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80 Cards in this Set
- Front
- Back
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what are the inflammatory cells and cell-derived inflammatory mediators?
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neutrophils, macrophages, eosinophils, mast cells, basophils
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describe neutrophils?
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major effector cell in acute inflammation; motile; phagocytic, short lived (few days in circulation, few hours in tissue), potent killing systems for microorganisms (limited phagocyticism)
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how do neutrophils arrive at inflammation?
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they are actively motile and respond to many chemotactic stimuli (bacterial products, C5a, LTB4, factors from other neutrophils, dead cells, collagen fragments, kallikrein, platelet activating factors, Ics, interleukins, lymphokines, monocyte-derived products, mast-cell derived products, fibrinopeptides)
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what do neutrophils secrete and when?
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neutrophil lysosomal proteases during phagocytosis or from cytotoxic release (death of neutrophil) so active against extracellular substrates
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what are neutrophils a source of?
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toxic oxygen radicals and contain potent lysosoma enzymes
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what do neutrophils contain?
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lysosomal granules: azurophil (primary), specific (secondary), tertiary (poorly characterized in animals)
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describe azurophil (primary) granules in neutrophils?
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large, electron dense granules primarily released into phagosome; require high level of agonist to release extracellularly before cell death, contain proteases (acid, neutral, cationic)
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what do acid proteases in azurophil granules do?
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degrade proteins at acid pH (bacteria and debris in phagolysoomes)
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what do neutral protease in azurophil granules do?
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degrade various extracellular components (basement membrane, collagen, fibrin, elastin, cartilage), cleaves kinin-type product from kininogen, activates complement system
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what do cationic protease in azurophil granules do?
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increase vascular leakage, cleave kinin-type substance from plasma kininogen, activate complement
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what do unchecked proteases from neutrophils cause at the inflammatory site?
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increased vascular permeability, chemotaxis, tissue damage
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what holds proteases from neutrophils in check?
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antiproteases in serum and tissue fluids (alpha1-antitrypsin an inhibitor of neutrophil elastase and alpha2-macroglobulin from liver)
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describe specific (secondary) granules in neutrophils?
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smaller, readily secreting extracellularly by lower concentration of agonists
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what do specific (secondary) granules in neutrophils contain?
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lactoferin, lysozyme, alkaline phosphatase, plasminogen activator, phospholipase A2
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describe tertiary granules in neutrophils?
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modified secondary granules, not well characterized in animals
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what triggers the Arachidonic acid metabolism by neutrophils?
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PLA2 in specific (secondary) granules
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what occurs during Arachidonic acid metabolism?
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PLA2 (phospholipase A2) from nuetrophils releases arachidonic acid from membrane phospholipids, the released intracellular arachidonic acid recruits various types of prostaglandins and leudotrienes
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briefly, what is produced by arachidonic acid metabolism?
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prostaglandins and leukotrienes which recruit more neutrophis and amplifies the inflammatory process
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what prostaglandins result from arachidonic acid metabolism?
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E, D, I, F, thromboxane A2 (long-chain lipid compounds ~C20 which are also synthesixed through COX pathway)
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how are prostaglandins produced?
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arachidonic acid metabolism and COX pathway
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what do prostaglandins (I2, E1, E2, D2) cause?
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vasodilation, fever, pain, increased vascular permeability
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what does prostaglandin TxA2 cause?
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vasoconstriction
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what do prostaglandins I2 and E2 do?
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modulate inflammatory cell function
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how do aspiririn and NSAIDs work?
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inhibit COX thus inhibiting prostaglandin synthesis
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how do corticosteriods work?
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inhibit prostaglandin release by inducing protein lipocortin which inhibits synthesis of PLA2 (membrane stabilizers) also inhibit phagocytic activity and lysosomal enzyme release
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which arachidonic acid metabolites cause vasoconstriction?
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TXA2, LTC4, D4, E4
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which arachidonic acid metabolites cause increased vasodilation?
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PGI2, E2, D2
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which arachidonic acid metabolites cause vascular permeability?
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LTC4, D4, E4
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which arachidonic acid metabolites cause chemotaxis?
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LTB4
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what does TXA2 do?
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cause vasoconstriction
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what does PGI2 do?
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increase vasodilation
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what does LTB4 do?
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vey potent chemotaxis, induces neutrophil aggregation and increasese adherence between neutrophils and endothelial cells
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what are leukotrienes also known as?
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SRS-A (slow reacting substances of anaphylaxis)
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how are leukotrienes generated?
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from pipoxygenase pathway (LOX pathway) during arachidonic acid in cell membranes during inflammatory reactions
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what do LTC4, LTD4, LTE4 do?
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selective smoother muscle contractions (bronchial) and vascular leakage during immeiate type hypersensitivity reactions
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how are prostaglandins and leukotrienes degraded?
