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Immuno 04 - Allergens, Allergies, and Asthma
HDPP final at UMMSM
62
Immunology
Graduate
12/08/2012

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Cards

Term
What are the methods of entry of allergens?
Definition
Inhaled, ingested, or contacted to skin or mucous membranes
Term
Allergy
Definition
A type 1 immediate hypersensitivity reaction
Term
Atopy
Definition
The propensity of an individual to produce IgE antibodies in response to various environmental antigens and to develop strong immediate hypersensitivity responses
Term
Allergen
Definition
Component that elicits an immediate hypersensitivity reaction.
Term
What are physical properties of antigens?
Definition
Usually proteins or chemicals bound to proteins. Low to medium molecular weight. Have stability, glycosylation, and high solubility in body fluids
Term
What are the important characteristics of antigens?
Definition
They require repeated exposure and do not stimulate innate immune responses
Term
What is the immune response to atopic disease?
Definition
TH2-mediated inflammation. Naive CD4 cells polarize into differentiated subsets in response to cytokines present in the early immune response
Term
What process does an APC go through to present an antigen?
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
Term
What happens to the naive T cell after the APC presents an allergen?
Definition
It differentiates and proliferates into TH2 cells that secrete TH2 cytokines, especially IL-4
Term
What is the principle effector function of TH2 cells?
Definition
Promote IgE-, eosinophil-, and mast cell-mediated immune reactions, which are protective against helminthic infections
Term
What is the type 1 hypersensitivity sequence of events?
Definition
1) first exposure
2) sensitization
3) second exposure
4) clinical allergy
Term
What happens during the first exposure to an antigen?
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
Term
What happens during sensitization?
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
Term
What reaction occurs to the first exposure?
Definition
No clinical reaction
Term
How is IgE produced?
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
Term
What is the difference between normal plasma IgE concentration and serum concentrations with helminthic infections and sever atopy?
Definition
Normal: <1ug/mL
Infection/atopy: >1000ug/mL
Term
What happens during the second exposure?
Definition
Antigen specific activation of mast cells requires cross-linking of IgE and results in release of mediators upon exposure
Term
What are the two phases of second exposure?
Definition
Immediate phase (minutes): vascular and smooth muscle responsiveness
Late phase (hours later): leukocyte recruitment and inflammation
Term
What are the effector cells of immediate hypersensitivity reactions and allergic disease?
Definition
Mast cells, basophils, and eosinophils
Term
What do mast cells, basophils, and eosinophils have in common?
Definition
All contain cytoplasmic granules whose contents are the major mediators of allergic reactions. All produce lipid mediators and cytokines that induce inflammation
Term
What is the FceR1 receptor?
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
Term
How are mast cells activated?
Definition
Cross-linking of 2+ FceR1 receptors with multivalent antigens. Not an all or none response
Term
What are the three biologic responses of MC activation?
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
Term
What are vasoactive amines?
Definition
Biogenic amines with low molecular weight that contain an amine group that work on blood vessels
Term
What is the major amine in humans?
Definition
Histamine
Term
What are the properties of histamine?
Definition
Binds to histamine receptors (H1, H1, and H3). Actions are short-lived
Term
What is the function of histamine?
Definition
Increase vascular permeability, stimulate smooth muscle cell contraction
Term
What is the function of MC enzymes?
Definition
Degrade microbial structures, tissue damage, remodeling
Term
How are the lipid mediators formed?
Definition
Rapid de novo synthesis after MC activation as products of arachidonic acids metabolism
Term
What are the most clinically important lipid mediators?
Definition
Prostaglandin D2 (PGD2)
Leukotrienes (LTC4, LTD4, LTE4)
Platelet-activating factor (PAF)
Term
What are the effects of prostaglandin D2?
Definition
Vasodilation, bronchoconstriction, neutrophil chemotaxis
Term
What are the effects of leukotrienes?
Definition
Prolonged bronchoconstriction, mucus secretion, increased vascular permeability
Term
What are the effects of PAF?
Definition
Chemotaxis and activation of leukocytes, bronchoconstriction, increased vascular permeability
Term
When are cytokines important in allergic response?
Definition
They are transcribed and synthesized de novo after MC activation and contribute to the late-phase of allergic reactions
Term
TNF-a
Definition
Cytokine for neutrophil and monocyte recruitment to area of inflammation, increased bronchial responsiveness
Term
IL-3
Definition
Cytokine for mast cell proliferation
Term
IL-4, IL-13
Definition
Cytokines for IgE production, mucus secretion
Term
IL-5
Definition
Cytokine for eosinophil action
Term
When are eosinophils abundant?
Definition
In the late phase of immediate hypersensitivity reactions
Term
What are the eosinophil mediators?
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
Term
Function of eosinophil preformed granules
Definition
Toxic to helminths, bacteria, and host cells
Degrades helminthic and protozoan cell walls
Tissue damage/remodeling
Term
Function of leukotrienes
Definition
Prolonged bronchoconstriction, mucus secretion, vascular permeability
Term
Function of cytokines
Definition
Eosinophil production and activation
Leukocyte chemotaxis/recruitment
Term
How does IgE affect eosinophils?
Definition
It is not activated by IgE, even though it has an FceR1, because the receptor lacks the signaling b chain
Term
What is the genetic pattern of atopy?
Definition
It often runs in families, but the full inheritance pattern is multigenic and expression is variable
Term
What are the important asthma-associated genes?
Definition
ADAM33, DPP10, PHF11
Term
What is the hygiene hypothesis?
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
Term
What are the clinical manifestations of type 1 hypersensitivity?
Definition
Allergic rhinitis, asthma, atopic dermatitis, food allergies, urticaria, medication allergy, anaphylaxis
Term
What is systemic anaphylaxis?
Definition
The most sever and life threatening form of immediate hypersensitivity caused by systemic antigen presence. Mast cells in several organs are simultaneously activated
Term
What can cause systemic presence of an antigen?
Definition
Injection, insect sting, skin/gut absorption
Term
What qualifies as anaphylaxis?
Definition
Symptoms in 2+ organs
Term
How is anaphylaxis treated?
Definition
Epinephrine inject intramuscularly
Antihistamines
Steroids
Albuterol if bronchospasm
IV fluids
Term
What labs can be done during anaphylaxis?
Definition
Serum tryptase, peaks 30 minutes-3 hours after onset
Histamine has a short half life but can collect 24 hour urine N-methylhistamine
Term
What are anaphylactoid reactions?
Definition
Non-IgE mediated anaphylacis: nonspecific MC activation, mimicking IgE-mediated anaphylaxis. Typically not as severe
Term
When does hypersensitivity reaction to RCM occur?
Definition
Usually within 1 hour of administration
Term
What are the risk factors for RCM hypersensitivity reactions?
Definition
Previous RCM reaction
Asthma
History of atopic disorders
Possibly the use of beta-blockers or NSAIDs
Term
How are RCM reactions related to shellfish allergy?
Definition
They are unrelated. Iodine and Iodide do not cause anaphylactic reactions and are structurally unrelated to shellfish allergens
Term
What is the skin prick test?
Definition
A method of evaluation of IgE-mediated sensitization
Term
What is the wheal and flare reaction?
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
Term
What is RAST?
Definition
Radioallergosorbent test. Uses radioactive isotopes to provide qualitative results
Term
What is ImmunoCAP?
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.
Term
What is immunotherapy?
Definition
Method of lessening allergic response by giving injections of diluted antigen that are slowly increased
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