09-PATHOLOGY

Hodgkin lymphoma neopl:non neoplastic cell=1:100 classic-CD15+,30+,20–,45–(LCA), Pax5, Oct2, Prob1 NS MC LD(HIV+ve)-neopl:non neopl=1:10 LR

LP-CD15–,30–,20+,45+

Reed-Sternberg cell(germinal centre Bcell) -Hodgkin lymphom lacunar(owl eye nucleus)-NS owL eye-cLassicaL HL mononuclear-MC,LR Popcorn-LPRx-ABVD regimen

non Hodgkin lymphoma neoplast>non neoplast cell staging-morphology of cell Bcell high grade DLBCL Burkitt lymphoma mantle cell lymphoma

low grade follicular indolent CLL(bone marrow,bld)/SLL(LN,Spleen)

→ Richter transformat-low grade high maltoma Tcell Anaplastic Large Cell Lymphoma(ALCL) angiocentric lymphoma angioimmunoblastic lymphoma mycosis fungoides/Sezary synd(disseminated MF) enteropathy(coeliac ds) associated Tcell lymphoma

Aim4a

iims.i

n

lineage marker Bcell-CD10,19,21,22,23,79a, Pax5, Oct2, Prob1 T cell-CD2,3,4,5,7,8 NK cell-CD16,56 Plasma cell-CD38,138

lymphocyte sp marker ALCL-CD30, EMA, ALK1 BCLL/SLL-CD5,23 Burkitt lymphoma-Bcl6, CD20 follicular lymphoma-Bcl2 hairy cell leukem-annexinA1, CD25,103, DBA44 mantle cell lymph-cyclinD1(Bcl1), CD5,CD23–

morphology ALCL-doughnut cell, halmark cell BCLL/SLL-small cleaved/smudge cell Burkitt lymphoma-starry sky follicular lymphoma-follicular cell, buttock cell hairy cell leukemia-cell with hair like projection, fried egg app, TRAP+ve mycosis fungoides-cerebriform nucl, Sezary cell, Pautriers abscess

genetic marker ALCL-t(2;5) Burkitt lymphoma-t(2;18), t(8;14)/cmyc protooncogene, t(8;22) DLBCL-cmyc follicular lymphoma-t(11,18) MCL-t(11,14)

plasma cell neoplasm plasma cell leukemia =MM+peripheral bld plasma cell> 20%(>2000/mm³) multiple/plasma cell myeloma(MM) =clonal proliferation of plasma cell+ M protein>30g/l+ end organ damage C-hyperCalcemia R-Renal insufficiency A-Anaemia B-Bone lesion

smouldering/asymptomatic myeloma =MM–end organ damage monoclonal gammopathy of undetermined significance =plasma cell<10%+ M protein<30g/l+ no end organ damage

Aim4a

iims.i

n

multiple myeloma Mott cell(grape like inclusion in cell) flame cell(bluish) Russel body Dutcher body starry sky app

myeloid neoplasm myeloproliferative neoplasm proliferation of mature myeloid cell cytosis of affected lineage cytopenia of other lineage <20%blast

CML, polycythemia vera, essential thrombocytosis, c/c neutrophilic leukemia, c/c eosinophilic leukemia, mastocytosis prim myelofibrosis-obliterat marrow fibrosis, collagen deposit in marrow, leukoerythroblastosis, teardrop RBC(dacryocy te) myelodysplastic synd dysplasia in myeloid precursor cytopenia of affected lineage norm other lineage hypercellular bone marrow <20%blast refractory cytopenia RCUD(unilineage dysplasia) RCMD(multilineage) RARS(ref anaem with ring sideroblast) RAEB (ref anaemia with excess blast)

MPN/MDS/atypical CML (BCR-ABL–ve, Ph chr 9-22–ve) <20%blast c/c myeomonocytic leukemia

JMML(Juvenile MyeloMonocytic Leukemia) AML >20%blast <20%blast+t(8:21)/t(15:17) WHO classific AML with recur genetic abnorm AML a/w MPN AML a/w MDS Down synd ass AML therapy related AML AML not otherwise specified

