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
|
Definition
| Cytokine for mast cell proliferation |
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Term
|
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
|
Definition
| Prolonged bronchoconstriction, mucus secretion, vascular permeability |
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Term
|
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
|
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
|
Definition
| Method of lessening allergic response by giving injections of diluted antigen that are slowly increased |
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