Cells of the Immune System

1. 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 Cells of the Immune System

2. Lymphocytes • “Naïve” (unprimed) B and T cells are indistinguishable • Small, motile, non-phagocytic • Ag binding induces entry to cell cycle G1S  G2 at which point, called lymphoblasts • L’blasts soon differentiate into effector and memory cell populations

3. B Lymphocytes • Named from “B”ursa of Fabricius; bone marrow in humans • Distinguished by synthesis and display of Ab’s on cell • High numbers (1.5x105 Ab’s/cell) – all w/ same Fab • Other surface molecules: Class II MHC for Ag presentation CR1 + CR2 - complement receptors CD32 - receptor for IgG CD40 - critical receptor between B and TH; leads to diff to plasma + memory cells

4. 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 TH cells produce clone of effector cells • Activated TC cells, coming in contact with MHC I/Ag/ cytokines become CTL  eliminate altered cells

5. 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

6. 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

7. 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

8. Activities of MØ:Oxygen-dependent killing • Activated MØ produce reactive oxygen and nitrogen intermediates • The “respiratory burst” activates oxidase enzymes which reduce O2 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

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

11. 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