Aim4a

iims.i

n

M0-AML without differentiat M1-AML without maturat M2-a/c myeloblastic leukemia(MC) M3-a/c promyelocytic leukemia-DIC, t(15:17)-good progn, multiple Auer rod(prim

granule), Rx-All transretinoic acid M4-a/c myelomonocytic leukemia-gum infiltration, HSM M4Eo-M4+eosinophilia-i(16)-good progn M5-a/c monoblastic leukemia, gum hyperplasia M6-a/c erythroid leukemia-glycophorin A, NSE–ve M7-a/c megakaryoblastic leukemia-Down synd

Dx-myeloblast-abundant granular cytoplasm, multiple prom nucleoli, Auer rod, azurophilic granule promyelocyte-Faggot cell monoblast-abundant agranular cytoplasm, folded nucleus lymphoblast-scanty agranular cytoplasm, no nucleoli

cell—special stain—CD marker myeloblast-myeloperoxidase,Sudan black-MPO,CD117 promyelocyte-MPO,Sudan black,weak NSE-MPO,CD117 monoblast-strong NSE-CD11,13,15,33, 64,lysozyme,NSE erythroblast-PAS-glycophorin megakaryoblast-esterase-CD41,42,61

myeloid/granulocytic sarcoma extramedull prolifer of blast MPO>CD117

CML Ph chr-22,tyrosine kinase c/c phase <10%blast accelerat phase 10-20%blast blast phase ≥20%blast myeloid sarcoma

polycythemia vera Hb(g%)-mal>18.5,fem>16.5

↓ sr erythropoietin- JAK2 mutat

essential thrombocytosis

Aim4a

iims.i

n

PLT>4.5lac/dl↑↑ bone marrow- megakaryocyte

JAK2 mutat

ALL t(4;11) L4-mature Bcell Tcell lymphoblastic-mediastin mass

myeloid sp marker CD4,11b,13,15,33,117,cMPO

CD marker-cell CD1a-thymocyte,Langerhans cell CD3-panTcell CD13,14,15,53-monocyte,macrophage CD15,30-classical Hodgkin ds CD16(ADCC),56-NK cell CD19-panBcell CD20-lymphocyte predominant HL CD21-EBV receptor CD31(PECAM1)-diapedesis CD34-aplastic anemia,rolling CD38,138-plasma cell CD41-PLT CD45-all leukocyte(leukoc comm Ag) CD45RA-medullary(naive Tcell) CD45RB-all leukocyte CD45RC-subunit T medullar thymocyte, naive Tcell CD45RD-subunit T cortical thymocyte, memory Tcell CD55,59-PNH CD95(FAS)-death recept domain, extrinsic pathway apoptosis CD99-Ewing sarcoma CD99(mic2)-ALL CD117-GIST,granulocytic sarcoma CD133-astrocytic glioma CD271-p75 nGF receptor

bone marrow fibrotic(dry tap)-myelofibrosis, hairy cell leukemia, megakaryoblastic leukemia intensely hypercellular-leukem, lymphom reduced cellularity-aplastic anemia, sickle cell anemia, radiation, trauma, HIV, decompression sickness, TB, typhoid, SLE

Aim4a

iims.i

n

↑ glioma-tm initiating capacity, self renewal, undifferentiat cellular phenotype

amyloid tm multiple myeloma insulinoma med ca thyroid neuroendocrine tm

SmCC lung chromogranin, synaptophysin, neuron sp enolase-nuclear moulding, Azopardy effect

palisading tm cell(ABCS) Adamantinoma BCC Craniopharyngioma Schwannoma

self regression hemangioma melanoma neuroblastoma retinoblastoma

tm showing CSF dissemination germ cell tm ependymoma choroid plexus tm medulloblastoma prim CNS lymphoma high grade astrocytoma

sarcoma with high nodal met(RACES) Rhabdomyosarcoma Angiosarcoma Clear cell sarcoma Epithelioid sarcoma Synovial sarcoma

tm showing Rosette(REMEN) Retinoblastoma Ewing sarcoma Medulloblastoma

Aim4a

iims.i

n

Ependymoma Neuroblastoma

chemoresistant tm ca stomach ca UB SCC head&neck soft ts sarcoma

sarcophagus unfused phagosome in cytoplasm lipofuschin-wear&tear pigment

sk m hypertrophy→ αmyosin βmyosin(less energy)

age—breast—uTerus Puberty-hP-hP preg-hp>ht-hT>hp lact-ht-involutn menopause-atrophy-atrophy

metaplasia sq metaplasia-resp tract,endocx Barett esoph-intest,columnar Hurthl cell/oncocyt-Hashimoto thyroiditis

