OE L26 Regulation of Salivary Defence Mechanisms

Question 1

What are the nasopharynx associated lymphoid tissues (NALT)?

Answer 1

Tonsils and adednoids

Question 2

Which cells are interspersed between epithelial cells of the mucosa?

Answer 2

M cells

Question 3

What are the functions of M cells?

Answer 3

M cells can take up viral particles, the viral particle is then transcytosed into connective tissue.

Question 4

What are the main APC in CT?

Answer 4

Dendiritic cells-migrate to nearest lymph node or NALT to present viral peptides to T and B cells.

Question 5

Which receptor recognises viral peptides on the APC?

Answer 5

MHC class I receptor

Question 6

What happens when the viral peptide and MHC class I receptor is presented to the cytotoxic T cell receptor?

Answer 6

CD8+ T cells (killer/cytotoxic cells) are activated, which differentiate into killer T cells, which secrete perforin and granzyme to destroy viral infected cells.

Question 7

What happens when the viral peptide and MHC class II receptor is presented to the T helper cell receptor?

Answer 7

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.

Question 8

Describe plasma (plasma B) cells.

Answer 8

“Antibody factories”.

Produce large quanities of soluble antibodies (for mucosal immune responses IgA production is of main interest)

Question 9

Describe memory B cells.

Answer 9

Carry the antibody on their cell surface and remain in the body to be used in response to a second wave of infection

Question 10

IgA crosses from plasma to the lumen to fight infection in mucosal membranes. How does IgA cross the epithelial layer?

Answer 10

• 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

Question 11

What does sIgA stand for?

Answer 11

Secretory immunoglobulin IgA dimer.

Question 12

Viral defence can become impaired if there are delayed T cell responses, explain this.

Answer 12

• 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

Question 13

What type of secretion is formed by the minor salivary glands?

Answer 13

Mucous secretions

Question 14

What is the role of bicarbonate in saliva?

Answer 14

Regulates the buffering capacity of saliva

Question 15

Mucous and serous secretions produce saliva of differing compositions, what protein is found in high concentrations in serous secretions?

Answer 15

Alpha amylase (0.4-1g/l)

Question 16

Describe the sturcture and function of alpha amalyase.

Answer 16

• It is a calcium metalloenzyme
• 4 forms
• Hydrolyses alpha-1,4-glycosidic linkages
• Breaks down starches
• Clears starchy food debris from the mouth

Question 17

What glycoproteins are found on the enamel surface?

Answer 17

Mucins.

Question 18

Describe the structure and function of mucins on the enamel surface.

Answer 18

• 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

Question 19

What are the 2 main mucin sub-families?

Answer 19

1. Muc58/MG1: high molecular weight, biased distribution of oligosaccharide chains, allows binding of calcium ions
2. Muc7/MG2: low molecular weight, near uniform distribution of oligosaccharide chains, promotes bacterial agglutination to then be swallowed and removed from oral cavity

Question 20

What is the main form of bacterial/viral defence in the mouth?

Answer 20

sIgA.

• Bind to viral partciles to prevent further replication
• Bind to bacteria to cause bacterial agglutination, can then be swallowed

Question 21

How does lysozyme defend against bacteria?

Answer 21

• An endoglycosidase

- Cleaves β-N-acetylmuramic acid residues from bacterial cell walls, therefore causes lysis of the bacteria

Question 22

How does lactoferrin defend against bacteria?

Answer 22

• An iron binding protein
• Binds ferric ion which is an essential microbial nutrient
• Bactericidal effects on micro-organisms that require ferric iron for growth

Question 23

How does salivary peroxidase defend against bacteria?

Answer 23

• Bacteria produce hydrogen peroxidase
• Salivary peroxidase oxidises salivary thiocyanate to hypothiocyanite
• Hypothiocyanite converts hydrogen peroxide to water
• Hypothiocyanite blocks bacterial glycolysis and kills bacteria

Question 24

How do innate immunity scavenger receptors defend against bacteria?

Answer 24

• Present in saliva and tears
• E.g. glycoprotein-340 (gp340) interacts with streptococcal surface molecules causing aggregation, can then be swallowed and removed

Question 25

Histatins are present in serous granules, desribe their structure.

Answer 25

• 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

Question 26

Describe the functions of histatins.

Answer 26

• 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

Question 27

What are defensins?

Answer 27

A type of antibacterial peptide.

Question 28

Describe the 2 major types of defensins/

Answer 28

1. Neutrophil/alpha defensins: derived from neutrophils, produced as precursors and activated through cleavage, stored in granules.
2. Epithelial/beta defensins: derives from epithelial cells, respond to high bacterial load and induced by inflammatory cytokines, i.e. during perio disease

Question 29

What 2 proteins regulate calcium levels?

Answer 29

• Acidic proline rich phosphoprotein

- Statherin

Question 30

Describe acidic proline rich phosphoprotein.

Answer 30

• 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

Question 31

Describe statherin.

Answer 31

• 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

Question 32

What components are added to saliva substitutes and why?

Answer 32

• Lysozyme to cause bacterial cell wall cleavage
• Lactoferrin to remove essential iron from bacteria
• Peroxidase to generate OSCN- (a bacteriocidal molecule)

Question 33

Evaluate the diagnostic potential of saliva.

Answer 33

• 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