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 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 Inflammatory cells Contain cytoplasmic granules Neutrophils Eosinophils Basophils Neutrophil Stages of granulocyte maturation Neutrophils 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 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 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 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 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 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 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