Macrophages siamon gordon
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This document discusses macrophages and their roles in innate immunity. It covers various macrophage receptors like the mannose receptor, dectin-1, scavenger receptors, and toll-like receptors that allow macrophages to recognize and respond to microbes, apoptotic cells, and other molecules. Macrophages can be classically or alternatively activated, leading to different functional phenotypes. The document also examines macrophage heterogeneity, differentiation, and interactions with other cells in tissues, inflammation, and infection.
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Macrophages siamon gordon
- 1. MACROPHAGES IN INNATE IMMUNITY, INFLAMMATION AND INFECTION: ROLE OF RECEPTORS SIAMON GORDON siamon.gordon@path.ox.ac.uk
- 2. Elie Metchnikoff (1845-1916) Zanvil A Cohn (1926-1993) George Mackaness (1924-2007) Philip D’Arcy Hart (1900-2006) Charles A Janeway, Jr (1943-2003)Russell Ross (1929-1999) SIGNIFICANT FIGURES IN MACROPHAGE RESEARCH
- 3. MACROPHAGES IN INNATE IMMUNITY • PHAGOCYTOSIS, ENDOCYTOSIS – RECOGNITION AND CLEARANCE OF ALTERED SELF, FOREIGN • TROPHIC E.G. HAEMATOPOIESIS, ANGIOGENESIS • DEFENCE EXTRA/INTRACELLULAR MICROBES • INDUCTION AND EFFECTOR PHASES IMMUNITY – ADJUVANTICITY, APC, SUPPRESSION • INITIATION, PERSISTENCE AND REGULATION OF INFLAMMATION AND REPAIR • INTERACTIONS WITH OTHER HOST CELLS, LOCAL AND SYSTEMIC • TISSUE INJURY, CATABOLISM AND CYTOTOXICITY
- 4. D A Hume, D A Hughes DIFFERENTIATION AND DISTRIBUTION OF MACROPHAGES
- 5. THE EGF-TM7 FAMILY J Austyn, H-H Lin, M Stacey
- 6. KUPFFER CELLS F4/80+ SINUSOIDAL ENDOTHELIUM F4/80 NEGATIVE D A Hume
- 7. MICROHETEROGENEITY OF RESIDENT TISSUE MØ
- 8. TROPHIC INTERACTIONS: HAEMATOPOIESIS STROMAL MØ F4/80+ P R Crocker, L Morris, I Fraser
- 9. HAEMATOPOIETIC STROMA ADHESION OF ERYTHROBLASTS AND MYELOBLASTS, UPTAKE ERYTHROID NUCLEI
- 10. BONE MARROW PERIPHERAL BLOOD CCR2+ CD62L+ CX3CR1lo CCR2- CD62L- CX3CR1hi TISSUES MØ DC INFLAMMATION STEADY STATE RESIDENT TISSUE MØ? EG. SPLENIC MØ, KUPFFER CELLS, ALVEOLAR MØ, MICROGLIA, OSTEOCLASTS RESIDENT TISSUE DC? PATHOGEN CLEARANCE RESOLUTION OF INFLMMATION ANTIGEN PRESENTATION PROGENITOR MONOBLAST PROMONOCYTES MONOCYTES CD14+ CD16+ Ly-6lo /Gr-1lo CD14++ CD16- Ly-6hi /Gr-1hi MONOCYTE HETEROGENEITY & RECRUITMENT P. Taylor
- 12. IMMUNE ACTIVATION - BCG-GRANULOMATA: LYSOZYME mRNA, IN SITU HYBRIDIZATION S Keshav RECRUITED/ACTIVATED MØ EXPRESS DIFFERENT PHENOTYPE FROM RESIDENT KUPFFER CELLS
- 13. TH1 TH2 IFN-γ DIFFERENTIAL ACTIVATION OF Mφ Markers MHC-II CD-80/86 iNOS TNF-α Functions KILLING Ag PRESENTATION INFLAMMATION MR DECTIN-1 ARGINASE Ym1 MØ FUSION CELL GROWTH TISSUE REPAIR WOUND HEALING CLASSICAL ALTERNATIVE IL-4/13 INNATE PHAGOCYTOSIS REGULATION OF ACTIVATION MICROBES/PRRs (TLR) MARCO CD200 S. Mukhopadhyay
- 14. FUNGI BACTERIAPATHOGENS CELLS VIRUSES LYMPHOCYTES TUMOR CELLS MACROPHAGES (FUSION) APOPTOTIC CELLS MOLECULES MATRIX SOLUBLE MACROPHAGE INTERACTIONS A. Plüddemann
- 15. PHAGOCYTOSIS OF APOPTOTIC THYMOCYTE CLEARANCE AND SUPPRESSION OF INFLAMMATION N Platt
