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177 Cards in this Set
- Front
- Back
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what type of hypersensitivity reaction is also known as delayed-type hypersensitivity reaction?
|
type IV
(aka cell-mediated hypersensitivity reaction) |
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what is a wheal and flare reaction?
|
the characteristic immediate reaction to an injected allergen in a skin test, in which an irregular blanched wheal appears, surrounded by an area of redness
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what common allergens cause systemic anaphylaxis?
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drugs
serum venoms peanuts |
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what are the five syndromes associated with type I hypersensitivity?
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systemic anaphylaxis
wheal and flare allergic rhinitis (hay fever) bronchial asthma food allergy |
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what is the route of entry of allergens in a systemic anaphylaxis syndrome?
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intravenous (either directly or after rapid absorption)
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what are the responses to systemic anaphylaxis?
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edema
increased vascular permeability tracheal occlusion circulatory collapse death |
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what are the common allergens in a wheal and flare syndrome?
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insect bites
allergy testing |
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what is the route of entry for wheal and flare syndrome?
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subcutaneous
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what is the response in a wheal and flare syndrome?
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local increase in blood flow
local increase in vascular permeability |
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what are the common allergens in allergic rhinitis (hay fever)?
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pollens (ragweed, timothy, birch)
dust-mite feces |
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what is the route of entry for allergens in allergic rhinitis syndrome?
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inhaled
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what are the responses in an allergic rhinitis syndrome?
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edema of nasal mucosa
irritation of nasal mucosa |
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what are the common allergens in a bronchial asthma syndrome?
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pollens
dust-mite feces |
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what is the route of entry in a bronchial asthma syndrome?
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inhaled
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what are the responses in a bronchial asthma syndrome?
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bronchial constriction
increased mucus production airway inflammation |
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what are the common allergens in a food allergy syndrome?
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shellfish
milk eggs fish wheat |
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what is the route of entry in a food allergy syndrome?
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oral
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what are the symptoms of a food allergy syndrome?
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vomiting
diarrhea pruritis (itching) urticaria (hives) anaphylaxis |
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what is pruritis?
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itching
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what is urticaria?
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hives
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what are the requirements of a type I hypersensitivity reaction?
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must be IgE-mediated
mast cells allergens |
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what type of hypersensitivity reaction is the only real allergic response?
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type I hypersensitivity reaction
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what are the allergens in a type I hypersensitivity reaction?
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small, soluble proteins derived from plants or animals, many of which are enzymatically active (often proteases)
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what type of response is activated by allergens in a type I hypersensitivity reaction?
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TH2 response
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what molecular weight is desired for allergens for type I hypersensitivity reactions?
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low molecular weight
enables allergen to diffuse out of particle, into mucus |
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what, required for T-cell priming, is essential for allergens to promote type I hypersensitivity reactions?
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fit into MHC class II protein's groove with high affinity (makes stable complex)
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what is the first stage of a type I hypersensitivity reaction?
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person is sensitized to antigen (exposure)
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what is required for the class switch to IgE in a type I hypersensitivity?
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IL-4 and/or IL-13 secreted by TH2 cells
CD40/CD40L interaction |
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to what is IgE bound in tissues (after it has been produced in response to an allergen)?
|
mast cells
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when will a patient notice that they have a type I hypersensitivity?
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upon second and subsequent exposure to allergen
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to what receptor on mast cells does the IgE bind?
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FcepsilonR1
an Fc receptor |
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what hapens to mast cells when bound IgE proteins interact with their specific antigen?
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become activated and amplify production of IgE
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in what ways does a mast cell amplify production of IgE?
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IL-4 secretion
CD40L on surface interaction with plasma cell |
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what is the alternative method of allergy testing?
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measurement of IgE levels in the blood, commonly known as a RAST Test
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how does the RAST test work?
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allergen is bound to a plate
patient's serum is added secondary anti-Ig ab (radiolabelled) is added quantitate |
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what replaced the radioimmunoassay version of the RAST test?
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ELISA
it is colorimetric, so it is easier to do anywhere and is safer |
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where do mast cells reside?
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mucosal and epithelial tissues
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how many FcepsilonR1 receptors are constitutively expressed on mast cells and basophils?
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100,000 - 200,000
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what will FcepsilonR1 bind to?
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ONLY IgE
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what is the tightest interaction of all antibody-Fc receptor interactions?
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IgE with FcepsilonR1
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why do IgE molecules stay bound to mast cells?
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very high affinity of FcepsilonR1 to IgE
increased stability of IgE when bound to mast cells (increased half life) |
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why is a bi-nodal response caused in type I hypersensitivities?
