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43 Cards in this Set
- Front
- Back
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why are phagocytes the most important cells?
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all phagocytes eat, digest and extrude
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what is phagocytosis?
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intracellular killing, inflammation and tissue damage; it is carried out by several cell types, including the neutrophils, monocytes/macrophages
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what are the diagnostic characteristics of neutrophils?
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characteristic multi-lobed nucleus, contains granules, CD 66 marker
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how do neutrophils fight infection?
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contain enzyme-rich lysosomes which can facilitate destruction of infectious microorganisms; most abundant white blood cells; short-lived phagocytic cells that die within a few hours after entry and form the pus at infection site
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how are monocytes and macrophages related?
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monocytes are the precuresors of the macrophages; monocyte has abundant cytoplasm that contains granules; following migration of the monocytes from blood to various tissues, they undergo further differentiation into macrophages; macrophages have different names in different locations
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what are the major functions of monocytes/macrophages?
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1. engulf, removal of bacteria and parasites, lysosomal granules break down materials into simple amino acids and sugars 2. cytokine producing cells: TNF-alpha, IL-1 and IL-8 3. Antigen-presenting cells, take up antigens, proces them by denaturation or partial digestion and present thme to T-cells
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what is the phagocyte response to infection?
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SOS signal:: N-formyl methionine-containing peptides; clotting system peptides; complement products; cytokines released by tissue macrophages; vascular adherence; chemotaxis; activation; phagocytosis and killing.
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what are the different receptors on phagocytes?
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seven alpha-helical receptor; toll-like receptor; mannose receptor
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what binds to the seven alpha-helical receptor on phagocytes?
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N-formylmethionyl peptide; chemokines, lipid mediators
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what is the result of a ligand binding to a seven alpha-helical receptor?
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increasted inegrin avidity; cytoskeleton changes--> migration to tissues
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what is the result of a microbe activated a toll-like receptor (CD14)?
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production of cytokines: reactive oxygen intermediates--> killing of microbes
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what are the differe macrophage/phagocyte receptors that induce phagocytosis?
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TLR4=LPS (lipopolysacharide, gram-) receptor; TLR2= LTA (lipoteichoic, gram+) receptor; FPR= fMLP (N-formylated peptides, gram+, gram-); mannose receptor
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what are the mechanisms by which ingested microbes are killed?
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microbes are ingested into phagosomes, which fuse with lysosomes, and the microbes are killed by enzymes and ROI= reactive oxygen intermediates and NO= nitrous oxide; the same substances may be released from the phagocyte and kill extracellular microbes.
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how does the phagocyte kill bacteria?
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the phagocyte first forms pseudopods that engulf the bacterium and this vesicle is called the phagosome; fusion of a lysosome graule with the phagosome to form the phgolysosome releases the lysosomal proteins into the phagolysosome. ends in release of bacterial fragments
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what does the phagolysosome release?
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lysosome proteases, defensins: production of peroxide, superoxide, hyperchlorus acid, nitric oxide; degradation of bacteria
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how do proteases and lysosomes affect bacteria?
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they destroy components of bacteria
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what are defensins?
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small cysteine-rich cationic proteins (18-45 aa). They insert into membranes, creating pores that cause components of bacteria to leak out
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how do ROIs affect bacteria?
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reactive oxygen intermediates are toxic to many bacteria; superoxide oxidises disulfide linkages and inactivates essential bacterial surface proteins
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what are examples of oxygen INDEPENDENT killing in the phagolysosome?
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lysosome: hydrolyses mucopeptides in the cell wall; lactoferrin: deprives pathogens of iron; hydrolytic enzymes (proteases) digest killed organisms.
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what are examples of oxygen DEPENDENT killing in the phagolysosome?
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ROI production is initiated by membrane-bound NADPH oxidase, which is activated by IFN-gamma; peroxide is produced from the breakdown of the superoxide radical + H+ and is catalyzed by SOD.
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what happens when macrophages cannot kill intracellular bacteria?
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granulomas may form; consist of a central core of infected macrophages which can include multinucleated giant cells formed by macrophage fusions, surround by large single macrophages often called epitheliod cells. Mycobacteria can persist in the cells of the granuloma; the central core is surrounded by T-cells
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what are the Killer cells?
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NK and LAK, ADCC (K) cells, activated macrophages, eosinophils, CD8 T-cells
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What are NK cells?
