JointJoint

JOINT ARCHITECTUREJOINT ARCHITECTUREJOINT ARCHITECTUREJOINT ARCHITECTURE

EPIPHYSEAL BONEEPIPHYSEAL BONE CARTILAGECARTILAGE SYNOVIAL MEMBRANESYNOVIAL MEMBRANE CAPSULECAPSULE LIGAMENTSLIGAMENTS MUSCLE & TENDONSMUSCLE & TENDONS BURSAEBURSAE

Synovial membraneSynovial membrane

SYNOVIAL MEMBRANESYNOVIAL MEMBRANESYNOVIAL MEMBRANESYNOVIAL MEMBRANE SUPERFICIAL LAYERSUPERFICIAL LAYER

Synovioblast: Synovioblast: A: macrophage likeA: macrophage like B: fibroblast likeB: fibroblast like C: intermediate cellC: intermediate cell

DEEP LAYERDEEP LAYER Fibroblast: Collagen Fiber (type III), Fibroblast: Collagen Fiber (type III),

elastinelastin VesselVessel Nerve TerminalNerve Terminal

Synovial membraneSynovial membrane

Function of synovialFunction of synovial• Low friction liningLow friction lining• NutritionNutrition• Joint stabilityJoint stability• Antigen processingAntigen processing• Production of collagen, Production of collagen, PG , metalloproteinasesPG , metalloproteinases

SYNOVIAL FLUIDSYNOVIAL FLUIDSYNOVIAL FLUIDSYNOVIAL FLUID CELLCELL

Count: 200 Count: 200 Monocyte: 95%Monocyte: 95% PMN: 5%PMN: 5%

FLUIDFLUID Hyaluronic AcidHyaluronic Acid Protein: 1/3 blood, low molecular weightProtein: 1/3 blood, low molecular weight GlucoseGlucose OthersOthers

Normal Synovial FluidNormal Synovial Fluid

Synovial fluid viscositySynovial fluid viscosity

RARA GoutGout

Normal Synovial FluidNormal Synovial Fluid

Inflammatory fluidInflammatory fluid

Infectious Synovial FluidInfectious Synovial Fluid

Uric Acid CrystalUric Acid Crystal

Calcium pyrophosphate Calcium pyrophosphate crystalcrystal

Calcium OxalateCalcium Oxalate Cholestrol CrystalCholestrol Crystal

Classification of joint Classification of joint effusionseffusions

Type of FluidType of Fluid Special Special FeaturesFeatures

Leukocytes/Leukocytes/mmmm33

NormalNormal Clear, colorless, Clear, colorless, viscousviscous

200200

NoninflammatoryNoninflammatory Clear, yellow, Clear, yellow, viscousviscous

200-2000200-2000

InflammatoryInflammatory Cloudy, yellow, Cloudy, yellow, decreased decreased viscosityviscosity

2000-100,0002000-100,000

(>75%PMN(>75%PMN))

SepticSeptic Purulent, Purulent, markedly markedly decreased decreased viscosityviscosity

Usually Usually >50,000>50,000

(>95% PMNs)(>95% PMNs)

JointJoint EPIPHYSEAL BONEEPIPHYSEAL BONE

CARTILAGECARTILAGE

SYNOVIAL MEMBRANESYNOVIAL MEMBRANE

CAPSULECAPSULE

LIGAMENTSLIGAMENTS

MUSCLE & TENDONSMUSCLE & TENDONS

BURSAEBURSAE

JointJoint EPIPHYSEAL BONEEPIPHYSEAL BONE

CARTILAGECARTILAGE

SYNOVIAL MEMBRANESYNOVIAL MEMBRANE

CAPSULECAPSULE

LIGAMENTSLIGAMENTS

MUSCLE & TENDONSMUSCLE & TENDONS

BURSAEBURSAE

CartilageCartilage

Layer:Layer: Superficial Superficial Intermediate Intermediate Deep Deep Tidemark Tidemark Calcified cartilage Calcified cartilage Subchondral Subchondral

CartilageCartilage Consist of :Consist of :

Water :70%Water :70% Type II collagenType II collagen Proteoglycan :Proteoglycan :

Aggrecan Sub Unit Unit Core ProteinCore Protein Glycosaminoglycans, Link ProteinGlycosaminoglycans, Link Protein

Hyaluronic AcidHyaluronic Acid Chondrocyte Chondrocyte

CartilageCartilage

CartilagCartilagee

Collagen in CartilageCollagen in Cartilage

Cartilage Cartilage

Function :Function :Reduce friction in the jointsReduce friction in the joints

LubrecinLubrecinWater cushionWater cushion

Absorb the shock Absorb the shock associated with locomotionassociated with locomotion