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mast cells immediately release stored granules and then synthesize stores of other mediators and release again (6-8 hours later)
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what is the intracellular process for the activation of a mast cell?
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2x "IgE/FcepsilonR1 complex" are crosslinked by antigen
receptors are phosphorylated phosphorylated receptors activate phospholipase which produces DAG and Ca2+ arachadonic acid is metabolized |
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what happens to a mast cell after it metabolizes arachadonic acid?
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degranulation, therefore release of preformed mediators (greater crosslinking results in more release)
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in mast cells, what mediators are synthesized de novo and cause the secondary reaction?
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leukotrienes
prostaglandins (also new granules of same mediators) |
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what enzymes are preformed mediators in mast cell granules? what is their function?
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tryptase, chymase, cathepsin G, carboxypeptidase
they remodel the connective tissue matrix |
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what toxic mediators are preformed mediators in mast cell granules? what is their function?
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histamine, heparin
toxic to parasites increased vascular permeability cause SMC contraction increase mucus production |
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what cytokine is a preformed mediator in mast cell granules? what is its function?
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TNFalpha
promotes leukocyte traffic into site of inflammation more vascular permeability more mast cells and eosinophils |
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what histamine receptor is involved in acute allergic reactions?
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H1 receptor for histamine
(there are three different receptors for histamine) |
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what are the secondary cytokine mediators produced by mast cells after activation?
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TNFalpha
IL-4 IL-13 IL-3 IL-5 GM-CSF |
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what are the biological effects of TNFalpha?
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promotes inflammation
stimulates cytokine production by many cell types activates endothelium |
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what are the biological effects of IL-4?
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stimulate and amplify TH2-cell response
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what are the biological effects of IL-13?
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stimulate and amplify TH2-cell response
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what are the biological effects of IL-3?
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promote eosinophil production and activation, mast cell and basophil production also
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what are the biological effects of IL-5?
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promote eosinophil production and activation, mast cell and basophil production also
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what are the biological effects of GM-CSF?
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promote eosinophil production and activation, mast cell and basophil production also
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what secondary chemokine mediator is produced in mast cells after activation?
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CCL3
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what are the biological effects of CCL3?
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chemotactic for monocytes, macrophages, and neutrophils
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what are the secondary lipid mediators produced by mast cells after activation?
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prostaglandins
Leukotrienes C4, D4, and E4 platelet-activating factor (PAF) |
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what are the biological effects of prostaglandins produced by mast cells?
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cause smooth muscle contraction
increase vascular permeability cause mucus secretion |
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what are the biological effects of leukotrienes C4, D4, and E4?
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cause smooth muscle contraction
increase vascular permeability cause mucus secretion |
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what are the biological effects of platelet-activating factor?
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chemotactic for leukocytes
amplifies production of lipid mediators activates neutrophils, eosinophils, and platelets |
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what is a good way to tell the difference between a type 1 hypersensitivity swelling versus a type 4?
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type 1 will be squishy due to larger amount of fluid in the area
type 4 will be relatively hard due to larger number of cells involved and in the area |
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what is the early phase of a type I hypersensitivity reaction?
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classic wheal and flare response, due to increased vascular permeability caused by histamines
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what is the late phase of a type I hypersensitivity reaction?
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widespread swelling after 6-8 hours due to newly synthesized leukotrienes and cytokines
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what are the effects of mast-cell activation and degranulation in the GI tract?
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increased fluid secretion
increased peristalsis expulsion of GI tract contents via diarrhea and vomiting |
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what are the effects of mast-cell activation and degranulation in the airways?
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decreased diameter
increased mucus secretion expulsion of airway contents via phlegm and coughing |
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what are the effects of mast-cell activation and degranulation in the blood vessels?
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edema
inflammation increased lymph flow increased carriage of antigen to lymph nodes |
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what are the symptoms of allergic rhinitis (which is short in duration)?
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sneezing/runny nose
local edema in nose blocked sinuses conjunctivitis in eyes |
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how do allergic rhinitis allergens enter body? how is this treated?
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enter mucous membrane in nose
teated mainly with anti-histamines |
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what are the symptoms of asthma (long duration)?
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bronchial constriction
chronic inflammation |
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where do asthma allergens activate the immune response?
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activate submucosal mast cells
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asthma is a key role for which mediators of type I hypersensitivity?
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late-acting/secondary mediators
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with what is asthma treated?
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anti-histamines
corticosteroids bronchodilators |
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what are the GI effects of ingested allergens?
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allergens pass into mucosal sites
allergens activate mucosal mast cells histamine induces smooth muscle contraction cramps and vomiting |
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what are the allergies caused by inhaled allergens?
