Host defences against microbial plaque Flashcards
The balance between what 4 things prevents the formation of periodontal diseases?
- Presence of pathogen
- Absence of beneficial species
- Host response
- Conducive environment around the oral cavity
What are the functions of the host defences?
- To keep bacteria out out of the periodontium| 2. Destroy any foreign microbes which succeeded in entering the system
What are the stages of plaque formation
- Pioneer species attach to the pellicle surface of a clean tooth2. These multiply to form micro colonies 3. Resulting in confluent growth of biofilm 4. This increases species diversity
Name the 5 things that help defend us from plaque
- Saliva
- Gingival epithelium
- Inflammation
- Immune system
- Mediators
What are the functions of saliva?
Washing effect – remove bacterial and food debris
Protects the oral mucosa w mucin and glycoproteins
antimicrobial effects, contains:
Peroxidase/hypothiocyanite
lysozymes/lactoferrin
antibodies (IgA)
What occurs if there is a lack of saliva?
Xerostomia
What are some factors that may cause Xerostomia?
- Patients who are mouth breathers
- Drugs/ alcohol
- Radiotherapy
- Patients who have had their salivary glands removed surgically
What are people with xerostomia more susceptible to?
Gingivitis| Cervical caries
What is the gingival epithelium’s role
effective barrier against micro-organisms, however it is permeable to
many small molecules. epithelium of the outer or oral surface of the gingiva is keratinized or para-keratinized, while the
sulcular/crevicular epithelium is thinner and not keratinized
What is the junctional epithelium permeable to?
- Bacterial products that need to go in2. Crevicular fluid and neutrophils that need to go out3. It becomes more permeable in disease
Describe the junctional epithelium in periodontal health. what are the 2 way movements of the bacteria ?
lies against enamel and extends up to CEJ
two way movement; connective tissue
to crevice/sulcus and sulcus/crevice to connective tissue.
Describe what happens to the junctional epithelium as periodontal health deteriorates
Junctional epithelium migrates apically| This eventually forms a pocket between the junctional epithelium and root surface
What is associated with the formation of a pocket between the junctional epithelium and root surface
Loss of connective periodontal attachment and loss of alveolar bone
What is inflammation?
It is a response of living tissue to injury and provides a rapid first line of defence
What are the 2 types of inflammation?
- Acute| 2. Chronic
What is acute inflammation?
inflammation has a relatively rapid onset and neutrophil polymorphs are the most abundant cells
Describe chronic inflammation
inflammation has a relatively insidious onset, prolonged course, slow resolution and lymphocytes, macrophages and plasma cells are the most abundant cells
What are the functions of the inflammatory response?
- To dilute by increasing crevicular fluid
- To wall off the inflammatory cells
- Destroy the inflammatory cells and the damaging pathogens
Describe the sources of the fluid response of inflammation
- Vasodilation
- Increased permeability of endothelial cells
- Fluid and plasma proteins are release into the tissues and through GCF
- inflammatory exudate
What is the inflammatory exudate
plasma proteins like antibodies and compliment that are released into the tissues and through GCF
How many proteins are involved in the compliment system?
9
Why does the compliment system play an important role in the fluid response of inflammation?
- It is responsible for mass cells producing histamine
- Chemotaxis for neutrophils
- Responsible for lysis and inhibition of a few species off bacteria
- Can lead to opsonisation for phagocytosis
What do we expect to see as the fluid response of inflammation is occurring ?
- Increased crevicular fluid flow
- Gingival erythema
- Oedema and selling of the gingiva
Name the key components of the cellular response of inflammation
- Neutrophils| 2. Macrophages
Why are neutrophils important?
Critical in preventing periodontal diseases
Enters gingival crevice
forms a layer on the surface of plaque biofilm
Describe the function of neutrophils in response to UNATTACHED bacteria
recognizes and binds bacteria (opsonisation)
Phagocytosis – Process by which ingestion of solid particles by
throwing pseudopodia around it
production of antibacterial agents
digest micro-organisms within lysosomes (Phagosomes)
expel remnants
Causes bystander damage
What can bystander damage cause?