Biomechanic of JointBiomechanic of Joint

Biomechanic of JointBiomechanic of Joint

COLLAGEN COLLAGEN BIOSYNTHESISBIOSYNTHESIS

CollagenCollagen

Triple helixTriple helix

Normal CartilageNormal Cartilage

Normal cartilageNormal cartilage

Cartilage LayersCartilage Layers

INFLAMMATIONINFLAMMATION??

inflammationinflammation

* Essential defense mechanism responseEssential defense mechanism response Of living tissue to InjuryOf living tissue to Injury* Only in vascularized tissueOnly in vascularized tissue* Increased blood flowIncreased blood flow* Increased capillary permeabilityIncreased capillary permeability* Leukocyte migration into siteLeukocyte migration into site

YOUR ACTIVE IMMUNE DEFENSESYOUR ACTIVE IMMUNE DEFENSES

Innate Immunity- invariant (generalized)- early, limited specificity- the first line of defense

Adaptive Immunity- variable (custom)- later, highly specific- ‘‘remembers’’ infection

INNATE IMMUNITYINNATE IMMUNITY

Innate immunity consists of:Innate immunity consists of:

BarriersBarriers

Cellular responseCellular response phagocytosisphagocytosis Neutrophil,Neutrophil, NK (natural killer) and mast cellsNK (natural killer) and mast cells

Soluble factorsSoluble factors

When you were born, you have an immunity is also called nonspecific immunity.

INNATE IMMUNITYINNATE IMMUNITY Barriers Barriers

PhysicalPhysical

skinskin hairhair mucousmucous

ChemicalChemical

sweatsweat tearstears salivasaliva stomach acidstomach acid urineurine

Innate immunityInnate immunity CelluarCelluar Macrophage-MonocyteMacrophage-Monocyte Neutrophil, mast cellNeutrophil, mast cell PlateletPlatelet Basophil, EosinophilBasophil, Eosinophil HomoralHomoral CoagulationCoagulation FibrinolysisFibrinolysis ComplementComplement Kinin , plasmin & plasminogen Kinin , plasmin & plasminogen ProstaglandinsProstaglandins

Monocyte- macrophageMonocyte- macrophage

Origin : bone marrow stem cellOrigin : bone marrow stem cell PhagocytosisPhagocytosis Ag recognitionAg recognition Ag processingAg processing Ag presentationAg presentation CytokineCytokine

Monocyte- macrophageMonocyte- macrophage

Origin : bone marrow stem cellOrigin : bone marrow stem cell PhagocytosisPhagocytosis Ag processingAg processing Ag presentationAg presentation CytokineCytokine

Origin : bone marrow stem cellOrigin : bone marrow stem cell PhagocytosisPhagocytosis Ag processingAg processing Ag presentationAg presentation Cytokine Cytokine

Monocyte- macrophageMonocyte- macrophage

Origin : bone marrow stem cellOrigin : bone marrow stem cell PhagocytosisPhagocytosis Ag processingAg processing Ag presentationAg presentation Cytokine Cytokine

NeutrophilsNeutrophils

WBCs – are WBCs – are phagocyticphagocytic, like macrophages, like macrophages

neutrophils also release neutrophils also release toxic chemicalstoxic chemicals that destroy that destroy everything in the area, including the neutrophils everything in the area, including the neutrophils themselvesthemselves

NeutrophilNeutrophil

Origin : bone marrow stem cellOrigin : bone marrow stem cell Structure : highly condensed , Structure : highly condensed ,

segmented , multilobedsegmented , multilobed functionfunction

Chemotxis : Chemotxis : Phagocytosis Phagocytosis Enzyme Enzyme

InflammationInflammation

InflammationInflammation

InflammationInflammation

SELECTINS

Progressive Activation

INTEGRINS

Postcapillary venule

CaptureSlow Rolling

Firm Adhesio

nTransmigration

Chemoattractant

Rolling

Leukocyte migration

Respiratory burstRespiratory burst

CoagulationCoagulation

FibrinolysisFibrinolysis

FibrinFibrin

FibrinFibrin stimulates stimulates cytokinescytokines production by macrophagesproduction by macrophages

Fibrin split productsFibrin split products are are chemoattractantchemoattractant

Platelet Platelet

Coagulation Coagulation Inflammation Inflammation

Platelet activating factorPlatelet activating factor Serotonin Serotonin Arachidonic acid productArachidonic acid product

