Cells of the Immune System Lymphoid lineage: –Central cells of the IS –responsible for adaptive IR –Provide diversity, specificity, memory,self – nonself recognition –20-40% of WBC’s –99% of cells in lymph Includes three cell types: B cells T cells Natural Killer cells Myeloid lineage: –Central cells of innate immunity –responsible for triggering inflammation, phagocytosis, antigen presentation, cytokine release –60-80% of WBC’s Includes: PMN granulo’s – neutrophils eosinophils basophils Mononuclear - monocytes agranulo’s macrophages

Lymphocytes “Naïve” (unprimed) B and T cells are indistinguishable –Small, motile, non-phagocytic Ag binding induces entry to cell cycle G 1  S  G 2 at which point, called lymphoblasts L’blasts soon differentiate into effector and memory cell populations

B Lymphocytes Named from “B”ursa of Fabricius; bone marrow in humans Distinguished by synthesis and display of Ab’s on cell High numbers (1.5x10 5 Ab’s/cell) – all w/ same F ab Other surface molecules: Class II MHC  for Ag presentation CR1 + CR2 - complement receptors CD32 - receptor for IgG CD40 - critical receptor between B and T H ; leads to diff to plasma + memory cells

T Lymphocytes Named as they mature in Thymus gland Membrane receptors: TCR recognizes Ag ONLY when bound to MHC on self cells –CD4 binds to MHC II (TH cells are Class II restricted) –CD8 binds to MHC I (TC cells are Class I restricted) CD28 – receptor for co-stimulatory B7 molecules on APC’s CD45 – signal transducer Activated T H cells produce clone of effector cells Activated T C cells, coming in contact with MHC I/Ag/ cytokines become CTL  eliminate altered cells

Natural Killer Cells Discovered in 1976 Population of “T-like” cells; defend vs tumors/viral-inf cells No typical T or B cell receptors Recognize target cells 2 ways: Recog cells with reduced MHC I and unusual surface characterisitcs or Bind to opsonized tumor/virally inf cells and perform ADCC *Newly discovered NK1-T cells which exhibit TCR and release hi levels of cytokines  stim AB production/ inflammation

Myeloid lineage: Mononuclear phagocytes Monocytes + Macrophages –Promonocytes enter blood –Mature to form monocytes –Monocytes migrate to tissues and may become “fixed” or dendritic cells Fixed Macrophage: –alveolar; kuppfer; histiocytes; mesangial; microglial; osteoclasts

Activities of MØ: Activation & Phagocytosis Activation occurs by: - inflammation -cytokines from TH (esp IFN-  ) Activated MØ better at phagocytosis and APC than resting Process of phago: chemotaxis  pseudopodia  phagosome + lysosome  residual body  exocytosis

Activities of MØ: Oxygen-dependent killing Activated MØ produce reactive oxygen and nitrogen intermediates –The “respiratory burst” activates oxidase enzymes which reduce O 2 to: superoxide, hydrogen peroxide, and hydroxyl anions –Myeloperoxidase of lysosomes produces hypochlorite –MØ triggered by bacterial CW’s and T cell cytokines express nitric oxide synthetase which catalyzes the production of nitric oxide, a potent antimicrobial gas

Activities of MØ: Oxygen-independent killing Activated MØ also produce: – lysozyme and hydrolytic enzymes –defensin peptides –And secretion of TNF- 

Activities of MØ: Ag presentation & cytokine secretion Activation stimulates  MHC II + B7 co-stim »Efficient TH activation; important in both humoral and cell-mediated IR’s Secretion of cytokines: »IL-1 stimulates lymphocytes »IL-6, TNF-  stim fever and inflam Also Complement proteins and Hydrolytic enzymes