Cells of inflammation and Immunity G. Wharfe 2005

Cells of inflammation and Cells of inflammation and ImmunityImmunity

G. WharfeG. Wharfe

20052005

Immune systemImmune system

Detect and respond to antigensDetect and respond to antigens

Protects against pathogenic microorganismsProtects against pathogenic microorganisms

Also elicits response against noninfectious foreign Also elicits response against noninfectious foreign organismsorganisms

Used in inflammatory response and tissue repairUsed in inflammatory response and tissue repair

Immune responseImmune response

Response needs to be quick and efficientResponse needs to be quick and efficient

Two systemsTwo systems– InnateInnate– AdaptiveAdaptive

Cells of IRCells of IR

All derived from BM stem cellsAll derived from BM stem cells

Influenced by growth factorsInfluenced by growth factors

Begin as multipotent stem cellBegin as multipotent stem cell

Develop into committed stem cellsDevelop into committed stem cells

Innate immune systemInnate immune system

First to respondFirst to respond Limits infection before adaptive responseLimits infection before adaptive response Usually involve nonlymphoid cellsUsually involve nonlymphoid cells Cells are macrophages and polymorphonuclear Cells are macrophages and polymorphonuclear

neutrophils(PMN)neutrophils(PMN) Also involves complement and acute phase Also involves complement and acute phase

proteinsproteins If innate immunity cures infection-no adaptive If innate immunity cures infection-no adaptive

immunity developsimmunity develops

Normal haematopoiesisNormal haematopoiesis

Adaptive immunityAdaptive immunity

Inducible antigen specific responseInducible antigen specific response Primary lymphoid organs produce Primary lymphoid organs produce

lymphocytes capable of responding to lymphocytes capable of responding to various antigensvarious antigens

Lymphocytes form naïve pool in bloodLymphocytes form naïve pool in blood Lymphocytes circulate in peripheral Lymphocytes circulate in peripheral

lymphoid organslymphoid organs Location for Ag-dependent IRLocation for Ag-dependent IR

ImmunoglobulinImmunoglobulin

Cells of innate immune systemCells of innate immune system

All are bone marrow derivedAll are bone marrow derived Lineage commitment depends on stromal Lineage commitment depends on stromal

contact and cytokinescontact and cytokines Dendritic cells-Antigen presenting cellsDendritic cells-Antigen presenting cells Develop from peripheral blood monocyte Develop from peripheral blood monocyte

precursorsprecursors Found in the interstitium and T cell areasFound in the interstitium and T cell areas Stimulate Ag specific T cellsStimulate Ag specific T cells

Phagocytic cellsPhagocytic cells

PMN’sPMN’s

MacrophagesMacrophages

GranulocytesGranulocytes

Inflammatory cellsInflammatory cells Contain cytoplasmic granulesContain cytoplasmic granules NeutrophilsNeutrophils EosinophilsEosinophils BasophilsBasophils

NeutrophilNeutrophil

Stages of granulocyte maturationStages of granulocyte maturation

NeutrophilsNeutrophils

Major phagocytic granulocyteMajor phagocytic granulocyte Contain multilobed nucleusContain multilobed nucleus Neutrophilic granulesNeutrophilic granules Respond to chemotactic stimuliRespond to chemotactic stimuli Activated by macrophage and endothelial Activated by macrophage and endothelial

derived cytokinesderived cytokines Major cell of acute inflammationMajor cell of acute inflammation Primary effector cells in IR to pyogensPrimary effector cells in IR to pyogens

NeutrophilsNeutrophils

Have Fc receptors for IgG and c’Have Fc receptors for IgG and c’

Bind and phagocytose opsonised antigensBind and phagocytose opsonised antigens

Link between 2 arms of immune systemLink between 2 arms of immune system

Regulates activation and recruitment of Regulates activation and recruitment of macrophages by cytokinesmacrophages by cytokines

PhagocytosisPhagocytosis

Principal mechanism of pathogensPrincipal mechanism of pathogens Enter site of infection Enter site of infection Opsonins produced to allow phagocytosisOpsonins produced to allow phagocytosis Taken into vacuoleTaken into vacuole Killing by aerobic or anaerobic mechanismsKilling by aerobic or anaerobic mechanisms Cytokine inductionCytokine induction

PhagocytosisPhagocytosis

EosinophilEosinophil

EosinophilsEosinophils

Contain eosinophilic granulesContain eosinophilic granules Express Fc receptors for IgEExpress Fc receptors for IgE IgE prevalent in parasitic infectionsIgE prevalent in parasitic infections IgE mediates activation of eosinophil killing IgE mediates activation of eosinophil killing

mechanismsmechanisms Role in immediate hypersensitivity to Role in immediate hypersensitivity to

allergensallergens Cause tissue injury and inflammationCause tissue injury and inflammation