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allergic rhinitis
asthma |
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what are the skin effects of ingested allergens in a type I hypersensitivity?
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allergens enter blood
allergens enter connective tissue in skin mast cells are activated hives appear on skin, as does atopic dermatitis (eczema) angioedema appears beneath the skin |
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what is atopic dermatitis?
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eczema
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what is angioedema?
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a swelling, similar to hives, but the swelling is beneath the skin rather than on the surface
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what is peculiar in atopic patients?
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high serum IgE levels
high absolute eosinophil counts exacerbated by constant exposure to many allergens |
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what are the effects of allergens in the blood?
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systemic anaphylaxis
- allergen moves throughout body - activation of mast cells - systemic inc. vascular permeability - airway constriction (asphyxiation) |
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what causes systemic anaphylaxis?
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**injected drugs (e.g. penicillin)**
bee/wasp venoms food (e.g. peanuts) |
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how is systemic anaphylaxis treated?
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epinephrine
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what is a hapten?
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a small molecule that can produce an immune reaction only when attached to another protein
(ex. penicillin) |
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what is the biological effect of eosinophil peroxidase?
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toxic to targets by catalyzing halogenation
triggers histamine release from mast cells |
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what is the biological effect of eosinophil collagenase?
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remodeling of connective tissue matrix
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what is the biological effect of major basic protein?
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toxic to parasites and mammalian cells
triggers histamine release from mast cells |
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what are the biological effects of eosinophilcationic protein?
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toxic to parasites
neurotoxin |
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what are the biological effects of eosinophil-derived neurotoxin?
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neurotoxin
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what are the biological effects of IL-3, IL-5, and GM-CSF?
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amplify eosinophil production by bone marrow
cause eosinophil activation |
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what are the biological effects of CXCL8?
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promotes influx of leukocytes
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what enzymes are released by eosinophils?
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eosinophil peroxidase
eosinophil collagenase |
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what toxic proteins are released by eosinophils?
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major basic protein
eosinophil cationic protein eosinophil-derived neurotoxin |
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what cells are the bridge between innate and adaptive immune responses?
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basophils
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what is hypereosinophilia known to damage?
|
heart
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what is the classic way to test for allergic reactions?
|
skin testing
sub-cutaneous injections (small, non-immunogenic doses) of allergens, which produce very localized wheal and flare reactions |
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what is the allergic triad?
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asthma
eczema rhinitis |
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what is Atopy?
|
predisposition to allergic responses by individuals with high levels of IgE
(40% of western population) |
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what is epinephrine used for? why?
|
treat anaphylactic reactions
supports blood pressure and cardiac function, as well as relaxing smooth muscle (esp. respiratory) |
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what is cromolyn sodium used for? why?
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prophylactic in asthmatics
prevents degranulation by stabilizing membranes |
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what effect do methylxanthines have?
|
inhibit phosphodiesterase
maintain cAMP levels |
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what are the three classes of anti-histamines? what are their actions?
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diphenhydramine - H1 receptors
cimetidine - H2 receptors fexofenadine - H1 receptors (long-acting) |
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what type of anti-histamine is allegra? what is its advantage?
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fexofenadine anti-histamine
poorly crosses blood-brain barrier |
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for what are corticosteroids used? how do they function?
|
allergies in skin, which are results of ongoing inflammatory responses or secondary sequellae
inhibit cytokine gene transcription |
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what are the four proposed methods to desensitize allergies?
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blocking antibodies
shift balance of TH1-TH2 cells activate regulatory T cells create anergy of specific T cells |
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what is anergy?
|
lack of reaction by body's defense mechanism (immune system) to foreign antigens
(type of peripheral lymphocyte tolerance) |
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what is the theory behind blocking antibodies as a method of desensitizing an allergy?
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inject small amounts of antigen (better injection than oral or inhaled) and shift antibody production from IgE to IgG4 - when this antibody's concentration is high enough, it will bind the allergen before it reaches IgE bound to mast cells
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what is the drawback to attempting to block antibodies?
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wrong dosage can cause anaphylaxis
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what is the theory behind shifting the balance of T-helper cells?
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use cytokines to promote TH1 cells (IL-12, IL-2)
use inhibitors to block TH2 cytokines (antibodies against IL-4, IL-5, etc.) |
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what is the theory behind creating anergy of allergen-specific T cells?
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vaccinate with allergen specific peptides, but with no adjuvant
inactivates response, because costimulatory molecules are not produced, so T cells are not activated |
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what is an adjuvant?
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a pharmacological or immunological agent which modifies the effect of other agents
(in the case of vaccines, it boosts the immune response to create a long-lasting memory response) |
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what is involved in a type II hypersensitivity reaction?
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IgG or IgM- mediated cytotoxicity
activation of complement phagocytosis by macrophages |
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what is another name for type II hypersensitivity reactions?
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antibody dependent cellular cytotoxicity (ADCC)
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what types of cells are destroyed in type II hypersensitivity reactions?
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red blood cells
platelets other tissues |
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how can penicillin (as a model for drug-induced reactions) cause type II hypersensitivity?
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binds to red blood cells, creating new epitopes which are then recognized by the immune system as foreign - IgG and/or IgM bind the epitopes and the cells are either lysed by complement or by phagocytosis via macrophages
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what is an epitope?
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part of antigen that is recognized
(aka antigenic determinant) |
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what is hemolytic anemia?
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lack of sufficient RBCs, due to premature destruction of them
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what is the ultimate effect of a penicillin-induced type II hypersensitivity reaction?
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hemolytic anemia
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what is a probable binding target (other than RBCs) for drugs that induce type II hypersensitivity reaction?
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platelets
(leads to thrombocytopenia and pupura) |
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what is thrombocytopenia?
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low serum platelet count
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what is pupura?
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appearance of red or purple discolorations on the skin that do not blanch on applying pressure, caused by bleeding underneath the skin
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what is goodpasture's syndrome?
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a type II hypersensitivity reaction in which the body develops antibodies against kidney membranes
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what is commonly caused by goodpasture's syndrome?
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renal failure
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how is Goodpasture's syndrome treated?
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plasmapheresis and steroid/cytotoxics
(cytotoxics kill off B cells) |
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what type of hypersensitivity reaction are transfusion reactions?
|
type II hypersensitivity reactions
|
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what happens in ABO incompatible blood?
|
natural antibodies coat RBC's and activate complement which lyses the cells, causing hemolytic anemia
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what happens in Rh incompatability?
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(must be the second Rh-pos child to Rh-neg mother - first initiates antibodies)
mother's anti-Rh IgG crosses placenta, binds to fetal blood cells, opsonizes, and they are phagocytosed, leading to anemia and jaundice |
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what is a Coombs Test?
|
a test to detect maternal IgG antibodies (which could bind to fetal red blood cells)
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what is caused by ABO incompatability or Rh incompatability between fetus and mother?
|
erythroblastosis fetalis (mother's antibodies attack fetal red blood cells)
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how is the direct Coombs test used?
|
directly detects antibodies bound to the surface of RBCs by agglutinating them
|
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how is the indirect Coombs test used?
|
detect non-agglutinating anti-Rh antibodies in mother's serum
incubate Rh+ cells with mother's serum, and then use Coomb's reagent to agglutinate RBCs |
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what is Coombs reagent (used in both direct and indirect Coombs test)?
|
antibody against human Ig (rabbit, antihuman antibody)
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when do type III hypersensitivity reactions generally appear?
|
approximately 10 days
|
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what are type III hypersensitivity reactions?
|
complexes develop between IgG and soluble antigens, and then deposit somewhere (determined by pathology) and inducing an inflammatory response
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what is an arthus reaction?
|
localized type III hypersensitivity reaction which must be right at the sight of injection (which indicates that pre-existing antibodies are required)
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what is serum sickness?
|
a type III hypersensitivity reaction in which a large bolus of a drug is given to a patient, and that bolus is so persistent that the patient can develop antibodies before it is metabolized and the antibodies begin attacking that serum
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what is rheumatoid arthritis?
|
type III hypersensitivity reaction in which the complexes get stuck in joints
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what happens early in the immune response of a type III hypersensitivity reaction?
|
few antibodies
excess antigen small immune complexes are formed which do not activate complement and are not cleared from circulation |
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what happens in intermediate stages of the immune response of a type III hypersensitivity reaction?
|
comparable amounts of antigen and antibody
large immune complexes form that fix complement and are cleared from circulation |
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what happens in late stages of immune response of a type III hypersensitivity reaction?
|
excess antibody
little antigen medium-sized immune complexes form that fix complement and are cleared from circulation |
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what is usually the first organ to shut down in a type III hypersensitivity reaction?
|
kidneys (because they filter)
|
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what is the process of local inflammation during a type III hypersensitivity reaction?
|
locally injected antigen binds an IgG antibody and this complex activates complement, cleaving C5 and C5a binds to its receptor on the mast cell - in addition, binding of immune complex to FcgammaRIII on mast cell induces degranulation causing local inflammation, increased fluid and protein release, phagocytosis and blood vessel occlusion
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what diseases result from IV injection of antigens in type III hypersensitivities? where do immune complexes deposit in each?
