Saliva 3 Flashcards
5.1 Secretory immunoglobulin-a
IgA1 vs. IgA2
IgA exists in two ______, IgA1 and IgA2.
While IgA1 predominates in _____ (~____%),
IgA2 percentages are higher in _______ than in ____ (_____ in secretions);
the ratio of IgA1 and IgA2 secreting cells___________________________of the human body:
IgA1 is the predominant IgA subclass found in serum. Most _____tissues have a predominance of____-_____ cells.
In IgA2, the heavy and light chains are not ____________, but with _____________. In secretory lymphoid tissues (e.g., _______________), the share of ________ production is larger than in the non-secretory lymphoid organs (e.g. _______________).
Both IgA1 and IgA2 have been found in _________ like ______, ____ and _____, where _____ is more prominent than in the _____. _____ antigens tend to induce more IgA2 than ____ antigens.
The dimeric IgA molecule.
1 _-chain
2 _-chain
3 _-chain
4 ______ ________
IgA1 vs. IgA2
IgA exists in two isotypes, IgA1 and IgA2. While IgA1 predominates in serum (~80%), IgA2 percentages are higher in secretions than in serum (~35% in secretions); the ratio of IgA1 and IgA2 secreting cells varies in the different lymphoid tissues of the human body:
IgA1 is the predominant IgA subclass found in serum. Most lymphoid tissues have a predominance of IgA-producing cells.
In IgA2, the heavy and light chains are not linked with disulfide, but with monovalent bonds. In secretory lymphoid tissues (e.g., gut-associated lymphoid tissue, or GALT), the share of IgA2 production is larger than in the non-secretory lymphoid organs (e.g. spleen, peripheral lymph nodes).
Both IgA1 and IgA2 have been found in external secretions like colostrum, maternal milk, tears and saliva, where IgA2 is more prominent than in the blood. Polysaccharide antigens tend to induce more IgA2 than protein antigens.
Serum vs. Secretory IgA
It is also possible to distinguish forms of IgA based upon their ______- serum IgA vs. secretory IgA.
In secretory IgA, the form found in secretions, polymers of ___ IgA monomers are linked by ___________; as such slgA holds a molecular weight of ________.
One of these is the __ chain (joining chain), which is a _____ of molecular mass 15kD, rich with ______ and structurally completely different from other immunoglobulin chains. This chain is formed in the IgA-secreting cells.
Serum vs. Secretory IgA
It is also possible to distinguish forms of IgA based upon their location - serum IgA vs. secretory IgA.
In secretory IgA, the form found in secretions, polymers of 2-4 IgA monomers are linked by two additional chains; as such slgA holds a molecular weight of 385,000.
One of these is the J chain (joining chain), which is a polypeptide of molecular mass 15kD, rich with cysteine and structurally completely different from other immunoglobulin chains. This chain is formed in the IgA-secreting cells.
Serum vs. secretory IgA
The oligomeric forms of IgA in the _____(mucosal) secretions also contain a _______ of a much larger molecular mass (70 kD) called the ________ ______ that is produced by _____ cells.
This molecule originates from the ____-__ receptor (130 kD) that is responsible for the uptake and transcellular transport of oligomeric (but ____ ______) IgA across the _____ cells and into _____ such as tears, saliva, sweat and gut fluid.
Serum vs. secretory IgA
The oligomeric forms of IgA in the external (mucosal) secretions also contain a polypeptide of a much larger molecular mass (70 kD) called the secretory component that is produced by epithelial cells.
This molecule originates from the poly-Ig receptor (130 kD) that is responsible for the uptake and transcellular transport of oligomeric (but not monomeric) IgA across the epithelial cells and into secretions such as tears, saliva, sweat and gut fluid.
5.2 5.2 Lysozyme/Proteases
Present in numerous ___ and most ______
Oral LZ is derived from at least ____ sources
_____
_____
_____
_____
Biological function:
Classic concept of ________ activity of LZ is based on its ______ activity (______ ___ _______ bond between _____ and ____ in the _____ layer.
Gram ____ bacteria generally more ____ than gram ____because of outer ____ layer
Present in numerous organs and most body fluids
Oral LZ is derived from at least four sources
major and minor salivary glands, phagocytic cells and gingival crevicular fluid (GCF)
Biological function
Classic concept of anti-microbial activity of LZ is based on its muramidase activity (hydrolysis of b(1-4) bond between N-acetylmuramic acid and N-acetylglucosamine in the peptidoglycan layer.
