggrin protein defects (causes itching) which allows the allergen to penetrate easier
Extreme cases lead to hives
- subcutaneous mast cell degranulation
- leads to vasodilation and edema
Intradermal skin tests
Used to determine if someone is allergic to allot he most common allergens
- patient is monitored for immediate reaction and 8-48hrs after for delayed reaction
has a rare chance of causing new sensitization and late-phase reactions to an allergen
Systemic anaphylaxis
Occurs when allergens enter the blood
- causes mass degranulation of mast cells
- causes immediate vomiting, malaise, systemic edema and vasodilation
Treatment = Epi pen and corticosteroids (if needed)
