OE L26 Regulation of Salivary Defence Mechanisms Flashcards
What are the nasopharynx associated lymphoid tissues (NALT)?
Tonsils and adednoids
Which cells are interspersed between epithelial cells of the mucosa?
M cells
What are the functions of M cells?
M cells can take up viral particles, the viral particle is then transcytosed into connective tissue.
What are the main APC in CT?
Dendiritic cells-migrate to nearest lymph node or NALT to present viral peptides to T and B cells.
Which receptor recognises viral peptides on the APC?
MHC class I receptor
What happens when the viral peptide and MHC class I receptor is presented to the cytotoxic T cell receptor?
CD8+ T cells (killer/cytotoxic cells) are activated, which differentiate into killer T cells, which secrete perforin and granzyme to destroy viral infected cells.
What happens when the viral peptide and MHC class II receptor is presented to the T helper cell receptor?
CD4+ T cells are activated, which present the viral peptides to B cells.
The B cell receptor is a membrane bound antibody and activated B cells differentiate into plasma or memory B cells.
Describe plasma (plasma B) cells.
“Antibody factories”.
Produce large quanities of soluble antibodies (for mucosal immune responses IgA production is of main interest)
Describe memory B cells.
Carry the antibody on their cell surface and remain in the body to be used in response to a second wave of infection
IgA crosses from plasma to the lumen to fight infection in mucosal membranes. How does IgA cross the epithelial layer?
- IgA is a dimeric molecule (2 antibodies bound together)
- It is secreted as a pro IgA molecule, binds to pro IgA receptor on the basolateral side of the epithelial cell and is endocytosed, IgA secreted into the lumen
What does sIgA stand for?
Secretory immunoglobulin IgA dimer.
Viral defence can become impaired if there are delayed T cell responses, explain this.
- Killer T cells require signals from interferon-gamma (cytokine) for a timely response to infection
- Patients with severe covid-19 were found to have impaired interferon-gamma signalling pathways and some had auto-antibodies which neutralised interferon-gamma
What type of secretion is formed by the minor salivary glands?
Mucous secretions
What is the role of bicarbonate in saliva?
Regulates the buffering capacity of saliva
Mucous and serous secretions produce saliva of differing compositions, what protein is found in high concentrations in serous secretions?
Alpha amylase (0.4-1g/l)
Describe the sturcture and function of alpha amalyase.
- It is a calcium metalloenzyme
- 4 forms
- Hydrolyses alpha-1,4-glycosidic linkages
- Breaks down starches
- Clears starchy food debris from the mouth
What glycoproteins are found on the enamel surface?
Mucins.
Describe the structure and function of mucins on the enamel surface.
- Large family of glycoproteins, can be divided into sub-families
- They allow growth of less harmful bacteria on the tooth surface e.g. S.mutans do not grow as successfully
What are the 2 main mucin sub-families?
- Muc58/MG1: high molecular weight, biased distribution of oligosaccharide chains, allows binding of calcium ions
- Muc7/MG2: low molecular weight, near uniform distribution of oligosaccharide chains, promotes bacterial agglutination to then be swallowed and removed from oral cavity
What is the main form of bacterial/viral defence in the mouth?
sIgA.
- Bind to viral partciles to prevent further replication
- Bind to bacteria to cause bacterial agglutination, can then be swallowed
How does lysozyme defend against bacteria?
- An endoglycosidase
- Cleaves β-N-acetylmuramic acid residues from bacterial cell walls, therefore causes lysis of the bacteria
How does lactoferrin defend against bacteria?
- An iron binding protein
- Binds ferric ion which is an essential microbial nutrient
- Bactericidal effects on micro-organisms that require ferric iron for growth
How does salivary peroxidase defend against bacteria?
- Bacteria produce hydrogen peroxidase
- Salivary peroxidase oxidises salivary thiocyanate to hypothiocyanite
- Hypothiocyanite converts hydrogen peroxide to water
- Hypothiocyanite blocks bacterial glycolysis and kills bacteria
How do innate immunity scavenger receptors defend against bacteria?
- Present in saliva and tears
- E.g. glycoprotein-340 (gp340) interacts with streptococcal surface molecules causing aggregation, can then be swallowed and removed
Histatins are present in serous granules, desribe their structure.
- Histatins are small peptides rich in histidine residues
- Histatins also have serine residues which can be phosphorylated and bind to HAP
- Part of histidine sequence also induces migration of oral keratinocytes for wound healing
Describe the functions of histatins.
- Migration of oral keratinocytes to enhance wound healing
- Antibacterial and antifungal properties, neutralises high bacterial or fungal load (can be used to modify implant surfaces)
- Can regulate enamel mineral homeostasis
What are defensins?
A type of antibacterial peptide.
Describe the 2 major types of defensins/
- Neutrophil/alpha defensins: derived from neutrophils, produced as precursors and activated through cleavage, stored in granules.
- Epithelial/beta defensins: derives from epithelial cells, respond to high bacterial load and induced by inflammatory cytokines, i.e. during perio disease
What 2 proteins regulate calcium levels?
- Acidic proline rich phosphoprotein
- Statherin
Describe acidic proline rich phosphoprotein.
- Proline rich phosphoprotein
- Negative N-terminus composed of phosphorylated serine residues which allow calcium binding (prevents precipitation)
- C-terminus rich in proline which binds bacteria
Describe statherin.
- Tyrosine rich phosphoprotein
- Negative N-terminus composed of phosphorylated serine residues which interact with calcium to maintain calcium balance and inhibit precipitation
- C-terminus rich in tyrosine residues, binds actinomyces, causes conformational change in shape upon binding to tooth surface
What components are added to saliva substitutes and why?
- Lysozyme to cause bacterial cell wall cleavage
- Lactoferrin to remove essential iron from bacteria
- Peroxidase to generate OSCN- (a bacteriocidal molecule)
Evaluate the diagnostic potential of saliva.
- Can be used to detect viral respiratory infections e.g. PCR test for Sars-Cov-2
- Non-invasive
- Potential use for breast cancer diagnosis using specific tumour markers
- Disadvantage: under stimulated conditions saliva would be diluted, therefore may be below detection limit