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large, granular lymphocytes (10%); develop in the bone marrow; circulate in the blood: part of the innate immune system; no specific antigen recognition (ie. do NOT have TCR or BCR receptors); function is to cell killing and the secretion of cytokines (IFN_gamma)
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how are NK cells activated?
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activated by cytokines= TNF, IFN-alpha, IFN-beta made by infected macrophages
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what stage of the immune response are NK cells involved in?
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NK cells control the initial infection until the adaptive immune system can eliminate the virus
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what do activated NK cells secrete?
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pore-forming toxins leading to target cell lysis (Dedensins????) + enzymes that induce apoptosis of target cell by enhanced fragmentation of its nuclear DNA + secretion of cytokines= IFN_gamma
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what positive feedback loop is stimulated by NK cells?
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TNF-alpha, IL-12--> NK cells--> IFN_gamma ---> TNF-alpha, IL-2, which produces more NK cells
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how do NK cells recognize their target?
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recognize antibody-covered target cell by Fc_gamma_III receptor (CD16); also recognizes altered self molecules via MHC I molecules
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what happens when a NK cell encounters a an infected cell?
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(assuming antibody binds antigen on surface of the target cell); Fc_gamma_RIII receptors on NK cells recognize bound antibody; Cross-linking of the Fc receptors signals the NK cells to kill the target cell; Target cell dies by apoptosis
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why aren't normal cells killed by NK cells?
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NK cells express non-TCR-related receptors called killer-cell inhibitory receptors (KIRs) which bind MHC class I molecules; when ligated, KIRs protect the cell from being killed by the NK cell
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what happens to KIRs in infected or cancerous cells?
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infected or cancerous cells have reduced MHC class I on their surfaces. Thus, when such cells encounter NK cells, they fail to engage tese killer-cell inhibitory receptors (i.e. cannot stimulate a negative signal) and therefore activate NK cell releases granule contents to kill the target cell
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what is ADCC?
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Antibody-depdendent cellular cytotoxicity; mechanism by which antibodies enhance innate immunity; neutrophils, eosinophils, macrophages and especially NK cells show enhanced killing of target cell that are precoated with specific IgG antibody==> the lytic process is called antibody dependent cellular cytotoxicity; recognition of bound antibody occurs through a low-affinity receptor on the leukocyte called Fc_gamma_RIII (CD16)
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what is a LAK cell?
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lymphokine activated killer cell: kills transformed and malignant cells (i.e. cancer and tumor cells); IL2 and IFN stimulate LAK cells which stimulates granulocytes
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what is the proportion of B cells to lymphocytes and what type of immunity?
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B-lymphocytes= 10-15% of lymphocytes in blood--> plasma cell--> antibodies= Antibody-mediated immunity
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what is the proportion of T-cells to lymphocytes and what type of immunity?
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T-lymphocytes=75-80% of lymphocytes in blood; subclasses exist; cell-cell contact and/or lymphokine secretion (e.g. help activate B lymphocytes)== cell-mediated immunity
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what are null cells?
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null cells: 10% of lymphocytes?? in blood? include specialized lymphocytes; lack T or B cell surface NK cells that kill certain tumor markers and virus-infected cells
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what are the main functions of lymphocytes in immunity?
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1. mediate adaptive immune response 2. antigen specificity 3. clonal expansion 4. memory
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how do you get from a lymphoid progenitor to a plasma cell?
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lymhoid progenitor--> B-lymphoblast--> B-lymphocyte--> plasma cell
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what do cytotoxic CD8 T cells release?
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granules that contain PERFORIN and GRANULYSIN which make pores in the target-cell membranes through which the granzymes can enter and cleave certain cell proteins that initiate apoptosis
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what do activated cytotoxic T cells express?
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activated cytotoxic T cells express the cell-surface cytokine Fas Ligand, which binds to Fas molecule on the target cell surface. This interaction sends signals to the target cell to undergo apoptosis through the caspase family.
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what is the difference between NK cells and lymphocytes with respect to their antigen recognition?
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NK cells== no specific antigen recognition; do no express T-cell receptor; Do no express Ig genes; Lymphocytes== antigen specific
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what is the difference between NK cells and lymphocytes in their location and formation?
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NK cells= circulate in blood; part of the innate immune system; Lymphocytes== clonal expansion
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what are the key elements of bacterial killing for Phagocytes vs. Cytotoxic cells?
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Phagocytes== 1. O2-independent killing (proteases, lysozymes, defensins) 2. O2-dependent killing (ROIs) 3. NO mediated killing; Cytotoxic cells= NK, LAK, K (ADCC), CD8 T
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