Host Response to Periodontal Bacteria Flashcards
How doe bacteria induce damage to periodontal tissues?
Attach, colonize the crevice, and sometimes invade
Release substances that directly damage host
Activate the host’s own inflammatory and immune systems leading to host damage
Which method of bacteria-induced damage does the most damage?
Bacteria activating the host’s own inflammatory and immune system
What are the different types of major microbial virulence factors?
Ability to invade periodontal epithelium
Metabolic waste products that have direct cytotoxic effects
Damaging bacterial enzymes
Immunostimulatory molecules
What are the mechanisms of periodontal defense?
Prevention of bacterial entry (passive)
Innate immune response
Acquired immune response
How does the periodontium prevent bacterial entry?
Shedding of epithelial cells into the oral cavity - inhibits colonization
Intact epithelial barrier that is hard to penetrate
Positive fluid flow into the gingival crevice (has the capability to shed bacterial and discourages penetration)
What is the structure of the endothelium and what occurs during inflammation?
When endothelial cells are growing, they grow until the contact another cell, and there’s a protein that maintains a tight connection
During inflammation, those proteins are lost and small gaps form increasing permeability
Fluid escapes and can clear bacteria in the epithelium
What are the different types of innate immune responses?
Complement system
Oral mucosa produces anti-microbial peptides (defensins)
Oral epithelium produces pro-inflammatory cytokines
Antimicrobial effect of antibodies, lactoferrin, lysozyme
Phagocytic function of neutrophils and macrophages
Adaptive or acquired immunity
Second line of defense
Specific response to bacterial antigens
Ag recognition, immune memory, and clonal expansion are all hallmarks of adaptive immunity
How does clonal expansion aid in adaptive/acquired immunity?
Provides the capability to produce a wide-scale release of a specific antibody
What is the host defense hierarchy?
Serum compliment Neutrophil Monocyte/Macrophage Lymphocyte If none of these can resolve it, then you get a systemic infection
What parts of the mouth play a major role in innate immunity?
Salivary glands
Mucosa
Tongue
Crevice
Salivary gland contribution to innate immunity
Saliva has a bunch of compounds that play defensive roles, such as sIgA, Mucins, Agglutinin
Mucosa contribution to innate immunity of the oral cavity?
TLR receptors - detect features of bacteria
TLR receptors
Recognize conserved microbial-associated molecular patterns
Expressed by all cells
Signals for cells to produce cytokines, chemokines, antimicrobial peptides, nitric oxide, and eicosanoids
Essentially how the body recognizes there is an attack
What are the biological activities of Lipopolysaccharides (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-a)
What are the 2 ways to activate the complement system?
1) Classic - contact antibody labeled microbe
2) Alternate - contact bacterial cell walls
What is the role of C3b in the complement system?
Enhances the efficiency of phagocytosis
What is the role of C3a and C5a in the complement system?
Enhance mast cell degeneration and inflammation
Mast cells release histamine, TNF-a, nitric oxide, and IL-1 - and these things make the endothelium more leaky
Membrane attack complex
Forms during the complement pathway
Creates pores in a microbe so it lyses itself
What is the role of cytokines in the innate immune system?
Involved in the coordination of inflammatory and immune resonses
What cytokine(s) provide pro-inflammatory activity?
IL-1
TNF-a
What cytokine(s) provide chemotactic activity
IL-8
What is the role of prostaglandins in innate immunity?
Induce vasodilation and cytokine production - makes vessels leakier
PGE2 induces production of matrix metalloproteinases by fibroblasts and osteoclasts, which damage periodontal tissue
Where do prostaglandins come from?
Derived from arachidonic acid
Produced by activated macrophages and other cells
What is the role of matrix metalloproteinases in innate immunity?
Degrade extracellular matrix
If the host can breakdown ECM, it can give neutrophils and macrophages better access to bacteria
Concentrations are higher in inflamed gingiva
An example is PMN collagenase (which degrades the major structural protein in the gingiva)
What is the role of Proteinase inhibitors in innate immunity?
Antagonize inflammation
Inhibit degradation of matrix proteins
What are the two major proteinase inhibitors?
