pathogenic mechanisms in periodontics part 2 Flashcards
What is the primary function of PMNs?
chemotaxis, phagocytosis, and bacterial killing.
How does a phagosome mature?
fusing with lysosomes, forming a phagolysosome.
How do neutrophils recognize opsonized pathogens?
Fc receptors (FcγRIIa) or complement receptors (Mac-1) on their membrane
What happens after neutrophils recognize a pathogen?
The pathogen is internalized into a nascent phagosome.
What is the lab finding associated with a lack of PMN and monocyte cell-surface Mac-1 & LFA-1?
α-subunit of Mac-1 and LFA-1 (CD11b, CD11c)
What functional defects occur with the absence of Mac-1 and LFA-1?
defective leukocyte adherence and impaired adherence-dependent functions, including:
Spreading
Aggregation
Orientation
Ab-dependent cytotoxicity
Phagocytosis
Why is there bone loss in Leukocyte Adhesion Deficiency (LAD) syndromes?
No PMN’s to protect gingiva from invasion by bacteria
Bacteria get into tissues, LPS activated inflammatory cells (macrophages)
This activates osteoclasts
T or F: There is a correlation between clinical attachment loss and CD18 expression on peripheral neutrophils of LAD-1 patients
True
Why does not scaling, oral hygiene, and antibiotic treatment help with bone loss in LAD syndromes?
issue lies in the absence of PMNs to combat bacterial invasion and the resulting immune response, so mechanical debridement and antibiotics do not resolve the underlying problem of immune dysfunction.
What immunopathology is associated with LAD-1 deficiency in periodontitis?
increased IL-17A cytokine mRNA expression levels in periodontitis lesions, contributing to excessive inflammation and tissue destruction.
What does immunohistochemistry reveal about IL-17A in LAD-1 gingiva?
elevated IL-17A expression in LAD-1 gingiva surrounding extracted teeth, indicating heightened inflammatory activity in these tissues.
What role does Th-cell differentiation play in cell-mediated immunity?
promotes by increasing macrophage function.
How does Th-cell differentiation affect humoral immunity?
enhances by increasing antibody production.
What inflammatory responses are promoted by Th-cell differentiation?
PMN response and autoimmune reactions.
What challenges the concept that LAD periodontitis is mainly due to impaired PMN surveillance of infection?
The ineffectiveness of mechanical and antibiotic treatments in LAD challenges this concept.
How do local microbiota and defective PMN recruitment contribute to LAD periodontitis?
They lead to increased IL-17 production, which drives immunopathology.
What is the primary cause of disease pathology in LAD periodontitis?
Increased IL-17 is the main driver of disease pathology in LAD periodontitis.
What is diminished in Leukocyte Adhesion Deficiency (LAD) type II?
Rolling is diminished due to a lack of receptors for endothelial P-selectin and E-selectin.
What receptors are missing in LAD type II?
gp150-Lewis X and Sialo-Lewis X, which are receptors for P-selectin and E-selectin.
What are the oral manifestations of LAD type II?
severe periodontitis in children, gingivitis, and oral ulceration.
What chemotaxis and microbial activity defects are seen in Chediak-Higashi Syndrome?
Chemotaxis defect and sluggish microbial activity, despite increased oxygen consumption and H2O2 production.
Which enzyme deficiencies are associated with Chediak-Higashi Syndrome?
Cathepsin G and Elastase deficiency.
What are the systemic complications of Chediak-Higashi Syndrome?
Lymphomatous-like illness during adolescence, progressive peripheral neuropathy, severe periodontitis, and oral ulceration.
What is the primary hematological characteristic of neutropenia, agranulocytosis and Myelosuppression?
Diminished phagocyte numbers leading to infections and periodontal disease.
What are the key immune defects in Hyper-IgE (Job’s Syndrome)?
Chemotaxis/chemokinesis defect and cytokine dysfunction.
What are the oral manifestations of Hyper-IgE (Job’s Syndrome)?
Periodontitis and oral ulcerations.
What is missing in Specific Granule Deficiency?
Specific granules, including lactoferrin, defensins, and gelatinase, due to packaging problems.
What are the oral manifestations of Specific Granule Deficiency?
Severe periodontitis and oral ulceration.
What is the key defect in Chronic Granulomatous Disease?
Sluggish killing of catalase-positive bacteria due to the absence of oxygen reduction (no H₂O₂ production).
How does inflammation present in Chronic Granulomatous Disease?
There is diminished ability to “turn off” inflammation, leading to excessive inflammation.
What are some clinical manifestations of Chronic Granulomatous Disease?
Lymph node suppuration, oral ulceration, and occasional periodontitis.
What is the main phagocyte defect in Papillon-Lefevre Syndrome?
Decreased phagocyte chemotaxis and diminished chemotaxin binding affinity.
What are the key clinical features of Papillon-Lefevre Syndrome?
Palmar-plantar hyperkeratosis and severe periodontal disease affecting both primary and permanent dentition.
What is the role of PMNs in periodontal disease?
provide important protective mechanisms in periodontal infection, and their lack or impaired function is associated with severe periodontal disease.
How can a lack of PMNs impact the immune system in periodontal disease?
The lack of PMNs may induce an over-reaction of the immune system, such as an increased Th17 response, as seen in Leukocyte Adhesion Deficiency (LAD).
What do PMNs release to kill bacteria after phagocytosis in periodontal disease?
hydrolytic enzymes like MMP-8 and acid hydrolases to kill bacteria after phagocytosis.
What pro-inflammatory mediators are released by PMNs in periodontal disease?
platelet-activating factor, thromboxane, and leukotrienes.
