Host Response to Periodontal Bacteria Flashcards
What are the four major microbial virulence factors?
- Ability to invade periodontal epithelium
- Damaging bacterial enzymes
- Immunostimulatory molecules
- Direct cytotoxic effects of bacterial metabolic waste products.
Which bacterial species are known to be good invaders of the periodontal epithelium?
A.a
P.g
_______ are Arg-Specific Proteases that are associated with P.gingivalis.
Gingipains
_____ from gram negative bacteria and ______ from gram positive bacteria are immunostimulatory molecules (virulence factors).
LPS
Lipoteichoic Acids
Which immunostimulatory molecule is produced by bacteria and stimulates leukocyte chemotaxis?
Formylpeptides
What are three mechanisms of periodontal defense against pathogenic bacteria?
- Prevention of bacterial entry (Passive protection)
- Innate Immune Response (non-specific, first line)
- Acquired/Adaptive Immune Response (specific, second-line, antibody)
Shedding of _______ into the oral cavity inhibits bacterial colonization of mucosa (passive protection).
epithelial cells
How does “positive fluid flow” act as a passive protective mechanism of periodontal defense?
GCF starts in the capillaries of the connective tissue and flows through the junctional epithelium in order to clear the pocket/gingival crevice. This countercurrent discourages bacterial adherence
Gingival crevicular fluid originates as ________ fluid.
gingival tissue interstitial
Inflammation is associated with increased _______.
Permeability (leakage of proteins through gaps)
Epithelial cells are attached by _______ that will lose their integrity in the case of inflammation.
tight junctions
Which line of defense includes the complement system, defensins, and cytokines?
Innate Immunity (first line of defense)
What are defensins?
anti-microbial peptides
_____ and _____ are universal signals of infection that help recruit inflammatory cells.
IL-8
TNF-alpha
Which cytokine is responsible for attracting neutrophils in the early stages of infection?
IL-8
________ function of neutrophils (PMNs) and macrophages is part of the innate response.
Phagocytic
What is the purpose of the complement system?
C3a and C5a molecules act to recruit phagocytes, opsonize bacteria, activate mast cells, and eventually lyse bacterial cells more quickly.
Ag recognition, immune memory, and clonal expansion are hallmarks of ________ immunity.
adaptive (specific)
True or False: The flow rate of crevicular fluid is greater than that of saliva.
False. Saliva is much greater.
How does innate immunity play a major role in defense of the oral cavity?
By clearing bacteria before they colonize and by
releasing antimicrobial peptides and histamines
_______ play a major role in induction of the innate immune response.
TLRs
True or False: TLRs are expressed by all cells; including epithelial cells, PMNs, monocytes, and macrophages.
True
What is the action of TLRs?
They signal for cells to produce cytokines, chemokines, antimicrobial peptides, nitric oxide, and eicosanoids. Major role in induction of the innate immune response.
LPS is a gram_____ bacterial virulence factor that activates _______.
negative
the complement system, PMNs, macrophages, and B-cell mitogen activity
True or False: LPS (endotoxin) stimulates bone resorption and prostaglandin synthesis.
True
______ induces Tumor Necrosis Factor Alpha.
LPS
Within the complement system, the classic pathway is activated by _______ and the alternate pathway is activated by _______.
bacterial antibody
contact with a bacterial cell wall
What is the end result of complement activation?
Enhanced swelling (inflammation)
Opsonization of bacteria/Phagocytosis
Formation of the attack complex/Lysis
Which cells will produce cytokines (3)?
Macrophages
Bone cells
Fibroblasts
Which two important cytokines are pro-inflammatory?
IL-1 and TNF-alpha
Which cytokine is primarily responsible for chemotactic activity?
IL-8
_______ are mediators of innate immunity.
Prostaglandins
From what are prostaglandins derived?
metabolism of arachidonic acid
Prostaglandins induce _______ and cytokine production.
vasodilation
PGE2 is a prostaglandin that induces the production of matrix _________ by fibroblasts and osteoclasts which damages periodontal tissue.
metalloproteinases
Which cells produce matrix metalloproteinases?
fibroblasts
osteoclasts
True or False: Matrix metalloproteinase concentration is higher in inflammed gingiva than in healthy ginigiva.
True
Which matrix metalloproteinase is responsible for degrading the major structural protein in gingiva?
PMN collagenase
Why would the host want to degrade its own collagen matrix via metalloproteinase?
to allow neutrophils to gain better and quicker access
What is the action of proteinase inhibitors in innate immunity?
to antagonize inflammation by inhibiting degradation of matrix proteins; Alpha2 macroglobulin and Alpha1 antitrypsin
Name two important antimicrobial peptides that mediate the innate response.
Defensins
Calprotectin
______ are produced by salivary gland epithelial cells in order to inhibit bacteria and fungi.
Defensins
_______ is produced by epithelial cells, PMNs, monocytes and macrophages to inhibit bacteria and fungi.
calprotectin
How does calprotectin inhibit bacteria and fungi?
by chelating zinc
_____ cells release vasoactive amines in order to change the permeability of capillaries. They are found in connective tissue around mucosal surfaces.
