Granulomatous Inflammation 4 (2)

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  • 8/6/2019 Granulomatous Inflammation 4 (2)


    Definition:Definition: Specific type of chronicSpecific type of chronicinflammation characterized byinflammation characterized by

    formation of granulomaformation of granuloma

    GranulomaGranuloma is a small, localized andis a small, localized andnodular mass, aboutnodular mass, about 0.50.5--2 mm2 mm inindiameter, and formed mainly bydiameter, and formed mainly byaggregates ofaggregates ofactivated macrophagesactivated macrophages

    (Epithelioid cell)(Epithelioid cell) surrounded by collarsurrounded by collarof mononuclear leukocytes principallyof mononuclear leukocytes principallylymphocyteslymphocytes and occasionallyand occasionally plasmaplasmacellscells..

    GranulomatousGranulomatous inflammationsinflammations

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    Epithelioid cellsEpithelioid cells [[ pathognomonicpathognomonic cells]cells]

    -- Large, abundant pale eosinophilicLarge, abundant pale eosinophilic

    cytoplasm, large vesicular nucleuscytoplasm, large vesicular nucleus

    -- CytokinesCytokines fusion intofusion into

    multinucleated giant cellsmultinucleated giant cells

    LanghansLanghans giant cells:giant cells: Peripheral nuclei;Peripheral nuclei;

    horsehorse -- shoe or bipolar patternsshoe or bipolar patterns

    Foreign body giant cells:Foreign body giant cells:

    Randomly scattered nuclei, mostlyRandomly scattered nuclei, mostly

    towards the center of the celltowards the center of the cell

    OldOld granulomasgranulomas develop an enclosing rim ofdevelop an enclosing rim of

    fibroblasts and collagen fibers.fibroblasts and collagen fibers.

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  • 8/6/2019 Granulomatous Inflammation 4 (2)


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    Causes ofCauses of granulomatousgranulomatous inflammation:inflammation:

    11-- InfectiveInfective granulomasgranulomas::

    -- Bacterial:Bacterial: T.B.T.B., leprosy,, leprosy, rhinoscleromarhinoscleroma-- Spirochetes: SyphilisSpirochetes: Syphilis

    -- Parasites: SchistosomiasisParasites: Schistosomiasis

    -- Deep fungal infection:Deep fungal infection: HistoplasmosisHistoplasmosis22-- Non infectiveNon infective granulomasgranulomas::

    Silicosis,Silicosis, beryliosisberyliosis, dust, dust

    33-- Unknown:Unknown: SarcoidosisSarcoidosis

    Mechanisms ofMechanisms of granulomatousgranulomatous inflaminflam.:.:

    11-- Indigestible particlesIndigestible particles

    22-- CellCell -- mediated immunitymediated immunity

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    Types:Types:11-- Foreign body granuloma:Foreign body granuloma:

    -- Inert indigestible F.B.: talk powder,Inert indigestible F.B.: talk powder,surgical suturessurgical sutures

    -- No immune responseNo immune response

    -- Epithelioid cells & F.B. giant cellsEpithelioid cells & F.B. giant cells

    22-- Immune granuloma:Immune granuloma:Immunogenic indigestible particlesImmunogenic indigestible particles

    CellCell--mediated immune responsemediated immune response

    * Infectious agents:* Infectious agents:TuberculosisTuberculosis, leprosy,, leprosy, rhinoscleromarhinoscleroma

    syphilis, bilharziasissyphilis, bilharziasis

    * Non infectious agents:* Non infectious agents: Sarcoidosis,Sarcoidosis,

    catcat--scratch dis., silicosis,scratch dis., silicosis, beryliosisberyliosis

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    TuberculosisTuberculosisChronicChronic granulomatousgranulomatous inflaminflam. disease. disease

    Risk factors:Risk factors:

    -- Poverty, malnutrition, overcrowding,Poverty, malnutrition, overcrowding,

    lack of adequate medical carelack of adequate medical care

    Decreased T cell mediated immunity:Decreased T cell mediated immunity:

    *Diabetes mellitus,*Diabetes mellitus, chch. lung disease,. lung disease,

    chch. Renal failure, Hodgkins lymphoma. Renal failure, Hodgkins lymphoma

    *AIDS,*AIDS, immunosuppressionimmunosuppression

    multimulti--drug resistant TB bacilli *drug resistant TB bacilli *

    1.7 billion/ world *1.7 million death/ yr1.7 billion/ world *1.7 million death/ yr

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    Causative organism:Causative organism:

    Mycobacterium tuberculosis:Mycobacterium tuberculosis:

    -- Slender, curved, rodSlender, curved, rod--shaped, nonshaped, nonmotile, acidmotile, acid-- fast (fast (ZeihlZeihl -- NeelsenNeelsen).).

