Transcript Lecture 5

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 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
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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