Mast
PMNs are made in _______ and deployed from the blood to assist with innate immunity.
bone marrow
Acute inflammation or injury ______ vascular permeability, resulting in redness, edema, and increased ________ flow.
increases
gingival crevicular fluid
Cleavage products ____ and ____ of the complement system will activate mast cells and release histamine, Nitric Oxide, ____ and _____.
C3a
C5a
IL-1
TNF-alpha
What will bacterial LPS stimulate? What is LPS?
Stimulation of macrophages
Lipopolysaccharide endotoxin present in bacteria
What are the four mechanisms for antimicrobial release from PMNs in the early stages of infection?
- Secretion
- Respiratory burst (H2O2 causes dna damage)
- Phagocytosis (efficient; granule filled lysosome)
- Lysis or apoptosis (worse case scenario)
Mechanisms of bacterial killing by PMNs can be either ______ or ______.
oxidative
non-oxidative
What does elastase degrade?
extracellular matrix
How is a chemotactic gradient established adjacent to the junctional epithelium?
Neutrophils leave post-capillary venules through gaps in the endothelial cells. They then travel through the connective tissue toward the junctional epithelium and crevice. Chemotactic molecules are highest near the JE.
Which chemotactic molecules are most important in attracting PMNs?
LTB4, IL8, fmet-leu-phe, and C5a
A leukocyte contacts, _____, _____, and then extravasates out of a blood vessel prior to reaching the site of inflammation.
rolls, sticks
PMN extravasation involves ______molecules for adhesion and _______ molecules which bridge the gap between cells and extracellular matrix.
e-selectin
integrin
PMNs release granules which contain what kind of mediators?
Microboidal enzymes, serine proteases, metalloproteases, and acid hydrolases
In chronic periodontitis, is the number of plasma cells less than or greater than B lymphocytes?
Plasma cells > B lymphocytes
In chronic periodontitis, is there a greater proportion of B or T lymphocytes?
more B than T
In chronic periodontitis, which cell type makes up about 50% of the cells in the periodontal lesion?
plasma cells
True or False: LPS, bacterial proteins, or other compounds can serve as an antigen.
True
Macrophages and _______ cells function as Antigen Presenting Cells.
Langerhans
How many glycoprotein chains does a T-cell receptor have? What are the types?
two
alpha and beta
The alpha and beta glycoprotein chains have _______ that determine the type of immune response.
variable segments
True or False: T-cell receptors are different between chronic and aggresive periodontitits.
True
What are cytokines?
messenger proteins that transmit signals to other cells
What do Th1 cytokines regulate?
cell mediated immunity (IL-2, IFN-gamma, TNF-alpha)
What do Th2 cytokines regulate?
proliferation of B cells (IL-4,5,6,10,13)
The balance between stable and progressive periodontitis rests on which cytokine?
IL-10
High levels of IL-10 is associated with _____ progressive periodontitis.
less
What do Tc Cells do when they recognize MHC class 1 bound to antigen?
they destroy the infected cell
Are Tc Cells commonly found in periodontitis?
No, not many Tc Cells are found which suggests that viruses and invasive bacteria are not major players
Humoral immunity is triggered in response to _______.
soluble antigens
Ag-Ab complexes will activate ______ and facilitate ______.
complement
opsonization
Th2 cytokines (IL4,5,6,10,13) activate B cells to ______.
plasma cells
What are the two types of B cells?
conventional
autoreactive
What are conventional B cells?
they produce antibodies against bactera; levels decrease in healthy and treated sites
What are autoreactive B cells?
they produce auto-antibodies; levels do not decrease after treatment
After a B cell is activated by an antigen, what are its three fates?
- becomes memory cells specific to that antigen
- secretes antibody to that antigen
- becomes plasma cells that will make antibody to that antigen
What is avidity?
Ag-binding differs among antibody subclasses; not all are capable of effective opsonization or complement activation
Which is more common in chronic periodontitis, IgG1 or IgG2?
IgG1
Which is more common in aggressive periodontitis, IgG1 or IgG2?
IgG2
Which is less effective, IgG1 or IgG2?
IgG2
What is different about antigen recognition in IgG2 compared to other subclasses?
IgG2 recognizes carbohydrate antigens (LPS)
most others recognize protein antigen
Periodontal microbe specific antibodies are produced by plasma cells within the _______ and travel back to the gingiva via blood vessels.
Lymph nodes
Antibodies are produced locally by _____cells which are controlled by type ____ helper cells; cell-mediated immune activity is regulated by type____ helper cells.
plasma antibody (type 2) cell-mediated (type1)
_______ of relevant immune cells takes place within the periodontal lesion.
Homing
______ cells are among the most predominant and active secretory cells in advanced periodontal lesions.
Plasma
True or False: the ratio IgG subclasses are similar in serum and GCF.
True
True or False: An individual’s ability to mount a specific Ab response to bacteria in the subgingival biofilm does not indicate a patient’s susceptibility to disease or ability to respond to treatment.
False
_______ are essential polysaccharides and polynucleotides that differ little from one pathogen to another but are not found in the host.
PAMPS