Gram negative bacteria generally more resistant than gram positive because of outer LPS layer
Lactoferrin
_____ secretion from ____ and ___ glands
______ release into ____
Inactivated in presence of ________
Iron free state = _____-_________
Apo-lactoferrin does what? ________________
May lead to _____ if not _____ of the____ _____ from pathogenic microorganisms
Nutritional immunity (____ _______)
Some microorganisms (e.g., E. coli) have adapted to this mechanism by producing __________.
They_____________________than lactoferrin
Iron-rich enterochelins are then ______ by bacteria
Lactoferrin, with or without iron, can be _____________________.
In unbound state, a direct ___________
lSerous secretion from major and minor glands
lLeukocytes release into GCF
lInactivated in presence of high [Fe3+]
lIron free state = apo-lactoferrin
lApo-lactoferrin irreversibly directly binds to bacteria
lMay lead to agglutination if not expropriation of the essential metal from pathogenic microorganisms
Nutritional immunity (iron starvation)
Some microorganisms (e.g., E. coli) have adapted to this mechanism by producing enterochelins.
bind iron more effectively than lactoferrin
iron-rich enterochelins are then reabsorbed by bacteria
Lactoferrin, with or without iron, can be degraded by some bacterial proteases.
In unbound state, a direct bactericidal effect
5.4 Histatins
Anti-_____activity
Histatin ____ is known to kill _____ _____
Increases_____ _____
Histatin ______ are known ____ _____ _____ that can migrate through epithelial tissues
Inhibit ____ ______
Histatin _
Anti-fungal activity
Histatin 5 is known to kill Candida albicans
Increases wound healing
Histatin 1 & 2 are known wound closing factors that can migrate through epithelial tissues
Inhibit matrix metalloproteinases
Histatin 5
5.6 Mucins/Agglutinins
Lack __________________
______ molecules with ___, _______ ______structure
____ backbone (____) with _____ side-chains
Side-chains may end in _____ charged groups, such as sialic acid and bound sulfate
____, _________ water (resists ________)
Unique ______ properties (e.g., high _____, _______, and low _____)
____ major mucins (____ and _____)
Lack precise folded structure of globular proteins
Asymmetrical molecules with open, randomly organized structure
Polypeptide backbone (apomucin) with CHO side-chains
Side-chains may end in negatively charged groups, such as sialic acid and bound sulfate
Hydrophillic, entraining water (resists dehydration)
Unique rheological properties (e.g., high elasticity, adhesiveness, and low solubility)
Two major mucins (MG1 and MG2)
5.6 Mucins/Agglutinins
___ _____
_____ coating about hard and soft tissues
Primary role in ______ of _______ ______
Concentrates ___________ molecules at ______ interface
______
Align themselves with _____________ (characteristic of asymmetric molecules)
Increases_____qualities (film strength)
Film strength determines how effectively ______________________.
_____ __ _______ ______
_____ adhere to ___ may result in_____, or
_________ may be unable to ___________
______ _______
Mucin oligosaccharides mimic those on __________________
React with _________, thereby blocking them
Tissue Coating
Protective coating about hard and soft tissues
Primary role in formation of acquired pellicle
Concentrates anti-microbial molecules at mucosal interface
Lubrication
Align themselves with direction of flow (characteristic of asymmetric molecules)
Increases lubricating qualities (film strength)
Film strength determines how effectively opposed moving surfaces are kept apart
Aggregation of bacterial cells
Bacterial adhere to mucins may result in surface attachment, or
Mucin-coated bacteria may be unable to attach to surface
Bacterial adhesion
Mucin oligosaccharides mimic those on mucosal cell surface
React with bacterial adhesins, thereby blocking them
5.7 Cystatins
Are____ of ___________
Are ubiquitous in many ______ _____
Considered to be _____ against unwanted _____
- _____ proteases
- ____ ____
May inhibit proteases in _____ tissues.
Also have an effect on ____ ______ _______.
Are inhibitors of cysteine-proteases
Are ubiquitous in many body fluids
Considered to be protective against unwanted proteolysis
bacterial proteases
lysed leukocytes
May inhibit proteases in periodontal tissues.
Also have an effect on calcium phosphate precipitation
Summary
Anti-microbial proteins in Saliva
Statherin - a ___ that______________and allows for _______
Mucin - cause ____ to _____
Lysozyme -____ (depressed by ___ and ___)
Lactoferrin - combines with ____ and ____ to _____ _____ and ___________
Salivary peroxidase - reacts with salivary ______ when _____ is around and forms _____ which _______________________.
