Lecture 3 Flashcards
When it comes to periodontal disease, what is responsible for nearly all the destruction seen?
(Indirect injury) The host’s response to to antigenic bacterial plaque
When it comes to periodontal disease, the host’s immune system is responsible for nearly all the destruction seen. What does it do to tissue?
Alter tissue and causes irreversible changes in architecture
For disease to develop, what three things need to be present
A causative agent, favorable environment and susceptible host
A diseases onset and severity is determined by
Interaction of host with microorganisms
Bacterial plaque contributes to periodontal breakdown by
Direct injury to tissues
Indirect activation of host inflammatory and immune systems
How does bacterial plaque directly injure tissues?
Caused by bacterial toxins, enzymes and products of metabolism
Bacterial toxins
• Exotoxins
Proteins released by organisms
• Endotoxins - lipopolysaccharides
Cytotoxic agent released from cell wall of gram negative bacteria
Initiate inflammation and cause destruction
Bacterial enzymes facilitate___
Name some bacterial enzymes
Bacterial penetration
• Collagenase
• Hyaluronidase
• Chondroitin sulfatase
• Proteases
• Elastases
How does bacterial plaque indirectly injury tissues?
• Chronic bacterial accumulation results in persistent antigenic stimulus
• Bacterial waste products and toxins are recognized by body as foreign - antigens
• Stimulate a host response: inflammatory and immune systems
• Defense mechanism or response of body against pathogens- Protective
• Same response also causes tissue destruction- Destructive
What explains episodic and site specific nature of disease?
Intensity variation
• Intensity varies from individuals
• Local immune response intensity varies from site to site
• One site with active disease and high levels of inflammatory cells
•Second site with no disease and normal levels of inflammatory cells
Bacterial irritation either indirectly or directly initiates___
The inflammatory response
•a series of protective responses
What is some observable alterations in tissue during an inflammatory response?
Vascular permeability, dilation, infiltration of leukocytes that results in erythema, heat, pain, edema, loss of tissue function
What are the three stages of inflammation?!
Immediate, acute and chronic
What leukocytes control the immediate, acute and chronic stages of inflammation?
Agranulocytes
Granulocytes
Describe acute inflammation from start to finish
- Invasion of pathogens or injury
- Inflammatory cells migrate by chemotaxis (Process of leukocytes to locate and migrate to injury site)
• Neutrophils (PMNs)
• Monocytes → macrophages (histiocyte)
• Lymphocytes (Plasma cells from B lymphocytes) - Aim is to eliminate bacteria
•Phagocytosis: Process by which cells ingest particles of larger size and prevent spread of invading bacteria - If injury minimal and brief and source removed, then tissue undergoes regeneration or repair
Describe chronic inflammation
Injury continues weeks, months or indefinitely
Immune system activated after long duration: next line of defense
Leukocytes seen under inflammation response
Granulocytes: Neutrophils, Basophils, Eosinophils
Agranulocytes: monocytes and lymphocytes
The leukocytes have differing cell counts that can be used in
Detection and monitoring of disease states
Neutrophils
• Polymorphonuclear leukocyte (PMNs)
• Large White Blood Cell
• Most numerous of all WBCs (70%)
• Hallmark of acute inflammation
• Essential for control of bacterial infections
• Responds to chemotactic substances
• Arrive 1st during inflammatory response
• Phagocytosis
•Releases prostaglandin and cytokines during phagocytosis
• Short lived
• Releases destructive enzymes collagenase, elastase, and MMP
Eosinophils
Few in number
Prominent in allergic reactions
Basophils
Increase vascular permeability allow more phagocytic cells to enter into injury site during inflammation
Lymphocytes
Inflammatory response
• Can revert to blast-like cell
• Multiply as immunologic need arises
• Plasma cell
• Seen and most numerous in chronic inflammation;immune response happening in background
Immune response
Primary cell involved in the immune response
Derived from stem cells in bone marrow that migrate to lymphoid tissue/organ then matures
Role is to recognize and respond to antigens
• B lymphocytes
• T lymphocytes
• NK lymphocytes
Monocytes
Inflammatory response
• Large white blood cells
• 2nd cell to participate in inflammatory response
• Phagocytosis function
• Called monocytes in bloodstream but differentiate into macrophages in the tissues
• Seen and most numerous cell in chronic inflammation
•Remain in tissues to repair damages
•Produce destructive enzymes collagenase and MMP
• Produces cytokines and prostaglandins
Immune response
•Macrophages process and present antigens to B-lymphocyte
Macrophages development from
Agranulocytes then monocytes then macrophages
This biochemical mediator is a major source in inflamed periodontal tissue
Prostaglandin
Mast Cell
• Inflammatory mediator
• Increases vascular permeability
• Advances inflammatory response
• Role in anaphylaxis, usually localized
Immune response
• Defends the body against injury
• Recognize, recruit, and eliminate
• Works in background of already activated inflammatory response
• Necessary for complete recovery
• May also result in increased injury and disease
• Involves complex network of lymphocytes
• Immunity: Aim is for host to develop resistance to specific antigens. Lymphocytes have capacity to remember thereby will have a quicker response on second exposure
Immune response to an antigen can take one of two forms:
• Humoral immunity
• Cell Mediated immunity
B lymphocytes
• Derived from stem cells
• Reside in lymphoid tissue once mature
• Two types exist:
• Plasma Cell: Produce antibodies or immunoglobulins - 9 classes with structural differences
• Memory Cell
• Retains memory and clones itself in presence of antigen
Which type of immunity is most effective against periodontal pathogens?
Humoral immunity
How are macrophages involved in humoral immunity?
