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Post Reply Close Saving..... Edit Comment Close Premium member Presentation Transcript CHRONIC INFLAMMATION: CHRONIC INFLAMMATIONDEFINITION: DEFINITION Inflammation of prolonged duration (weeks/months) in which- ~active inflammation, ~tissue destruction & ~attempts at repair are proceedings simultaneously.CARDINAL SIGNS OF ACUTE INFLAMMATION: CARDINAL SIGNS OF ACUTE INFLAMMATION Heat Redness Swelling Pain Loss of function Celsus (1 AD) VirchowInflammation Outcome - Resolution: Inflammation Outcome - Resolution Chronic Inflammation Abscess Sinus Fistula Ulcer Acute Inflammation Healing InjuryCHRONIC INFLAMMATION: CHRONIC INFLAMMATION Prolonged process in which tissue destruction & inflammation occur at the same time. ACUTE vs. CHRONIC INFLAMMATION Flush, Flare & Wheal Acute inflammatory cells - Neutrophils Vascular damage More exudation Little or no fibrosis Little signs - Fibrosis Chronic inflammatory cells – Lymphocytes, Macrophages Neo-vascularization No/less exudation Prominent fibrosisSlide 7: CHRONIC INFLAMMATIONCauses: Causes Persistent infection by certain microorganisms (of low toxicity) Prolonged exposure to potentially toxic agents- ~ exogenous ( e.g silicosis) ~ endogenous ( e.g atherosclerosis) AutoimmunityGENERAL FEATURES: GENERAL FEATURES MONONUCLEAR CELL INFILTRATION TISSUE DESTRUCTION & NECROSIS – brought by activated macrophages . PROLIFERATIVE CHANGES – proliferation of small vessels & fibroblastsSlide 10: Mononuclear cell infiltration Fibrosis Tissue destructionSYSTEMIC EFFECTS: SYSTEMIC EFFECTS FEVER ANEMIA LEUCOCYTOSIS RAISED ESR SECONDARY SYSTEMIC AMYLOIDOSISClassification: ClassificationCells involved in chronic inflammation: Cells involved in chronic inflammation Mononuclear–phagocyte system (MPS) Lymphocytes Plasma cells Eosinophils Mast cells Neutrophils (in some cases)MONONUCLEAR PHAGOCYTE SYSTEM: MONONUCLEAR PHAGOCYTE SYSTEM Closely related cells of bone marrow origin- ~ Blood monocytes (t1/2- 1 day) ~ Tissue macrophages (t1/2- several months) Kupffer cells (liver) Histiocytes Alveolar macrophages Microglia (CNS) Osteoclasts (bone) Langerhans ’ cells & Dendritic cells(skin) Macrophages of bone marrow Tingible body cells of germinal centres lymph node Littoral cells of splenic sinusoids Mesangial cells of glomerulusMONOCYTE MACROPHAGE SYSTEM: MONOCYTE MACROPHAGE SYSTEMSlide 16: MACROPHAGE MONOCYTESlide 17: Key macrophage events 1. Recruitment from circulation 2. Local Proliferation 3. Immobilization 4. Differentiation (microglia, kupffer , alveolar macrophage, osteoclasts ). MacrophageRole of macrophages in inflammation: Role of macrophages in inflammation Phagocytosis & pinocytosis Antigen processing & antigen presentation Constituent of granulomas Regulate lymphocyte response Secretion of biologically active substancesProducts released by macrophages: Products released by macrophages ENZYMES- ~ Neutral proteases ( elastases, collagenases, PA) ~ Acid hydrolases ( phosphatases, lipases) PLASMA PROTEINS- ~ Complement components (e.g. C1 to C5, properdin) ~ Coagulation factors (e.g. Factor V, VIII, tissue factor ) Reactive metabolites of oxygen Nitric oxide Eicosanoids Cytokines (IL-1, TNF, IL-8) Growth factors (PDGF,EGF,FGF,TGF- β )LYMPHOCYTES: LYMPHOCYTES Ab production & humoral immunity (B-cells) Cell mediated immunity (T-cells) - CD4+ helper cells - CD8+ suppressor cells Regulate macrophage responsePLASMA CELLS: PLASMA CELLS Develop from activated B-lymphocytes Antibody synthesis & secretion -against persistent Ag or -altered tissue componentsEOSINOPHILS: EOSINOPHILS Inflammation associated with - allergic responses - parasitic infestations