英文版微生物学授课讲义-lecture-05

1、BIOL 5331BIOL 533Lecture 5Medical MicrobiologyBIOL 5332Barriers to entry See Schaechter text, Table 6.1Mucous membranescovered by protective layer of mucus Mechanical and chemical barrier that allows proper functioning Cross-linked gel structure composed of glycoprotein subunitsBIOL 5333Entraps part

2、icles and prevents them from getting to mucus membrane Hydrophilic: allows passage of a number of bodily substances Antimicrobial substances (lysozyme and peroxidase) Can withstand substantial weight, but still be propelled by ciliaBIOL 5334Role of constitutive defenses List of humoral mediators of

3、constitutive defenses (See Schaechter text, Table 6.2)BIOL 5335Role of constitutive defenses, contd. Inflammatory response does not require previous contact with microorganism Elicited by complex effectors, many of which are complement system Normally at basal level and must be further increased by

4、presence of microorganisms in tissues Most important consequence of activity is phagocyte attractionBIOL 5336Interaction of constitutive (inflammatory response) and inducible defenses (immune response) Inducible response cannot occur without constitutive mediators Mediators lead to induction of immu

5、ne response and also defend against microbial invaderBIOL 5337General aspects Reaction to tissue injurymanifested by pain, swelling, heat, and throbbing of location Location appears red and shiny, hot and painful to touch as a result of changes in local blood vessels and lymphatics Tissues may retur

6、n to normal or scarring may resultBIOL 5338Tissues may return to normal or scarring may result; depends on extent of damage done: By injury By infecting microbes By inflammatory responseBIOL 5339Description of changes Blood supply increases to affected part due to vasodilation Capillaries become mor

7、e permeable, allowing fluid and large molecules to move into tissues Consequence of inflammation pH of inflamed tissues lowered Production of lactic acidantimicrobialBIOL 53310Molecular basis of inflammatory response and acute phase response Inflammatory response starts with activation of complement

8、 or of blood-clotting cascade Complement and clotting are interactive Either can set off the other Normally, clotting is seen when acute inflammatory response is severeBIOL 53311Inflammatory response leads to production and release of a number of chemical effectors of inflammation responsible for va

9、scular permeability, vasodilation, and pain Histamine Kinin Leukotrienes and prostaglandinsBIOL 53312Histamine is one of best-known Dilates blood vessels and increases permeability Mechanism of production Three peptides (C3a, C4a, and C5a; anaphylotoxins) produced by activation of complement system

10、Stimulate release of histamine from mast cellsBIOL 53313Kininsmall basic peptides Alter vascular tone Increase permeability May initiate or potentiate release of other chemical mediators from leukocytesBradykinin is best-knownBIOL 53314Production of kininsHageman factor activated during inflammation

11、 (one of substances that can activate is LPS) Induces production of kinins Also plays important role in blood coagulation Cleavage of precursor kininogens activated by enzymes (kallikreins) produced during clotting cascade or release from granulocytesBIOL 53315Leukotrienes and prostaglandins Act on

12、motility and metabolism of wbc Two plus certain phospholipids cause aggregation of blood platelets (important to stop bleeding) Prostaglandins synthesized in hypothalamus act on temperature regulatory centers of brain and cause feverBIOL 53316Aspirin prevents both synthesis and effects of prostaglan

13、dinsFever provides: Important warning sign of infection Interference with antimicrobial mechanismBIOL 53317Injured tissue cells release inflammatory mediators that activate inner lining (endothelium) of capillariesBIOL 53318Within capillaries, selectins (cell adhesion molecules) Psel then Esel Rando

14、mly attract and attach neutrophils Slow them down; cause to move through capillariesBIOL 53319Encounter inflammatory activators Integrins on neutrophils (adhesion receptors) Attach to endothelial receptorsICAM1intracellular cell adhesion moleculeVCAMvascular adhesion moleculeBIOL 53320Neutrophils st

