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65 Cards in this Set
- Front
- Back
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Normal Microbial Flora
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-10% of cells in body are of human origin
-90% are commensal microbial flora -diferent anatomical sites areassociated with their own characteristic flora |
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Commensal Flora
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-microbes that have evolved to adhere to and grow in a particular loation
-once established they are the resident flora at that site |
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Transient Flora
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-microbes ill equipped to exploit the area they come into contact with body
-easily removed from body |
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Oral Ecology
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-portal of entry for food
-acces to transient flora -diverse and rich commensal flora with distinct ecological sites (saliva, teeth, tongue etc) |
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Pathogens in Oral Cavit
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-Strep Pyogenes
-Strep Pneumonia -Candida Albicans |
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Oral flora dominated by what kind of bacteria?
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-alpha hemolytic strep
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Bacteria metabolic relationship to oxygen
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- Anaerboic: may survive in oxygen but don't grow because they might be killed in the oxygen while dividing
- Facultative: it has the facility to be able to switch between aerobic and anaerobic (e.coli some of the enteric bacteria can do either) - Aerotolerant anaerobic (like the alpha hemolytic strep can tolerate) - Microaerophilic- like the oxygen amt just right sensitive to atmospheric but need a little bit of oxygen to grow - Capnophilic- relationship to CO2 need elevated carbon dioxide |
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Infant- Predentate Oral Flora
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-alpha hemolytidc Strep (attached to epithelial surfaces)
-strep Salivarius -influence of breast feeding |
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Eruption of teeth
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-mineralized non-sloughin surfaces
-pellicle as salivary source -mutans strep, strep orali and strep sanguis (all obligate hard surface colonizers and antagonistic/competitive) -gingival crevice |
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oral infections may afect the course and pathogenesis of a number of systemic diseases such as....
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-diabetes
-CV disease -premature birth -respiratory disease |
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Significance of Oral disease
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-spread of infection from oral cavity as result of transient bacteremia
-injury from circulating oral microbial toxins -inflammation caused by bacterial component-virulence determinants -subgingival dental plaque as reservoirs of gram negative bacteria, resulting in inflammatory mediators |
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What is the best sample source for determining what the bacteria are in oral cavity?
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depends on what area you are interested in because it is a complex environment
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What determines differences in areas of bacteria?
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-pH, surfaces, temp differences, metabolic differences, ionic differences etc
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Which will attach faster the salivary components or the bacteria?
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-The salivary components. This forms the pellicle which the bacteria then can attach to.
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How much saliva do we produce per day?
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1-2L
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Amylase
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-this digests starch and all bacteria cannot digest starch but when it is digested it turns to sugar which bacteria can use
-therefore having amylase in saliva may help bacteria |
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Salivary Glands
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-Submandibular gland. (mixed) Wharton's duct
-Sublingual gland. (mucous) -submand/sublingual = 70% of saliva -Parotid gland. (serous) Stensons duct. 30% of whole saliva -Minor glands contribute 1-2% of whole saliva |
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Which gland mixes best and gets around oral cavity best?
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The parotid because it is more watery because of serous content and less mucous.
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Whole saliva
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-a mixture of secretions from all of the glands
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Lysozyme
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-muramidase
-hydrolyzes the peptidoglycan (cell wall polymer of N-acetlyl muramic acid and N-acetyl glucosamine) -results in bacterial lysis |
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Lactoferrin
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-glycoprotein capable of high affinity binding of iron
-deprives bacteria of iron as essential nutrient -regulate the valence of iron preventing its particpation in generation of oxygen free radicals |
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Secretory peroxidases
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-catalyzes interaction between hydrogen peroxide and selected halides such as SCN- (thiocyanate)
-generates highly reactive oxidized species. Saliva has alot of thiocynate which when around hydrogen peroxide (formed by bacteria) and the salivary peroxidase it forms OSCN-(hypothiocyanate). This oxidizes sulfhydryls of bacterial enzymes necessary for their metabolism results in reversible inhibition of bacterial metabolism - some bacteria are capable of restoring enzymatic activity and bacterial metbolism (i.e. resistant to the peroxidase action) |
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Salivary agglutins
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-variety of glycoproteins rich in carbs that are cabpable of clumping bacteria together.