→ myositis ossificans-m bone

cell inj cell Swelling(earlieSt), hydropic change, memb bleb reversible-focal chromatin condensat, EM-small amorph densit irreversib-cell memb damage, chromatin condensation(pyknosis), fragmentation(karyorrhexis), dissolution(karyolysis), large amorphous density

apoptosis intrinsic>extrinsic

→ ↑ Cytosol Cytochrome C+Apaf1(apoptosis activat fact1) endonuclease,caspase most CHaracteristic feature-CHromatim Condensation hallmark in nucleus-internucleosomal fragmentation of chromosome earlieSt change-cell Shrinkage no lipase in apoptosis

caspase

Aim4a

iims.i

n

executioner-3,6,7 initiator intrinsic/mitoch pathw-9 initiator extrins/death recept path-8,10

p53→ → ↑ stimulat proapoptotic gene memb permeability

proapoptotic gene BAX,BAD,BID,BIM,BAKantiapoptotic gene BCl2,BClX

necroptosis=necrosis+apoptosis→ → → RIPgene free radical mitoch damage

↑ → ↓ →( permeability apoptosis)( ATP necrosis)

free radical OH–(hydroxyl anion)-most potent O2–(superoxide anion)-least potent cell component most sensitive to free radical inj-lipid source UV ray,ionising radiation NADPH(phagocyte) oxidase(resp burst) MPO chemical/drug Heber Wiess rxn Fenton rxn xanthine oxidase

scavenger vitA,C,E mineral-Zn,Se,Mo,fenton glutathione(Cys) glutathione peroxidase superoxide dismutase Cu,Zn-Cytosol Mn-Mitochondria

catalase(peroxisome) health immunity

fertilisation ds ageing G6PD Alz ds,Parkinson ds

Aim4a

iims.i

n

lipid peroxidation→ PUFA DNA damage

Fenton rxn→ Fe++ Fe+++&free radical

calcification dystrophic-γGandy body spleen, TB, lymphoma, neuroblastoma metastatic-multiple myeloma, parathyr ca, SqCC lung, metastatic bone tm

necrosis pseudolaminar-in cerebral neocortex-neuronal loss& gliosis are uneven fibrinoid-malign HTN, PAN, a/c RF, RA, HSP, SLE, SABE, HBV, malign fat-chalky white

monocyte-αnaphthyl esterase

a/c inflammation→ → ↑ → transient vasoconstrict(1st sign) vasodilat vasc permeabilit(hallmark) stasis

→ margination→ rolling(weak binding-selectin P,L,E)

→ adhesion(strong bind-integrin-ICAM, VCAM, CD34)→ diapedesis(crossing-PECAM1/CD31)

chemotaxis(chemotaxin-C3a,C5a, IL1, leukotrieneB4, TNFα, bact product, chemokine, kallikrine)

endothelial cell contraction=5-10minendoth cell retract-aft 4-6h, persist-24h

chemokine C-X-C 1AA separating 2cysteine-IL8(neutrophil) C-C βchemokine-eotaxin(eosinoph), MCP1, MIP1(macrophage), RANTES C lymphotaxin(lymphocyte) C-X3-C fractalkine(lymphocyte, monocyte)

leukotrieneB4-maj activator& chemotact agent for WBC, potentiate adhesion to cellwall

