Host Responses to Periodontal Bacteria Flashcards
When acteria attach and colonize ___ ___ and invade periodontal soft tissue they induce damage to periodontal tissues.
gingival crevice
T/F. The bacteria release substances that directly damage host cells and activate the host’s own inflammatory and immune systems, leading to host tissue damage.
True
What are four categories of major microbial virulence factors?
- ability to invade periodontal epithelium
- direct cytotoxic effects of bacterial metabolic waste products
- Damaging bacterial enzymes
- immunostimulatory molecules
What bacterial waste products have direct cytotoxic effects?
ammonia
indole compounds
fatty acids (propionic and butyric acids)
hydrogen sulfide
___ from A. a kills leukocytes and ___ are Arg-specific proteases from P. g.
Leukotoxin; Gingipains
Immunostimulatory molecules include ___ (endotoxin) from gram-negative, ___ acids from gram-positives, gingipains (___-specific protease), ___ that stimulate leukocyte chemotaxis and other surface antigens.
LPS; Lipoteichoic; Arg; Formylpeptides
What is a passive protective defense mechanism by periodontal epithelium?
prevention of bacterial entry
What are two active protective defense mechanisms by periodontal epithelium?
innate and acquired (adaptive) immune responses
Prevention of bacterial entry involves ___ of epithelial cells into the oral cavity to inhibit bacterial colonization of mucosa, maintaining an intact epithelial barrier and ___ fluid flow into the gingival crevice.
shedding; positive
Gingival ___ fluid originates as gingival tissue ___ fluid.
crevicular; interstitial
In the blood vessels, what is associated with increased permeability? How does this happen?
inflammation
collagen of the basement membrane is degraded and plasma proteins are loss when junctions become leaky
The complement system is part of the ___ immune response and induces bacterial ___, promotes phagocyte recruitment (___) and phagocytosis by ___ of bacteria, and helps activate ___ cells, which increases vascular permeability.
innate; lysis; chemotaxis; opsonization; mast
The oral ___ produces anti-microbial peptides (e.g., defensins) and the oral epithelium produces pro-inflammatory ___.
mucosa; cytokines
___ and ___ are universal signals of infection that help recruit inflammatory cells and ___ attracts neutrophils in the early stages of infection.
IL-1ß; TNF-α; IL-8
T/F. The adaptive immune response uses Antimicrobial effect of antibodies, lactoferrin, lysozyme and phagocytic function of neutrophils (PMNs) and macrophages.
False, The INNATE immune response uses Antimicrobial effect of antibodies, lactoferrin, lysozyme and phagocytic function of neutrophils (PMNs) and macrophages.
What is the second line of defense is a specific response to bacterial Ag that utilizes Ag recognition (highly specific), immune memory, and clonal expansion?
adaptive or acquired immunity
T/F. Bacteria can only colonize subgingival environments.
False, they can colonize supra- and subgingival environments
The supragingival environment depends on saliva whose flow rate is ___ than gingival fluid in the subgingival environment.
faster
The idea is to clear the bacteria before they colonize.
saliva 0.4-2ml/min
gingival fluid 20ul/h
As part of the innate immune response, ___-___ receptors are found on the oral mucosal ___ and recognize ___ microbial-associated molecular patterns (including LPS, lipoteichoic acid and flagellae).
Toll-like; surface; conserved
Where are TLRs expressed?
on all cells, including epithelial cells, PMNs, monocytes and macrophages
What does the TLRs signal for cells to produce?
cytokines, chemokines, antimicrobial peptides, nitric oxide and eicosanoids
What types of cells release LPS (endotoxin)?
gram-negative bacteria
What are the biological activities of LPS (endotoxin)?
Complement activation PMN activation Macrophage activation B-cell mitogen activity Stimulation of bone resorption Stimulation of prostaglandin synthesis Induction of Tumor Necrosis Factor (TNF-α)
Innate immunity uses ___ to enhance the efficiency of ___.
complement; phagocytosis
Which part of the complement system recognizes bacterial cell wall features? Which has bacteria coated with Ab?
cell walls = alternative pathway
antibody on microbe = classical pathway
What are the pro-inflammatory cytokines? Chemotactic?
Pro-inflammatory activity: IL-1β, TNF-α
Chemotactic activity: IL-8
In the innate immune system, ___ (especially PGE2) are derived from ___ acid and induce ___ and ___ production.
prostaglandins; arachidonic; vasodilation; cytokine
___ induces production of matrix ___ by fibroblasts and osteoclasts, which damage periodontal tissues.
PGE2; metalloproteinases
What do matrix metalloproteinases do? Give an example.
degrade ECM
PMN collagenase degrades the major structural protein in gingiva
T/F. Concentrations of matrix metalloproteinases are lower in inflammed gingiva than in healthy gingiva.
False, Concentrations of matrix metalloproteinases are HIGHER in inflammed gingiva than in healthy gingiva.
