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