Lactoperoxidase - adsorbs to ______ altering ______________.
Histatins – ______ _____ _____
Cystatins –Affects _________________.
Statherin - a PRP that stabilizes inorganic ions and allows for supersaturation
Mucin - cause bacteria to aggregate
Lysozyme - antibacterial (depressed by iron and copper)
Lactoferrin - combines with iron and copper to protect lysozyme and deprives bacteria of these metals
Salivary peroxidase - reacts with salivary thiocyanate when H2O2 is around and forms hypothiocyanite which inhibits bacterial glucose metabolism
Lactoperoxidase - adsorbs to hydroxyapatite altering primary bacterial attachment
Histatins – Antimicrobial wound closers
Cystatins – Affects mineral balance of the tooth
Physiological Harmony
Altered Oral Ecology
Mechanical Prop, Stimulus, Acinar cells
Substrate, Bacteria, Host
Etiology of Salivary Hypofunction
- D_______________________ (e.g., ____ ______)–>_______
- M___________ (e.g., ________)–> _____
- M___________________ (e.g., ______)–>_____
- D______________ (e.g., _____)–> _____
- A________________–> ______
- Damage to Acinar Units (e.g., radiation, Sjogren’s)–>acinar
- Medications (e.g., blocking agents)–> stimulus
- Mechanical obstruction (e.g., sialoliths)–>mechan
- Dehydration (e.g., diuretics)–> acinar
- Chronic alcoholism–> acinar
- Sialolith
The Cascading Effect of Saliva Loss
Decrease salivary flow
- Mild moderate and severe_______
- ____ and ____
- Difficulty___, ____ and____
- ____ ____ ____, ___ ____
Decrease salivary flow
- Mild moderate and severe dry mouth
- Discomfort and Pain
- Difficulty chewing, swallowing and speaking
- Oral fungal infections, tooth decay
Xerostomia
- Dry mouth
- Clinical History
- History of ____
- Yes
- _____
- no
- _______
- ________
- _________
- Yes
- _________
- No
- ____
- _____
- _____
- ______
- yes
- ______
- No
- ______
- yes
- Yes
- Yes
- Dry mouth
- Clinical History
- History of Radiotherapy
- Yes
- Post-radiation Xerostomia
- no
- Sialometry
- Reduced Saliva rate
- History of xerogenic med intake
- Yes
- Pharmacological Xero
- No
- Dry eyes
- SS serum
- Lip biopsy
- Conn tissue disease?
- yes
- secondary SS
- No
- primary SS
- yes
- Dry eyes
- Yes
- Sialometry
- Yes
~ Causes of Non-neoplastic ~
~ Salivary Gland Enlargement ~
____
____
_____
_____
Infection
Inflammation
Obstructive
Co-Morbitity Effects
Infection
____ ______ - ___ (___, ____),____
____ ____ ______
_____ _____- _____ ,_____
Acute sialadenitis - viral (mumps, CMV), bacterial
Recurrent acute sialadenitis
Chronic sialadenitis - tuberculosis, actinomycosis
~ Acute Sialadenitis Mumps ~
_____ cause of acute ____ swelling of the ____ gland in _____
Due to _______ infection
____- illness is followed by acute____ painful parotid swelling
Resolves ______ over ____ days
Occasionally parotid swelling may be____
Occasionally may affect ____________
Similar clinical picture may occur with ____________or _______ _____ ____
Commonest cause of acute painful swelling of the parotid gland in children
Due to paromyxovirus infection
Flu-like illness is followed by acute bilateral painful parotid swelling
Resolves spontaneously over 5 -10 days
Occasionally parotid swelling may be unilateral
Occasionally may affect submandibular glands
Similar clinical picture may occur with Coxsackie A or B or parainfluenza virus infection
~ Bacterial Sialadenitis ~
Acute ascending bacterial sialadenitis usually affects the____ glands
Due to __________ or_________ infection
Incidence of this condition is ____
Used to be seen in _______________ patients with ____________
Presents with ____ tender swelling of the ____ gland
____ can often be _________
Sialogram is______
Treatment is with _____ ____-____ _____
Late presentation can cause a ______ _____ to develop
Acute ascending bacterial sialadenitis usually affects the parotid glands
Due to staphylococcus aureus or streptococcus viridans infection
Incidence of this condition is decreasing
Used to be seen in dehydrated post-operative patients with poor oral hygiene
Presents with painful tender swelling of the parotid gland
Pus can often be expressed from the duct.
