APPP 21: Hypersensitivity Reactions Flashcards
What are hypersensitivity reactions?
altered immunological response to an antigen that results in disease or damage to host
What are the 2 ways that hypersensitivity reactions can be classified by?
- mechanisms that cause the disease (Gell and Coombs classification – type I-IV)
- source of antigens
What are the 3 sources of antigens that can cause hypersensitivity reactions?
- allergy: over-reactivity to otherwise unharmful environmental antigens or chemicals
- autoimmunity: disturbance of immunological tolerance of self-antigens
- alloimmunity: immunological reactions against tissues of another individual (blood transfusion, organ transplant, fetus during pregnancy)
Type I Hypersensitivity
- IgE mediated
- classic allergy
- onset in minutes
Type II Hypersensitivity
- IgG/IgM mediated
- cytotoxic reactions
- onset in hours to days
Type III Hypersensitivity
- IgG/IgM
- immune-complex diseases
- onset in hours to weeks (1st encounter)
Type IV Hypersensitivity
- T cell
- delayed type hypersensitivity
- onset in 2-3 days
Mechanism of Allergic Response
How does degranulation occur?
- allergen binds IgE/FceR1 on mast cell surface
- cross-links of two IgE to activate degranulation signal with tyrosine phosphorylation
- Ca2+ influx
- degranulation and release of inflammation mediators
- granule contents include histamine, proteases, chemotactic factors (ECF, NCF)
What is an immediate phase event?
- release of histamine and cytokines by mast cells
- occurs within minutes following exposure to allergens
What is a late phase event?
- induction and continuing synthesis of eicosanoids, cytokines, and chemokines
- immune cell infiltrate (eosinophils and others)
- smooth muscle contraction, edema
- may last hours to days, and lead to chronic inflammatory reaction
Mechanism of Allergic Response
What is sensitization?
- first antibodies made following antigen presentation are from IgM or IgG classes
- repeated exposure is needed for switching (to IgE) in the presence of correct cytokines (IL-4)
Mechanism of Allergic Response
What is the effector stage?
- high affinity IgE receptor (FceR1) found on mast cells, basophils, and activated eosinophils
- subsequent to sensitization, increasing number of mast cells are primed with (already binding to) IgE on surface
How are we exposed to allergens?
commonly though mucosal exposure
- airway
- gastrointestinal
- urogenital
Type I Hypersensitivity Reactions
What is localized anaphylaxis?
target organ responds to direct contact with allergens
Type I Hypersensitivity Reactions – Localized Anaphylaxis
Lung
- disease
- major symptoms
- common allergens
- route
- asthma
- wheezing, dyspnea
- pollens, dust, danders
- inhalation
Type I Hypersensitivity Reactions – Localized Anaphylaxis
Nose/Eyes
- disease
- major symptoms
- common allergens
- route
- rhinitis (hay fever)
- running nose, itchiness
- pollens
- mucous membrane
Type I Hypersensitivity Reactions – Localized Anaphylaxis
Skin
- disease
- major symptoms
- common allergens
- route
- urticaria (hives)
- itchiness and blisters
- foods, medications
- ingestion
Type I Hypersensitivity Reactions – Localized Anaphylaxis
GI Tract
- disease
- major symptoms
- common allergens
- route
- allergic gastroenteropathy
- vomiting, diarrhea
- foods
- ingestion
Type I Hypersensitivity Reactions
What is systemic anaphylaxis?
systemic vasodilation and smooth muscle contraction leading to severe bronchiole constriction, edema, and hypotension (shock)
- tachycardia, arrhythmia, cyanosis, and cardiac arrest can occur
- anaphylactic shock requires immediate medical interventions
- biphasic presentations up to 30% of cases
Type I Hypersensitivity Reactions
What is atopy?
associated with genetic predisposition for localized anaphylaxis
- atopic individuals have higher levels of IgE and eosinophils
Type I Hypersensitivity Reactions – Genetic Predisposition
What are the candidate polymorphic genes related to atopy? (5)
- IL-4 receptor
- IL-4 cytokine (promoter region)
- FceRI: high affinity IgE receptor
- class II MHC (present peptides promoting Th2 response)
- inflammation genes
Type I Hypersensitivity Reactions – Genetic Predisposition
What is the allergic triangle?
people who have one atopic condition are more likely to develop another atopic condition, and the trigger factors for each may be the same
Type II: Cytotoxic Hypersensitivity
What is this hypersensitivity mediated by?
inappropriate binding of antibodies (IgG or IgM) to a tissue cell surface antigen, including:
- extrinsic antigens presented on a cell surface following an infection
- chemical that modified a cell surface component (ie. penicillin binding to RBC and quinine binding to platelet)
- self antigen (auto-immune disease)
Type II: Cytotoxic Hypersensitivity
Antibody binding directs cellular toxicity of target cells through ____________. (2)
- classical complement pathway MAC
- immune cell mediated ADCC