Term
| Define allergy in its most simple terms |
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Definition
| Immunologically induced tissue damage |
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Term
| How are allergic diseased identified? |
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Definition
| Allergic diseases are characterized by inflammation and tissue dysfunction in response to environmental immunogens called allergens |
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Term
| Is hypersensitivity the same as allergy? |
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Definition
Hypersensitivity has become virtually synonymous with allergy and neither term should be used to describe non-immunologic phenomena
(Unfortunately hypersensitivity, or simply sensitivity, is used many different contexts) |
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Term
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Definition
| Undesired pharmacological response expected to occur with the usual dose in most, if not all, patients. |
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Term
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Definition
Undesired pharmacological response expected to occur with excessive dose in most, if not all, patients
This includes adverse reactions in patients with impaired drug metabolism or clearance where the dose is excessive for the circumstances. |
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Term
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Definition
| Undesired and unexpected pharmacological response occurring with the usual dose (or less) in some patients. Note that the reaction should only be unexpected the first time. |
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Term
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Definition
| Undesired and unexpected immunologic response occurring with the usual (or less) therapeutic dose in some patients. |
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Term
| Are idiosyncrasy and allergy always unpredictable and not dose related? Explain |
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Definition
No.
Sometimes subsequent doses produce no reaction
Sometimes there is cross-reactivity
Severity can increase with increased dose |
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Term
| What three things are required for the occurrence of allergic diseases? |
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Definition
1. Sensitization/immunization to allergen
2. Exposure to allergen
3. Nonimmunologic factors (tissue hyperresponsiveness, inflammatory mediators, etc) |
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Term
| What are the two major limitations of the Coombs and Gell mechanistic classification of allergic disease? |
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Definition
1. Clinical allergy can involve more than one mechanism
2. Virtually all of the manifestations of allergy can also be caused by nonimmunologic mechanisms. |
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Term
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Definition
| Intermediate, IgE Mediated, Anaphylactic |
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Term
| What is the immune effector for Type I allergy? |
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Definition
IgE
Cytotropic for mast Cells and basophils via Fcε receptors |
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Term
| How long can passively transferred IgE bind to mast cells? |
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Definition
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Term
| How many Fcε receptors are there per effector cell? |
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Definition
About 270,000
Quite a lot! |
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Term
| What is required for cell activation (mediator release) by Ige? |
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Definition
| Cross-linkage of two IgE molecules by specific allergen; i.e., antigen must be polyvalent. |
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Term
| List three conditions in which Type I allergy will not occur despite presence of antigen |
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Definition
1. Insufficient antibody of required specificity
2. Antibody excess (not enough antigen)
3. Antigen excess |
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Term
What are the cells involved in early phase Type I Allergy?
What are the cells involved in late phase Type I Allergy? |
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Definition
Early phase—Mast Cells (and Basophils)
Late Phase—Eosinophils and Neutrophils |
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Term
| What other receptors are on mast cells besides Fcε receptors? |
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Definition
| Autonomic (β-adrenergic, cholinergic), histamine, etc |
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Term
| List some non-immunologic stimulators of mediator release involved in Type I allergy |
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Definition
| opiates, radiocontrast media, etc |
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Term
| List some inhibitors of mediator release involved in Type I allergy |
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Definition
| Cromolyn, β-adrenergics, methylxanthines, corticosteroids |
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Term
| List mediators of type I allergy |
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Definition
| Histamine, Leukotrienes, TNFα, Platelet Activating Factor (PAF) |
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Term
What are the mediators involved in early phase Type I Allergy?
What are the mediators involved in late phase Type I Allergy? |
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Definition
Early phase: Histamine and some other preformed mediators
Late phase: PAF and arachidonic acid metabolites, eosinophil and neutrophil mediators |
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Term
| List shock tissues involved in Type I allergy |
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Definition
Respiratory Tract
Skin
GI tract
Other |
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Term
| List atopic disease caused by Type I allergy |
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Definition
allergic rhinitis (hay fever), allergic asthma,
atopic dermatitis,
allergic gastroenteropathy |
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Term
| List NON-atopic disease caused by Type I allergy |
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Definition
anaphylaxis,
urticaria,
angioedema |
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Term
| List the three phases in a type I allergy time course |
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Definition
1. Sensitization
2. Early phase
3. Late phase |
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Term
| Describe the sensitization phase in a type I allergy time course |
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Definition
| Nearly always unapparent at the time but appears to follow the classic patterns of primary and secondary immune responses. |
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Term
Describe the early phase in a type I allergy time course
How long is it? What causes it? |
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Definition
May occur virtually immediately (0-30 minutes) upon exposure and the reaction is maximal within 60 minutes.