INNATE IMMUNITY Humeral

Complement Complement

Membrane attack Membrane attack complexcomplex

Arachidonic acid productArachidonic acid product

YOUR ACTIVE IMMUNE DEFENSESYOUR ACTIVE IMMUNE DEFENSES

Innate Immunity- invariant (generalized)- early, limited specificity- the first line of defense

Adaptive Immunity- variable (custom)- later, highly specific- ‘‘remembers’’ infection

1. Barriers - skin, tears

2. Phagocytes - neutrophils, macrophages3. NK cells and mast

4. Complement and other proteins

Specific ImmunitySpecific ImmunityAdaptive immunityAdaptive immunity

AugmentsAugments mechanisms of mechanisms of nonspecific defense nonspecific defense

Has Has memorymemory about specific about specific pathogenspathogens

BB lymphocytes –humoral immunity lymphocytes –humoral immunity TT lymphocytes-cell mediated lymphocytes-cell mediated

immunityimmunity

Specific DefenseSpecific Defense

The Adaptive Immune The Adaptive Immune ResponseResponse

Acquired immunityAcquired immunity

Acquired immunityAcquired immunity

Cellular : T-cellCellular : T-cell Humeral Humeral

immunity : B-cellimmunity : B-cell

IMMUNE REACTIONIMMUNE REACTIONIMMUNE REACTIONIMMUNE REACTION

ANTIGENANTIGEN MACROPHAGEMACROPHAGE

T CELLT CELLB CELLB CELLANTIBODYANTIBODY

IMMUNE COMPLEXIMMUNE COMPLEX

INFLAMMATIONINFLAMMATION

Genetic Background

TARGETTARGET PMNPMNCYTOKINECYTOKINE

SUPEROXIDE ANIONSSUPEROXIDE ANIONSLYZOSOMAL ENZYMES

IL- 1

CYTOKINES

ComplementComplement

ClearanceClearance

Neuro-Endocrine

Triggering Agent

Inflammatory Response

Genetic Background Neuroendocrine axis

Types of AntigensTypes of Antigens

Exogenous antigensExogenous antigens Endogenous antigens Endogenous antigens

( autoantigen)( autoantigen)

Exogenous antigensExogenous antigens

most proteins or polysaccharidemost proteins or polysaccharide Larger the molecule the better the Larger the molecule the better the

immune responseimmune response Components of microbesComponents of microbes Food allergensFood allergens Dust-microbes, pollen etc.Dust-microbes, pollen etc.

T-Dependent T-Dependent AntigensAntigens

Processing of exogenous Processing of exogenous antigens (protein)antigens (protein)

ANTIGEN PROCESSINGANTIGEN PROCESSINGANTIGEN PROCESSINGANTIGEN PROCESSING

ANTIGENANTIGEN

DR

MACROPHAGE

IL -1

ANTIGEN

DR

MACROPHAGE T-CELL

IL -2

ANTIGEN RECOGNITIONANTIGEN RECOGNITIONANTIGEN RECOGNITIONANTIGEN RECOGNITION

HSPHSPHSPHSP POLYPEPTIDE 60-90 KD EVERY ALIVE CELL RESPONSE TO STRESS CELL HOUSEKEEPING RELATIVE IDENTITY

DIFFERENT SPECIES More than 65% IN HSP 65

– HUMAN & MYCOBACTERIUM

RA, BD, etc.. ANTIGEN

Heat shock proteinHeat shock protein

Super antigenSuper antigen

Triggering Agent

Inflammatory Response

RA

Genetic Background Neuroendocrine axis

Genetic : HLAGenetic : HLA

HLA-IHLA-I

HLA-HLA-BB,HLA-,HLA-CC, HLA-, HLA-XX HLA-HLA-EE HLA-HLA-J , J , HLA-HLA-A,A,HLA-HLA-H, H, HLA-HLA-G G , ,

HLA-HLA-FF

HLA-IIHLA-II HLA-DPHLA-DP,,HLA-DMHLA-DM,, TAP1,2TAP1,2 HLA-DQHLA-DQ,,DRDR C4b,C4aC4b,C4a Factor BFactor B

HLA-IIIHLA-III

C2C2 HSP-70HSP-70 LTLTββ TNFTNF

HLA-SystemHLA-System

APC & T CellsAPC & T Cells

LymphocytesLymphocytes

Produced in red bone marrowProduced in red bone marrow -2 types-2 types

B lymphocytes B lymphocytes T lymphocytesT lymphocytes

Based upon surface glycoproteins-CD4, CD8Based upon surface glycoproteins-CD4, CD8

