Pathology and mechanisms of destruction Flashcards
What are 4 histological features of the inflammatory lesion caused by plaque?
- Extensive collagen loss
- Epithelial proliferation
- Bone loss
- Cellular inflammatory infiltrate
- Neutrophils
- Macrophages
- T lymphocytes
- Plasma cells
What is the general cycle of pathogenesis?
- Bacteria causes both inflammatory response and tissue damage.
- Inflammatory response changes the environment- further increasing the bacteria in the area
- The inflammtory response also causes tissue damage.
- Tissue damage and inflammatory response also trigger tissue repair:
What are the 2 molecular mediators of disease activity i.e the 2 sources of molecules that cause breakdown?
- Bacterial virulence factors
- Signalling molecules controlling host response.
- They either become dysregulated or exaggerated causing damage.
Give 3 bacterial virulence factors.
- Secreted by the bacteria
- Enzymes - break down collagen
- Leukotoxin - dampens affects of immune response. - Metabolites
- They ingress into connective tissue via the junctional epithelium and cause damage. - Structural components of the bacteria released during growth or death of the bacteria
- They alter host response or damage directly via endotoxins or fimbriae.
What 4 things can bacterual virulence factors do?
- Breakdown host tissues directly (enzymes)
- Damage/kill host cells (toxins)
- Stimulate host-mediated tissue breakdown (e.g. bone resorption)
- Stimulate inflammatory/immune response.
What is the mechanism of action of bacterial virulence factors?
- PAMPs - Pathogen Associated Molecular Patterns (e.g. LPS)
- These bind to cell surface receptors on macrophages - e.g. TLRs (Toll-Like Receptors)
- Results in cytokine stimulation and immune activation:
What are 3 consequences of host reponses?
- They can prevent serious progressive infection.
- May also result in local tissue damage.
- Also stimulate attempts at tissue repair.
Give 3 molecular mediators of host responses.
- Vasocative Inflammatory Mediators (e.g. Histamines)
- They create an environment for immune cells to localise to the area needed. - Cytokines (inter-cellular soluble protein messengers)
- Interleukin-1, IL-6, IL-8, IL-10, TNF, Interferons, etc - Prostaglandins, leukotrienes
- Both lipid derived molecules.
Why do host repsonses cause local tissue damage?
Local tissue damage provides access for the inflammatory response.
hat are 2 ways tissue damage occurs?
- Bacterial Virulence Factors
- Direct tissue damage by enzymes
- Indirectly by stimulating host responses - Inflammatory responses
- Cytokines and other mediatros stimulate host mediated collagen breakdown, bone resorption etc.
What are the 2 ways connective tissue damage occurs?
- Direct bacterial actions
- Enzymes like collagenase - Host mediated actions
- Cells - Fibroblasts and Macrophages
- Enzymes - MMPs and Cathepsins
- Regulated by INFLAMMATORY CYTOKINES (IL-6)
What are matrix metalloproteinases and what are they important in?
- Series of metal ion (Zn2+) containing enzymes regulating connective tissue turnover and breakdown.
- Important in normal function, chronic inflammatory diseases, cancer metastates.
What are matrix metalloproteinases produced by?
Fibroblasts and macrophages.
What are matrix metalloproteinases stimulated by?
Inflammatory cytokines, LPS, PGs.
What are matrix metalloproteinases inhibited by?
Chelating agents such as tetracylines.
Give 4 examples of matrix metalloproteinases.
- Collegenases (MMP-1, 8 and 13)
- Gelatinases (MMP-2, 9)
- Stromelysins (MMP-3, 10, 11)
- Elastases
What cell in the body is responsible for bone resorption?
Osteoclasts.
How do osteoclasts form?
- Pre-monocyte has a RANK (receptor activator of NF-KB)
- A RANKL (RANK ligand) which is either membrane bound or secreted by lymphocytes and osteoblasts binds to RANK.
- This induces osteoclasts.
How is the formation of osteoclasts inhibited?
- OPG binds to RANK
- Blocking RANKL from binding and as result inhibiting osteoclast formation and bone resorption.
In periodontitis what are the levels of OPG?
Reduced
- In periodontitis what are the levels of RANKL expression and why?
- High
- High
- Inflammatory cytokines, PGs and bacterial virulence factors such as P. gingivalis all induce RANKL.
What is the ratio of RANKL:OPG in progressive periodontitis and what does this show?
- High
- Shows higher chance of bone resorption.
In chronic inflammation and periodontal disease what is the balance between tissue damage and tissue repair?
Tissue damage is in balance with attempts at repair.
What are the attempts at repair in inflammation and what are they regulated by?
- Reparative responses include granulation tissue formation (vascular immature connective tissues) and fibrosis (scarring)
- Regulated by inflammatory cytokines such as IL-1, TGF-Beta