-also sticky for other salivary molecules including secretory IgA possible permitting synergism between these two species |
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Antimicrobial peptides
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-small weight peptides that are alpha helical in structure and perturb the bacterial membrane.
-defensins of neutrophils and histatins of saliva are these -may be alternatives to traditional antibiotics |
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Innate soluble factors of mucosal immunity
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1. lysozyme
2. lactoferrin 3. Secretory peroxidases 4. Agglutinins 5. Antimicrobial peptides |
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Aquired factors of mucosal immunity
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-Secretory IgA
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Scretory IgA
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-principal immunoglobulin of mucosal secretions of normally healthy people
-Secretory IgM in people with selective IgA deficiency |
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Secretory IgA
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-local factor
-polymeric ->ratio of IA2:IgA1 -earlier maturation -distinct antigen repertoires |
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Greater ration of IGA2 in secretory IgA
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-pathogens produce proteases that are specific for IgA1.
-IgA2 is resistant to these proteases giving the secretory IgA an advantage at mucosal surfaces |
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Sites of synthesis (serum vs. secretory IgA
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-serum IgA synthesized and secreted by plasma cells (B-cell) in the spleen and lymp nodes. Antibody circulates in the blood.
-secretory IgA is synthesized by plasma cells in the lamina propria at mucosal surfaces. NOT DERIVED from blood. |
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Polymeric nature of Secretory IgA
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-generally dimeric and larger
-J chain synthesized by plasma cell small protien. initiates the association of Ig Subunits disulfide bridged - IgA subunits joined before secretion from the plasma cell |
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Secretory component
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-80Kd protein synthesized by epithelial cells at mucosal surfaces
-plasma cells secrete dimeric/multimeric IgA in the lamina propria proximal to the basal surfaces of these epithelial cells -membrane associated secretory component (100Kd) serves as a receptor (PIgR) for these IgA -transported through cell by pinocytosis -secreted on distal surface by proteolytic cleavage of the membrane anchoring sequence of secretory component. |
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pIgR
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-poly immunoglobulin receptor
-this is on membrane of epithelial cell and becomes part of membrane of the vessicle the secretory IgA is transported in and eventually a piece of it will stay with the secreted IgA. |
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Secretory component function
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-requires J chain for association
-is disulfide bridged when secreted -protects against acid hydrolysis and proteolysis -permits SIgA to function in varied and adverse environments |
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Earlier maturation of secretory IgA
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-reaches adult levels at 13 months of age
-Serum IgA doesn't reach adult levels until puberty -we need the secretory IgA earlier in life! |
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Secretory IgA has distinc antigen repertoire
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-recognizes antigens common to mucosal surfaces not generally evoked by systemic immunization
-serum IgA is stimulated by parenteral (systemic) immunization |
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Routes for stimulation of SIgA
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-local antigen presentation can stimulate antigen commitment of IgA synthesizeing B-cells (like in salivary glands)
-antigen ingestion (oral polio vaccine) results in expression of antibodies at remote mucosal surfaces (saliva, tears, milk, urogenital tract) -common mucosal immune system: MALT (mucosal associated lymphoid tissue) -sites of specialized antigen processing (Peyes patches -GALT, NALT- upper respiratory tract) |
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Cellular components of mucosal imune system
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-intraepithelial lymphocytes
-laminal propria lymphocytes -Mucosal lymphoid follicles (M cells) |
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Intraepithelial lymphocytes
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-CD8+ T cells
-limited range of specificities |
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Lamina propria lymphocytes
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-large number of activated B cells and plasma cells- IgA producing (60-70% of toal produced)
-T cells- CD4+ -macrophages, eosinophils, mast cells |
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Mucosal lymphoid follicles (M cells)
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-eyes patches, appendix, tonsils etc
-B cells (50-70%), T cells (CD4+) 10-30% - M cells : pinocytotic lack microvilli, not APC |
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Innate Cellular Imunity
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-rapid response without induction or maturation
-neutrophils, monocytes, mast cells and histiocytes sense pathogenic structures -responses include phagocytosis, proinflammatory cytokines, co-stimulatory molecules- Ag presentation -innate-adaptive interface |
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Inflammation
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-margination, rolling, attachement, diapedesis, chemotaxis & phagocytosis
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Systemic innate defense factors