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most are unstable and rapidly convert to other forms (often active) by isomerization and hydrolysis, but more stable forms and degraded by tissue-bound enzymes especially in the liver/lung
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what is platelet-activating factor chemically?
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acetyl glyceryl ether phosphocholine
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what does PAF stand for?
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platelet activating factor
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where does PAF come from?
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synthesized from membrane phospholipids by activation of PLA2, then released from anigen-stimulated basophils and mast cells during platelet degranulation and from stimulated neutrophils at endothelial cells, blood monocytes, macrophages
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what does PAF from mast cells/basophils cause?
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vasodilation
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what does PAF from neutrophils cause?
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increased vascular permeability
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what does PAF from monocytes/macrophages cause?
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leukocytes adhesion to endothelium, chemotaxis, degranulation, and osidative burst
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what does PAF from endothelium cause?
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platelet activation
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what does PAF from platelets cause?
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stimulate other mediators (elcosanoids)
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what are elcosanoids?
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arachidnoic acid metabolites
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what type of inflammation contains macrophages?
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chronic inflammation
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what, basicly, are macrophages?
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actively phagocytic, major inflammatory cell of chronic inflammation, scavenger of dead cells, fragments, bacteria, foreign material
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how long are macrophages active?
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can arrive within 4-5 hours at acute inflammatory site, dominant cell by 48 hours, long lived with weeks or months in tissues (can replicate)
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what do macrophages synthesize and release?
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variety of enzymes, reactive metabolites or oxyge, eicosanoids, cytokines, growth factors, nitric oxide
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what cytokines are released from macrophages?
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Interleukin 1 (IL1) and Tumor Necrosis Factor (TNF) and interleukin 8 (IL-8)
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IL1 & TNFa are produced by what?
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activated macrophages stimulated by endotoxin, immune coplexes, toxins, physical injury, inflammatory processes (IL-1 is produced by many cells)
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what is TNFb produced by?
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activated T cells
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briefly, what is IL-1?
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endogenous pyrogen
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briefly, what is TNF?
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cachetin
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how do IL-1 and TNF induce effects?
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autocrine (self), paracrine (immediate vicinity), endocrine (systematically)
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what secretes IL-8?
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macrophages and other cells
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what does IL-8 do?
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chemoattactant and activator of neutrophils and cytokine inducer (especially of IL-1 and TNF)
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what are some actions of the cytokines released from macrophages?
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stimulate synthesis of adhesion molecules, release of PGI2 and PAD, increase procoagulant properties of endothelial cells, induce synthesis of acute-phase reactants (fever, pain)
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what other amplifier of inflammation do macrophages produce?
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arachidonic acid metabolites
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where are eosinophils from?
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bone marrow > blood (6-24 hours) > tissue (4-12 days)
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what are chemoatractants for eosinophils?
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PAF, histamine, C5a
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what do eosinohpils have receptors for?
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IgE, IgG, IgA, complement components
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what do eosinophils activate?
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synthesis of prostaglandins and leukotrienes and the release of preformed mediators
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what are the functions of eosinophils?
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late phase reactions of IgE mediated immediate hypersensitivity reaction (eg parasites, allergies)
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describe the histology of eosinophils?
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bright pink granules, bilobed Mickey Mouse ear nucleus
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what granules do eosinophils contain?
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major basic protein, eosinophilic cationic protein, peroxidase, vasoactive lipid mediators
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what do major basic protein granules do?
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toxid to helmintes and some protozoa, destructive to surrounding tissue
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what do eosinophiliic cationic protein granules do?
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damages helmintes
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what do peroxidase granules do?
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contain HOCl1
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what do vasoactive lipid mediator granules do?
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contain arachidonic acid metabolites
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when are basophils present?
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a rare cell in circulating blood
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when are mast cells present?
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normally present in CT adjacent to blood vessels and are long lived
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what do both basophils and mast cell contain?
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granules with preformed vasoactive mediators (histamine and seratonin)
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what do both basophils and mast cell secrete?
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PAF and AA metabolites
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secretion of mediators in basophils and mast cells are triggered by what?
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IgE-mediated immediate type hypersensitivity reactions, C3a & C5a, neuropeptides (substance P), cytokines (IL-1, IL-8), exogenous chemicals (snake, bee venom, drugs, etc), physical injury (trauma, irradiation, heat, cold)
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what do vasoactive amines do?
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dilation of arterioles, incrased vascular permeability in post-capillary venules
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what are some examples of vasoactive amines?
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histamine and serotonin
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what is the source for histamine?
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mast cells, basophils, platelets
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what is the duration of histamine?
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short half life, up to 30 minutes
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what is the source for serotonin?
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platelets, mast cells (rodents)
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