What is the role of oxidative burst in periodontal disease protection?
produces oxygen radicals that are toxic to cells and tissues, helping to kill bacteria.
How does PMN hyperactivity contribute to periodontal disease pathology?
can cause destruction of the periodontium via release of hydrolytic enzymes
production of oxygen radicals
release pro-inflammatory mediators
What is the consequence of PMN hypoactivity in periodontal disease?
can result in lack of protection from periodontal pathogens
How can the immune-inflammatory response against bacterial plaque be viewed?
“two-edged sword” — protective by controlling bacterial infection but potentially destructive due to excessive quantities of enzymes, inflammatory mediators, and immunopathology in certain individuals.
What are the protective aspects of the immune-inflammatory response against bacterial plaque?
production of antibodies and the activity of polymorphonuclear neutrophils (PMNs) to control bacterial infection.
How can the immune-inflammatory response become destructive?
when there are excessive quantities of destructive enzymes, inflammatory mediators, and immunopathology, leading to tissue damage.
What contributes to pathogenesis?
T cells
What contributes to protection?
B cells
How can Th1-cells and B-cells contribute to periodontal destruction?
secrete inflammatory cytokines that promote increased macrophage activation, leading to tissue damage and periodontal destruction.
How can T-cells contribute to periodontal destruction?
secrete cytokines that promote the conversion of osteoclast precursors into osteoclasts, leading to bone resorption and periodontal destruction.
How can Th17-cells contribute to periodontal destruction?
secrete cytokines that enhance the inflammatory response and promote autoimmunity, contributing to tissue damage and periodontal destruction.
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How do T-cells contribute to bone resorption in periodontal disease?
increasing RANKL and decreasing OPG levels in the GCF of patients with periodontitis. This imbalance promotes osteoclastogenesis.
What is the difference in RANKL levels between gingival tissues in periodontal disease and healthy gingival tissues?
significantly elevated in gingival tissues with periodontal disease
Which cells are the source of RANKL in the bone resorptive lesions of periodontal disease?
T-cells and B-cells
What are the key factors contributing to periodontal disease progression?
Presence of periodontopathic bacteria
High levels of proinflammatory cytokines and prostaglandins
Production and activation of MMPs and RANKL
Low levels of IL-10, TGF-b, TIMPs, and OPG
How do inflammatory mediators contribute to matrix degradation and bone resorption in periodontal disease?
Proinflammatory cytokines, prostaglandins, MMPs, and RANKL promote matrix degradation and bone resorption, while low levels of IL-10, TGF-b, TIMPs, and OPG reduce protective factors, contributing to tissue destruction.
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What are pro-resolving lipid mediators and their origin? (Godson et al. 2000; Serhan et al, 2006; Canny et al. 2002; Arita et al. 2005; Campbell et al. 2007)
Pro-resolving lipid mediators, such as lipoxins, resolvins, and protectins, are derived from polyunsaturated fatty acids (PUFAs).
When are pro-resolving lipid mediators biosynthesized, and what is their role in inflammation?
They are biosynthesized during the resolution phase of acute inflammation, with an anti-inflammatory effect: stopping neutrophil infiltration, enhancing the uptake of apoptotic PMNs, and promoting antimicrobial defense mechanisms and bacterial clearance on mucosal surfaces.
How do pro-resolving lipid mediators like PD1 affect leukocyte infiltration in periodontitis?
PD1 has a potent action, blocking over 90% of further leukocyte infiltration, specifically stopping PMN migration in mice with induced periodontitis.
What is the effect of RvE1 on PMN infiltration, and how does it compare to PD1?
RvE1 (10 ng) significantly reduces PMN infiltration, but the response is less than PD1 (10 ng); however, when combined, the reduction in infiltration is even greater.
Pro-resolving lipid mediators: Author
Serhan et al. 2006
What effects did RvE1 treatment have on bone loss and osteoclast density in ligature-induced periodontitis?
prevented bone loss, reduced osteoclast density, and decreased inflammatory cell infiltration compared to the placebo group.
How did RvE1 treatment affect the expression of inflammation-related genes?
reduced the expression of inflammation-related genes, returning the expression profile to a state more similar to health.
What impact did RvE1 have on the subgingival microbiota in experimental periodontitis?
caused shifts in the rat subgingival microbiota, suggesting that inflammation significantly impacts the local environment and bacterial growth conditions.
How is the resolution of acute inflammation described?
active process
What role do neutrophil-derived proinflammatory mediators play in inflammation?
Leukotrienes and prostaglandins, can intensify the inflammatory process.
How can neutrophils promote the resolution of inflammation?
change phenotype to generate protective mediators derived from polyunsaturated fatty acids (PUFAs), promoting inflammation resolution.
What is the role of biofilms in periodontal disease?
Microbial periodontal pathogens are found in ecologic complexes within biofilms.
How might periodontitis and systemic diseases be linked?
bacterial seeding and common disease mechanisms, such as common inflammatory mechanisms and/or modifying factors.
What are key characteristics of periodontitis?
excessive production of inflammatory cytokines (e.g., interleukins, tumor necrosis factor), prostanoids (e.g., prostaglandin E2), and enzymes (including matrix metalloproteinases, MMPs).
What role do monocytes and lymphocytes play in periodontitis?
engage in chronic immunologic functions, including tissue remodeling, within the gingival connective tissues.
How do monocytes and lymphocytes contribute to tissue destruction in periodontitis?
produce mediators such as prostaglandins and cytokines that mediate tissue destruction.