Sialogram is contraindicated
Treatment is with parenteral broad-spectrum antibiotics
Late presentation can cause a parotid abscess to develop
~ Salivary Gland Enlargement ~
INFLAMMATION
___ ____
______
_____ ____
____ ____ _____ _____
______ _____
____
Sjogren’s syndrome
Sarcoidosis
Mikulicz’s syndrome
Diffuse infiltrative lymphocytosis syndrome
Granulomatous sialadenitis
Idiopathic
~ Diffuse Infiltrative Lymphocytosis Syndrome ~
Diffuse infiltrative lymphocytosis syndrome
___ lymphocytic infiltrate associated with ____
Often involves____ _____ (present in __-__% of US HIV+ patients vs. up to __% in Africa)
Also affects ___ glands, ___, ___, ___, ___,____, __, _____
____ on ___ scale, 0: _____, 4: __________ of 50 or more mononuclear cells in a 4-mm2 area of a section
Micro: resembles_____ syndrome; ____ ____ ____ atypia common in advanced HIV patients
Diffuse infiltrative lymphocytosis syndrome
CD8+ lymphocytic infiltrate associated with HIV
Often involves salivary glands (present in 1-6% of US HIV+ patients vs. up to 50% in Africa)
Also affects lacrimal glands, kidney, muscle, nerve, liver, lung, GI, breast
Graded on 0-4 scale, 0: no infiltrate, 4: 2+ foci of 50 or more mononuclear cells in a 4-mm2 area of a section
Micro: resembles Sjogren’s syndrome; salivary ductal epithelial atypia common in advanced HIV patients
Mikulicz’s Disease
Also called ____ ___________ _____
Presents as ____ _____, ____ enlargement of____ and ____ glands
May ____ during acute____
May be confined to ________, usually part of ___
Increased incidence with ____
Initially polyclonal, may evolve into _____ (diffuse large B cell, rarely Hodgkin’s lymphoma, peripheral T cell lymphoma)
Gross:__________areas and occasional ___
Also called benign lymphoepithelial lesion
Presents as slow, bilateral, symmetric enlargement of salivary and lacrimal glands
May subside during acute infections
May be confined to salivary gland, usually part of Sjogren’s syndrome
Increased incidence with HIV
Initially polyclonal, may evolve into lymphoma (diffuse large B cell, rarely Hodgkin’s lymphoma, peripheral T cell lymphoma)
Gross: solid gray-white areas and occasional cysts
Mikulicz’s Disease
First reported in 1890
Painless
Which glands? Parotid and Submandibular
Elevated serum IgG4 conc
infiltration of plasma cells expressing IgG4 with fibrosis
One of the igG4- related sclerosing diseases
Mikulicz’s Disease
First reported in ___
___
Which glands?
____ ____ ____ ____
infiltration of plasma cells expressing ___ with ___
One of the ___- ____ ______ diseases
~ Mikulicz’s Disease ~
Description:
Benign and chronic dacryoadenitis with bilateral painless swelling of lacrimal and salivary glands and____ or ____ _______.
Associated with ____ and ____ but _____ and ______.
It may be caused by t____, l____,l_____,p______, s_____, s_____, or g_____.
Onset may occur in conjunction with ______________,____ infection, or ______.
Some authors consider this disease and the Sjögren syndrome as identical, but others suggest they are separate entities because of the absence of _________ in Mikulicz disease.
Description: Benign and chronic dacryoadenitis with bilateral painless swelling of lacrimal and salivary glands and decreased or absent lacrimation.
Associated with dry mouth and dry eyes but no arthritis, and vision blurring.
It may be caused by tuberculosis, leukemia, lymphosarcoma, poisoning, sarcoidosis, syphilis, or gout.
Onset may occur in conjunction with respiratory tract infection, oral infection, or tooth extraction.
Some authors consider this disease and the Sjögren syndrome as identical, but others suggest they are separate entities because of the absence of rheumatoid arthritis in Mikulicz disease.
~ Mikulicz’s Disease ~
Micro: marked _______ _____ with lymphoid follicles surrounding solid epithelial nests;
also scattered____ and _____cells;
excess ____ basement membrane material ______ between cells;
also ____ ____and _____,
_____ lesions,
_____ B cells
; usually no ____,
no involvement of ____ ducts
Micro: marked lymphocytic infiltration with lymphoid follicles surrounding solid epithelial nests; also scattered histiocytes and dendritic cells; excess hyaline basement membrane material deposited between cells; also acinar atrophy and destruction, lymphoepithelial lesions, monocytoid B cells; usually no fibrosis, no involvement of large ducts
