host response in perio disease Flashcards
What does the masticatory epithelium consist of?
Gingival epithelium
Sulcular epithelium (<1mm)
Junctional epithelium
What is the junctional epithelium?
Specialised Flattened cells- hemidesmosome attachment to c. tissue and enamel/cementum Basement membrane Wide intercellular spaces-porous Susceptible to bacterial infection V rapid cell turnover
What are the stages of periodontitis?
Initial
Moderate
Severe (potential for tooth loss)
Advanced (extensive tooth loss, potential for loss of dentition)
What is the pathogenesis of perio disease?
Complex interplay between host response, microbial challenge and modifying factors
Dysbiosis of microbial community
What host factors influence oral health?
Saliva
Epithelium
Inflam response
What is the role of saliva?
Innate immunity
-Secretory IgA
~Secretory component added as IgA passes through epithelial cells
~Binds to bacteria +/ products to stop their function
Lactoferrin-
~Binds to and sequesters free iron required for bacterial growth
~Binds LPS, forming peroxide, increasing membrane permeability—>bacterial death
Antiviral/antifungal activity
Salivary thoiocynate-
~activates hypothiocyanous acid to bind to cysteine residues in proteins to disrupt function
Antimicrobial peptides-
~beta-defensins- highly cationic- inserts into bacterial membrane creating pores—>lysis
~cathelicidin peptides- punches holes also esp. lipoprotein membranes
~cathepsin C- serine protease released mainly by neutrophils, activates other proteases, cleaves ECM components
What is the role of the epithelium?
- Desquamation- sheds w any attached bacteria
- Permeability barrier
- J. Epithelium more permeable than oral epithelium
- Stimulate inflam/immune response by releasing cytokines eg. IL-1
What is ginigival crevicular fluid?
Inflam exudate containing complement C1-9, antibodies, clotting factors and kininogens
C3a and C5a- vascular changes- stimulate histamine release, promote formation of leukotrienes/prostaglandins which attract phagocytes by chemotaxis and aid phagocytosis via opsonisation
C5-9- membrane attack complex destroying microorganisms
Antibodies- IgG/IgA- act as opsonin to aid phagocytosis
Clotting factors- fibrin forms barrier, thrombin and factor XII promote inflam
Kininogens- convert to kinins by proteases eg. Bradykinin- similar to histamine, promote inflam
What are the limitations of gingival crevicular fluid?
Becomes modified in crevice
Bacteria can metabolise some components
C’, Ig and others partly consumed/degraded in crevice
Up to 1ml fluid may be lost per day in saliva
What are the functions of neutrophils in periodontitis?
Produce neutrophil extracellular traps
Kill microbes by antimicrobial peptides
Neutrophils die in process
Patients w-
< neutrophils have increased perio destruction eg. Cyclic neutropenia
Defective neutrophil function deficiency in cathepsin C have increased perio destruction eg. Papillon lefevre syndrome
Impaired neutrophil function may contribute to perio in diabetes and downs
What are the functions of macrophages in periodontitis?
Stimulate immune response by presenting antigens and releasing cytokines and chemokines (IL-1 and TNF)
Phagocytose
Stimulate fibroblasts and endothelial cells for healing
LPS/IFN-gamma T cells promote monocyte differentiation into activated macrophage
What is the adaptive immune response?
Humoral immunity- B cells
~production of antibodies via plasma cells
Cell mediated immunity- T cells
~immune regulation and cytotoxic T cell killing of virally infected and neoplastic cells
Antigen penetrates epithelium, phagocytosed by macrophages and dendritic cells
Travel to lymph nodes where Ag is presented which present it
T and B cell activation
Antibody secreted in plasma and enters crevice in GCF
Some antibody is produced locally in tissues by plasma cells
Bacteria swallowed and antigens recognised in gut mucosal associated lymphoid tissue so IgA secreted in saliva
What is the role of an antibody in host defence?
Binds to bacteria- acts as opsonin, activates neutrophil enzyme secretion, prevents bacterial attachment, activates C’
Binds to soluble factors- neutralises toxins and inhibits enzymes
What is a periodontal pocket?
Pathologically deepened gingiva sulcus that may occur by coronal movement of gingival margin, apical displacement of gingiva attachment or both
What causes tissue damage in perio disease?
Bacterial products
~endotoxins- damage epithelium/fibroblasts
~bacterial enzymes (eg. collagenases)- break down c. tissue
~LPS, capsular material, peptidoglycans, muramyl dipeptide stimulate immune response
~proteases- bone resorption
Host products
~neutrophils release enzymes
~C’
~macrophages produce IL-1, IL-6, RANKL- bone resorption
~inflam mediators (eg. prostaglandins)- bone resorption
