Inflammation & Allergy
7 important questions on Inflammation & Allergy
Two types receptor Fc Ice
- FceRI
- high-affinity, expressed mast cells and bast cells
- CD23
- low-affinity
Antigen induces degranulation through FCeRI
- Cross-linking of FceRI by allergen recruits and acticvates LYN, which phosphorylates ITAMS. --> SYK tyrosine kinase is activated
- Syk phosphorylates LAT, which recruits and activates PLC-y
- PLC-y generates IP3, which causes calcium release from ER stores
- calcium induces secretion of the contents of the mast cell's preformed granules
Factors for mast cell growth
- Stem-cell factor, IL-3, th2 associated cytokines such as IL-4, IL-9
growth and survival depend op activation of PI-3-kinase in mast cell by Kit
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Release mast cells
- Toxic mediator - Histamine
- increase local blood flow and vessel permeability
- major stimulus for itching and sneezing
- Cytokines and chemokines
- lipid mediator - Prostaglandin
- recruits Th2 cells, eosinophils and basophils
- enzymes
- MCt = mucosal epithelial, express typtase
- MCct = submucosa, express trptase, cathepsin G
The inflammatory cascade produced by mast cells activation is amplified by the recruitment of eosinophils, basophils, Th2 and B cells
Two function eosinophils
- Release toxic granules proteins and free radicals, kill microbes but also damage host tissue
- synthesize chemical mediators, such as prostaglandins, leuktriens and cytokines to amplify inflammatory response
Why is eosinophils strictly regulated
- production
- Th2 cells produce IL-5, which increase production of eosinophils.
- migration
- CCR3 regulates entry of eosinophils into tissue. Eotaxins (CCL11, CCL24, CCL26) can bind to CCR3.
- eotaxins attractt basophil and cause degranulation
Speed allergie reaction
- Immediate reaction
- IgE-mediated mast-cell activation
- late-phase reaction
- caused by continued synthesis an release of inflammatory mediators by mast cells, such as CGRP and VEGF
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