Pathogenesis Part 1 Flashcards
what type of plaque casues gingivitis
supragingival plaque
swelling =
edematous
redness =
erthema
what type of plaque is involved in periodontitis?
subgingival plaque
what type of immunity is non-specific?
innate immunity- always there
what stages of periodontal disease does BOP occur
bleeding on probing occurs in the early, established and advanced lesion (acute gingivitis, chronic gingivitis and periodontitis)
what stage of periodontal disease does a periodontal pocket form?
advanced lesion-periodontitis
what stage of periodontal disease does cytoplasmic alterations of fibroblasts occur?
early lesion - acute gingivitis
what stage of periodontal disease do white blood cells migrate into the junctional epithelium and gingival sulcus?
initial lesion- clinically healthy
what stage of periodontal disease does the proliferation, apical migration and lateral extension of junctional epithelium occur?
established lesion - chronic gingivitis - 2-3wks
when do the basal cells of the junctional epithelium begin to proliferate?
early lesion - acute gingivitis - 4-7days
what stage of periodontal disease are immunoglobulins (antibodies) present in the connective tissue and junctional epithelium?
established lesion - chronic gingivitis - 2-3wks
what stage of periodontal disease does alveolar bone loss occur?
Occurs histologically in the advanced lesion from periodontitis- greater than 3 weeks
what stage of periodontal disease do lymphoid cell accumulate?
early lesion - acute gingivitis - 4-7 days
what stage of periodontal disease do plasma cell become cytopathologically altered?
advanced lesion- periodontitis
what stage of periodontal disease does the loss of perivascular collagen begin?
initial lesion 2-4 days
what stage of periodontal disease is distant bone marrow converted into fibrous connective tissue?
advanced lesion - periodontitis
When does fluid begin exudation from the gingival sulcus?
initial lesion
what stage of periodontal disease are there periods of quiescence and exacerbation?
advanced lesion - periodontitis
what stage of periodontal disease is there a predominance of plasma cells with out bone loss?
established lesion- chronic gingivitis
what can be stimulated to destroy collagen and ECM?
fibroblasts
what are the 4 types of cells of the innate immune response?
- mast cells 2. acute phase proteins 3. complement 4. PMN’s
what affect does TNF alpha have?
TNF alpha recruits granulocytes to the area of inflammation, induces fever
what affect does histamine have?
histamine dilate and increases permeability of blood vessels
what affect do leukotrines have?
leukotrines dilate small blood vessels, chemotaxis of leukocytes
what affect do prostaglandins have?
prostaglandins increase vascular permeability, regulate the immune response
what is the difference in hyperresponsive, normal, and hyporesponsive groups to periodontitis?
Hyperresponsive - NUG/ refractory perio Normal - clinincally obvious perio, gingivitis Hyporesponsive - group doesnt get periodontitis
what type of immunity is adaptice and specific?
acquired immunity
What types of cells are involved in the acquired immunity?
monocytes/ macrophages lymphocytes
When monocytes/ macrophages are involved what can occur?
if unresolved or resolved chronic inflammation can occur
What can occur if the serum compliment is unable to stop the invasion of bacteria?
acute inflammation recruit PMN’s
What happens if lymphocytes are able and unable to fight an infection?
able - chronic inflammation unable - systemic infection
What type of cell is involved in both the acquired immunity and the innate immunity?
monocytes/macrophages
What two types of cells cause acute inflammation?
neutrophils and serum complement
what is c-reactive protein? what does is do?
C-reactive protein is an acute phase protein. it is produced by the liver and serves to bind lysophosphatidylcholine (on surface of dying bacteria) to activate the complement system. It has a higher affect on heart attacks than LDL!!
What are five types of cells that increase the risk of heart disease?
- c-reactive protein 2. fibrinogen 3. complement 4. namose binding protein 5. metal binding protein
what activates the serum complement?
complement is activated by antigen-antibody interaction
What % of normal proteins in blood is the serum complement?
10%
Where is the complement made? and by what?
the liver, small intestine made by mononuclear cells
What type(s) of complement cause inflammation? What do they do?
C3a and C5a -the release of mast cell mediators = increased permeability of blood vessels and phagocytes can enter tissues
What part of complement forms an antibody coat over the bacteria?