↑ bradykinin- vasc permeability receding ds, maj basic prot-eosinophil

Aim4a

iims.i

n

5HT-vasoconstrictor

Pseudomonas-neutrophil virus-lymphocyte HSR-activat lymphocyte, macrophage, plasma cell allergy-eosinophil

molecular carcinogenesis↑ proliferat protooncogene mutat

→ → protooncogene(norm-code for GF) mutat oncogene(abnorm) oncoprot-sis signal transducer-RAS(K,H,N), tyrosine kinase nuclear regulat prot mutat-myc(c,n,l), jun,fos

tm suppress gene mutat-p53(molecular policeman), Rb, PTEN(Phosphatase TENsin homologue)↓ death inh of apoptosis

Cmyc-Cardiac hypertrophy

cell cycle→ → → → G0 G1 S G2 M→ G1 S-cyclinD,CDK4

→ S G2-cyclinA,CDK2→ G2 M-cyclinB,CDK1→ G1 M-cyclinE,CDK6

G1=12h S=4-6h(centriole self duplicat) G2=5-6h M=2h

↑ tm cell total cell cycle time- /norm

cyclin-CDK D-4,6 E-6,2 A-2 B-1

G1S checkpt-detect Preexisting mutat-P53> Rb G2M checkpt detect Replication error-Rb> p53 p53-G1S>G2M Rb-G1S>G2M

Aim4a

iims.i

n

→ ↑ → ↓ → → ↓p53 p21 cyclinD,CDK hypophosphorylat Rb Rb binding to E2F

↓ G1-l asparaginase(E coli), steroid( phospholipaseA2) S(topoisomerase I)-antimetabolite, camptothecin, topoisomerase I inh(irinotecan, topotecan) G2(topoisomerase II)-bleomycin, epipodophyllotoxin(etoposide, teneposide) M-vinka alkaloid(vincristin, vinblastine), taxan(paclitaxel, docitaxel), ixabepilon, griseofulvin, estramustin, colchicine, erbulin

growth fraction %of tm cell in cell cycle=15-20

labile cell continuously multiplying-all epith, bone marrowquiescent cell multiply if induced-hepatocyte, pancr,nephronpermanent cell postmitotic phase, cant multiply-myocyte, neuron

Kohler&Milstein hybridoma techniq Ab production-fusing Ab forming spleen cell with myeloma cell

TNFα↑ vasc permeability in a/c inflam

intrinsic Tyr kinase activity replication hepatocyte malign transf of norm cell overexpres-HCC, astrocytoma, Menetrier ds

TNFBet angiogenesis antiinflamm Bone morphogenic prot chemotaxis fibrogenic growth inhiBitor for epith cell&WBC invasion metast

IFNγ→ → convert activated macrophage epitheloid cell giant cell granuloma

nGF

Aim4a

iims.i

n

neuron keratinocyte memory B lymphocyte

TGF antiinflammat proliferat of fibrous ts↓ metalloproteinase

arachidonic acid metabolite prostaglandin lipoxin leukotriene

PG-Pain

PGI2(prostacycline) vasodilat↓ PLT aggregat

PG-produce by PGD2-mast cell PGE2-neutrophil,macrophage PGI2-endothelial cell TXA2-PLT

pyrogen exogen-bact tox endogen-IL1,IL6, TNFα,INFα, ciliary neurotropic factor→↑ → ↑ →PGE2(hypothalam) thermoregulatory set pt fever

ASSman focus-infraclav(lung apex) lesion of Sec TB Ghon focus-lesion at lung(rt) perip+ LN in prim TB cardiac polyp-PM fibrinous clot

a spare in atherosclerosis radial a ulnar a renal a mesenteric a

part of atherosclerotic plaque fibrous cap-dense collagen, sm m

Aim4a

iims.i

n

shoulder-Tcell, macrophage, sm m core-LDL, foam cell(macrophage, sm m engulf lipid) extracellular hyaline change, Chlamydia pneum

microcytic hypochromic anem Fe def anem, Pb poisoni, sideroblast anem, anem of c/c dsmicrocytic hereditary spherocytosis

Fe def anem↓ prelatent- sr ferritin(earliest,most sensit)