BasophilBasophil

BasophilsBasophils

In circulation –basophilsIn circulation –basophils

In tissue- Mast cellsIn tissue- Mast cells

Express Fc receptors for IgEExpress Fc receptors for IgE

Release chemical mediators of immediate Release chemical mediators of immediate hypersensitivityhypersensitivity

MonocyteMonocyte

MacrophagesMacrophages

Main cells of chronic IRMain cells of chronic IR Regulators of specific acquired responseRegulators of specific acquired response Fewer numbers than neutrophilsFewer numbers than neutrophils Peaks in hours to daysPeaks in hours to days Participate in both acute and chronic Participate in both acute and chronic

inflammationinflammation Phagocytose apoptotic PMN’sPhagocytose apoptotic PMN’s

Tissue macrophagesTissue macrophages

Second major class of phagocytic cellsSecond major class of phagocytic cells Provide innate immunity and initiate host Provide innate immunity and initiate host

defensesdefenses Release inflammatory cytokinesRelease inflammatory cytokines Act as APCAct as APC Link between innate immunity and acquired Link between innate immunity and acquired

humoral and cellular immunityhumoral and cellular immunity

Cells of monocyte macrophage Cells of monocyte macrophage systemsystem

LymphocytesLymphocytes

B lymphocyteB lymphocyte

T lymphocyteT lymphocyte

NK lymphocyteNK lymphocyte

LymphocyteLymphocyte

LymphocytesLymphocytes

Mediate adaptive immune responseMediate adaptive immune response Recognize antigen specificallyRecognize antigen specifically Each clone has antigen specificityEach clone has antigen specificity Arrange V, J and D elements if Ig and T cell Arrange V, J and D elements if Ig and T cell

receptor genes to form different clonesreceptor genes to form different clones B lymphocytes recognize native AgB lymphocytes recognize native Ag T lymphocytes recognize processed AgT lymphocytes recognize processed Ag

LymphocytesLymphocytes

Ag binds to receptor Ag binds to receptor

Lymphoid activation and Clonal expansionLymphoid activation and Clonal expansion

Effector cells or products all have same Effector cells or products all have same specificity as parent cellspecificity as parent cell

Inactivation of self reactive clones Inactivation of self reactive clones

LymphocytesLymphocytes

Ag independent maturation occurs in primary Ag independent maturation occurs in primary lymphoid organslymphoid organs

Ag dependent occurs in secondary lymphoid Ag dependent occurs in secondary lymphoid organsorgans

Cells are indistinguishable morphologicallyCells are indistinguishable morphologically

Phenotypically and functionally differentPhenotypically and functionally different

B lymphocyte developmentB lymphocyte development

B lymphocytesB lymphocytes

Generate Ab responseGenerate Ab response Formed with other white cells in BMFormed with other white cells in BM Ab neutralize pathogens, opsonize Ab neutralize pathogens, opsonize

pathogens, activate complementpathogens, activate complement Act as APC for T cellsAct as APC for T cells Generate memory B cellsGenerate memory B cells

Plasma cellPlasma cell

Plasma cellsPlasma cells

Not usually found in PBNot usually found in PB

Responsible for Ig productionResponsible for Ig production

T lymphocyte developmentT lymphocyte development

T cellsT cells

Generate CMIGenerate CMI Directly by differentiating into cytotoxic T Directly by differentiating into cytotoxic T

cellscells Indirectly by activating macrophagesIndirectly by activating macrophages Help B lymphocytesHelp B lymphocytes Develop from BM progenitors which migrate Develop from BM progenitors which migrate

to thymusto thymus CD4 and CD8CD4 and CD8

T cell functionsT cell functions

Delayed hypersensitivity Delayed hypersensitivity Cell mediated immunityCell mediated immunity Graft rejectionGraft rejection Contact allergic reactionsContact allergic reactions Cytotoxic responses to other cellsCytotoxic responses to other cells Facilitate Ab production by B cellsFacilitate Ab production by B cells Memory T cellsMemory T cells

Lymphoid organsLymphoid organs

Interaction of lymphocyte with virusInteraction of lymphocyte with virus

NK cellsNK cells

Also known as LGLAlso known as LGL Target virus infected cellsTarget virus infected cells Target tumor cellsTarget tumor cells Have receptors for IgGHave receptors for IgG Mediate ADCCMediate ADCC

Immune responseImmune response

Differences between cells of innate Differences between cells of innate immunity and lymphocytesimmunity and lymphocytes

Different ways of recognizing Different ways of recognizing microorganismsmicroorganisms

DirectDirect IndirectIndirect Specific Ag recognitionSpecific Ag recognition

CytokinesCytokines

Molecules secreted by cells(lymphocytes) Molecules secreted by cells(lymphocytes) and which affect the function of other cellsand which affect the function of other cells

Secreted in response to specific stimulusSecreted in response to specific stimulus

Interleukin is a type of cytokineInterleukin is a type of cytokine

Role of interleukinsRole of interleukins