Transcription
Basic immunologyLecture 7.Innate immunity, inflammatory reactionTimea Berki
Innate and Adaptive ImmunityFig. 1-1Abbas, Lichtman, and Pillai. Cellular and Molecular Immunology, 7 th edition. Copyright 2012by Saunders,an imprintofofElsevierCopyright 2011 by Saunders,an imprintElsevier Inc.Inc.
Routes of Antigen EntryFig. 6-3Abbas, Lichtman, and Pillai. Cellular and Molecular Immunology, 7 th edition. Copyright 2012by Saunders,an imprintofofElsevierCopyright 2011 by Saunders,an imprintElsevier Inc.Inc.
Activation of the immune systemFig. 2-6Copyright2011 bybySaunders,an imprintElsevier Inc.Abbas, Lichtman, and Pillai. Cellular and Molecular Immunology, 7th edition. Copyright 2012Saunders,anofimprintof
Effector phase: cells and antibodies reach thesite of infectionFig. 2-6Copyright2011 bybySaunders,an imprintElsevier Inc.Abbas, Lichtman, and Pillai. Cellular and Molecular Immunology, 7th edition. Copyright 2012Saunders,anofimprintof
Local acute inflammation
Acute, local inflammation:- Infection or tissue-injury initiate the cascade of non-specific reactions- Immediate reaction- Its role is to inhibit the spreading of infection and tissue injuryCelsus: 4 signs of inflammation: - rubor (red), calor (hot), dolor (painfull),tumor (swelling) functio laesa (loss of function)3 main events: 1. Vasodilation – minutes2. Increased capillary permeability, fluid efflux, oedema3 Phagocytes migration: - hoursGoldsby RA, Kindt TJ, Osborne BA:Kuby Immunology 4th Edition, 2000.
Cellular components
Molecular mediators of inflammationPlasma enzyme mediators:- kinin kallikrein system- Fibrinolytic system- Complement cascade- Clotting cascadeLipid mediators:leukotrienes,prostaglandins (PGE)Chemoattractants:-Chemokines: IL-8-Complement components- PAF (platelet activatingfactor)Inflammatory cytokines:IL-1, IL-6, TNFalphaGoldsby RA, Kindt TJ, Osborne BA:Kuby Immunology 4th Edition, 2000.
Mediators of inflammation
Initation of acute inflammationGoldsby RA, Kindt TJ, Osborne BA:Kuby Immunology 4th Edition, 2000.
Leukocyte Recruitment Into TissuesFig. 3-3Copyright2011 byan imprintElsevier Inc.Abbas, Lichtman, and Pillai. Cellular and Molecular Immunology, 7th edition. Copyright 2012bySaunders,Saunders,an ofimprintof
Chemokine action
Functions Served by Leukocyte MigrationFig. 3-1All lymphocyte circulates approx. 1-2 times per day.Copyright2011 byan imprintElsevier Inc.Abbas, Lichtman, and Pillai. Cellular and Molecular Immunology, 7th edition. Copyright 2012bySaunders,Saunders,an ofimprintof
Recognition of pathogens, phagocytosisPRR „Pattern Recognition Receptors”àBinding to the PAMPS of microbesPAMP „Pathogen Associated MolecularPatternsJaneway CA Jr, Travers P, Walport M, Shlomchik MJ. Immunobiology, 2005.
Phagocyte receptorsAbbas, Lichtman: Cellular and MolecularImmunology 5th Edition, 2005.
OPSONIZATION
Neutrophil extracellular traps (NETs)Networks of extracellular fibers, primarily composed of DNA fromneutrophils, which bind pathogens and granule content.
Mast cells and their activationTLR4 – LPS àIL-1β, TNF-α, IL-6 and IL-13, without mast cell degranulationTLR2 – peptidoglycan à mast cell degranulation and production of IL-4 and IL-5, IL-6, IL-13TLR3,7,9 – Poly (I:C), CpG oligonucleotid à release of pro-infalmmatory cyítokines and chemokinesthey express several hundred thousand high affinity receptors for IgE (FcεR1) and thus respond to IgEdirected antigensexpress the pathogen-recognizing Toll-like receptors (TLRs) which probably account for the ability of mastcells to mount an effective innate immune response
Maturation of Macrophages and DCsFig. 2-2Copyright2011 bybySaunders,an imprintElsevier Inc.Abbas, Lichtman, and Pillai. Cellular and Molecular Immunology, 7th edition. Copyright 2012Saunders,anofimprintof
Role of macrophages in acute inflammation:classical activationResting macrophage: àPhagocytosisLPSActivated macrophage: à antigenpresentation, MHCII cytokine-productionIFNγHyperactivated macrophage: à citotoxicity(TNFα)MHCII Abbas, Lichtman, Pillai: Cellular andMolecular Immunology 7th Edition, 2012.Janeway CA Jr, Travers P, Walport M, Shlomchik MJ. Immunobiology, 2005.
Activated macrophages produce infalmmatorycytokinesLPS originated from Gram – bacterium LPS activates the macrophages, thoseproduce various cytokinesLocal effectsActivation ofendothel andeffectorlymphocytesChemotaxis ofleukocytes,Activation ofeffector cellsActivates vascularendothelium andincrease ntibodyproductionSystemic effectsfever,IL-6 productionGM-CSFComplementIFNαfever,septic shockJaneway CA Jr, Travers P, Walport M, Shlomchik MJ. Immunobiology, 2005.fever,Production of acutephase-proteinsActivates NK-cells,Th cells induceTh1 differentiation
Polarization of macrophagesAbbas, Lichtman, Pillai: Cellular andMolecular Immunology 7th Edition, 2012.Janeway CA Jr, Travers P, Walport M, Shlomchik MJ. Immunobiology, 2005.
Dendritic cell maturation and polarizationCLR: C-typelectin receptor CR3Toll-like receptors (TLRs), RIG-I-like receptors, NOD-like receptors, scavengerreceptors, and C-type lectin receptors (CLRs), CR complement receptor
Outcomes of acute inflammation
Systemic inflammation
Local and systemic effects of TNFTNF inhibitors,SteroidsAbbas, Lichtman, Pillai: Cellular andMolecular Immunology 7th Edition, 2012.
Systemic acute inflammation acute phase reactionBone marrowGoldsby RA, Kindt TJ, Osborne BA:Kuby Immunology 4th Edition, 2000.
Acute phase proteins in serum
Nobel Laureates in 2011 for medicine and physiologyJules A. HoffmannBruce A. BeutlerRalph M. Steinmann
Janeway CA Jr, Travers P, Walport M, Shlomchik MJ. Immunobiology, 2005. Phagocyte receptors Abbas, Lichtman: Cellularand Molecular Immunology 5th Edition, 2005. OPSONIZATION. Neutrophil extracellular traps (NETs) Networks of extracellular fibers, primarily composed of DNA from . Janeway CA Jr, Travers P, Walport M, Shlomchik MJ. Immunobiology .