↓ ↑ latent- sr total Fe, TIBC→ ↓ → ↓ → ↓ clinical-anisocytosis MCV MCH/Hb RBC

response to therapy↑ 2d- sense of well being↑ 4d- reticHb%

↑ 5-10d- retic count 15d-regenerat of filiform papillae

↑ → ↑ → ↑ → ↑ 2-3w- RBC MCH Hb% MCV 2mth-nail,skin change 6mth-replenishment of store

hereditary spherocytosis ankyrin band3 αspectrin anion exchanger pallidinhereditary elliptocytosis spectrin(biconcave shape) glycophorin C protein 4.1

Hb βchain67(AGAL BMS)

→ Val Asp-Bristol→ Val Glu-Milwaukee→ Val ALa-Sydney

→ HbC(Cooley Hbemia)-β6-Glu Lys→ HbD-β121-Glu glutamine

→ HbE-β26-Glu Lys→ HbS-β6-Glu Val

Aim4a

iims.i

n

sickle cell anem→ T A

→ GUG GAG→ Glu(β6) VAl

→ electrophoresis(pH=8.6) mobility anode Glu>Val,HbA>HbS sickling agent-Na dithionate↓ sickling-Na cyanate

a/c chest synd in sickle cell anem-new pulm infiltrate on CXR, infn& infarction

Hb electrophoresis→ + –-CSFA

Hb(FAASC)-elution time(min) F=1 A=2.5 A2=3.5 S=4.5 C=5

bone marrow-fat cell:RBC=1:1

AIHA(WoGayaCM) Warm(IgG) Cold(IgM)

paroxysmal cold Hburia cong syphilis, mumps, measles

Coomb test(IgG) DCT-Ag detected(DoG) ICT-Ab detected

hemolytic anem Coombs+ve-SLE,Scleroderma Coombs–ve-HSP,HUS,TTP

PNH→ →↓ clonal stem cell disord acq mutat PIGA gene GPI anchor prot

MIRL(Memb Inhib Reactive Lysis)-CD59 decay accelerating factor-CD55 C8 binding prot alkaline phosphatase

Aim4a

iims.i

n

AChsterase↑ → → ↑ → altern pathw complem med intravasc lysis noct Hburia CO2 acidosis

complic-intravasc thromb, aplast anem, Budd Chiary synd↑Ix-Ham test, glycerol lysis, sucrose lysis, LDH

Mx-bld transfusion, stem cell transpl

bld grp fucose-fucosal transferase-H gene(fnal), h gene(nonfnal-Bombay bld grp) N acetyl galactose-NAG transferase-B N acetyl galactosAmine-NAG Aminyl transferase-A

screening of inf before transfusion(5ds) HIV(NACO), HCV, HBsAg, VDRL, malaria

bld storage RBC(sedimentation) frozen(–65°C)-glycerol-10y liquid(routine-+1-+6°C)

↓ ↓ acid citrate(triNaCa chelater)dextrose- 2,3DPG- O2 delivery-21d↑ ACD+NaH2PO4( 2,3DPG)-21d

↑ CPDA(adenine- ATP)-35d CPD-SAGM(Saline Adenine Glycerol Mannitol)-42d

PLT whole bld(+20-+24°C)-PLT life span=7d, used<5d, 1unit=6×WB single donor PLT-apheresis

FFP(ABO matching req)→ → → whol bld (<8h) plasma all coag fact (–18°C)-1y

cryoppt→ → FFP centrifuge cryoppt(fact VIII=80 -120unit, 150mg fibrinogen, vWF,

factXIII)-–18°C-1y liquid plasma

→ ↓ → → WB(1-6°C) (>24h- factVIII,V) plasma separate liquid plasma

transfusion related a/c lung inj-6h

clotting factor-name I-fibrinogen(rouleaux format) II-prothrombin III-ts factor IV-Ca V-proaccelerin/heredit labile fact/activat globulin VI-accelerin VII-proconvertin/sr prothromb convers accelerator(SPCA)

Aim4a

iims.i

n

VIII-antihemophilic factor IX-christmas fact/plasma thromboplastin component X-Stuart factor XI-plasma thromboplastin antecedent XII-Hagemen factor XIII-fibrin stabilizing factor/fibrinase XIV-prekallekrein XV-kallekrein XVI-PLT factor

blding cascade→ → → → I-XII XI IX VIII X→ E-VII X→ → → → → C-X II (I unstable fibrin) XIII stable clot