Weakly phagocytic Effector functions by degranulationEosinophilic granule proteins: Eosinophilic granule proteins Biologically active proteins Includes- ~ Major basic protein (MBP) ~ Eosinophilic cationic protein ~ Eosinophilic derived neurotoxins ~ Eosinophil peroxidaseMAST CELLS: MAST CELLS Bear receptor for Fc portion of IgE Ab Degranulate when cross linked with Ag Basophilic granules- - Histamine - proteoglycans - glycosidasesEFFECTS OF MAST CELL DEGRANULATION ON CELLULAR COMPONENTS: EFFECTS OF MAST CELL DEGRANULATION ON CELLULAR COMPONENTSRole of neutrophils: Role of neutrophils Persist in some forms of chronic inflammation Induced by - persistent microbes or - mediators produced by macrophages & T-lymphocytes Example- chronic osteomyelitis, chronic damage in lungs (smokers)MONONUCLEAR CELL INFILTRATION: MONONUCLEAR CELL INFILTRATION Emigration of monocytes into extravascular space ↓ Transformation into larger tissue macrophage ↓ Activation of macrophages - -increased size -increased lysosomal enzymes -more active metabolism, -greater ability to phagocytose ↓ Secretion of biologically active substances ↓ Non-immune activation Activated T-cell IFN-gamma EndotoxinSlide 31: Unchecked secretion of biologically active substances -Toxic O2 metabolites -Proteases -Neutrophil chemotactic factors -Coagulation factors -AA metabolites -Nitric oxide ↓ TISSUE INJURY -Growth factors (PGDF,FGF,TGF- β ) -Fibrogenic cytokines -Angiogenesis factors (FGF) -”Remodelling collagenesis” ↓ FIBROSISMechanism of macrophage accumulation: Mechanism of macrophage accumulation Recruitment of monocytes from circulation ~ Chemotactic stimuli for monocytes - chemokines (by macrophages & lymphocytes) MCP-1( monocyte chemoattractant protein) -C5a -growth factors (PDGF,TGF- β ) -break down fragments of collagen & fibronectin Local proliferation of macrophages Immobilization of macrophages within site of inflammation ( role of certain cytokines-MIF & oxidized lipids)Granulomatous inflammation: Granulomatous inflammation It is a distinct pattern of chronic inflammatory reaction characterized by focal accumulations of activated macrophages, which often develop an epithelial-like ( epithelioid ) appearance (GRANULOMA).Granuloma: GranulomaPRIMARY GRANULOMATOUS CONDITIONS: PRIMARY GRANULOMATOUS CONDITIONS BACTERIAL- ~Tuberculosis ~ Leprosy ~ Syphilis ~ Granuloma inguinale ~ Brucellosis ~ Cat scratch disease ~ Tularemia FUNGAL- ~ Histoplasmosis ~ Coccidiomycosis ~ Blastomycosis ~ Cryptococcosis ~ Actinomycosis PARASITIC- ~ Schistosomiasis ~ TrichiniasisPRIMARY GRANULOMATOUS CONDITIONS: PRIMARY GRANULOMATOUS CONDITIONS FOREIGN BODY TYPE- ~ Foreign body granulomatosis ~ Silicosis ~ Talc Granuloma METAL INDUCED- ~ Berylliosis ~ Zirconium granulomatosis MISCELLANEOUS- ~ Sarcoidosis ~ Crohn’s Disease ~ Wegener’s granulomatosis ~ Giant cell arteritisMajor features: Major features Mononuclear cell infiltration -lymphocytes -plasma cells -macrophages - epithelioid cells Giant cells Necrosis (+/-) FibrosisEpithelioid cells: Epithelioid cells These are activated macrophages with epithelial ( squamous ) cell like appearance Cells with indistinct cell boundaries -abundant pale staining granular cytoplasm -elongated/oval, slipper shaped nuclei Weakly phagocyticEPITHELIOID CELLS: EPITHELIOID CELLSGIANT CELLS: GIANT CELLS When macrophages ( epithelioid ) cells fail to deal with microbes to be removed, they fuse together to form multinucleated giant cells. 