Host Responces Flashcards
what are the cells involved in bone loss?
- Osteoclost
- Osteoblast
- fibroblasts
- Macrophage.
what is the function of Osteoclasts?
bone resorbing.
what is the function of osteoblast?
bone forming
what is thefunction of fibroblasts?
form and maintain collagenous matrix.
what is the function of macrophages?
active member of the tissues defense.
what do monocytes form one they have fused together?
osteoclasts.
what growth factors control monocytes?
RANKL
what cells produce RANKL?
Osteoblasts.
how does RANKL bind to a monocyte?
binds to a specific receptor on the monocyte membrane.
how do osteoclasts degrade bone?
through pumping protons (H) ito the adjacent bone to dissolve mineral and then potent enzymes (Cathepsin K) to break down bone matrix,
what is the function of Cathepsin K?
to break down bone matrix.
what is meat when the bone is dynamic?
it responds to changes in loading - so that the ratio of bone formation / removal is dependent on the applied stress.
what is bone removal/ formation dependent on?
the applied stress.
what cells mediate bone removal/formation? and how?
osteoblasts.
via the production of RANKL.
How is stress in bone detected? (both directly and indirectly)
directly = by osteocytes and osteoblasts detecting it mechanically
indirectly - macrophages which respond to loading by producing cytokines (IL-1)
what does the production of IL-1 increase?
increases the production of RANKL by osteoblasts.
what exogenous plaque bacterial derived materials can cause bone destruction?
lipo-polysaccharide LPD.
What are the effects of plaque to bone loss?
- LPD (plaque bacteria derived materials) act on osteoblasts - increasing production of RANKL.
- LPD causes macrophages to increase IL-1 production.
what are the effects of IL-1 increase to bone loss?
- triggers fibroblasts to produce IL-1
- stimulates fibroblasts to produce IL-6
- acts on fibroblasts to produce collagenase
- act on osteoclasts to up-regulate Cathespisin K production.
what are the effects of IL-6 in bone loss?
increases the effectiveness of RANKL.
what are the effects of Cathepsin K production in bone loss?
increases the effectiveness of individual cells in degrading bone matrix
what are some examples of local factors in perio disease?
- anatomical factors (morphology, PRS, enamel pearls etc)
- Pt habits (mouth breathing, smoking)
- latrogenic factors (ortho appliances +denture, restorations)
- microbiological factors (colonisation of crevice+root surface.)
- pre-existing deposits and disease.
what are some examples of systemic factors in perio disease?
- environmental factors + metabolic factors (drugs, gingival overgrowth, sex hormones, diabetes)
- Genetic /inherited factors (down symdrime, papillon lefevre sysdrom, hypophatasia, ehlers-Danlos syndrome)
- Behavioural (smoking)
- Lifestyle (stress)
- Haemoatological (Chediak-Higashi, Neutropenia, Leukaemia)
what effects can having diabetes cause in regards to perio disease?
- increase susceptibility to perio disease - related to level of glucose control.
- decreased neutrophil function
- decreased collagen synthesis
- increased collagenolytic activity
- increase periodontal pathogens in sub-gingival biofilm
Perio disease can also effect diabetic control.
what are the effects of down syndrome in regards to perio disease?
- increase susceptibility due to defect of neutrophil chemotoxis.
- Oh is poor and they tend to be mouth breathers.
what are the effects of Papillon Lefevre syndrime in regards to perio disease?
- defect of neutrophil chemotaxis and phagocytosis.
- rapid perio destruction.
what are the effects of Ehlers-Danlos syndrome in regards to perio disease?
- disorder of collagen formation.
- Type 8 associated with severe perio distruction
- hyperextensible skin etc
wwhat are the effects of hypophatasia in regards to perio disease?
- low levels of enzyme alkaline phosphatase
- defective mineralisation and formation of cementum
- teeth exfoliate and get rickets.
what are the effects of smoking in regards to perio disease?
- result in fibrotic gingivae with rolled margins
- increase pockets / recession anteriorly, bone loss, calculus, furcation.
- decrease in gingival bleeding and BOP.
- effects composition of bacterial flors, increasing cytokine release and so increasing the destruction of matrix.
what are the effects of stress in regards to perio disease?
- depresses immune system.
how does an individual get chediak-Higashi?
through genetics.
what are the effects in the mouth of acute leukaemias?
- slightly like gingival overgrowth.
- gingival swelling, excessive random bleeding, and gngival ulcerations.
what age group is most likely to be effects by Actue leukaemias?
under 20’s - often children.
what age group is most likely to be effects by chronic leukaemias?
older age groups.
what are the 3 histopathological stages of gingivitis?
- Initial
- Early
- Established.
what are the initial features of plaque-induced gingivitis?