|
vasculitis - blood vessel walls
nephritis - renal glomeruli arthritis - joint spaces |
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what disease results from subcutaneous injection of antigen in type III hypersensitivities? where are immune complexes deposited?
|
arthus reaction - perivascular area
|
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what disease results from inhaled antigens in type III hypersensitivities? where do the immune complexes deposit?
|
farmer's lung - alveolar/capillary interface
|
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what is the prototypic form of type III hypersensitivity?
|
hypersensitive pneumonitis
|
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what are the features of hypersensitive pneumonitis?
|
inhaled antigens
large quantities of antigens IgG instead of IgE deposit immune complexes in lungs inflammatory response |
|
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what are the different subsets of hypersensitive pneumonitis?
|
farmer's lung
thatched roof workers disease cheese washer's disease paprika worker's disease |
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what mediates type IV hypersensitivity reactions?
|
antigen-specific effector T cells
|
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what are the consequences of delayed-type hypersensitivity syndrome?
|
local skin swelling
erythema induration cellular infiltrate dermatitis |
|
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what are the consequences of contact hypersensitivity syndrome?
|
local epidermal reaction
erythema cellular infiltrate vesicles intraepidermal abscesses |
|
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what are the consequences of gluten-sensitive enteropathy (celiac disease)?
|
villous atrophy in small bowel
malabsorption |
|
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when do type IV hypersensitivity reactions show up?
|
a few days after exposure to antigen
|
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what type of hypersensitivity is a tuberculin test?
|
type IV hypersensitivity
|
|
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what strain of mycobacterium tuberculosis is used to vaccinate?
|
BCG strain
|
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what are the stages of a type IV hypersensitivity?
|
antigen introduced subcutaneously
antigen processed by APCs TH1 effector cell recognizes antigen TH1 effector cell releases cytokines vascular endothelium is vasodilated T cells, phagocytes, fluid and protein recruited to injection site visible lesion appears |
|
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what is the role of TH1 chemokines in delayed-type hypersensitivity reaction?
|
recruit macrophages to site of antigen
|
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what is the role of IFNgamma in delayed-type hypersensitivity reaction?
|
activates macrophages
increases release of inflammatory mediators |
|
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what is the role of TNFalpha and lymphotoxin in delayed-type hypersensitivity reaction?
|
local tissue destruction
increased expression of adhesion molecules on local blood vessels |
|
|
what is the role of IL-3 and GM-CSF in delayed-type hypersensitivity reaction?
|
monocyte production by bone marrow stem cells
|
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what is the role of TH1 cells in a delayed-type hypersensitivity reaction?
|
secrete chemokines
secrete IFN-gamma secrete TNF-alpha secrete lymphotoxin secrete IL-3 secrete GM-CSF |
|
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what type of hypersensitivity reaction is poison ivy?
|
type IV hypersensitivity reaction
|
|
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what is the antigen in a poison ivy reaction?
|
pentadecacatechol
|
|
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what is the immune reactant in a type I hypersensitivity?
|
IgE
|
|
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what is the immune reactant in a type II hypersensitivity?
|
IgG
|
|
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what is the immune reactant in a type III hypersensitivity?
|
IgG
|
|
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what are the immune reactants in a type IV hypersensitivity?
|
TH1 cells
TH2 cells CTL |
|
|
what is the effector mechanism for a type I hypersensitivity?
|
mast-cell activation
|
|
|
what are the two effector mechanisms possible for a type II hypersensitivity?
|
complement fixation and FcR+ cells (phagocytes, NK cells)
antibody alters signalling |
|
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what is the effector mechanism for type III hypersensitivity?
|
complement and phagocytes
|
|
|
what effector mechanism do TH1 cells drive in a type IV hypersensitivity?
|
macrophage activation
|
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what effector mechanism do TH2 cells drive in a type IV hypersensitivity?
|
IgE production
eosinophil activation mastocytosis |
|
|
what effector mechanism do CTLs drive in a type IV hypersensitivity?
|
cytotoxicity
|
|
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what are examples of type I hypersensitivity reactions?
|
allergic rhinitis
asthma systemic anaphylaxis |
|
|
what are examples of type II hypersensitivity reactions?
|
some drug allergies (e.g. penicillin)
|
|
|
what are some examples of type III hypersensitivity reactions?
|
serum sickness
arthus reaction |
|
|
what are examples of type IV hypersensitivity reactions?
|
contact dermatitis
tuberculin reaction chronic asthma chronic allergic rhinitis |
