Cells of the Immune System Lymphoid lineage: –Central cells of the IS –responsible for adaptive IR –Provide diversity, specificity, memory,self – nonself.
Post on 18-Jan-2016
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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 lymphIncludes three cell types:
B cellsT cellsNatural 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 G1 S G2 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 (1.5x105 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
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
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 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
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
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