- 17. COMPLEMENT RECEPTORS (INTEGRINS) Fc RECEPTORS (Ig SUPERFAMILY) LECTINS SCAVENGER RECEPTORS TOLL-LIKE RECEPTORS TLRs OPSONIC RECEPTORS NON-TLR RECEPTORS NTRs NF-κB IRF MyD88/TRIF NF-κB NOD-LIKE RECEPTORS NLRs RIG-LIKE HELICASES RLHs ASC CASPASE-1 MyD88/ TRIF IRF ? VACUOLE TLRs MITOCHONDRIAL ADAPTER PROTEINS ITAM ITIM - + A. Plüddemann SENSING THE ENVIRONMENT: MØ RESPONSE
- 18. MANNOSE RECEPTOR EGF-TM7 TOLL-LIKE RECEPTOR MARCO SCAVENGER RECEPTOR AI MACROPHAGE RECEPTORS C N N C DECTIN 1 C N E E E E E C N CD200 S S S S S S S S S S TREM1/DAP12 CD36 CN CD200R A. Plüddemann
- 19. DECTIN-1 • β-GLUCAN RECEPTOR, C-TYPE LECTIN-LIKE, Ca++ INDEPENDENT • ITAM-LIKE MOTIF • MØ, DC, PMN • UPTAKE ZYMOSAN, SELECTED FUNGI, E.G. C.ALBICANS, P. CARINII • SECRETION TNFα - COLLABORATION TLR 2/6 • UNKNOWN SUGAR INDEPENDENT INTERACTION T LYC Y CL Dectin-1 Murine βGR-A Y CL Y CL βGR-B Human G. Brown
- 20. MANY BUT NOT ALL FUNGI EXPOSE LIGAND FOR DECTIN-1 UPTAKE OF C ALBICANS BY MACROPHAGES S. Heinsbroek YEAST FORMS AND PSEUDOHYPHAE
- 21. Brown GD (2006) Dectin-1: a signalling non-TLR pattern-recognition receptor Nat Rev Immu 6: 33–43 doi:10.1038/nri1745 DECTIN-1 MEDIATED SIGNAL TRANSDUCTION
- 22. SR-AI CLASS F SRECLOX-1 CLASS B CLASS D CLASS E SR-PSOX CLASS G FEEL-1 CLASS A SR-AII MARCO CD 36 SR-BISCARA5 SRCL c c F F F F F F F CN CN C N * * E N C CLASS H E E E E E E E E E E E E E E E E E E E E E E CD 68dSR-C I CLASS C N C C N C C SoSo C C SoSo SCAVENGER RECEPTORS N N A. Plüddemann
- 23. SR-A & NEISSERIA MENINGITIDIS (NM) • PHAGOCYTOSIS UNOPSONISED NM – ALL STRAINS • POTENT IMMUNOMOCULATOR - PRO-INFLAMMATORY CYTOKINES • UPTAKE NM UNCOUPLED FROM TNFα PRODUCTION • LIPID A IS NOT SR-A LIGAND, ALTHOUGH NEEDED FOR CYTOKINE RELEASE – LPX MUTANT NM. L. Peiser
- 24. MENINGOCOCCAL SEPTICAEMIA – HAEMORRHAGIC RASH
- 25. MYCOBACTERIUM TUBERCULOSIS, HIV, DENGUE VIRUS CANDIDA ALBICANS PNEUMOCYSTIS CARINII LYSOSOMAL HYDROLASES, MYELOPEROXIDASE, TISSUE PLASMINOGEN ACTIVATOR, THYROGLOBULIN MANNOSE RECEPTOR (MR): OVERVIEW SULPHATED GLYCOPROTEIN HORMONES ANTERIOR PITUITARY MICROBE RECOGNITION:SELF RECOGNITION: FNII SO4-(3)-Gal- SO4-(3/4)-GalNAc- CR MANNOSE, FUCOSE, GlcNAc CTLD COLLAGENS L. Martinez-Pomares
- 26. POTENTIAL ROLE IN • PREVENTION OF EXCESSIVE INFLAMMATION • HOST DEFENCE AGAINST PARASITIC INFECTIONS PROPERTIES OF ALTERNATIVELY ACTIVATED MACROPHAGES • UPREGULATION OF MANNOSE RECEPTOR, MHC II MOLECULES • UPREGULATION OF ARGINASE I • INDUCTION OF Ym-1/2 (= CHITINASE) AND FIZZ-1 (RESISTIN-LIKE PROTEIN) • RELEASE OF SELECTIVE CHEMOKINES (E.G. CCL17 AND 22) • MACROPHAGE FUSION • NO SPECIFIC SURFACE MARKERS IDENTIFIED SO FAR NB SPECIES DIFFERENCES ALTERNATIVE MACROPHAGE ACTIVATION
Editor's Notes
- Our results stress the fact that the mannose receptor is at the interface between homeostasis and immunity. We have demonstrated binding to pathogens such as.....................but also detected binding to further endogenous ligands such as ................ It is of interest to note that proteins considered autoantigens in many autoimmune diseases are been characterised as MR ligands as it is the ase for myeloperoxidase, thryroglobulin, componens of basal membrane. An organs were abundant MR binding activity can be detected are targeted by the immune system in some diseases as it is the case for salivary glands and exocrine pancreas. Which leads us to the next subject: