Term
What are the methods of entry of allergens? |
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Definition
Inhaled, ingested, or contacted to skin or mucous membranes |
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Term
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Definition
A type 1 immediate hypersensitivity reaction |
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Term
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Definition
The propensity of an individual to produce IgE antibodies in response to various environmental antigens and to develop strong immediate hypersensitivity responses |
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Term
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Definition
Component that elicits an immediate hypersensitivity reaction. |
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Term
What are physical properties of antigens? |
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Definition
Usually proteins or chemicals bound to proteins. Low to medium molecular weight. Have stability, glycosylation, and high solubility in body fluids |
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Term
What are the important characteristics of antigens? |
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Definition
They require repeated exposure and do not stimulate innate immune responses |
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Term
What is the immune response to atopic disease? |
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Definition
TH2-mediated inflammation. Naive CD4 cells polarize into differentiated subsets in response to cytokines present in the early immune response |
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Term
What process does an APC go through to present an antigen? |
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Definition
It enounters and processes the antigen, travels to the draining lymph node, and presents the antigen to various naive T cells until it encounters a T cell specific for that antigen |
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Term
What happens to the naive T cell after the APC presents an allergen? |
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Definition
It differentiates and proliferates into TH2 cells that secrete TH2 cytokines, especially IL-4 |
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Term
What is the principle effector function of TH2 cells? |
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Definition
Promote IgE-, eosinophil-, and mast cell-mediated immune reactions, which are protective against helminthic infections |
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Term
What is the type 1 hypersensitivity sequence of events? |
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Definition
1) first exposure 2) sensitization 3) second exposure 4) clinical allergy |
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Term
What happens during the first exposure to an antigen? |
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Definition
Antigen specific activation of TH2 cells and B cells, B cell class switching, and IgE antibody production. IgE circulates through the blood to mast cells |
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Term
What happens during sensitization? |
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Definition
IgE Ab bind to mast cells and basophils via the high-affinity IgE receptor FceR1. These mast cells are ready for quick reaction on subsequent exposure |
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Term
What reaction occurs to the first exposure? |
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Definition
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Term
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Definition
B cell isotype switching to IgE heavy chain is T cell dependent via activation of TH2 cells and secretion of IL-4 and IL-13 |
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Term
What is the difference between normal plasma IgE concentration and serum concentrations with helminthic infections and sever atopy? |
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Definition
Normal: <1ug/mL Infection/atopy: >1000ug/mL |
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Term
What happens during the second exposure? |
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Definition
Antigen specific activation of mast cells requires cross-linking of IgE and results in release of mediators upon exposure |
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Term
What are the two phases of second exposure? |
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Definition
Immediate phase (minutes): vascular and smooth muscle responsiveness Late phase (hours later): leukocyte recruitment and inflammation |
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Term
What are the effector cells of immediate hypersensitivity reactions and allergic disease? |
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Definition
Mast cells, basophils, and eosinophils |
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Term
What do mast cells, basophils, and eosinophils have in common? |
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Definition
All contain cytoplasmic granules whose contents are the major mediators of allergic reactions. All produce lipid mediators and cytokines that induce inflammation |
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Term
What is the FceR1 receptor? |
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Definition
A receptor on MC and basophils that has a high affinity for IgE, allowing it to become a receptor for antigen on these cells |
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Term
How are mast cells activated? |
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Definition
Cross-linking of 2+ FceR1 receptors with multivalent antigens. Not an all or none response |
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Term
What are the three biologic responses of MC activation? |
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Definition
1) Secretion of pre-formed granules containing vasoactive amines and enzymes by exocytosis (degranulation) 2) Synthesis and secretion of lipid mediators 3) Synthesis and secretion of cytokines |
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Term
What are vasoactive amines? |
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Definition
Biogenic amines with low molecular weight that contain an amine group that work on blood vessels |
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Term
What is the major amine in humans? |
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Definition
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Term
What are the properties of histamine? |
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Definition
Binds to histamine receptors (H1, H1, and H3). Actions are short-lived |
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Term
What is the function of histamine? |
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Definition
Increase vascular permeability, stimulate smooth muscle cell contraction |
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Term
What is the function of MC enzymes? |
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Definition
Degrade microbial structures, tissue damage, remodeling |
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Term
How are the lipid mediators formed? |
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Definition
Rapid de novo synthesis after MC activation as products of arachidonic acids metabolism |
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Term
What are the most clinically important lipid mediators? |
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Definition
Prostaglandin D2 (PGD2) Leukotrienes (LTC4, LTD4, LTE4) Platelet-activating factor (PAF) |
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Term
What are the effects of prostaglandin D2? |
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Definition
Vasodilation, bronchoconstriction, neutrophil chemotaxis |
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Term
What are the effects of leukotrienes? |
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Definition
Prolonged bronchoconstriction, mucus secretion, increased vascular permeability |
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Term
What are the effects of PAF? |
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Definition
Chemotaxis and activation of leukocytes, bronchoconstriction, increased vascular permeability |
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Term
When are cytokines important in allergic response? |
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Definition
They are transcribed and synthesized de novo after MC activation and contribute to the late-phase of allergic reactions |
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Term
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Definition
Cytokine for neutrophil and monocyte recruitment to area of inflammation, increased bronchial responsiveness |
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Term
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Definition
Cytokine for mast cell proliferation |
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Term
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Definition
Cytokines for IgE production, mucus secretion |
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Term
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Definition
Cytokine for eosinophil action |
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Term
When are eosinophils abundant? |
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Definition
In the late phase of immediate hypersensitivity reactions |
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Term
What are the eosinophil mediators? |
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Definition
Preformed granules: major basic protein, eosinophil cationic protein, eosinophil peroxidase, lysosomal hydrolases, lysophospholipase Lipid mediators: leukotrienes C4, D4, E4 Cytokines: IL-3, IL-5, GM-CSF, and eotaxin |
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Term
Function of eosinophil preformed granules |
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Definition
Toxic to helminths, bacteria, and host cells Degrades helminthic and protozoan cell walls Tissue damage/remodeling |
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Term
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Definition
Prolonged bronchoconstriction, mucus secretion, vascular permeability |
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Term
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Definition
Eosinophil production and activation Leukocyte chemotaxis/recruitment |
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Term
How does IgE affect eosinophils? |
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Definition
It is not activated by IgE, even though it has an FceR1, because the receptor lacks the signaling b chain |
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Term
What is the genetic pattern of atopy? |
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Definition
It often runs in families, but the full inheritance pattern is multigenic and expression is variable |
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Term
What are the important asthma-associated genes? |
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Definition
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Term
What is the hygiene hypothesis? |
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Definition
Increase of atopic diseases in industrialized countries is due to decreased infections. Activation of the innate system by microbes shifts immune response toward TH1 inflammation and away from TH2 |
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Term
What are the clinical manifestations of type 1 hypersensitivity? |
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Definition
Allergic rhinitis, asthma, atopic dermatitis, food allergies, urticaria, medication allergy, anaphylaxis |
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Term
What is systemic anaphylaxis? |
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Definition
The most sever and life threatening form of immediate hypersensitivity caused by systemic antigen presence. Mast cells in several organs are simultaneously activated |
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Term
What can cause systemic presence of an antigen? |
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Definition
Injection, insect sting, skin/gut absorption |
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Term
What qualifies as anaphylaxis? |
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Definition
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Term
How is anaphylaxis treated? |
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Definition
Epinephrine inject intramuscularly Antihistamines Steroids Albuterol if bronchospasm IV fluids |
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Term
What labs can be done during anaphylaxis? |
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Definition
Serum tryptase, peaks 30 minutes-3 hours after onset Histamine has a short half life but can collect 24 hour urine N-methylhistamine |
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Term
What are anaphylactoid reactions? |
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Definition
Non-IgE mediated anaphylacis: nonspecific MC activation, mimicking IgE-mediated anaphylaxis. Typically not as severe |
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Term
When does hypersensitivity reaction to RCM occur? |
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Definition
Usually within 1 hour of administration |
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Term
What are the risk factors for RCM hypersensitivity reactions? |
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Definition
Previous RCM reaction Asthma History of atopic disorders Possibly the use of beta-blockers or NSAIDs |
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Term
How are RCM reactions related to shellfish allergy? |
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Definition
They are unrelated. Iodine and Iodide do not cause anaphylactic reactions and are structurally unrelated to shellfish allergens |
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Term
What is the skin prick test? |
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Definition
A method of evaluation of IgE-mediated sensitization |
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Term
What is the wheal and flare reaction? |
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Definition
A reaction to an allergen used to diagnose allergies. Appears within 5-10 minutes and subsides in <1hr. Depends on IgE and presence of sensitized dermal MC, results from mediators of immediate phase |
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Term
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Definition
Radioallergosorbent test. Uses radioactive isotopes to provide qualitative results |
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Term
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Definition
An allergen is coated on the CAP and patient serum containing IgE is added and binds. FLuorogenic substrates and conjugates are added. Fluorescence is generated and detected to provide quantitative results. |
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Term
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Definition
Method of lessening allergic response by giving injections of diluted antigen that are slowly increased |
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