A little bit of damage to the surrounding tissues
Describe the function of neutrophils in response to bacteria in the plaque matrix
-attach to plaque matrix
-secrete antibacterial enzymes
hydrogen peroxide
hypochlorous acid
-Kill bacteria
-dissolve plaque matrix
-Causes bystander damage
What is a recognised side effect to the host defence system?
Bystander damage
Where do macrophages develop?
They develop from monocytes in the blood
What do macrophages play an important role in?
Both immunity and inflammation
Where do macrophages emigrate too?
They emigrate to inflamed gingival tissue| Few of them enter the gingival crevice
What role do macrophages have in inflammation?
- Phagocytosis 2. Secrete tissue degrading enzymes 3. They secrete compliment components 4. They secrete mediators
Name some functions macrophages secrete in relation to inflammation
-tissue degrading enzymes
-complement components (plasma proteins killing pathogens)
-mediators e.g IL-1 TNF, Prostaglandins
What type of inflammation is periodontal disease implicated by?
Both acute and chronic
What is gingivitis usually characterised by biochemically?
An increase in leukotriene B4 in the gingival crevicular fluid
What is leukotriene B4 a product of?
Degranulating neutrophils in the sulcus
What is periodontitis usually characterised by biochemically?
increase in prostaglandin E2. IL-1β and tumor necrosis factor α which represent an activation of macrophages and lymphocytes within the tissue
Describe the acquired immune response
It is stimulus specific and has memory It is initiated by antigens Antigens are recognised by lymphocytes
What are the 2 aspects of the immune responses?
- Humoral| 2. Cell mediated
Which cells are involved in the humeral response?
B lymphocytes undergo differentiation to give:1. Plasma cells 2. Immunoglobulins
Which cells are involved in the cell mediated response?
T lymphocytes there are 2 types:| 1. T helper cells 2. T cytotoxic cells
What activates the humoral response?
- Bacteria 2. Toxins3. Other plaque antigens
Describe the humoral response
- Antigen presented by the macrophages 2. B lymphocytes recognise foreign antigens and undergo clonal expansion 3. B lymphocytes differentiate into plasma cells under T lymphocytes are initiated 4. Antibodies are produced
What type of antibodies make up the majority of the humoral response?
IgG makes up 75% of the antibodies in the humoral response
Describe the antibody production in the saliva
- Bacteria is swallowed in the saliva 2. Antigens recognised in the gut 3. IgA secreted into the saliva
Describe the antibody production in the gingiva
- Antigens penetrate gingiva 2. Antigens carried to lymph node outside the ginigva 3. Antibodies IgG and IgM are secretes into the plasma pass to GCF
What are the 2 mechanism by which antibodies fight off antibodies?
-Binding to bacteria
Inhibiting attachment
opsonisation
activating complement
inhibiting metabolism
-Binding to soluble factors
neutralizing toxins
inhibiting enzymes
What does the cell mediated immune response regulate?
Regulates plasma cell differentiation and role in periodontal disease
What are some defects in the host response?
- Quantitative defect: Reduction in neutrophil number
- Qualitative defect: Defective neutrophil function
What can a reduction in neutrophil number cause?
- Cyclic neutropenia 2. Agranulocytosis these can have a clinical effect on gingiva and periodontal tissues
Name some genetic conditions that can result in defective neutrophil function
Downs syndrome Diabetes
Papillon- Levfevre syndrom
Chediak-Higashi syndrom
Leucocyte adhesion deficiency
Name some mediators?
- Histamine
- Bradykinin
- Cytokines
- Prostaglandins
- Metalloproteinases (e.g collagenase, gelatinase, stromolysins)
What are histamine and bradykinin associated with?
Vasodilation| Increased vascular permeability
Describe Cytokines
They are soluble proteins
They are secreted by cells
They transmit signals
The inflammatory and immune response
Give examples of Cytokines
IL-1 , TNF
What is the role of Cytokines?
To amplify inflammatory response
How do Cytokines amplify the inflammatory response
- They activate macrophages
- Activate lymphocytes
- Causes cells to release prostaglandins and more Cytokines
- Causes endothelial cels and fibroblast proliferation
- Causes fibroblasts to release collagenase
- Indices bone resorption
What do Prostaglandins do?