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Epithelial cells
-mechanical barrier -initial response -bioactive molecules Vasoactive Molecules -nitric oxide -histamine -bioactive lipids endothelial cells & platelets complement macromolecules (lysozyme, transferrin etc) phagocytic cells |
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Pathogen associated molecular patterns (PAMP)
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-LPS
-peptidogylcan -lipoteichoic acid -lipoproteins -bacterial CpG DNA |
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Pattern recognition receptors (PRR)
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-fMLP receptors
-toll-like receptors (TLR) -selected over the course of evolution -insects, plants and mammals |
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Pattern recognition receptors
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-TLR4 recognizes LPS (gram negative)
-TLR2 recognizes gram positive -TLR9 bacterial DNA |
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Phagocytosis
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-opsonization of target (antibody complement)
-receptors on phagocyte -toll like receptors -phagosome membrane -granule fusion |
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Granules
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-have membrane around them because they are a membrane contained vesicle
-can have proteins in the membrane that are unique to that membrane -two different kind of granules some with them in the matrix and some only with it in the membrane -lactoferrin and myeloperoxidase are two types of granules in PMNs |
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Bactericidal mechanisms of PMN oxygen dependent:
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NADPH oxidase
1. superoxide generation 2. myeloperoxidase (primary lysosomal granule) -H2O2 dependent generation of HOCL 3. hydroxyl radical generation |
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Bactericidal mechanisms of PMN oxygen independent:
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. specific granule components: lactoferrin, lysozyme
2. defensins 3. cationoic peptides/proteases |
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Membrane Interactive Peptides
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-defensins
-lactoferrin -complement components -Membrane attack complex (MAC) -opsonins (C3b/iC3b) |
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lactoferrin antimicrobial activity bacteriostatic
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-iron deprivation due to high affinity for iron
-inhibition of metabolism through interaction with membrane |
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lactoferrin antimicrobial activity bacteriocidal
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-generation of toxic radicals through iron transition
-lactoferricin- alpha helical membrane interactive domain (peptide fragment of lactoferrin) |
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Myeloperoxidase
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-primary granules of neutrophil
-released into phagosome -H2O2 + Cl- ---> HOCL (bleach) -bactericidal (not reversible) |
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Lactoperoxidase
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-cannot use Cl-
-salivary peroxidase -H2O2 + SCN - (saliva) ---> Enz-S-SCN + OH- -reversible inhibition of bacterial enzymes |
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PMN Dysfunctions
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-leukocyte adhesion deficiencies
-severe congenital neutropenia (kostmans disease) -idiopathic chronic neutropenia -cyclic neutropenia- mutation in ELA2 -chronic benign neutropenia -chemotactic dfects -chronic granulomatous disease -granule dysfunctions- MPO deficiency, Chediak-Higashi syndrome, specfic granule dificiency -papillon- Lefevre- cathepsin C deficiency |
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Leukocyte adhesion deficiencies
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-severe periodontal disease associated with the failure of the PMN to reach sites of infection.
-not direct evidence of protective function of PMN LAD type 1- CD18 defect LAD type 2- CHO fucosylation |
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Neutropenias
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- when you have <500 PMN/mm^3
-normal is about 4,000 variety of causes -best evidence of protective role for neutrophils |
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Chemotactic dfects
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-localized juvenile perio, diabetes etc
-different forms of perio -receptors and mediators |
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Neutrophil respiratory burst
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-neutrophil metabolism is independent of O2
-consumes large amount of O2 when stimulated -O2 is converted to super oxide anion and hydrogen peroxide -products resonsible for oxidative killing |
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Chronic Granulomatous disease
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-defect in NADPH oxidase results in inability to mount a respiratory burst
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Granule dysfunctions
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-(Chdediak Higashi syndrome- giant lysosumes due to granule fusion dysfunctions
-specific granule deficiencies including lactoferrin, defensins, elastase etc. |
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Roles of Neutrophils in Perio
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Protective
-phagocytosis and killing Destructive Releasing granular enzymes (elastase etc) releasing toxic oxygen species (O2-, H2O2 etc) releasing inflammotory mediators (TNF-alpha, IL-1) |
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PMN modulation by inflammatory mediators
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-priming is mechanism where dormant neutrophils acquire a state of preactivation that enables an enhanced response to be genreated once the cells are activated
-priming agents are LPS and cytokines |