The effects are largely attributable to histamine and some other preformed mediators. |
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Term
Describe the late phase in a type I allergy time course
How long is it? What causes it? |
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Definition
Occur 3-4 hours after the initial reaction. Usually maximal within 6-12 hours and generally resolve within 24 if no further allergen exposure.
Late phase reactions are more persistent, involve different cells (e.g., eosinophils, neutrophils) and mediators, and respond somewhat differently to therapy. |
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Term
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Definition
Cytotoxic Allergy
The same thing as ADCC! |
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Term
| What are the immune effectors of type II allergy? |
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Definition
| IgG or IgM, activating the complement system |
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Term
| List the two types of cytotoxicity mechanisms |
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Definition
1. Complement-Mediated Cytotoxicity (direct lysis of mammalian cells, as occurs with bacteria, is not common.)
2. ADCC |
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Term
| List shock tissues involved in Type II allergy |
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Definition
| Circulating blood cells but potentially any cell |
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Term
| What are the antigens in type II allergy? |
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Definition
Endogenous or exogenous epitope on the target cell surface.
This includes a variety of autoantigens, alloantigens (ABH, Rh), and foreign substances (e.g., virus, drug) |
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Term
| What kind of manifestations appear in type II allergy? |
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Definition
a. Hemolytic anemia, neutropenia, thrombocytopenia
b. Transfusion reactions, alloimmune disease of newborn, autoimmune disease
(Vary depending on type of cell destroyed) |
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Term
| What is the most common mechanism of drug-induced cytotoxicity? |
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Definition
| Direct toxicity- resulting from cytotoxic, antineoplastic, and/or immunosuppressive agents |
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Term
| Describe the time course of a Type II allergic reaction |
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Definition
| Cytolysis may begin within several hours after exposure in the case of a foreign antigen but there is considerable variation in the time of onset of symptoms depending upon the tissue. |
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Term
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Definition
| Immune Complex Disease Arthus-Type |
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Term
| What are the immune effectors of type III allergy? |
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Definition
| IgG (except IgG4) or IgM complement-fixing antibodies |
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Term
| How does type III allergy begin? |
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Definition
Antibody binding to the allergen results in complement activation.
Complement generates anaphylatoxins (i.e., inflammation) and chemotaxins. Neutrophils migrate to the area, phagocytize the immune complexes, and release lysosomal enzymes. |
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Term
| List shock tissues involved in Type III allergy |
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Definition
| Vessels and/or some extravascular sites in kidneys, joints, lungs, skin |
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Term
| List pathology that can result from type III allergy |
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Definition
Vasculitis
Local Arthus reaction
Systemic serum sickness
Autoimmune disease- RA, lupus |
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Term
| Describe the time course of type III allergy |
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Definition
| Inflammation is apparent within 2-12 hours of exposure in a sensitive individual |
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Term
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Definition
Cell-Mediated
Delayed Hypersensitivity Tuberculin-Type |
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Term
| What are the immune effectors of Type IV allergy? |
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Definition
| CD4+ or CD8+ effector T cells |
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Term
| What are the mediators of classic delayed hypersensitivity reaction (eg tuberculin reaction) from type IV allergy? |
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Definition
| CD4+ effector cells; likely the same as TH1 cells which promote inflammation mediated to a large extent by macrophages |
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Term
Describe cytotoxic reactions of type IV allergy
Give an example |
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Definition
Mediated largely by CD8+ T cells to environmental allergens
Not well characterized. Allograft rejection may be the best model. |
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Term
| List shock tissues involved in Type IV allergy |
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Definition
| Virtually any tissue but skin reactions are very common |
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Term
| Describe manifestations of Type IV allergy |
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Definition
| Inflammation, possible tissue destruction |
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Term
| What is the most common clinical syndrome of Type IV allergy? |
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Definition
| Allergic contact dermatitis |
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Term
| Describe the time course of a Type IV allergy reaction |
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Definition
Onset in sensitive individuals at 8-12 hours with maximum reaction at 48-72 Hours
(for tuberculin reaction, at least. Can be earlier or longer depending on sensitivity.) |
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