PT(Prothrombin Time-measured at<2h at room temp, <4h at 22-24°C) ts thromboplastin

→ E-VII XaPTT(activat Partial Thromboplastin Time) phospholipid, kaolin, silica

→→ I-XII XTT(Thrombin Time) thrombin

→ X fibrinreptilase time(modif TT) reptilase-thrombin agonist(not antag by heparin) norm-heparin toxicity↑ -afibrinogenemia

fact XIII def PT-norm, aPTT-norm, TT-norm

→ urea lysis test-5Murea lysis of unstable clot dry clot wt-stable>unstable

PLT fn disorder→ aGGreGation-PLT PLT-Gp IIb,IIIa recept-ADP, collagen-Glanzman thrombasthenia

→ aDheSion-PLT enDoth-Gp Ib,IX recept-ristocetin-vWF, giant PLT-BernarD Soullier synd

PLT aggregation↑ -ADP, TXA2, epinephrine, 5HT, vWF, fibrinogen, collagen, immune complex,

thrombin, thrombospondin↓ -PGI2, NO, endothelin, bradykinin

Aim4a

iims.i

n

PLT granule α-fibrinogen, fibronectin, factV,VIII, PDGF, TGFβ, PLT fact4 δ(dense body)-ADP, Ca, histamine, 5HT, epinephrine

ITP↑ IgGanti GpIIb-IIIa/Ib-IX, spleen norm, PLT destruct

spontan blding-PLT<20000/mm³

lysosomal granule prim(azurophilic) granule req high level of agonist to be released potentially more destructive secrete-MPO, acid hydrolase, elastase, defensin, phospholipaseA2, nonsp

collagenase sec(sp) granule req low level agonist secrete-lysozyme, lactoferrin, alk PO4ase, T4collagenase, phospholipaseA2

anticoagulant EDTA-hematology Li heparin-pl biochemistry, isolation of virus plain-sr biochemistry Na Citrate(3.2%)-Coagulat assay

↓ → ↓ NaF- enolase glycolysis(1-2%glu loss/h) SPS(0.3%Na Polyanethal Sulfonate)-bld culture

ESR tube Wintrobe-100mm,EDTA Westergren-300mm,triNa citrate modif Westergren-EDTA

cell-life span neutrophil(in circulation)=4-8h monocyte(in circulat)=1-3d neutrophil(in ts)=2-5d PLT=7-10d lymphocyte(short lived)=3w monocyte(in ts)=mth-y RBC=120d lymphocyte(long lived)=3y

Aim4a

iims.i

n

Lardaceous spleen-Red pulp, splenic Sinus(SaRLa) sago spleen-white pulp, splenic follicle

opportunistic inf in AIDS-CD4 cell count CMV<50 Cryptococcus<100 Pneumocystis jiroveci<200 Toxoplasma<200 Tuberculosis<400

neuronal migration disord heterotop-grey matter fragm in abnorm locat brain Lissencephaly-complete Lack gyri& sulci microgyri-multiple small gyri pachygyria-coarse gyri

fixative electron microscope-2.5%glutaraldehyde FNAC/pap smear-90%ethanol HPE/Bx-10%neutral buffer formalin immunofluorescence-frozen sample

bone 30%organic T1collagen(90%), prot, bone sialoprot, alk phosphatase 70%inorganic[hydroxyapatite-Ca5(PO4)3(OH)] CaPO4,CaCO3,CaF2,Ca(OH)2,citrate

collagen(Gly-X-Y)n fibrous prot,strength,flexibility collagen molecule(tropocollagen)-3polypeptide chain each chain-lt handed helix twisted together-rt handed helix helices are parallel 40nm gap b/n 2tropocollagen-hydroxyapatite deposit most abundant prot=25%

→ → protocollagen (lysyl hydroxylase, prolyl hydroxylase, vitC, molec O2, αKG →hydroxylat of Pro&Lys) collagen

collagen(type28)—distribut ts—genetic disorder I-ubiquitous in hard&soft ts, skin, tendon, bone, cornea(MC)-osteogenesis imperfecta 1,Ehlers Danlos synd7