Alpha-2 macroglobulin (broad spectrum proteinase inhibitor)
Alpha-1 antitrypsin (broad spectrum proteinase inhibitor and potent inhibitor of PMN collagenase)
What are the major antimicrobial peptides?
Defensins
Calprotectin
Defensins
Inhibit bacteria and fungi
Produced by salivary gland epithelium
Calprotectin
Inhibit bacteria and fungi by chelating zinc
Produced by epithelium, PMNs, Monocytes, and Macrophages
What are the cellular elements of innate immunity, and where are they found?
Neutrophils - deployed from the blood
Macrophages - found in organs and tissues
Mast cells - found throughout the body, especially CT subadjacent to mucosal surfaces
What are the ways PMNs deliver antimicrobial substances to bacteria in the early stages of an infection?
Secretion
Respiratory burst
Phagocytois
Lysis apoptosis
How are PMNs recruited to the gingival crevice?
PMNs start in circulation
Presence of plaque can be communicated to the CT by proteases, LPS, f-Met-Leu-Phe
Those things talk to macrophages, which release cytokines (TNF, IL-1)
This increases adhesion molecule expression - and these can bind to neutrophils, which then go to the site
What is the difference between innate immunity and adaptive immunity, when it comes to pathogen specificity?
Innate: inherent biological responses
Adaptive: based on recognition of antigens, immune memory, and clonal expression
In periodontitis, how do the number of cells compare?
Plasma cells > B lymphocytes > T lymphocytes
Th1 cells responsibility
Regulate cell-mediated immunity
Release cytokines to recruit cytotoxic t-cells
Th2 cells responsibility
Release cytokines that activate B cells
B2 cells
Conventional
Make antibodies to respond to invaders/bacteria
Decrease in healthy and treated sites
B1 cells
Autoreactive
Make antibodies to respond to host tissue
Numbers do not decrease after treatment (this allows the response to amplify if seen again)
T cell receptor structure
Receptor has 2 glycoprotein chains (a and B) with variable segments
Variable segments determine the type of immunity response
T/F - TCR in periodontitis are different before and after therapy
True - this leads to a different type of immune response
T/F - TCR is the same between chronic and aggressive periodontitis
False - TCR is DIFFERENT between chronic and aggressive periodontitis - leading to a different type of immune response
What makes the 2 types of t-helper cells different?
Their cytokine profiles are different
Which cytokines communicate with Th1?
IL-2
INF-gamma
TNF-alpha
Which cytokines communicate with Th2?
IL-4 IL-5 IL-6 IL-10 IL-13
What is IL-10 an indicator of?
It can contribute to both Th1 and Th2
It normally knocks down cell-mediated response, and increases humoral response
Lots of IL-10 = stabilized perio lesion
Little IL-10 = lesion can be progressing
T cell response
Cytotoxic t cells (Tc) are activated by cytokines
Respond to intracellular pathogens
Antigens from these pathogens bind MHC-1 molecules
Tc recognize this antigen presentation and destroy infected cells
Cytotoxic T-cell contribution to periodontitis
There aren’t many Tc cells found in periodontitis
This suggest that viruses and invasive bacteria are not major players
B cell response
Hummoral immunity (antibody mediated) is triggered in response to soluble antigens
Ag-Ab complex activates complement
Ag-Ab complex facilitates opsonization
Th-2 cytokines activate B cells to plasma cells
How can antibody alone protect cells?
Block entry of toxins
Immobilize bacteria
Agglutinate bacteria
How can an antibody plus its compliment protect cells?
Lyses bacteria
How can an antibody plus a cell protect cells?
Opsonizes bacteria, fungi for phagocytosis
Activates extracellular killing
Avidity
Ag-binding differs among antibody subclasses
Not all are capable of effective opsonization
How do IgG2 and IgG1 numbers differ in periodontitis?
IgG2 > IgG1 in aggressive periodontitis
BUT IdG1 > IgG2 in chronic periodontitis
Where does the homing of relevant immune cells take place?
Within the periodontal lesion
Which T-helper cell outnumbers the other in chronic periodontal lesions?
Th2 > Th1
What is the most predominant and active secretory cell in advanced perio lesions?
Plasma cells
An individual’s ability to mount a specific Ab response to bacteria in the subgingival biofilm may indicate what?
Their susceptibility to the disease and the ability to respond to treatment
