1 / 15

mast cells in lung tissue

mast cells in lung tissue. basophil. Basophil and Mast cell : introduction. bone marrow derived granulocytes myeloid lineage Paul Ehrlich 1879 deep violet blue metachromatic acidic mambrane-bound granules basophils usually less than 0.2% of WBC secretory function. mast cell : function.

johana
Download Presentation

mast cells in lung tissue

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript


  1. mast cells in lung tissue

  2. basophil

  3. Basophil and Mast cell : introduction • bone marrow derived granulocytes • myeloid lineage • Paul Ehrlich 1879 deep violet blue metachromatic acidic mambrane-bound granules • basophils usually less than 0.2% of WBC • secretory function

  4. mast cell : function • distributed in organs which interface with exterior: lung, nasal tissue, skin, gut. • sentinel or surveillance function • increase (mast cell hyperplasia) associated with • parasite infections • allergy • mastocytoma (rare) • increase in blood precursors - basophils

  5. Mast cell : IL-3, 4 and SCF (c-KitL) • Mast cell recruitment, proliferation, maturation and maintenance requires the stromal cell and autocrine growth factor stem cell factor (c-kit ligand) and IL-6 • Chemotaxis to SCF, TGF, MCP-1, chemokine-fractaline. • T-cell derived IL-3 and IL-4/13 seem to be required for differentiation • Secretagogues (IL-3, neuropeptides NGF and substance P) may act by releasing endogenous SCF • SCF stimulation inhibited by TGF • IL-3/4 differentiation inhibited by GM-CSF

  6. Mast cell : connective tissue (CTMC) and mucosal (MMC) CTMC MMC • location ubiquitous lung, gut • granules/cell 20 uniform 10 variable sized • histamine/cell 15 pg 1.3 pg • LTC4/PGD2 1:40 25:1 • lifespan >6 months <40 days • anti-allergic drugs susceptible relatively resistant • T cell -independent -dependent • fixation saffranin alcian blue • proteoglycan heparin chondroitin sulphate • protease tryptase plus chymotryptase • IgE staining surface cytoplasm + surface • compound 48/80 susceptible resistant

  7. IMMUNOLOGICAL: Allergen-IgE FcER1 cross linking Antigen-IgG2a / IgG4 FcgammaR cross linking. Anaphylotoxins: C3a C5a Eosinophil major basic protein. NON-IMMUNOLOGICAL: Substance-P, NGF Polymyxin-B Compound 48/80 (CTMC) Venoms Irradiation and heat Cytokines: SCF (c-Kit ligand); GM-CSF; (IL-3/IL-4/IL-13). Mast cell : receptors and degranulation

  8. Mast cell degranulation

  9. Pre-formed Histamine Eosinophil chemotactic factor of anaphylaxis (ECF-A) Val-Gly-Ser-Glu and Ala-Gly-Ser-Glu Neutrophils - LTB4 Neutral proteinases, tryptase, chymotryptase Oxidative enzymes Granule matrix proteoglycans: heparin or chondroitin sulphate Newly-generated Lipid mediators Arachadonic acid metabolites: PGD2 LTB4, C4, D4, E4. Platelet activating factor (PAF). CytokinesTNF-a, TGF-b, IL-6, IL-3, IL-4, IL-5, IL-9, IL-10, IL-13, IL-8, (IFN-g). Mast cell : mediators

  10. Mast cell : mediator function Vaso-dilatation, smooth muscle contraction • histamine - immediate, prostanoids - prolonged Inflammation • eosinophil and neutrophil chemotactic factors • oxidative enzymes • cytokines Tissue remodelling • granule matrix proteoglycans • neutral proteinases, collagenase

  11. Mast cell : protective function against parasites • mast cell hyperplasia and IgE super-abundance is common in nematode infection • mast-cell deficient or IgE knock-out mice seem equally able to eliminate parasitic nematodes • anti-gram negative bacterial function noted in mouse coecal pouch model

  12. mast cells protect against bacterial infection • Mast cell produce TNFalpha on contact with bacterial fimbriae (Klebsiella pneumoniae) • TNF stimulates recruitment of neutrophils and macrophages which engulf bacteria. • NO controls MC mediator release • Echtenacher, B. Nature 1996;381:75-80 • Prodeus et al. Nature 1997;390: 172-5

  13. Mast cell : pathogenic role in allergy • site-specific mast cell hyperplasia and specific IgE abundance is common in allergic disease • anti-mast cell therapies are effective in allergy - anti-histamines, steroids, cromoglycate

  14. mast cells and nerves

  15. Mast cell : summary • distributed mainly for surveillance. • regulate acute inflammatory reactions by rapid production of mediators:via IgE - immediate hypersensitivity.via antibody-independent mechanisms e.g. pathogen products • amplify innate immune/inflammatory responses by recruiting effector cells from the blood • histamine and prostanoids increase vascular permeability • proteases modulate local tissue environment/remodelling • proteases increase permeability of epithelial cells. • heterogeneity indicates tissue-specific adaptation for local function • mast cells have a role in protective responses possibly when localised to micro-environments and when mediator concentrations are low - deleterious anaphylaxis may be due to rapid and generalised production of large quantities of mediators within a tissue.

More Related