- They cause capillary dilation
- Increase endothelial permeability
- PGE2 causes bone resorption
What are Prostaglandins produced by
arachidonic acid in cell membranes of inflammatory cells
Give examples of metalloproteinases
- Collagenase
- Gelatinase
What are metalloproteinases involved in?
Connective tissue destruction
What are metalloproteinases produced by?
Fibroblasts, Monocytes, Neutrophils
What are metalloproteinases induced by?
IL-1
What are the major regulators of immunoinflammatroy responses that categorise periodontitis?
Cytokines Chemokine Prostaglandins
What is bystander damage a prominent feature of?
Of chronic inflammatory disease
How can we identify risk patients
- Medical history
- Social history
- Family history
- Smokers
- Host response based diagnostics kits
How does bystander damage happen?
Bacteria initiates disease by activating host mechanism that destroys supporting structure. Subsequent damage of crestal alveolar bone.
How can we tailor treatment to high risk patients
- Liaison with there GP
- Give the oral hygiene aids
- Give them smoking advice
- Be selective about our use of adjunctive antibiotics
- Prognosis of periodontal surgery
- regular maintainence
What do Cytokines, Chemokine ,Prostaglandins have a major role in
They are major regulators of immunoinflammatroy responses that categorise periodontitis
what causes damage in periodontist, bacteria or the host response?
Periodontitis is an inflammatory disease initiated by bacteria but it is the host response that causes the majority of the damage to the periodontium
name the 2 host responses triggered by plaque
innate immunity & aquired immunity
describe innate immunity
innate:
First line of defence mechanism
Rapid response
Non-specific and lack memory
When not controlled or when
dysregulated causes collateral tissue
damage
E.g., Saliva, gingival epithelium, GCF,
complement system, PMNLs
(Polymorphonuclear neutrophils) and
Pattern recognition receptors
describe acquired immunity
Takes longer to develop
Slow response
Specific and has memory
More efficient
E.g., T lymphocytes, B lymphocytes,
immunoglobulins – IgG
(Predominantly seen in GCF), IgA
(Predominantly seen in saliva)
what is a compliment activation pathway?
complex series of interacting plasma proteins which form a
major effector system for antibody- mediated immune reactions.
what do many complement components exist ?
inactive precursors;
once the complement component is activated, what happens?
component may behave as an enzyme which cleaves several molecules of the next component in the sequence. Each precursor is cleaved into two or more fragments: major ‘b’, minor ‘a’
what is the major fragment made of?
has two biologically active sites: one for binding to cell membranes or the triggering complex, and the other for
enzymatic cleavage of the next complement component.
what is the minor fragment made of?
have important biological properties in
the fluid phase.
what is the primary purpose of the complement pathway?
remove or destroy antigen, either by direct lysis or by opsonisation.
what is classical pathway activated by?
binding of IgM or IgG to antigen causes a conformational change in the Fc region of the antibody to reveal a binding site for the first component in the classical pathway, C1.
what is the central reaction in alternate pathway?
likewise to classical one, is the activation of C3. The alternative pathway, however, generates a C3 convertase without the need for antibody, C1, C4 or C2.
What is the most important activators of alternate pathway ?
bacterial cell walls and endotoxin. Thus, the alternative pathway is responsible for innate defence against dental biofilm.
2 components of gingivitis?
fluid (increased crevicular fluid flow and gingival oedema)
cellular (neutrophils and (later) macrophages)
the pro inflammatory cytokines IL-1 and TNF are strongly associated with what?
periodontitis lesions
different cytokines patterns at diff sites suggest what?
specific regulatory patterns may be involved in stable and active lesions.
do disease active sites have a characteristic of either a predominant TH-1 or TH-2 lymphocyte response?
naauuuuur
primary mediators of tissue destruction in periodontitis
Prostaglandin E2, possibly COX 2
people with severe diseases have elevated levels of what?
PGE2
PGE2 levels are determined by what
cyclooxgenase2 enzyme and cytokines esp IL-1 & TNF