C3b - forms antibody coat (opsinization)- helps to internalize the bacteria faster
what is the alternative pathway(non-specific) for complement activation/ cleavage?
endotoxins, IgG cleave C3 into C3a and C3b
what is the half life of PMN’s?
5-90 hours
How do PMN’s adhere to the endothelium?
via selectins, adhesins- ICAM and ELAM
Diapedesis
process of squeezing through endothelium
Chemotaxis
directed movement to an increase concentration
What affect does NADPH oxidase have? When is it activated?
increase in NADPH oxidase activity on surface of cells and granules helps to phagocytize bacteria. Activated in respiratory burst
PMN’s are attracted to what?
F-MLP (formyl methionine, leucine, phenylalanine) bacterial cells have this- released as bacteria turn over
What are secondary granules?
specific granules -lysosyme, NADPH oxidase, collagenase, lactoferrin
What are primary granules?
azurophilic granules -myeloperoxidase, deffensins, elastase, cathepsin
explain the process of rolling
PMN’s slow down and roll on membrane, grab onto adhesins / ICAM on endothelium and the leave the blood via diapedesis and undergo chemotexis and then phagocytize bacteria.
epitopes on bacteria cells bind to?
the FAB region of antibodies
macrophages are long lived cells that are involved in what type of immunity?
both innate and acquired immunity
are PMN’s antigen presenting cells?
No but macrophages, dentritic cells, and plasma cells are
the interaction of LPS with macrophages with endotoxins results in the release of what?
- PGE2 2. TNF alpha 3. IL-1- beta 4. MMP’s
what molecules of complement are most typically associated with acute inflammation?
C3a and C5a
what is true about the IL-1 gene polymorphism?
it can be used as a measure of susceptibility for periodontal disease in some patient populations
the initial microbial infection is primarily accomplished by what?
- antigen-antibody response 2. complement 3. mast cells 4. PMN’s
c-reactive protein is what type of protein? What part of the immune response is it part of?
-acute phase protein -innate immune response
chemokinesis
movement of cells due to chemical or physical stimulation
chemotaxis
a specialized type of chemokinesis that is the directed movement of cells towards an increasing chemical gradien
the chemotractant that results from the proteolytic breakdown of complement is?
C5a
c-reactive protein present in the blood is indicative of what?
inflammation of the whole body
what purpose does c-reactive protein serve in the innate immune system?…. it binds to what?
it binds to lysophosphatidylcholine (on surface of dying cells) to activate the complement system
what enzyme activates complement?
c3 convertase enzyme
where is complement produced? by what?
the liver and small intestine by mononuclear cells
how is complement activated in the alternative pathway?
by LPS, endotoxins, aggregated IgG
what is a virulence factor that helps bacteria avoid opsonization?
hydrophilic bacteria
opsonization is activated by what complement product?
c3b
What does the complement particle C3a bind to and do?
C3a binds to the mast cell which releases TNF alpha which causes IL-8 to alter the endothelial surface = vasodilation
PMN’s express’s __________ Endothelium express’s ________
PMN’s- selectins Endothelium- Adhesions/ ICAM
complement causes vasodilation through what?
cytokine - IL-8 alters the endothemial surface - caused when C3a binds to a mast cell
what is an example of an end cell?
PMN
tertiary granules
cathepsin and gelatinase
how does the membrane attack complex in complement work?
creates holes in the membrane of bacteria ex- chlorahexadine
what are the chemotractants for PMN’s from macrophages/ monocytes?
leukotrine B4 IL-8
what are the chemotractants for PMN’s from serum/ plasma (proteolytic breakdown of complement)?
C5a
what are the chemotractants for PMN’s from bacteria?
f-met peptides
what are the chemotractants for PMN’s from mast cells?
neutrophil chemotactic factor
what are the chemotractants for PMN’s from the endothelium?
endothelial IL-8
what are the chemotractants for PMN’s from B-cells and macrophages?
IL-1
what response is the preferred method of killing for PMN’s?
oxidative response via NADPH oxidase
what enzymes are involved in the oxidative response of PMN’s?
- NADPH oxidase 2. cytochrome B 3. myeloperoxidase
What are the products of the respiratory burst?
- HOCL (hypochlorous acid) 2. H2O2 (hydrogen peroxide) 3. O2 -
what causes the green color of pus in infections?
myeloperoxidase
what are proteas inhibitors?
stop enzymes when dumped into connective tissue.
what causes frustrated phagocytosis?
