Download - BIOT 307: MOLECULAR IMMUNOLOGY
BIOT 307: MOLECULAR IMMUNOLOGY
Cells and OrgansMarch 7-9, 2011
IMMUNE CELLS
• B lymphocytes• T “• NK• Macrophages• Dendritic Cells
Antigen-presenting cells (APCs), non-specific
Antigen Specific
characteristic (See Fig. 2-2)• antigen receptors - B, T, NK• cell surface markers – all• functions - all
NATURAL KILLER (NK)
• Large granular lymphocytes• Lack cell-surface markers like B and T cells,
pattern recognition markers (PRRs), Ig or TCR gene rearrangements
• Positive for– FcR(CD16) receptor for binding to Fc of Ig
• Activated by cytokines (IL-2, -12, -15, -18) and CCL5 and migrate to inflamed or tumor tissue– Lymph nodes, peripheral blood, spleen and liver
NATURAL KILLER (NK)
• Influence specific acquired IR– Secrete IFN-γ and TNF-α neutrophil,
macrophage (Φ) activation– Activation cytokine secretion that activates NK
cells• Killing– Tumor cells– Cells infected by intracellular pathogens, e.g.,
viruses
NATURAL KILLER (NK) T CELLS
• Killing– Direct: recognize
altered MHC I, i.e., its lack, on target cells
– Two receptor superfamilies• Inhibitory• Activating
NK: Killing by Antibody Dependent Cellular Cytotoxicity (ADCC)
Killing: Indirect• Fc portion of Ab
bound to Ag on target cell binds to FcR on NK
• Fas on target cell binds to Fas ligand on NK
• Release of perforin and granzymes
ADCC FUNCTIONS IN MANY CELLS
• NK• Eosinophils• Macrophages• Monocytes• neutrophils
IMMUNE CELLS
• B lymphocytes• T “• NK• Macrophages• Dendritic Cells
Antigen-presenting cells (APCs), non-specific
Antigen Specific
characteristic (See Fig. 2-2)• antigen receptors - B, T, NK• cell surface markers – all• functions - all
MACROPHAGE (Φ)= major scavenger
ROUTE 1: monocyte into circulation inflamed tissues inflammatory Φ and DCs
ROUTE 2: Monoblast promonocyte monocyte tissue tissue (resident) macrophages (Φ) – different in different tissues
• .
MACROPHAGE (Φ)• large quantities in the spleen, lymph
nodes, alveoli, and tonsils; 50% found in the liver as Kupffer cells
• In tissue 2-3 mo..
MACROPHAGE INGESTING YEAST CELL
MACROPHAGE FUNCTIONS• Accessory• Secretory• Effector• Regulatory
MACROPHAGE FUNCTIONS• Accessory: Encounter and internalize Ag
• Endocytosis• Phagocytosis
ROUTE: APC amplifiersCell surface receptors recognize Ag
ingestion Ag processing in lysosomes cell surface presentation of peptides to T cells activated - activate specific immune response
MACROPHAGE• Varied and prolific secretory abilities– Pro-inflammatory cytokines– Attractants for neutrophils, immature
dendritic cells, natural killer cells, and activated T
– Pro-apoptotic factors– Chemokines, cytokines, lytic enzymes,
complement components, oxygen radicals, NO, bioactive lipids, interleukins 1, IL-12, TNF-α and growth factors, self-activators.
MACROPHAGE ACTIVATION• Stimulated by Th cytokines• Inflammatory promoting cytokines• Bacterial cell wall components –
lipopolysaccharide (LPS)• IFN-γ further activates Φ better functioning
• Fully activated• Larger, ruffled, gene expression of effector
molecules
MACROPHAGE ACTIVATION
NUMEROUS EFFECTOR CELL FUNCTIONS
• Ag presentation• Kill microorganisms, tumor cells• Make Φ cytokine and chemokine production• Activate T cells
Notes for slide on previous page• Effector function of phagocytosis and killing of
phagocytosed microbe• Reactive oxygen intermediates (ROIs) produced by
phagocyte oxidase from oxygen• Nitric oxide (NO) produced by inducible nitric oxide
synthase (iNOS) from arginine lysosomal enzymes• Other effector functions:• produce cytokines of innate immunity: TNF, IL-1,• Chemokines produce growth factors helping tissue
remodeling and enhance antigen presentation by increasing MHC molecules and costimulators
MACROPHAGE REGULATORY ROLES
• Control IR– T-cell proliferation• Cel-cell contract• Monokines
– Suppress lymphocyte proliferation• IFN-γ• Prostaglandins• Reactive oxygen species• NO
MACROPHAGE ROLES: IMMUNITY & INFLAMATION
1. inflammation and fever2. lymphocyte activation3. tissue reorganization4. tissue damage5. microbicidal activity6. tumoricidal activity
Some bacteria subvert
Φ function• Receptor-mediated recognition• Phagocytosis• movement into lysosome• Perturb • ROS synthesis• RNI•Acidification
• Ag processing• Ag presentation• Signaling
LEGEND FOR FIGURE ON PREVIOUS PAGE: Macrophages = sentinels and first line of defense against infection.
Bacterial pathogens have subvert Φ function (in dark blue). Microbes can interfere with receptor-mediated recognition, phagocytosis and trafficking of bacteria to degradative lysosome. Bacteria that enter Φ avoid destruction by perturbing the signaling that is required for the production of reactive oxygen intermediates (ROIs), reactive nitrogen intermediates (RNI) and acidification (H+). Interfering with Ag processing or presentation prevents Φ from alerting other cells to infectious agent. Bacterial pathogens have several mechanisms for interfering with kinase and lipid signaling within infected Φ. Perturbation of Φ signaling: alter cell survival, transcription and secretion of soluble cytokines that recruit cells coordinate their responses to clear the microbe.
MACROPHAGE FUNCTIONS