09/10 - Host Responses to Periodontal Bacteria Flashcards
How do bacteria induce damage to periodontal tissues?
- bacteria attach and colonize the gingival crevice; some species can invade periodontal soft tissue
- bacteria release substances that directly damage host cells
- bacteria activate the host’s own inflammatory and immune systems, leading to host tissue damage
What are the (4) major microbial virulence factors?
- ability to invade periodontal epithelium
- direct cytotoxic effects of bacterial metabolic waste products (ammonia, intole compounds, fatty acids, hydrogen sulfide)
- damaging bacterial enzymes (leukotoxin, gingipains)
- immunostimulatory molecules (LPS from gram-negative, lipoteichoic acids from gram-positive, gingipains, formylpeptides, other surface antigens)
What are the (3) mechanisms of periodontal defense?
- prevention of bacterial entry (passive protection by periodontal epithelium)
- innate immune responses (non-specific, first line of active defense)
- acquired (adaptive) immune responses (specific, second line of active defense)
What are the (3) ways to prevent bacterial entry?
- shedding of epithelial cells into the oral cavity (inhibits bacterial colonization of mucosa)
- intact epithelial barrier
- positive fluid flow into the gingival crevice
Gingival crevicular fluid originates as ___.
gingival tissue interstitial fluid
What are the 4 effects of the complement system?
- induces bacterial lysis
- promotes phagocyte recruitment (chemotaxis)
- promotes phagocytosis by opsonization of bacteria
- helps activate mast cells, which increases vascular permeability
During the innate immune response, oral mucosa produces ___ and the oral epithelium produces ___.
- antimicrobial peptides
- pro-inflammatory cytokines
___ and ___ are universal signals of infection that help recruit inflammatory cells. ___ attracts neutrophils in the early stages of infection.
- IL-1beta
- TNF-alpha
- IL-8
The innate immune response has the antimicrobial effect of ___, ___, and ___ as well as the phagocytic effects of ___ and ___.
- antibodies
- lactoferrin
- lysozyme
- neutrophils
- macrophages
___, ___, and ___ are hallmarks of adaptive immunity.
- antigen recognition
- immune memory
- clonal expansion
Serum complement and neutrophils cause ___. Monocytes and macrophages and lymphocytes cause ___.
- acute inflammation resolution
- chronic inflammation resolution
What are the (5) reservoirs of supragingival bacteria?
- tongue
- oral mucosa
- tonsils
- saliva
- supragingival plaque
What are the (4) reservoirs of subgingival bacteria?
- periodontal soft tissues
- dentinal tubules
- furcations
- subgingival calculus
___ plays a major role in defense of the oral cavity.
innate immunity
Toll-like receptors (TLRs) have a major role in ___. They recognize ___.
- induction of innate immune response
- conserved microbial-associated molecular patterns (including LPS, lipoteichoic acid and flagellas)
What cells express toll-like receptors?
all cells, including epithelial cells, PMNs, monocytes, and macrophages
TLRs signal for cells to produce ___, ___, ___, ___, and ___.
- cytokines
- chemokines
- antimicrobial peptides
- nitric oxide
- eicosanoids
What are the (8) biological activities of LPS (endotoxin)?
- complement activation
- PMN activation
- macrophage activation
- B-cell mitogen activity
- pyrogenicity
- stimulation of bone resorption
- stimulation of prostaglandin synthesis
- induction of Tumor Necrosis Factor (TNF-alpha)
What are the 2 pathways of the complement system?
- classical pathway
- alternative pathway
What cytokines are involved in pro-inflammatory activity?
IL-1beta, TNF-alpha
What cytokine is used for chemotactic activity?
IL-8
Prostaglandins are derived from ___ and produced by ___ and other cells.
- arachidonic acid
- activated macrophages
What do prostaglandins induce, especially PGE2?
- vasodilation
- cytokine production
- production of matrix metalloproteinases by fibroblasts and osteoclasts which damage periodontal tissues
What do matrix metalloproteinases do? Where are the concentrations the highest? Name an example of a metalloproteinase.
- degrade extracellular matrix
- concentrations are higher in inflamed gingiva than in healthy gingiva
- PMN collagenase (degrades the major structural protein in gingiva)
What does proteinase inhibitors do? What are 2 examples and what does each example do?
- antagonize inflammation; inhibit degradation of matrix proteins
- alpha-2 macroglobulin: broad spectrum proteinase inhibitor
- alpha-1 antitrypsin: broad spectrum proteinase inhibitor and potent inhibitor of PMN collagenase
What are the 2 types of antimicrobial peptides discussed in lecture? What does each do? Where is each produced?
- DEFENSINS: inhibit bacteria and fungi; produced by salivary gland epithelium
- CALPROTECTIN: inhibits bacteria and fungi by chelating zinc; produced by epithelium, PMNs, monocytes, and macrophages
Neutrophils are deployed from ___. Macrophages are found in ___. Mast cells are found ___, especially ___.
- blood
- organs and tissues
- throughout the body
- connective tissue subjacent to mucosal surface
Acute inflammation or injury increases ___, resulting in ___, ___, and ___.
- vascular permeability
- redness
- edema
- increased gingival crevicular fluid flow
PMN deliver ___ to bacteria in the ___ stages of infection.
- antimicrobial substances
- early
True or false: PMNs kill only by oxidative mechanisms.