Aim4a

iims.i

n

II-cartil, IVD, vitreous-achondrogenesis II III-hollow organ, soft ts, healing, fetal skin, CVS, lung-vascul Ehlers Danlos synd4 IV-BM, glomerul, lens-Goodpasture synd(α3), Alport synd(α5) V-soft ts, bld vess, placenta-classical Ehlers Danlos synd VII-dermoepidermal jn-epidermolysis bullosa

angiofollicular LN hyperplasia-Castleman ds

HLA 6/6-total mismatch=85-90%survival 0/6-total match=92-97%survival

GVHD(Runt ds in animal) allogenic BMT, liver, unirradiated bld, not in skin a/c-GIT, liver, skin c/c-fibrosis-lung, musculoskeletal syst, kidn not involved

type of graft-donor autogenous/autogenic/autograft-self isologous/syngeneric/syn/isograft-twin allogenic/homo/allograft-genetically unrelated member same sp hetero/xenograft-diff sp orthoptic-anat norm site heterotopic-anat abnorm site

interleukin↑ IL1- differentiat of T,B cell, pyrogenic, induce a/c phase prot, bone marrow proliferat,

↑ ↑pyroptosis(cell death in bact inf), vasc permeability, IL2 recept on Tcell, recruit WBC, not Tcell IL

↑ IL2- differentiat, growth of T,B cell, cytotoxicity of T,NK cell, secret of lymphokine IL3-multiCSF

↑ ↑ IL4- T,B cell, IgG1,IgE production, class switching↑ ↑ IL5- eosinophil, IgA,IgM production↑ IL6- B cell differentiat, IgG production, a/c phase protein, Stauffer synd, myeloma

↑ ↓cell proliferation, osteoclast, by E,Castleman ds IL7-B&T cell GF IL8-neutrophil chemotactic factor IL9-T cell growth

↓ IL10- IFN product&mononucl cell fn,UC↑ IL11- a/c phase prot↑ IL12- NK cell↓ ↑ IL13- mononuclear cell fn, mast cell↑ ↑ IL17- neutrophil, monocyte

Aim4a

iims.i

n

↑ ↑ IL22- neutrophil, monocyte antiinflam-IL4,10,13

prim lymphoid organ bone marrow thymussec lymphoid organ Td(Tcell) spleen(periarteriolar lymphoid sheath) LN(paracortical area) MALT CLT bone marrow

Ti(Bcell) spleen(cortex,medull,germinal centre)

Ag recognition molecule BCR(Bcell receptor)(valency=2) TCR MHC-I MHC-II

Ag Td(thymus dependent)

→ → → exotoxin,soluble prot(more Agic) proc by APC stimulat Tcell stimulat Bcell class switching+, affinit maturation+, memory+ Ti(thymus independent) Ti1-LPS endotoxin Ti2-capsule,struct prot

→ cant be proc by APC stim Bcell directly complement activat+

prot Ag-more immunogenic, Tcell depend, no tolerance, all type Ab, memory resp+, req proces by Ag present cell, quickly metab carb Ag-less immunogenic, Tcell indep, immunolog tolerance+, IgM,IgGAb, memory–, no req processing, slow metab

cell Tcell(70%) CD4+,helper,class II restricted

CD8+,cytotoxic,class I restricted(produce perforin) Bcell(10-20%) NK cell(5-15%)

Aim4a

iims.i

n

large granular lymphocyte, azurophilic granulocyt, CD16-Fc tail recept to IgG, Ab depend cytotoxicity