15、ick to endothelium and stop moving Undergo dramatic shape changes; migrate through wall into tissue spaceBIOL 53321Inflammatory mediators released by injured tissue also raise acidity in extracellular fluidDecrease in pH activates extracellular enzyme kallikrein; splits bradykin from precursorBIOL 5

16、3322Bradykin binds to receptors on capillary wall, opening junctions between cells; allows leukocytes and fluid into tissuesAlso, simultaneously binds to mast cells in connective tissue Activates mast cells (by influx Ca+2) degranulation; release of preformed mediators histamineBIOL 53323If nerves d

17、amaged, they release substance P; also bind to mast cells, increasing preformed mediator release Histamine makes intercellular junctions in capillary wall wider, so more fluid, leukocytes, kallikrein, and bradykinin precursors move out, causing edemaBIOL 53324Bradykinin then binds to nearby capillar

18、y cells and stimulates production of prostaglandins PGE2 and PGE2, causing tissue swelling Prostaglandins also bind to nerve endings, causing painBIOL 53325Change in mast cell plasma membrane permeability allows phospholipase A2 to be converted to arachidonic acidArachidonic acid proceeds through cy

19、clo- oxygenase pathway -OR- lipoxygenase pathway (depends on mast cell type)BIOL 53326Pathways yield synthesized mediators Prostaglandin E2 F2 Thromboxane A2 Slow-reacting substance LeukotrienesSee Prescott, Fig. 29.13 Biochemical Effects of InflammationBIOL 53327Acute phase responseduring inflammat

20、ion, certain proteins are released (chiefly from the liver) and their concentration rises in seraBIOL 53328Rise in sera is disproportionate C-reactive protein (reacts with C polysaccharide of pneumococci and other bacterial Ag) and serum amyloid A protein increase 1000 times or more1-antitrypsin and

21、 complement factor B increase by 2 or 3 foldBIOL 53329Different functions C-reactive proteinenhances inflammatory response by activating complement1-antitrypsininhibits proteases that function in inflammationBIOL 53330Other important proteins released Those that avidly bind iron and other metals Red

22、uces availability of required ions for microorganisms Helps inhibit microbe growthInduction of responseproteins (cytokines) formed by “activated monocytes”BIOL 53331Interleukin-1 (IL-1); endogenous pyrogen Causes fever by stimulating prostaglandins Stimulates proliferation of cells involved in immun

23、e response Enhances stickiness of inside surface of endothelial cells in capillaries to neutrophils Facilitate movement to particular areaBIOL 53332Tumor necrosis factor (TNF; cachectin) Has antitumor activity Causes weight loss (severe problem in certain chronic infections, such as tuberculosis and

24、 some cancers)BIOL 53333Characteristics of both IL-1 and TNF Play major role in “shock response” elicited during some serious bacterial infections Both made in response to presence of microorganismsBIOL 53334Other important cytokines Interleukin-2 Involved in proliferation of immunologically importa

25、nt cells Used therapeutically to treat certain tumors Interleukin-6 (hepatocyte-stimulating factor) Involved in synthesis of acute phase response proteins by the liverBIOL 53335General characteristics Comprises as many as 26 proteins found in sera and some as a part of cell membranes Mediates large

26、number of biological effects Interacts with other complex systems, including Blood-clotting Specific immune responseBIOL 53336Normally present at basal levelWhen activated, enhances antimicrobial defenses Making intruding bacteria susceptible to phagocytosis Causing lysis of bacteria Producing chemo

27、tactic substances Promoting inflammatory responseBIOL 53337Activation (proteolytic cleavage of precursor) in one of two ways that produce same end products Classical pathway:activated by presence of Ag-Ab complexes Alternative pathway: independent of Ab elicited by bacterial surface components, such as LPSBIOL 53338In patient studies, patients genetically lacking some of complement components are very susceptible to bacterial diseases (some life-threatening)Enhancing phagocytosis Recruitment of wbc by chemotactic protein Facilitation by proteins called opsoninsBIOL