- inflammation begins 24/48 hours after plaque accumulation begins.
what are the effects of inflammation during initial gingivitis?
causes vasodilation of tissues and causes an increas
how soon after plaque accumulation starts does inflammation begin?
24/48 hours.
what happens after approx 1 week after plaque accumulation?
- increase inflammatory infiltrate
- increase lymphocytes/ macrophages/ neutrophil migration.
- fibroblasts start to show sign s if cell damage.
- early loss of gingival collagen
- gingival swelling, resulting in deepening of the gingival crevis.
- rete peg proliferation
when do fibroblasts start to show signs of cell damage?
during early gingivitis (after 1 week of plaque accumulation)
what happens to the PDL during established gingivitis?
- increases inflammatory infiltrate (alot of plasma cells)
- PMN (neutrophils) predominates
- fibroblasts start to show signs of cell damage
- early loss of gingival collagen (but no loss of connective tissue)
what % of plasma cells make up the inflammatory infiltrate in established gingivitis?
10-30%
in what stage of peio disease do fibroblasts start to show signs of cell damage?
- during established gingivitis.
what happens to the PDL during periodontitis?
- inflammatory infiltrate extends
- plasma cells dominate (over 50%)
- loss of perio connective tissue attachment
- perio pockets.
- alveolar bone loss.
how is tissue damage in the epithelium during perio diseas?
- bacterial enzymes cause damage to keratinocytes.
- release of enzymes from neutrophils cause damage to keratinocytes.
-complement activation can cause cell dmaage.
-
how is tissue damage i connective tissue during perio disease?
- bacterial toxins are toxic to fibroblasts
- bacterial enzymes cause degradation of extra-cellular matrix components.
- enzymes from neutrophils cause break down of extra-cellular matrix component.
- complement activation causes damage to fibroblasts.
production of IL-1 +TNF increase secretion of collagenase + proliferation by fibroblasts. - ## production of TGfb and PDGF causes stimulation of fibroblast chematoxis.
what are some examples of bacterial -derived bone resorbing agents>?
- capsular (from Aa)
- Lipopolysaccharides
- Lipoteichoic acids
- Actinomyce resorbing factors
- Peptidoglycan
- Muramyl dipeptide
- bacterial lipoproteins
what are host derived cytokines that are bone resorbing agents?
- IL-1
- tumour necrosis factor (TNF)
- transforming growth factor beta
- platelet derived growth factor
- IL-6
what are other host0derived bone resorbing agents (thats are not cytokines)?
- Prostaglandins
- Leukotrienes.
what are some kep features of periodontal breakdown?
- apical migration of epithelium
- breakdown of PDL
- bone resorption.
In periodontitis what % of the cells are plasma cells in the inflammatory infiltrate?
over 50%
what are the effects of Perio tx after 1 week?
- reduction of neutrophils in gingival crevice
- inflammatory infiltrate starting to diminish
- reduction in gingival swelling
- some pocket epithelial lining will begin to heal
- begin to get fibroblast proliferation
what are the effects of perio tx after 1 month?
- maybe evidence of gingival recession
- new fibroblast tissue forming
- inflammatory infiltrate diminishing
- long epithelial attachment beginning to form
- alveolar bone re-models by not regeneration coronally.
what are the effects of perio tx 3-6 months after?
- lesion can become stable
- healing could result in recession
- only small number of neutrophils in gingival crevice
- junctional epithelial re-established with formation of long epithelial attachment.
- gingival connective tissue is mature with minimal inflammatory infultrate
- bone remodelling almost complete.
what are the clinical signs of healing of perio disease?
- reduced probing pocket depths
- reduced bleeding on probing
- gain in clinical attachment (reduced mobility)
- maybe recession
- possible bony infil in angular defects.
How does saliva protect us against microbial plaque?
- has antimicrobial effects: peroxidase / phothiocyanata / lysozymes / lactoferrin / antibodies (IgA)
what does the gingival epithelium consist of?
- oral sulcular epitherlium
- junctional epithelium
- oral gingival epithelium
what type of protection does the gingival epithelium give?
physical barrier.
what is the function of the inflammatory response?
- dilute (by increasing crevicular fluid)
- wall off (inflammatory cells)
- destroy/ damage pathogens (inflammatory cells)
what cells are involved in the inflammatory response?
- Neutrophils
- Macrophages.
what do neutrophils do to bacteria in a plaque matrix?
attach and secrete antibacterial enzymes that kill bacteria and dissolve plaque matrix.
what do neutrophils do to unattached bacteria in the mouth?
- phagocytosis
what is the function of a macrophage in inflammation?
- phagocytosis
- secrete tissue-degrading enzymes
- secrete complement components
- secrete mediators (IL-1 ad TNF)
what is the function of a macrophage in immunity?