FALSE. PMNs kill by oxidative and non-oxidative mechanisms.
PMN activities are triggered by ___. PMN surface has many ___.
- receptor binding events
- high affinity receptors
Describe the process of PMN recruitment to the gingival crevice.
- LPS proteases
- release of proinflammatory cytokines (IL-1, TNF)
- endothelial cells increase their adhesion molecule expression (CAM-1, ELAM-1)
- neutrophil-endothelial cell binding occurs and migration begins
- neutrophils follow chemotactic gradient through the junctional epithelium into the crevice
What are the steps in PMN extravasation?
- random contact
- rolling
- sticking
- extravasation
Rank the numbers of T lymphocytes, B lymphocytes, and plasma cells from most to least in chronic periodontitis.
plasma cells > B lymphocytes > T lymphocytes
In the adaptive immune response, ___ and ___ function as antigen presenting cells.
- macrophages
- Langerhans cells
The T-cell receptor has 2 ___ chains (alpha and beta). The variable segments determine ___.
- glycoprotein
- the type of immune response
True or false: TCR are different between chronic and aggressive periodontitis.
true
What are the cytokines associated with Th1 cells? With Th2 cells? What cytokine is associated with both?
- Th1: IL-2, IFN-gamma, TNF-alpha
- Th2: IL-4, 5, 6, 10, 13
- IL-10
Which helper T-cell has to do with cell-mediated immunity? Which has to do with antibody production?
- Th1
- Th2
Cytotoxic T-cells are activated by ___. Tc cells respond to ___. Antigens from these pathogens bind ___.
- cytokines
- intracellular pathogens
- MHC I molecules
True or false: Tc cells are found in high numbers in periodontitis.
FALSE. Not many Tc cells are found in periodontitis, suggesting that viruses and invasive bacteria are not major players.
Humoral immunity is triggered in response to ___. Antigen-antibody complex activates ___ and facilitates ___. Th2 cytokines activate ___.
- soluble antigens
- complement
- opsonization
- B cells to plasma cells
What are the 2 types of B cells? What does each do? Do their levels ever decrease?
- CONVENTIONAL: produce antibodies against bacteria; levels decrease in healthy and treated sites
- AUTOREACTIVE: produce auto-antibodies; levels do not decrease after treatment
What antibodies are prevalent in the primary response? In the secondary response?
- primary: IgM (first) and then IgG
- secondary: IgG (predominantly) and a little IgM
What are the mechanisms of antibodies acting alone? Antibody plus complement? Antibody plus cells?
- ANTIBODY ALONE: block entry of toxins and viruses; immobilizes bacteria; agglutinates bacteria
- ANTIBODY PLUS COMPLEMENT: lyses bacteria
- ANTIBODY PLUS CELLS: opsonizes bacteria and fungi for phagocytosis; activates extracellular killing
True or false: The avidity, or antigen binding, differs among antibody subclasses. Not all are capable of effective opsonization or complement activation.
true
Which antibody, IgG1 or IgG2, is more prevalent in chronic periodontitis? In aggressive periodontitis?
- chronic: IgG1
- aggressive: IgG2
IgG2 recognizes ___ while other subclasses mainly recognize ___.
- carbohydrate antigens (LPS)
- protein antigens
Describe the steps of a systemic humoral immune response to plaque antigens in the gingival crevice.
- plaque antigens diffuse through the JE
- Langerhans cells within the epithelium capture and process the antigens
- antigen-presenting cells (macrophages and Langerhans) leave the gingiva in the lymph
- antigen-presenting cells reach the lymph node and begin to stimulate lymphocytes to produce a specific immune response
- periodontal microbe specific antibodies are produced by plasma cells within the lymph nodes and travel back to the gingiva via blood vessels
- antibodies leave the circulation and are carried to the crevice in the transudate from the inflamed and dilated blood vessels
- antibody action on microbes in the crevice can result in killing, aggregation, precipitation, detoxification, opsonization, and phagocytosis of bacteria
Describe the steps of a local cellular immune response to plaque antigens in the gingival crevice.
- plaque antigens diffuse through the JE
- Langerhans cells within the epithelium capture and process the antigens
- antigen-presenting cells (macrophages and Langerhans) leave the gingiva in the lymph
- antigen-presenting cells reach the lymph node and begin to stimulate lymphocytes to produce a specific immune response
- periodontally specific B cells and T cells proliferate within the lymph nodes and enter the blood
- periodontally-specific lymphocytes “home” back to the periodontium and locate within the tissues where they begin their humoral and cell-mediated immune functions
- antibodies are produced locally by plasma cells which are controlled by Th2 cells; cell-mediated immune activity is regulated by Th1 helper cells
Homing of relevant immune cells takes place ___.
within the periodontal lesion
Which Th cells are more prevalent in chronic periodontal lesions?
Th2
Which cells are among the most predominant active secretory cells in advanced periodontal lesions?
plasma cells
True or false: The ratio of IgG subclasses are similar in serum and gingival crevicular fluid.
true
True or false: An individual’s ability to mount a specific antibody response to bacteria in the subgingival biofilm may indicate a patient’s susceptibility to the disease and ability to respond to treatment.
true
You can diagnose active periodontitis by screening ___ or screening ___.
- whole saliva
- gingival crevicular fluid
