Saliva and Mucosal defense mechanism Flashcards
What are some of the cell types that recognize pathogens?
epithelial, dendritic, endothelial, periodontal ligament fibroblasts, cementoblasts, osteoblasts, macrophages, neutrophils, monocytes, B and T lymphocytes
What are the five examples of pattern-recognition receptors?
TLR2
TLR4
TLR9
Nod1
Nod2
Is oral mucosa keratinized or non-keratinized?
Both!
non-keratinized - buccal, sublingual
keratinized - gingiva, palate
Pathogen-associated molecular patterns (PAMPs) and Damage-associated molecular patterns (DAMPs) lead to…
Pathogen recognition receptors (PRRs)
What are some examples of physical barriers in the oral mucosa?
- tight junctions, gap junctions, anchoring junctions
- high turnover rate
What are three types of oral epithelium?
orthokeratinized, parakeratinized, and nonkeratinized
What are the two main types of mucosal defense mechanisms?
physical barrier
microbiological-immune barrier
What are some examples of microbiological-immune barriers in the oral mucosa?
- diverse microbiota (>700 species)
- crosstalk between commensal microbes and host immune response
- anitmicrobial peptides
- communication between epithelium and innate/adaptive immune cells
What are the three major salivary glands?
parotid, submandibular, and sublingual glands
What activates the immuno-inflammatory response in the oral cavity?
dental biofilm
What is saliva made of?
99% water and 1% solids (proteins/electolytes)
What is the average daily secretion of saliva?
0.5-1.0 L
What is the NORMAL unstimulated whole saliva flow rate and what is the NORMAL chewing/stimulated whole saliva flow rate?
unstimulated = 0.3-0.4 mL/min
stimulated = 1.5-2.0 mL/min
What is the HYPOSALIVATION unstimulated whole saliva flow rate and what is the HYPOSALIVATION chewing/stimulated whole saliva flow rate?
unstimulated = <0.1 mL/min
stimulated = 0.5-0.7 mL/min
What is whole saliva?
complex, hypotonic, slightly acidic fluid
What type of salivary glands produces only serous?
parotid
What type of salivary glands produces mainly mucous but some serous?
sublingual
and minor glands
What type of salivary glands produces mainly serous and some mucous?
submandibular
Where is 90% of the total amount of saliva produced?
the three major salivary glands
What type of saliva does the von Ebner’s gland secrete?
serous only
What are the main functions of saliva?
❖ Lubrication and prevention of retrograde salivary gland infection
❖ Formation of acquired enamel and mucosal pellicles
❖ Clearance of dietary carbohydrates and microorganisms
❖ Taste and digestion
❖ Antibacterial, antifungal, and antiviral activities
❖ Buffering capacity (through bicarbonate, phosphate and protein systems)
❖ Nutritional source (to bacteria)
What are the two major salivary antibodies?
IgA (90-98%)
IgG (1-10%)
What are the important defense mechanisms of IgA?
- immune exclusion (binding antigens in saliva, mucosal surface, enamel pellicle)
- inhibition of microbial adhesion
- enhanced elimination by aggulination
Where does the monomeric IgA (small amount; only 15% of total IgA) in the oral cavity come from?
GCF
What is the basic antibody unti composed of?
two heavy chains
two light chains
What type of antibody is anti-parasitic and active in allergic responses?
IgE
(E like eosinophil; good way to remember)
What type of antibody is excellent at binding complement proteins, a pentamer, and the first made in a primary response?
IgM
What type of antibody is the most abundant in serum, has 4 subclasses, and offers long-term protection?
IgG
What type of antibody is a dimer or monomer and is the FIRST defense for mucosal surfaces?
IgA
(first defense in the mouth!)
What type of protein is large, highly glycosylated, and mainly from the mucous acinar cells (submandibular, sublingual, minor salivary glands)
mucins
Why are mucins good for lubrication and protection?
hydrophilic and contain much water
What are the four types of mucins in the oral cavity?
- MUC5B - reducing attachment and biofilm formation of S. mutans, reducing fungi formation (C. albicans), and reducing HIV-1 infection of T cells
- MUC7 - efficient in bacterial agglutination and clearance, and protecting other salivary proteins
- MUC1 - formation of the mucosal pellicle
- MUC4 - agglutination & cleansing of oral pathogens
Which mucins helps stop infections from bacteria, fungi, and viruses (such as HIV)?
