4. Pathology + Host Defence Flashcards
1
Q
LOs + EXTRA READING
A
Ten Cate’s Oral Histology - E-Book : Development, Structure, and Function, 9th ed 2018; Chapter 12, p283 and Chapter 9, p206
A Clinical Guide to Periodontology. Palmer, Richard; Ide, Mark; Floyd, Peter.
3rd ed. London : British Dental Association, 2013
[Carranza’s Clinical Periodontology. M. Newman, H. Takei DDS, F. Carranza
• Several relevant chapters for a more detailed account of the host response]
2
Q
HOST MICROBIAL INTERACTIONS
A
- whilst the bacteria may trigger the host response, the host response is actually what accounts for a lot of the damage that occurs during periodontitis
- plaque induced gingivitis + periodontitis are both chronic inflammatory conditions + therefore display inflammation as well as attempts at healing
- not all signs have to be present to establish that inflammation is present
3
Q
2 types of immunity?
Make more Q’s????
A
- both operate together
- both maintain healthy + help to prevent disease
4
Q
The gamma delta T cell subsets display functional heterogeneity
What does this enables them to do?
A
- enables them to play a role in immunosurveilance and gingival homeostasis
5
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A
EXTRA INFO
- dentogingival junction more closely, see tooth on far right, soft tissue on left
- no enamel in this section as it is a decalcified section
- during processing the enamel cap is lost
- epithelium is functioning as a barrier
- sulcular + junctional epithelia - relatively fewer strata within epithelium, distance from connective tissue + surface is relatively short
- most apical point of junctional epithelium may only be 3 cells or so in thickness
- adajacent epithelial cells, within junction epithelium, there are relatively fewer desmosomal junctions and relatively larger intercellular spaces
- within those spaces, often additional cells (eg neutrophils , lymphocytes
- within space between tooth + sulcular epithelium, there is gingival crevicular fluid (GCF), originating from vessels within the connective tissues
- fluid moves across the connective tissue out into the gingival sulcus + the contents of the blood vessels (immunoglobulins, neutrophils, etc) are helpful in maintaining health
- junctional epithelium is unusual as not just 1 basal lamina between the connective tissue + epithelium, there is also a basal lamina on the surface - enables junction epithelium to attach to tooth surface via demihesmidomes
- this functionality is believed to be connected to the relative immaturity of the junctional epithelial cells - immaturity is maintained by relatively high cell turnover - much higher than occurs in oral epithelium
- Additionally within connective tissue, have highly ordered + structured fibre systems
- well defined fibre bundles from the tooth into the gingiva and from the alveolar crystal bone into the gingiva - all part of the gingival fibre system
- in between fibres have proteoglycans + GAGs - all help to maintain tissue turgidity
- hence functional integrity of this junction (between the junctional epithelium + tooth) via relatively weak hemidesisomes, is reinforced by the functional integrity of the fibre system within the gingiva + the proteoglycan content between the fibres
- interface between the oral epithelium and the underlying connective tissue - is clear that interface is complicated by presence of rete pegs
- rete pegs increase the SA between the epithelium + connective tissue + contribute to mechanical stability
- if we have a loose at the junction epithelium + sulcular epithelium, it is clear that there is no rete pegs here hence that interface is relatively flat
- whilst on oral epithelial side, have multiple layers + cells held together closely with very little intercellular space and keratin layer on surface - all of these features ate consistent with a the barrier effect
- if we have a look at the sulcular junction epithelial side - have relatively shorter distance from connective tissue to surface, larger intercellular spaces + fewer desmisomal junctions across adjacent cells
- this is not compatible with the barrier effect BUT rather permeability
6
Q
Read through info (know???)
Cont. from last card
A
- GCF passage across the epithelium into that gingival sulcus is allowed BUT also things from outside can come in
- also no cornfield layer on the sulcular or junctional epithelium side
- as plaques accumulation extends + biofilm develops, there are changes in the relationship between the tissues
7
Q
Read through info (know???)
Cont. from last card
A
- changes in relationship between tissues when plaque accumulates
- far left = healthy tissue with enamel cap drawn in
- far right = changes that tend to occur as a result of bacteria on the outside
- shows slide where there is chronic inflammation
8
Q
Read through info (know???)
Cont. from last card
A
- ## in response to chronic inflammation sulcular + junctional epithelium have started to adopt features of the oral epithelia - (the host is creating a barrier) - although the Barrier is not successful in it’s entirety as there are ulcerated areas
9
Q
Read through info (know???)
Cont. from last card
A
- as a consequence of the of that infiltration, the highly ordered, highly structured fibre system is disrupted
- as that chronic inflammatory process continues in periodontitis, the fibre structure is completely destroyed + replaced with lymphocytes
- the histopathology of periodontal disease may be divided into initial, early, established + advanced lesions based on studies of experimental gingivitis in humans + periodontitis in animals
- an established lesion can persist for many years + a change to an advanced lesion, marks the transition from a chronic + successful defence to a destructive immune pathological mechanism which is periodontitis
- majority is plaque induced gingivitis
- most plaque induced gingivitis does not convert to periodontitis - only tiny minority of cases where that happens
- the factors responsible for the progression are unknown
- 2 theories
- host response may have changed
- or change in nature of bacterial plaque
- neutrophils are present through all these lesions (early, advanced, etc)
- what’s diff about advanced lesions is that neutrophils have a specific location - (effectively form wall of neutrophils within the junctional epithelium - unusual feature)
- in established lesions, within connective tissue - predominantly T-cells
10
Q
A
- complement = group of approx 20 proteins that function in a cascading process
- in each stage in process, a protein, is broken into a big and small bit
- the big bit contributes towards the formation of the membrane attack complex - which is used to kill bacteria
- small bit - often has some additional biological function
11
Q
3 complement activation pathways?
