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20 Cards in this Set
- Front
- Back
Place mast cell secretions on a timeline following mast cell activation (immediate, within minutes, and hours later):
Cytokines Leukotrienes Vasoactive amines Prostoglandins Proteases |
Immediate:
Vasoactive amines - vascular dilation, smm contraction Proteases - tissue damage Within minutes: Prostoglandins - vascular dilation Leukotrienes - smm dilation Hours later: - Cytokines (TNF-alpha) |
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Who makes TNF?
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Macrophages, T cells, and Mast cells.
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What are the principal cellular targets and biological effects of TNF?
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LEHMAN
Liver: synthesis of acute phase proteins Endothelial cells: activation (inflammation/coagulation) Hypothalamus: fever Muscle, fat: Metabolism Apoptosis Neutrophils: activation |
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What are IL-4 and IL-5 chemoattractants for?
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Eosinophils - important for small parasites.
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Where are macrophages located?
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In all epithelial areas, throughout CT, organs and lymphoid tissue
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What are the four major functions of Macrophages?
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CHAP
Cytokine and chemokine production and secretion Healing (wound repair management by stimulating angiogenesis and fibrosis) APC to T-cells (major link b/w innate/adaptive) Phagocytosis |
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What stimulates a macrophage to phagocytose?
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Ligation of PAMP receptors and opsonin receptors (both complement receptors and Fc Receptors)
(TLRs, Cytokines and Complements can also increase phagocytosis and affects the molecules secreted by activated macrophages) |
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What are two main methods macrophages kill phagocytosed material?
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1. Fusion of the phagosome with the lysosomes exposes the phagocytksed material to lysomal enzymes (nucleases, proteases, lipase's)
2. Activation of additional enzymes: Phagocyte oxidase: generates ROS/Respiratory burst NOS: nitric oxide synthetase; NO combines with superoxide to produce peroxynitrite, a strong oxidant |
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What are PMNs?
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Polymorphonuclear leukocytes - "neutrophils"
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Which cell often dies because of chemicals produced in the phagolysosome: Neutrophils or Macrophages?
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Neutrophils - ROS produced in phagolysosomes of neutrophils is lethal for both the phagocytksed pathogens AND for the neutrophils
Pus = dead pathogens + dead neutrophils Macrophages are usually NOT killed by chemicals generated in the phagolysosome. |
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What Cytokine in particular helps activate macrophages?
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IFN- gamma
(can be made by NK cells) |
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Name three macrophage secretions.
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IL-12: activates NK cells
TNF IL-1 |
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Describe the process of PMN diapidesis.
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Chemokines/Cytokines from activated Mast or Macrophages provide signals:
1. Rolling in blood vessel 2. Integrin activation by chemokines causes.... 3. Stable adhesion 4. Diapidesis into ECM; direction by chemokines |
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What are primary (azurophilic) granules?
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Found in neutrophils; contain proteases, lipases, nucleases, peroxidases but have a high concentration of myeloperoxidase which reacts hydrogen peroxide with chloride ions to produce hypochlorus acid (BLEACH!)
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What are secondary (specific) granules?
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contain lysozyme and lactoferrin
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How are eosinophils recruited/activated?
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Recruited: IL-4
Activated: IL-5 (also PAMP and allergens) |
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What occurs when eosinophils are activated?
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Similar to mast cells:
Degranulation Prostaglandins Leukotrienes Cytokines Unique: CAMP Cationic Proteins - Eosinophilic Acid phosphatase, elastase Major basic protein Peroxidase - Eosinophil (EPO) Also: Antihistamines Phagocytose bacteria and yeast |
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What is Major Basic Protein?
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Major component of eosinophil granules. Induces mast cell degranulation and digest sulfated proteoglycans like heparin and similar molecules in CT, in parasite cuticles, the "shell" around parasite eggs, protozoa cysts and in fungal cell walls.
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What does acid phosphatase, elastase do?
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degrade tissues, effetive at digesting thick epidermis of helminthes, yeast and fungi
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Describe septic shock.
What cells are activated? What are serum markers? What does it have endocrine effects on? What is the ultimate cause? |
End result of sepsis - widespread activation of mast cells and macrophages through TLRs usually as an acute inflammatory response to bacteremia.
TNF & IL1 are high in serum Endocrine effects on liver, bone marrow, and hypothalamus Systemic mast cell degranulation --> vascular permeability --> hypotension |