MUC5B
Which mucins protects other salivary proteins?
MUC7
What are the functions of amylase?
- facilitate bacterial fermentation of carbs
- facilitate adherence of bacteria to oral surfaces
- bind S. gordonii and S. mitis and promote their clearance
- modulate the adhesion, co-adhesion, and colonization of microbes
What protein is mainly secreted by serous acinar cells (parotid) and breaks down ingested starch into maltose, maltotriose, and dextrins?
alpha-amylase
Where can alpha-amylase be found?
saliva, pellicles, and dental plaque
What reaction does peroxidase systems catalyze?
thiocyanate to hypothiocyanite (via hydrogen peroxide)
What ions are involved in the peroxidase systems?
lactoperoxidase, myeloperoxidase (from leukocytes), thiocyanate (SCN−) ions, and hydrogen peroxide (from microbes).
What does hypothiocyanite inhibit?
- inhibits important bacterial metabolic processes
- exerts anti-microbial effects on S. mutans, lactobacilli, yeasts, several gram-negative species, and certain viruses
What are the anit-microbial properties of salivary lysozyme?
- hydrolysis of the β-1,4-glycosidic bonds between N-acetylmuramic acid and N-acetyl-d-glucosamine in gram-positive bacterial cell wall.
- aggregation of oral bacteria
- activation of bacterial autolysins, destroying the bacterial cell wall
- antifungal and antiviral activities
Where is lysozyme found?
saliva, pellicle, and dental plaque (just like alpha-amalyase)
What protein is secreted by serous acinar cells (major and minor salivary glands) as well as by neutrophils and GCF, and binds and sequesters iron to deprive bacteria and yeast?
lactoferrin
What are the three forms of lactoferrin?
iron-free
ferric lactoferrin
saturated lactoferrin
Where are proline-rich proteins produced and what percent of salivary proteins are they?
-produced by parotid and submandibular
- 25-30% of all salivary proteins
What are the three types of proline-rich proteins?
- acidic PRPs - inhibits spontanous precipitation of calcium phosphate salts
- basic PRPs - anti-HIV-1 activity; promotes C. albicans adhesion
- Glycolsylated PRPs - binds and agglutinates oral bacteria (promotes clearance); promotes C. albicans adhesion
What salivary glands are statherin found in?
parotid and submandibular (just like PRPs)
What are the functions of statherin (found in parotid and submand)?
- binds hydroxyapatite and contribute to pellicle formation
- inhibits spontaneous precipitation of calcium phosphate
- induces transition of C. albicans hyphae to yeast
- forms protein complexes with mucins
- promotes adhesion of A. viscous and possesses specific binding sites of P. gingivalis.
What are the 7 different proteoforms of cystatins in the saliva?
Cystatin-A, -B, -C, -D, -S, -SA & -SN
What protein are cysteine-containing phosphoroproteins that have proteinase inhibiting properties?
cystatins
What are the functions of cystatins?
- formation of the salivary pellicle
- affecting calcium phosphate precipitation
- cystatin SA inhibits A. actinomycetemcomitans while cystatin S inhibits proteolytic enzymes from
P. gingivalis. - Antifugal and antiviral activities
What proteins are a family of cationic peptides that bind to microbial cell membranes to promote aggregation to form pores, and possesse specific binding sites for zinc and copper?
histatins
What salivary glands produce histatins?
all major salivary glands
What do all three human hisatins (1, 3, 5) exhibit?
antifungal activity toward C. abicans
What are the “prototype” of cationic peptides that are found in the GCF and have two main subfamilies (alpha and beta)?
salivary defensins
What are the functions of salivary defensins?
❖ adsorb onto the bacterial cell membranes, leading to aggregation and integration (formation of ion channels and transmembrane pores)
❖ antifungal and antiviral activities
❖ exert various immune activator activities, including induction of certain cytokines and chemoattractivity for immature dendritic and memory T-cells.
What are the functions of GCF (gingival crevicular fluid)?
- cleanse materials
- imporve adhesion of the peithelum to the tooth (through plasma proteins)
- possesses antimicrobial properties
What are the two ways GCF can be represented?
transudate (healthy)
exudate (inflamed)
What is the main route of the GCF diffusion?
- through the basement membrane
- through the intercellular space of the junctional epithelium
- into the sulcus