40-50 µm Weakly phagocyticGiant cells: Giant cells Giant cells in inflammation Langhans ’ type Foreign body type Touton giant cells - Aschoff cells Tumor giant cells Reed-Sternberg cells Anaplastic tumor giant cells Giant cells in giant cell tumor of boneGiant cells: Giant cells Miscellaneous- Warthin finkeldy cells Osteoclasts , megakaryocyte , synctiotrophoblastVarious types of giant cells: Various types of giant cellsLanghan’s giant cell: LANGHANS’ TYPE Langhan’s giant cell Epithelioid cellForeign body type of giant cell: FOREIGN BODY TYPE Foreign body type of giant cellSlide 48: TOUTON GIANT CELLS Tuton giant cellSlide 49: TUMOUR GIANT CELLSSlide 50: REED STERNBERG CELLSSlide 51: WARTHIN FINKELDEY CELLS (Measles)GRANULOMA: GRANULOMA A microscopic aggregation of activated macrophages transformed into epithelioid cells surrounded by a collar of mononuclear leukocytes. With time, develops an enclosing rim of fibroblasts & connective tissue .FORMATION OF GRANULOMA: FORMATION OF GRANULOMA Injury ↓ Failure to digest the agent ↓ Weak inflammatory response ↓ Persistence of injurious agent ↓ T- cell mediated immune response ↓ ~Activation of T-cells ~ Monocyte chemotactic factor(C5a, MCP-1) ~Growth factors (PDGF, TGF- β ) ↓ Recruitment of circulating monocytes & Proliferation of tissue macrophages ↓ Accumulation of macrophages ↓ Activation of macrophages (IFN- γ , endotoxin, chemical mediator) ↓ transformation into epithelioid cells & giant cells ↓ GRANULOMAGRANULOMA FORMATION: GRANULOMA FORMATION CD CD4 + IFN g IL-12 TNF b IL-2 Th1 cytokines IL-12 Proliferation Granuloma Formation TGF- b PDGF IGF-1 Fibrosis IL-8, IL-15, IL-16, RANTES IL-1, TNF a , IFN g , IL-12, GM-CSF, MIP-1 a M FTUBERCULOSIS: TUBERCULOSIS Caseating granulomatous lesion Mycobacterium tuberculosis (Acid fast bacilli) Pathogenicity is related to the ability to escape killing by macrophages & induce delayed type of hypersensitivityFormation of tubercle: Formation of tubercle Initial neutrophilic response to TB bacilli ↓ Neutophils destroyed by organism ↓ Proliferation of macrophages (After~12 hrs) ↓ Phagocytosis of TB bacilli by macrophages ↓ Activate CD4+ T lymphocytesSlide 57: Morphological transformation of activated Macrophages ↓ Epithelioid cells ↓ Fuse to form giant cells ↓ Hard tubercle formation (Role of cytokines released in response to sensitised CD4+ Tcells & constituents of bacterial cell wall )Slide 58: Interaction of mycobacteria with activated T- cells - direct action of CD8+suppressor Tcell -action of CD4+helper Tcells ( via IFN- γ ) Direct toxicity of mycobacteria to macrophages ↓ Development of central caseation necrosis ↓ Soft tubercle (caseating granuloma of tuberculosis)Tubercular granuloma: Tubercular granuloma Giant cell Central caseating necrosis with epithelioid cells Collar of mononuclear cellsSlide 63: LEPROMATOUS LEPROSY Foamy histiocytes in dermis Uninvolved clear zoneSlide 64: Z-N staining Acid fast bacilli laden macrophages GlobiSlide 65: TUBERCULOID LEPROSY Hard tubercle Erodes basal layer of epidermis No clear zoneSlide 66: SYPHILIS Plasma cells Histiocytes Central cells are necrotic, without loss of architectureACTINOMYCOSIS: ACTINOMYCOSISSlide 68: SCHISTOSOMIASIS Egg of Schistosoma mansoni Scattered eosinophils GranulomaSlide 69: COCCIDIOMYCOSIS Granuloma Giant cell with spherules of C. immitisHistoplasmosis : Histoplasmosis Otherwise healthy individuals Immuno suppressed individuals Epitheliod granuloma Focal accumulations of Mononuclear cellsSARCOIDOSIS: SARCOIDOSIS Asteroid bodiesForeign body granuloma: Foreign body granulomaSlide 73: CROHN’S DISEASE Non caseating granulomaRheumatic granuloma: Rheumatic granulomaATHEROSCLEROSIS: ATHEROSCLEROSISATHEROSCLEROSIS: ATHEROSCLEROSISSlide 78: THANK YOU Dr. Ravi Jain P.G. student- III yr You do not have the permission to view this presentation. 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