CD4+THcell↑ ↑ ↑ TH1- Bcell(IgG), macrophage, CD8+Tcell, IL2, IFNγ↑ ↑ ↑ ↑ TH2- memory cell, Bcell(IgE), eosinophil, mast cell(T1HSR), IL4,5,6,13↑ ↑ TH17- neutrophil, monocyte

initiate T4HSR

MHC class I(A,B,C loci) expression-on all nucleated cell& PLT, except RBC restriction-CD8+Tcell fn-immun surveillance(self vs nonself), immunity against intracellular inf, graft

rejectn, GVHD, tm immunity class II(DR,DQ,DP) expression-on APC restriction-CD4+Tcell fn-prevent AI, GVHD, mixed leucocyt rxn

class III-C2,C4, proferdinB, chaperon, heat shock prot, TNFα,β

AgPresentingCell(bothMHC present) professional-dendritic cell> macrophage> Bcell nonprofess-glial cell, fibroblast, endoth cell ,thymic epith cell, thy follicular cell, pancr βcell ocular dendritic cell-HLA2

+ve selection thymic cortex-Tcell-self recognition, B cell-maturation–ve selection

↑ thymic medull-T,B cell- affinity for self MHC killed by apoptosis

B cell no. of monomeric Ig(M,D) on Bcell surf =1.5×10^5 1IgM activate=5C1q 2IgG activate=1C1q IgM,IgE-CH4 each domain=110 AA long carbohydrate region IgG,IgA,IgD-CH2

IgM,IgE-3 isotype-CH reg-class switching-germinal centre sec lymphoid organ idiotype-VH,VL(CDR-complement determining reg) reg

Aim4a

iims.i

n

affinity highest-IgG least-IgM

IgA pEpsin-cleave bEl hinge region-1f(ab)2 pApAin-cleav Abov hing reg-2f(ab)+1fc seruM IgA-Monomer secretory IgA-dimer, 2monomer join by Gly rich glycopeptide(J chain)

IgE Praunitz Kustner rxn cong def-Toxoplasma,Rubella,CMV RAST(Radio AllergoSorbent Assay)

complement system fn

↑ opsonisation-C3b(MI)( ×4000) immunocomplex clearance-C3b memb attack complex(MAC) mediated lysis-C5-9 chemotaxis-C5a anaphylotoxin-C5a,3a,4a

adaptive/classical/lectin pathway IgM/IgG+Ag bind C1q→ → C2 C2a,C2b→ → → → C4 C4a,C4b C4b2a C3

alterNATive/inNATe pathway→ free C3(bld) C3a

→ → → → → C3b B Ba,Bb C3bBb C3 C3 convertase act on C3 complement glycoprot intest-C1 macrophage-C2,4 spleen-C5,8 liver-C3,6,9

hapten<10kDa,unable to stimulate immune system epitope-smallest unit of Ag paratope-site on Ab that combin with Ag idiotope-sp Ag determinant of paratope

Abbreviations a-artery, AA-amino acid, abtc-antibiotic, AI-autoimmune bef-before, bel-below, b/l-bilateral, bld-blood, b/n-between, bn-benign, br-branch,

Aim4a

iims.i

n

Bx-biopsy ca-carcinoma, carb-carbohydrate, c/i-contraindication, c/l-contralateral, conc-concentration, cong-congenital, Cx-cervix d-day, def-deficient, ds-disease, d/t-due to, Dx-diagnosis E-estrogen fem-female, fr-from gld-gland, glu-glucose h-hormone idiop-idiopathic, i/l-ipsilateral, inf-infection, inj-injury lig-ligament, LL-lower limb, l/t-leading to m-muscle, maj-major, mal-male, MC-most common, met-metastasis, min-minor, mtx-methotrexate, Mx-management n-nerve, norm-normal P-progesterone, pl-plasma, prot-protein, pt-patient Rx-treatment SCC-squamous cell carcinoma, sr-serum, Sx-surgery, sz-seizure tm-tumour, ts-tissue UL-upper limb, u/l-unilateral vag-vagina, VC-vocal cord, vel-velocity, vert-vertebra, vit-vitamin, vol-volume w-week, wt-weight Xr-X ray y-year #-fracture °-degree

THESE NOTES ARE ONLY FOR THE PURPOSE OF GUIDANCE AND HELP TO PG ASPIRANTS, NOT FOR COMMERCIAL OR OTHER PURPOSE. REFERENCE HAS BEEN TAKEN FROM VARIOUS STANDARD TEXTBOOKS.

Aim4a

iims.i

n