T cellT cell

To be bornTo be born

T lymphocytes mature in T lymphocytes mature in thymusthymus

Self T cells undergo apoptosisSelf T cells undergo apoptosis

Pro_T

thymus

T lymphocytes mature in thymusT lymphocytes mature in thymus

MaturationMaturation

IL7

Pro_T

CD3

TCR

ApoptosisApoptosis

Exam?Exam?ResultResult

Death or lifeDeath or life

High affinity

Low affinity

Apoptosis

NEGATIVE SELECTIONthymus

APC

T cell

Differentiation

CD4 CD8

Tcell

Receptor :Receptor : 1)TCR1)TCRαβαβ or or γδγδ 2)CD-4 or CD-82)CD-4 or CD-8 3)CD-33)CD-3

T Cell ReceptorsT Cell Receptors

T Cell developmentT Cell development

Cell Differention of T Cell Differention of T CellCell

T-CELLST-CELLST-CELLST-CELLS RECEPTORRECEPTOR

EPITOPE SPECIFICITYEPITOPE SPECIFICITY APOPTOSISAPOPTOSIS CYTOKINESCYTOKINES

IL- 2, 3, 4, 5, 6, 10IL- 2, 3, 4, 5, 6, 10 IFNIFN - - GM - CSFGM - CSF

Macrophage-T cell Macrophage-T cell interactioninteraction

B CellB Cell

To be born?To be born?

B lymphocytes mature in bone B lymphocytes mature in bone marrowmarrow

Found mainly in spleen, lymph Found mainly in spleen, lymph nodes ,bone marrow nodes ,bone marrow

Circulate in blood Circulate in blood

B-CELLB-CELL

Clonal SelectionClonal Selection

B cell binds antigenB cell binds antigen Proliferates into clone with same receptor Proliferates into clone with same receptor

on surfaceon surface If T dependent antigen (proteins), T helper cell If T dependent antigen (proteins), T helper cell

will activate B cell to produce will activate B cell to produce plasma cellsplasma cells Some become Some become memory cellsmemory cells for long term for long term

immunityimmunity Self toleranceSelf tolerance

B & T cells that react with self antigens removed B & T cells that react with self antigens removed during early developmentduring early development

T-Independent AntigenT-Independent Antigen B cells can bind directly to large B cells can bind directly to large

antigens –capsule ( non antigens –capsule ( non protein )without T cellprotein )without T cell

Initiate clonal expansionInitiate clonal expansion T cells not always activated & T cell T cells not always activated & T cell

memory may not occurmemory may not occur

Antibody Antibody structure structure (diagram)(diagram)

Antibody structure (diagram)

Immunoglobulins (IgGs)Immunoglobulins (IgGs)

StructureStructure Bivalent antibody-monomerBivalent antibody-monomer

2 antigen binding sites2 antigen binding sites 4 peptide chains4 peptide chains 2 light chains and 2 heavy (longer) 2 light chains and 2 heavy (longer)

chainschains Joined together by disulfide bondsJoined together by disulfide bonds Molecule looks like letter YMolecule looks like letter Y

CytokinesCytokines

Function?Function?

Low molecular-weight Low molecular-weight proteinprotein

Mediate communication Mediate communication between cellsbetween cells

GROWTH FACTORSGROWTH FACTORSGROWTH FACTORSGROWTH FACTORS

Colony-stimulating factor:GM – CSF IL3

Growth factor:TGF PDGF

Connection with Connection with other system?other system?

NEURO-ENDOCRINE AXISNEURO-ENDOCRINE AXISNEURO-ENDOCRINE AXISNEURO-ENDOCRINE AXIS

IL - 1

HYPOTHALAMUS

PITUITARY GLAND

CORTISOLESTROGEN ANDROGEN

INFLAMMATIONIMMUNE REACTION

ApoptosisApoptosis

Programmed cell deathProgrammed cell death Rid body of excessive B & T cells Rid body of excessive B & T cells

etc.etc. Prevent leukemiaPrevent leukemia Rid of self cells without eliciting Rid of self cells without eliciting

inflammationinflammation

ApoptosisApoptosis

Apoptosis & FAS Apoptosis & FAS ReceptorReceptor

Apoptosis or cell deathApoptosis or cell death

A neutrophil (left) undergoes apoptosis, a series of changes including violent membrane blebbing and fragmentation of DNA. Apoptotic cells break into smaller pieces called apoptotic bodies that other body cells recognize and eat.

CELLS alive!