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