Cells of inflammation and Immunity

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Cells of inflammation and
Immunity
G. Wharfe
2005
Immune system
 Detect and respond to antigens
 Protects against pathogenic microorganisms
 Also elicits response against noninfectious foreign
organisms
 Used in inflammatory response and tissue repair
Immune response
 Response needs to be quick and efficient
 Two systems
– Innate
– Adaptive
Cells of IR
 All derived from BM stem cells
 Influenced by growth factors
 Begin as multipotent stem cell
 Develop into committed stem cells
Innate immune system
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First to respond
Limits infection before adaptive response
Usually involve nonlymphoid cells
Cells are macrophages and polymorphonuclear
neutrophils(PMN)
 Also involves complement and acute phase
proteins
 If innate immunity cures infection-no adaptive
immunity develops
Normal haematopoiesis
Adaptive immunity
 Inducible antigen specific response
 Primary lymphoid organs produce
lymphocytes capable of responding to
various antigens
 Lymphocytes form naïve pool in blood
 Lymphocytes circulate in peripheral
lymphoid organs
 Location for Ag-dependent IR
Immunoglobulin
Cells of innate immune system
 All are bone marrow derived
 Lineage commitment depends on stromal
contact and cytokines
 Dendritic cells-Antigen presenting cells
 Develop from peripheral blood monocyte
precursors
 Found in the interstitium and T cell areas
 Stimulate Ag specific T cells
Phagocytic cells
 PMN’s
 Macrophages
Granulocytes
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Inflammatory cells
Contain cytoplasmic granules
Neutrophils
Eosinophils
Basophils
Neutrophil
Stages of granulocyte maturation
Neutrophils
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Major phagocytic granulocyte
Contain multilobed nucleus
Neutrophilic granules
Respond to chemotactic stimuli
Activated by macrophage and endothelial
derived cytokines
 Major cell of acute inflammation
 Primary effector cells in IR to pyogens
Neutrophils
 Have Fc receptors for IgG and c’
 Bind and phagocytose opsonised antigens
 Link between 2 arms of immune system
 Regulates activation and recruitment of
macrophages by cytokines
Phagocytosis
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Principal mechanism of pathogens
Enter site of infection
Opsonins produced to allow phagocytosis
Taken into vacuole
Killing by aerobic or anaerobic mechanisms
Cytokine induction
Phagocytosis
Eosinophil
Eosinophils
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Contain eosinophilic granules
Express Fc receptors for IgE
IgE prevalent in parasitic infections
IgE mediates activation of eosinophil killing
mechanisms
 Role in immediate hypersensitivity to
allergens
 Cause tissue injury and inflammation
Basophil
Basophils
 In circulation –basophils
 In tissue- Mast cells
 Express Fc receptors for IgE
 Release chemical mediators of immediate
hypersensitivity
Monocyte
Macrophages
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Main cells of chronic IR
Regulators of specific acquired response
Fewer numbers than neutrophils
Peaks in hours to days
Participate in both acute and chronic
inflammation
 Phagocytose apoptotic PMN’s
Tissue macrophages
 Second major class of phagocytic cells
 Provide innate immunity and initiate host
defenses
 Release inflammatory cytokines
 Act as APC
 Link between innate immunity and acquired
humoral and cellular immunity
Cells of monocyte macrophage
system
Lymphocytes
 B lymphocyte
 T lymphocyte
 NK lymphocyte
Lymphocyte
Lymphocytes
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Mediate adaptive immune response
Recognize antigen specifically
Each clone has antigen specificity
Arrange V, J and D elements if Ig and T cell
receptor genes to form different clones
 B lymphocytes recognize native Ag
 T lymphocytes recognize processed Ag
Lymphocytes
 Ag binds to receptor
 Lymphoid activation and Clonal expansion
 Effector cells or products all have same
 specificity as parent cell
 Inactivation of self reactive clones
Lymphocytes
 Ag independent maturation occurs in primary
lymphoid organs
 Ag dependent occurs in secondary lymphoid
organs
 Cells are indistinguishable morphologically
 Phenotypically and functionally different
B lymphocyte development
B lymphocytes
 Generate Ab response
 Formed with other white cells in BM
 Ab neutralize pathogens, opsonize
pathogens, activate complement
 Act as APC for T cells
 Generate memory B cells
Plasma cell
Plasma cells
 Not usually found in PB
 Responsible for Ig production
T lymphocyte development
T cells
 Generate CMI
 Directly by differentiating into cytotoxic T
cells
 Indirectly by activating macrophages
 Help B lymphocytes
 Develop from BM progenitors which migrate
to thymus
 CD4 and CD8
T cell functions
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Delayed hypersensitivity
Cell mediated immunity
Graft rejection
Contact allergic reactions
Cytotoxic responses to other cells
Facilitate Ab production by B cells
Memory T cells
Lymphoid organs
Interaction of lymphocyte with virus
NK cells
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Also known as LGL
Target virus infected cells
Target tumor cells
Have receptors for IgG
Mediate ADCC
Immune response
Differences between cells of innate
immunity and lymphocytes
 Different ways of recognizing
microorganisms
 Direct
 Indirect
 Specific Ag recognition
Cytokines
 Molecules secreted by cells(lymphocytes)
and which affect the function of other cells
 Secreted in response to specific stimulus
 Interleukin is a type of cytokine
Role of interleukins
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