Macrophages carry antigens to lymph nodes and present it to B cells which recognize the antigen
Function of Antibodies in Host Defense
Prevent destruction of host cells
Bind to and neutralize bacteria or bacteria toxins forming immune complex
•more susceptible to phagocytosis
•activate the complement system
What is complement and where is it found?
Proteins circulating in plasma
Function of complement (5)
• Functions as a cascade - amplifies response
- Destroys pathogens (lysis)
• Creates a protein unit capable of puncturing bacterial cell membrane - Facilitates phagocytosis via opsonization
• (engulfs vs. marked with antigen 1st)
• Easier identification - Mediates degranulation of mast cells
• Release histamine
• Increased vascular permeability - Generates chemotactic factors
• Recruitment of additional phagocytic cells - Clearance of immune complexes
Pathways of Complement Activation
- Classical: antibodies bind to surface antigens
- Alternative: Endotoxins (lipopolysaccarides) activate system
- Binding of specific proteins to proteins or carbohydrates on bacteria
T lymphocytes
•Cellular immunity
• Derived from stem cells and mature in thymus
• Migrate to bloodstream and lymph nodes
• Intensifies response of other immune cells
• Have surface receptors on plasma membranes
• Three Types:
• T-Helper Cells- CD4
• T- Suppressor Cells
• T- Cytotoxic Cells- CD8
T - Helper Cells (CD4)
• Stimulate B lymphocyte to differentiate into plasma cells
• Enhance antibody response
• Secrete cytokines and activate phagocytic cells
T - Suppressor Cells (regulatory)
• Turn off function of B lymphocytes
T - Cytotoxic Cells (CD8)
• Stimulate cytotoxic activity in other cells
Natural Killer T Cells
Develops as result of antigen processing (antigen infected in cells)
Can produce antibodies
Cellular immunity most effective against
Fungi, viruses, cancer, and foreign tissue
What are inflammatory biochemical mediators?
Biologically active compounds secreted by immune cells
Stimulate the inflammatory response
What inflammatory biochemical mediators are responsible for tissue destruction in periodontitis?
Cytokines
Prostaglandins
MMPs
What cells make cytokines?
Neutrophils
Macrophages
Epithelial cells
Gingival fibroblasts
B lymphocytes
Osteoblasts
What do cytokines do?
Influence behavior of other cells by transmitting information or signals
• Signal immune system and recruit additional phagocytic cells at site
• Increase vascular permeability/increases movement of immune cells and complement into tissue
• Can initiate tissue destruction and bone loss in chronic inflammatory disease
Cytokines are named for their
Action
Name five types cytokines
• Macrophage activating factor
• Osteoclast activating factor
• Lymphotoxin: Associated with bone destruction periodontal disease
• Interferon: Antiviral properties
• Interleukins- new term
Macrophage activating factor
Osteoclast activating factor
Lymphotoxin
Interferon
Interleukins
Which cytokine is associated with bone destruction in periodontitis?
Lymphotoxin
What interleukins are important in periodontitis?
IL 1,6,8 and TNF-a
What are prostaglandins?
What are the series that we are focusing on?
Which of the series plays a role in periodontal bone destruction?
What cells are importance sources of prostaglandins?
Which cell in a major source in inflamed periodontal tissue?
What are its functions?
• Series of powerful inflammatory mediators
• D, E, F, G, H and I
• PGE - E series - role in periodontal bone destruction
• Important sources: Neutrophils and macrophages
• Macrophage is major source in inflamed periodontal tissue
Functions of Host Produced
Prostaglandins
• Increase vascular permeability and vasodilation → redness and edema
• Promote overproduction of destructive
MMP (matrix metalloproteinases)
enzymes
• Trigger osteoclast activity: Major mediators of alveolar bone loss
Which Prostaglandin plays a role in periodontal bone destruction?
PGE - E series - role in periodontal bone destruction
PG also play a huge role in inflamed periodontal tissue (macrophages is the source)
Important sources of prostaglandins
Neurophils and macrophages
Prostaglandins play a role in inflamed periodontal tissue. A major source for it in periodontal tissues is what cell?
Macrophages
Function of host produced prostaglandins
• Increase vascular permeability and vasodilation → redness and edema
• Promote overproduction of destructive
MMP (matrix metalloproteinases)
enzymes (Under healthy conditions facilitate turnover of CT matrix)
• Trigger osteoclast activity
• Major mediators of alveolar bone loss
Matrix Metalloproteinases
Major source
Other sources:
• Family of enzymes produced by various cells
• Major source: Neutrophils and gingival fibroblasts
• Other sources:
• Macrophages, junctional epithelial cells
These cells act together to break down connective tissue matrix
Major source of MMPs
Neutrophils and gingival fibroblasts
Other sources of MMPs
Macrophages, junctional epithelial cells
Function of Matrix Metalloproteinases both in normal circumstances and in disease
• Under healthy conditions facilitate turnover of CT matrix
MMPs overproduced in presence of bacterial infection → CT breakdown
•extensive collagen destruction
• degradation of periodontal tissues
• Collagen is structural framework for all periodontal tissues
In addition to the inflammatory and immune protective responses what are two other protective responses with regards to the oral cavity and periodontium?
Gingival or Sulcular Fluid
• More present during inflammation
• Inflammatory exudate composed of leukocytes(92%), enzymes and cellular elements
• Tetracycline concentrates in fluid: more useful antibiotic for treating periodontal disease
Saliva
• Lubrication - reduces incidence of caries
• Physical protection - coagulation factors
• Cleansing
• Buffering - maintains pH
• Remineralization - plaque formation and maturation