    -- Strictly aerobic, slowly growing,Strictly aerobic, slowly growing,

    hard to kill, resist dryness, sensitivehard to kill, resist dryness, sensitiveto UV radiation and acidic PH (

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    Mycobacterium tuberculosisMycobacterium tuberculosis

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  • 8/6/2019 Granulomatous Inflammation 4 (2)


    Mode of transmission:Mode of transmission:

    InhalationInhalation lunglung && tracheobronchial LNtracheobronchial LN

    IngestionIngestion M. BovisM. Bovis

    TTonsilsonsils && cervical LNscervical LNsIntestineIntestine && mesenteric LNsmesenteric LNs

    InoculationInoculation SSkinkin && draining LNsdraining LNs

    TransTrans--placental: Maternal systemic T.B.placental: Maternal systemic T.B.

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    Pathogenesis ( on primaryexposure):Pathogenesis ( on primaryexposure):

    11-- GlycolipidGlycolipid covercover accumulation ofaccumulation of

    PNLPNL llocalization (no lipase)ocalization (no lipase)

    22-- Accumulation ofAccumulation ofmacrophagesmacrophages

    fail to kill the organismfail to kill the organism freefree

    bacillary proliferationbacillary proliferation bacteremiabacteremia seedling of multiple sitesseedling of multiple sites

    33-- Macrophages partially destroy TBMacrophages partially destroy TB



    Ag short peptide expressed byAg short peptide expressed by

    macrophagesmacrophages on class II MHCon class II MHC

    moleculesmolecules hilarhilar LNLN ILIL--1212

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    44-- TT--helper CD4+helper CD4+ cellscells recognize therecognize thepresented Agpresented Ag sensitizedsensitized TTHH1 cells1 cells

    55-- Sensitized TSensitized THH

    1 cells1 cells

    CytokinesCytokines--ILIL--11 ClonalClonal expansionexpansion

    memory cellsmemory cells tuberculin +tuberculin +veve

    -- ILIL--22 AutoAuto--,, paracrineparacrine proliferationproliferation

    of T cellof T cell

    CytotoxicCytotoxic CD8+ TCD8+ T lymphocyteslymphocytes

    kill infected macrophageskill infected macrophages

    -- TNF,TNF, chemokineschemokines MonocytesMonocytes


    -- IFNIFN--KK Activates macrophagesActivates macrophages

    immunity = resistanceimmunity = resistance

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    Activated macrophage =Activated macrophage = Epithelioid cellEpithelioid cell

    -- Large cells, large vesicular nucleusLarge cells, large vesicular nucleus

    abundant pale eosinophilic cytoplasmabundant pale eosinophilic cytoplasm-- Increased ability toIncreased ability to phagocytosephagocytose &&

    killkill T.B. bacilliT.B. bacilli

    -- Express moreExpress more class II MHC moleculesclass II MHC molecules facilitate Ag presentationfacilitate Ag presentation

    -- TNF, ILTNF, IL--11,, chemokineschemokines promotepromote inflinfl

    -- Secret TGFSecret TGF--B, PDGF, FGFB, PDGF, FGF

    collagen synthesiscollagen synthesis fibrosisfibrosis

    1.1. Serve to eliminate the offending antigenServe to eliminate the offending antigen

    2.2. If sustainedIf sustained continued infl.continued infl. fibrosisfibrosis

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    55-- Collar ofCollar of lymphocyteslymphocytes surrounds thesurrounds theepithelioid cellsepithelioid cells small tubercle; 0.5small tubercle; 0.5--2 mm2 mm

    fusionfusion largelarge avascularavascular massmass necrosisnecrosis

    66 -- LanghansLanghans giant cells:giant cells:-- Fusion of Epithelioid cellsFusion of Epithelioid cells

    -- Large, deep eosinophilic cytoplasmLarge, deep eosinophilic cytoplasm

    -- Multinucleated with peripheral nucleiMultinucleated with peripheral nucleihorsehorse -- shoe or bipolarshoe or bipolar

    -- Digest and remove necrotic tissueDigest and remove necrotic tissue

    77-- Caseous necrosis (4Caseous necrosis (4--6 weeks):6 weeks):

    -- Caused byCaused by avascularityavascularity, liberation of, liberation ofcytotoxiccytotoxic factors,factors, cytotoxiccytotoxic CD8+ T cellsCD8+ T cells

    NEA:NEA: Dry, cheeseDry, cheese--like, friable, creamy yellowlike, friable, creamy yellow

    MPMP:: granular, eosinophilicgranular, eosinophilic

    Acidic, anaerobic mediaAcidic, anaerobic media Kill bacilliKill bacilli

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    Tuberculin +ve bactericidal activity

    hypersensitivity immunity

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    Fate ofTuberculous lesion:Fate ofTuberculous lesion:11-- HealingHealing

    -- High immunityHigh immunity-- Epithelioid cellsEpithelioid cells FGF & PDGFFG