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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