Term
| Which type of hypersensitivity reaction is an allergic reaction? |
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Definition
| Type I hypersensitivity reaction |
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Term
| Characteristics of IgE driven allergic reaction |
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Definition
1) smooth muscle spasm
2) increased vascular permeability
3) activation of inflammatory and coagulation cascades |
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Term
| Characteristics of IgE Fc |
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Definition
- has two Fc regions
1) a binding site for high affinity Fcε receptors on basophils
2) a binding site for lower affinity Fcε receptors on APC's |
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Term
| What causes a normal IgE response (i.e. not considered an allergy)? |
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Definition
| worms, certain parasites, other large organisms with relatively nonbiodegradable antigens. |
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Term
| Two types of mast cells? where are they located |
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Definition
Mast Cell T - only has tryptase and located in mucosal area
Mast Cell TC - has tryptase and chymase and located in skin and connective tissue |
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Term
| Two general functions of mast cells |
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Definition
- granule/content secretion
- APC induce B-cells to produce IgE |
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Term
| What do mast cells secret? |
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Definition
- heparin
- histamine
- proteases
- leukoriene
- inflammatory cell cytokines that include IL3,4,5,6,8,10,13,TNF alpha
-GM-CSF |
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Term
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Definition
1) aero allergens - pollen, animal dander
2) food allergens - usually milk, egg, peanut, shellfish, what, soy
3) Insect venoms - insects with chitin-polysaccaride
4) Many drugs - abiox |
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Term
What usually presents these allergens to B-cells?
Why does this process favor IgE production over IgG? |
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Definition
Dendritic cells, MHC Class II
- due to the TLR activated, the type of T-helper cell and cytokine milieu present during allergen presentation |
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Term
| What type of hypersensitivity reactions can drugs cause? |
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Definition
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Term
| Number of genes required to perform an allergic reaction, and three examples |
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Definition
- many:
1) T-bet gene, conrtolling INF-gamma synthesis
2) bronchial reactivity controlling gene
3) gene that controls mast cell signaling
4) Gene that controls FC epsilon receptor
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Term
What controls IgE serum levels?
What do IgE serum levels affect? |
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Definition
- MHC linked genes, maternal genes on chromosome 11 and other poorlly described genetic loci
- severeity of an allergic reaction is affected by circulating IgE levels |
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Term
| What is the role of the route of exposure in whether or not a patient will have an allergic response? |
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Definition
| - very small amounts on mucosal surface facilitates allergic responses in the atopic host |
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Term
| Eight key steps in allergic response |
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Definition
1) contact with antigen - usual mucosal but can be cutaneous
2) Uptake of allergen by APC via allergic TLR
3) DC produces IL4 NOT I12
4) Presentation of allergen with MHC II
5) TH2 activation - helped by DC and mast/basophil release of IL4, followed by TH2 production of IL4
6) Promotion of IgE class switching of B-cell via upregulation of FCεIII (CD-23) on mast cells
7) IL4 from TH2, Basophils and mast cells activate ε transcription in B-cells. |
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Term
| what part of the allergic response is varibale based on gene polymorphisms? |
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Definition
| - Whether or not there is IgG to IgE isotype switching of B-cells that will be induced by IL4 and IL13 |
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Term
| Upregulation of surface marker signals production of Il4 and Il13 in mast cells and basophils? |
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Definition
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Term
| What is unique about the episilon FC receptor on mast cells and basophils? |
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Definition
| - it is the only receptor that can be occupied by antibody not previously complexed with antigen |
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Term
| What happens after IgE binding to Fc's on mast cells and basophils? |
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Definition
- The cross-linked FC epsilon receptors then aggregate
- signal transduction occurs, activating calcium influx into armed mast cells and basophils which degranulate |
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Term
| What is responsible for the second drop in FEV1 after exposure to allergen? How long after exposure does it occur? |
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Definition
| - the second drop, at about 8 hours, is caused by recruitment of eosinophils |
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Term
When does the immediate allergic reaction occur?
What is it dependent on?
What two things cause it? |
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Definition
- occurs within 15 minutes of allergen exposure
- completely dependent on previous exposure and sensitization
- 1) multiple vasoactive mediators released from mas cells and basophils
2) Prostaglandin and leukotriene synthesis and release
3) Direct comlement activation by tryptase cleavage |
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Term
What is the late phase dependent on?
What is it characterized by? |
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Definition
- T-cell activation and cytokines Il3,4,5,13,TNF-alpha, GM-CSF and IL10.
- infiltration by eosinophils, neutrophils, additional mast cells, basophils and lymphocytes |
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Term
What is the role of IL3, 5 and GM-CSF during the late response?
What two additional role does IL5 play |
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Definition
- regulate growth and marrow realease of eosinophils.
- IL5 augments the chemotatic effect of a specific eosinophil chemokine called eotaxin.
- IL5 also increases FC-epsilon receptor display, augmenting the IgE reaction |
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Term
| What do eosinophils in the late phase of an allergic reaction produce? |
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Definition
- major basic protein
- leukotrienes
- cationic proteins |
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Term
| What causes allergic rhinitis? |
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Definition
| - Occurs when allergen binds to cells in the nasal submucosa and incites a chronic allergic inflammation reaction driven by continuous aeroallergen exposure. |
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Term
| What is the cause of urticaria? |
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Definition
| - IgE armed mast cells are activated in the skin |
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Term
| What causes acute and bronchial asthma? |
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Definition
| - IgE armed cells are recruited to submucosal sites of the pulmonary bronchi |
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Term
| Two early life situations that decrease likelihood later allergies? |
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Definition
- large families
- early day care |
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Term
| What is the effect of early exposure to childhood illnesses? |
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Definition
| - sets "normal" Th1 and Th2 responses to subsequent environmental antigen exposure |
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Term
| what is the role of Tregs in allergic responses? |
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Definition
| control synthesis of IgE to environmental antigens |
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Term
What example in mice shows the Tregs are involved in IgE synthesis?
What example in humans shows the converse of this? |
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Definition
- mice infected with gut worms are resistant to airway reactivity from dust mite sensitization. The resistance is due to CD4 Tregs that migrate from their gut.
- children successfully treated for worm infestation lead to allergty to dust mites later on |
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Term
What is the counter regulation hypothesis?
What cytokines are responsible? |
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Definition
- proposes that all types of infection causes down-regultion of both Th1 and Th2 repsonse
- This is by increased production of Il10 and TGF-beta |
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Term
| What may be the link between asthma and obesity? |
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Definition
| - adipocytes may produce cytokines such as leptin, that are pro-inflammatory and this may be an underlying factor. |
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Term
Steps in the radioallergosorbent tests (RAST)
What is the problem with RAST and skin tests? |
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Definition
1) patient's serum is added to a cellulose disc with covalently bound allergen
2) IgE present in the serum binds at allergen
3) after washing, radio labled anti-IgE is added.
4) radioactivity is detected with gamma counter.
- Problem: many times skin testing and RAST assays will be positive but the patient will have no clinical symptoms. |
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Term
Five techniques for treatment and prevention of allergy
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Definition
1) allergen avoidance
2) Anti-IgE therapy - monoclonal anti-IgE binds to circulating IgE at the site that binds to IgE receptor.
3) Desensitization - rerouting of IgE response by constructing allergen antigens that promote either Th1 responses and macrophage destruction of the antigen OR Th2 resposnses
4) Vaccines
5) infect patient with worms or sensitize them with worm antigens. |
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