___ inhibitors antagonize inflammation and inhibit degradation of matrix proteins.
Proteinase
Match the following:
- Alpha-2 macroglobulin
- Alpha-1 antitrypsin
A. broad spectrum proteinase inhibitor
B. potent inhibitor of PMN collagenase
- A
2. A AND B
___ are antimicrobial peptides that inhibit bacteria and fungi and are produced by ___ gland epithelium.
Defensins; salivary
___ is an antimicrobial peptide that inhibits bacteria and fungi by chelating ___ (anti-protease effect). It is produced by epithelium, PMNs, monocytes and macrophages.
Calprotectin; zinc
Which cells of the innate immune system are deployed from blood? Which are found in organs and tissues?
neutrophils (made in bone marrow)
macrophages
___ cells are found throughout the body, especially in ___ tissue adjacent to ___ surfaces. It contains ___ filled with vasoactive amines that can dramatically change ___ permeability.
Mast; connective; mucosal; granules; vascular
T/F. Acute inflammation or injury increases vascular permeability, resulting in redness, edema, and increased gingival crevicular fluid flow.
True.
PMNs deliver antimicrobial substances to bacteria in the early stages of infection. List a few examples on how this is done.
- secretion of granule enzymes and complement factors
- phagocytosis and destruction by lysosome, which is less damaging to the host
- respiratory burst of free radicals which can cause damage
- lysis or apoptosis occurs when neutrophils die and granule contents reach the outside (very damaging to host)
___ can participate in oxidative and nonoxidative (acid pH or lysosomal agents) bacterial killing.
neutrophils
What PMN activities are triggered by receptor binding events?
phagocytosis, adherence, chemotaxis
How are PMNs recruited to the gingival crevice?
the presence of a plaque on the JE causes bacteria to diffuse thru the JE and CT and interact with fibroblast and macrophages. This causes the release of proinflammatory cytokines which cause endothelial cells to increase their adhesion molecule expression. Neutrophil bind to endothelial cells and emigration begins and they migrate thru the JE into the crevice area. They also release chemotaxins to invite other cells to that area.
T/F. Variation in the release of primary and secondary granule enzymes by PMNs may indicate alterations in PMN function in different disease environments.
True.
___ immunity is an inherent biological response. ___ immunity is based on recognition of antigens, immune memory and clonal expansion.
Innate; Adaptive or acquired immunity
What is the adaptive host response in cell proportions in periodontitis lesions?
number of plasma cells > B lymphocytes > T lymphocytes
___ cells produce cytokines that act on B cells to make __ in humoral immunity. ___ or B2 cells make Ab to pathogens and their levels ___ in healthy and treated sites, but ___ or B1 cells make Ab to host cells but the levels do not ___ after treatment.
Th2; antibodies; conventional; decrease; autoreactive; decrease
What can serve as antigens in the adaptive immune response? What are the Ag presenting cells (APC)?
Ag = LPS, bacterial proteins APC = macrophages and langerhans cells
_-___ receptor has 2 glycoprotein chains (___ and ___) with ___ segments that determine the type of immune response
T-cell; alpha; beta; variable
TCR in periodontitis different before and after therapy
TCR different between chronic and aggressive periodontitis
What are messenger proteins that transmit signals to other cells?
cytokines
What cytokines are produced by Th1 and Th2 cells?
Th1: IL-2, IFN-gamma, TNF-alpha
Th2: IL-4, 5, 6, 10, 13
What is thought to regulate Th1 and Th2 balance in chronic periodontitis?
IL-10
suppress proinflammatory cytokines production
enhances humoral immunity
___ T cells (Tc) are activated by cytokines and respond to ___ pathogens whose antigens bind ___ molecules. Once these cells recognize this antigen presentation they destroy the infected cells.
Cytotoxic; intracellular; MHC I
T/F. Many Tc cells are found in periodontitis suggesting a role for viruses and invasive bacteria in this disease.
False, Not many Tc cells are found in periodontitis, suggesting that viruses and invasive bacteria are not major players
___ immunity ( or antibody mediated) is triggered in response to ___ antigens. The Ag-Ab complex activates ___ and ___ facilitates.
Humoral; soluble; complement; opsonization
Cytokines from which cells activate B cells to become plasma cells?
Th2 cells
T/F. Once B cells recognize antigen they divide and expand to create memory cells, that have a long life and amplify in response to the same antigen, and plasma cells, which make Abs for 2nd challenge.
True.
Initially Ig___ is released before Ig___ in the primary response, but the secondary response is due to Ig___.
M; G; G
T/F. Alone, antibodies bind toxins and keep them from interacting with the host cell. They can then immobilize and aggultinate bacteria. When a antibody is involved in complement, they can lyse bacteria, recruit leukocytes, and opsonize bacteria for increased efficiency of phagocytosis.
True.
Define avidity.
Ag-binding differs among antibody subclasses. Not all are capable of effective opsonization or complement activation.
Which is greater in chronic periodontitis, IgG1 or IgG2? Why?
IgG2