A
- classical pathway
- lectin pathway
- alternative pathway
12
Q
COMPLEMENT ACTIVATION PATHWAYS
-what is involve?
What do they all form?
Make Q’s
A
- at end membrane attack complexes are formed
13
Q
Alternative pathway steps after C3 convertase is formed?
A
14
Q
A
- research suggests neutrophils play a role in chronic inflam not just acute inflam
- they’re good at phagocytosis + activating bactericidal mechanisms, they can also control T-cell adaptive responses, effectively suppressing T-cell function + promoting humoral responses
- shows electron micrographs of neutrophil
15
Q
How do neutrophils work?
A
- cytosol is packed full of electron dense granules - that contain a n.o potent components
- capable of lysing bacteria
- lysozymes + matrix metalloproteinases - that can break down tissue components
- since these cells have very defined cytoskeleton, they are able to move around well
- there are a number of cell adhesion molecules that help in the process of extravasating
- the top part of diagram shows the role of e-selectin expressed on endothelial cells
- and how they can promote the rolling of neutrophils
- the interaction od s-lex + e-selectin is not sufficient to stop the neutrophil
- tight binding can only take place if additional cell surface cell adhesion molecules are produced
- ICAM-1 inter acting with LFA-1 is required to stop the neutrophil and signpost the exit point
- adjacent endothelial cells can separate, allowing the neutrophil to pass between 2 adjacent cells = process known as transmigration
- important role for IL-8 (also known as CXCL8R) = cytokine that has chemotactic properties + recruits neutrophils
- chemokine IL-8 promotes endothelial cell expression of ICAM-1 - which facilitates binding of LFA1-2, ICAM-1 and therefore the transmigration of the neutrophils
- another mechanism of getting across from inside of vessel = through one endothelial cellular process known as trans cellular transmigration
16
Q
A
- also have macrophages
- these cells are capable of producing a wide range of proteolytic substances as well as cytokines
- they circulate as monocytes within vessels
- once exit vessels and enter tissues = macrophages
- on entering tissues they can be activated + their cell size can therefore double
- their cell size can increase dramatically upon activation
Why have neutrophils and macrophages if they both have phagocytic function?
- macrophages have advantage of being able to present antigens to T-cells
- therefore promoting adaptive immune responses
- macrophages also have receptors for lipopolysacharide (CD14) also express TLR4 - important in recognising gram negative organisms
- TLR4 in combo with CD14 (LPS receptor) facilitates the recognition of pathogens
- they can also phagocytose components of bacteria and break down them down in phagolysosomes (similarly to neutrophils)
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22
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Active immunity
- 2 major groups?
- what cells they involve?
A
- very small group of gamma delta T-cells that don’t act like typical T-cells
23
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A
24
Q
3 diff ways antibodies can assist in protecting host?
What happens in each?
A
- neutralisation
- opsonisation
- complement activation
- immune complexes involving IgG + IgM can activate complements + lead to
- not all classes of antibodies can lead to complement activation - IgA + IgD do not
25
Q
A
- at any one point of time, there is not enough lymphocytes capable of recognising the antigens of importance (antigens challenging host ) therefore, specific Clones capable of recognising foreign antigen need to be amplified
- this is clonal selection + clonal proliferation
- so we end up with a large enough pool of relevant lymphocytes capable of turning into effector cells + eliminating antigen
26
Q
ADAPTIVE IMMUNITY
What T-cells are involved?
A
-
27
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A
28
Q
A
- dendritic cells, macrophages + B lymphocytes all of have common func of antigen presentation
- dendritic cells can present antigens with minus processing
- b-cells and acrophobia require more processing when antigen presenting
29
Q
A
- for an adaptive immune response, only need to involve either a T-cell + macrophage OR T-cell + B-cell or dendritic cell
- nature of antigen presenting cells is important
- upper row = macrophage engulfing + processing antigen and re pressing with MHC class II - this is required in order for T-helper cells to recognise the antigen
- lower image = antibody on B cell surface recognising antigen
- can be endocytosed, chopped up + antigen is reexpressed on cell surface with MHC class II
- there is then a diff in the nature of the antigen recognised by the antibody
(FOR T-cell recognition that is not the case)
30
Q
A
- for an adaptive immune response, only need to involve either a T-cell + macrophage OR T-cell + B-cell or dendritic cell
- nature of antigen presenting cells is important
- upper row = macrophage engulfing + processing antigen and re pressing with MHC class II - this is required in order for T-helper cells to recognise the antigen
- lower image = antibody on B cell surface recognising antigen
- can be endocytosed, chopped up + antigen is reexpressed on cell surface with MHC class II
- there is then a diff in the nature of the antigen recognised by the antibody
(FOR T-cell recognition that is not the case)
31
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A
- T-cell requires association with MHC class II so antigen can be recognised by antibodies
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33
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KEY POINTS SUMMARY 1
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34
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KEY POINTS SUMMARY 2
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35
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KEY POINTS SUMMARY 3
A
36
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KEY POINTS SUMMARY 4
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