HOCL can neutralize the protease inhibitors - mass tissue destruction
what is the inside structure of a plasma cell?
rough ER and large golgi apparatus to produce large amounts of antibodies (proteins)
what are epitopes? where are they located?
antigenic determinants present on the surface of bacteria
how do antibodies bind to bacteria?
antibodies bind with the FAB region to the Epitope.
PMN’s recognize what region of the antibody?
FC
what antibodies are present in the mouth?
IgG and IgA
how does IgG get into the mouth?
leaked into mouth by gingival crevicular fluid - but it is broken down easily
what antibody can cross into the placenta?
IgG
what are the functions of IgG?
opsonization, agglutination, complement fixation
what antibody makes up the majority of antibodies in the body?
IgG - 80-85%
IgA function?
protect mucous membranes by preventing the attachment of organisms. ex actively secreted by salivary glands - has the J chain to stabolize
functions of IgM?
opsonization, agglutination, complement fixation
first antibody produced during an immune response?
IgM
function of IgD?
facilitates development and maturation of the antibody response. located on the surface of B-cells
IgE function?
release granule contents in response to allergic reactions and parasitic infections
function of the J-chain in IgA?
interacts with the FC fragments of IgG molecules by disulfide bonds to help stabilize it
function of the secretor component of IgA?
provides protection against degradation enzymes in the digestive system
is the host in control in a systemic exposure?
no
what is the systemic response?
B-cell and interlukins
what is the monoclonal response?
antibodies produced to only 1 bacteria like Aa
polyclonal response
antibodies produced by B-cells to lots of different antigens
is LPS produced from gram (-) or (+) bacteria
gram (-) negative
the myeloid stem cell gives rise to what 5 things?
- PMN’s 2. Eosinophils 3. Basophils 4. Mast Cells 5. Monocytes (macrophages)
where are mononuclear phagocytes located?
all tissues of the body
half life of macrophages?
months- can reenter tissue and then back into circulation
2 roles of macrophages?
- take up microbacteria and neutralize it 2. scavenger role
which can be used multiple times, PMN’s or Macrophages or both?
only macrophages, PMN’s are end cells
what is the scavenger role of macrophages?
search for foreign cells and dead cells and phagocytize it
LPS stimulated what receptor of macrophages?
CD14 receptor of macrophages
the CD14 receptor of macrophages releases _______ which causes extracellular matrix destruction
MMP’s
fibroblasts can secrete _______ which leads to alveolar bone resorption
PGE2
what exposes the peptide fragments of the antigen on the macrophage?
major histocompatibility complex 2 - presents antigenic peptide on the surface
LPS stimulated what receptor of macrophages?
CD14 receptor of macrophages
the CD14 receptor of macrophages releases _______ which causes alveolar bone resorption
PGE2
the CD14 receptor of macrophages releases _______ which causes fibroblasts to activate negatively
IL-1 beta and TNF alpha
the CD14 receptor of macrophages releases _______ which causes extracellular matrix destruction
MMP’s
fibroblasts can secrete _______ which leads to alveolar bone resorption
PGE2
what exposes the peptide fragments of the antigen on the macrophage?
major histocompatibility complex 2 - presents antigenic peptide on the surface
helper T-cells and MHC 2 present the antigenic fragments to what?
b-cell - to create more b-cells and to create plasma cells
what are conditions that lead to monocyte deregulation?
diabetes and smoking
what is collagenase and where is it present?
present in fibroblasts and it break down tissues
what are MMP’s dependent upon?
manganese and magnesium ions (divalent cations)
what are TIMPS
tissue inhibitors or metalloproteases - inhibit MMP’s
how long does connective tissue take to repair?
6 weeks
60 year old patient with untreated periodontitis for whole life, how much attachment loss?
60 -20 years (adults dentition) = 40 years thus 4mm of attachment loss ideally
what causes macrophages to release lots of collagenases?
IL-1 and endotoxins
what is collagenase and where is it present?
present in fibroblasts and it break down tissues
purpose of scaling and root cleaning?
remove diseased cementum and restore the junctional epithelium
how fast does the epithelium grow?
1mm per day ( 0.5 mm per side of the circle)
how long does connective tissue take to repair?
6 weeks
the primary cell involved in the non-pathogenic breakdown of collagen in the gingiva is the _______
fibroblast