- process and prevent antigens
- secrete IL-1
what is the product of degranulating neutrophils in the sulcus?
leukotriene B4 in GCF
what is the process of the humoral immune response?
B cells undergo proliferation into plasma cells that secrete Ig.
what cells are involved in the cell mediated immune response?
T cells that are either T helper cells, or T cytotoxic cells.
Oncean antigen enters the body how does it get carried to the lymph nodes?
via macrophages
what % of antibodies produced are from the IgG family?
75%
what are the functions of antibodies?
- bind to bacteria (inhibitig attachment)
- binding to soluble factors (neutralizing toxins, inhibiting enzymes)
what are the defects in out host responses?
- reduced neutrophil number
- defective neutrophil functions (in some patients with conditions eg down syndrome, diabetes)
what are the effects of HIV on perio?
reduction in the number and function of T helper cells - so more susceptible.
what medication are aid in perio disease?
- Histamine + Bradykinin
- Cytokines
- Prostaglandins
- Metalloprotienases
what is the function of Histamine and Bradykinin?
vasodilation, they increase vascular permeability.
what is the function of cytokines?
they are soluble proteins that are secreted by cells. They transmit signals, and coordinate inflammatory and immune responses.
- amplify inflammatory responce (eg IL-1)
what is the function of prostaglandins?
produced from arachidonic acid in the cell membrane of inflammatory cells, they cause capillary dilation, endotherthial permeability and can cause bone resorption.
what cells produce metalloproteinsases?
fibroblasts, monocytes and neutrophils.
what is an example of a metalloproteinsase?
collagenase, gelatinase.
what happens during a Type 1 hypersensitivity reaction?
- IgE binds to common harmless antigens.
- narrowing airways
what happens during a Type ll hypersensitivity reaction?
- small molecules bind to cell surfaces and modify thier structure.
- then IgG binds to that
- Can be cause by drugs.
- can result in activation of complement, phagocytic cell or NK cells.
- can result in anaemia or abnormal bleeding.
what happens during a Type lll hypersensitivity reaction?
- soluble antigens + mediated by IgG
- antibody + antigen cluster together. This triggers immune effector functions and cells - causing tissue damage and pathology.
- smaller complexes are deposited on blood vessel walls attracting complement and leukocytes causing damage to blood vessels and tissues.
what happens during a Type lv hypersensitivity reaction?
- delays reaction
- mediated by antigen-specific effector T cells.
- foreign molecules will bind to host proteins, altering their structure and making them look different so they will be seen as foreign and nonself by the immune system.
why does autoimmune disease develop?
- genetic susceptibility
- Tolerance breakdown
- infection/ environmental exposure.
how can infections trigger autoimmunity?
- damage to a cell or tissue barrier.
- releasing perviously sequestered self antigens, rendering them accessible to self-reactive lymphocytes that may exist.
what is molecular mimicry?
where a pathogen may produce a molecule that resembles a host protein. Them once in the immune system and raised an immune response, the effector cells and antibodies produced may then recognise and attack the similar host structures.
what is organ specific autoimmune disease?
tissue damage is limited to the few organs that express the target autoantigen
what is an example of organ specific autoimmune disease?
Type 1 diabetes.
what is systemic autoimmune disease?
tissue damage that can happen at multiple site i the body - wherever the autoantigen is present.
what is an example of a systemic autoimmune disease?
Rheumatoid Arthritis
Systemic Lupus erythemastosus (SLE)
what cells does HIV-1 kill?
CD4 positive cells (T-Helper Cells)
How can opportunistic infection kill due to AIDs?
- CD4 levels have dropped below critical level - immune system collapses and pt has AIDs
- so opportunistic pathogens will cause severe disease.
why without any tx will HIV result in AIDs?
- CD4 cells are needed to control infection.
- antibodies produced in an immune response dont bind well to intact virus particles of infected cells
- HIV rapidly mutates, so they can escape recognition.
why is HIV drug resistant?
rapidly mutates.
but can be successful if taken in combinations.
what is the anti-HIV drug? and when does it need to be taken?
PEP.
needs to be taken up to 73 hours post exposure.
where in the mouth is HIV most likely to be found?
in GCF
what happens to the rate of HIV in GCF during perio disease?
increases.
Why in saliva is HIV non-infectious.
because saliva contains anti-HIV factors that block it from being infectious.
what id found in saliva that meant HIV non-infectious?
- Mucins - clump viral particles together.
- Mucins and agglutinin - may strip HIV of gp120.
- Secretory Leulocyte protease inhibitor produced by salivary glands binds to T helper cells and blocks HIV-1 gaining access and infecting the cell.
