Pathology + Host Defence Flashcards
Periodontal disease can be classified as?
A host microbial interaction
Non specific plaque hypothesis
Specific plaque hypothesis
What don’t both consider?
Both don’t consider host response
Keystone pathogen theory - what we use now - Certain species have an effect on their environment that is disproportional relative to their overall abundance.
For instance, Porphyromonas gingivalis is shown to be able to manipulate the innate immune system of the host
What causes most of the damage in periodontitis?
Bacteria may trigger host response but it is the HOST RESPONSE that causes most of the damage
What type of conditions are plaque induced gingivitis and Periodontitis
Chronic inflammatory conditions
Therefore display inflammation and atttemps of healing
Demonstrate cardinal signs of inflammation - not all signs have to be present
What are the two types of immunity?
Are they separate?
What do they include?
Which type of cells are of particular importance?
Important cells - γδ T cells
γδ T cells
Where are γδ T cells found?
What do γδ T cells display in host defence and what does this allow?
What is found in the epithelium?
1) Found in gingival tissues especially epithelium
Exist in small numbers
Have cytotoxic and t helper cell functionality
2) γδ T cells display Functional heterogeneity
Allows them to play a role in
1. Immunosurveillance
2. Gingival homeostasis
3) γδ T cells
Label this diagram
What is junctional epithelium?
Don’t need to learn just for understanding !
Part of the gingiva that attaches connective tissue to the tooth surface
What are the three types of epithelium in gingiva?
Oral epithelium
Sulcular epithelium
Junctional epithelium
What is the role of rete pegs?
Where are they found?
They increase the surface area between the epithelium and connective tissue which in turn contributes towards mechanical stability
Found on oral epithelium of the gingiva
Compare the Composition of the epitheliums
Sulcular epithelium
Junctional epithelium
Oral epithelium
Sulcular epithelium AND junctional epithelium -
- fewer strata in epithelium
- distance between connective tissue and surface is short (most apical part of Juncitonal epithelium is approx 3 cells thick)
- adjacent epithelial cells within JE have FEWER desmosome junctions and LARGER intercellular spaces
In the spaces =lymphocytes, neutrophils
- this means there is an aspect of PERMEABILITY (things can go in and out ) - so gingival crevicular fluid can go across epithelium into gingival sulcus and things out can come in
- no cornified or keratin layer
FROM INTERNET FOR UNDERSTANIDING - JE is more permeable than sulcular epithelium, meaning that fluids, immune cells and antimicrobial products are able to enter the oral cavity. However, permeability is bidirectional, meaning pathogens such as bacteria and their products can target this area. This results in the adjacent connective tissue space becoming infiltrated with immune cells such as Neutrophils, Lymphocytes and Plasma cells if disease occurs.
Oral epithelium -
- multiple layers
- cells held close together
- little intercellular space
- Rete pegs
- keratin layer
- THEREFORE BARRIER EFFECT
What layer is :
Oral epithelium?
Sulcular epithelium?
Junctional epithelium?
Oral epithelium - keratinised
Junctional - non keratinised
Sulcular - non keratinised
What does the space between the sulcular epithelium and the tooth contain?
Gingival crevicular fluid
(Originates from gingival tissues - vessels in connective tissues )
Fluid moves out into gingival sulcus
GCF contains immunoglobulins and neutrophils - help maintain health
What happens to the epithelium during the disease?
In response to chronic inflammation, Sulcular epithelium and junctional epithelium begin to adopt characteristics of oral epithelium - host creates a barrier
What are the four stages of lesions that lead to periodontitis?
1) initial lesion
2) early lesion
3) established lesion
4) advanced lesion
Lesions - represent the various stages, from the initial plaque deposits, to gingivitis and eventually periodontitis
Initial lesion
What is it localised to ?
What is there an increase in ?
What cells are present?
What do PMN (Polymorphonuclear neutrophils) do?
24-48 hrs
1) - Localised to gingival sulcus and subjacent periodontal tissue
- some perivascular loss of collagen within the gingival connective tissue
2) localised vasodilation - brings more IgG, complement, fibrin + PMN into the tissues. PMN migration occurs in response to IL-8
THERE IS AN INCREASE IN GINGIVAL CREVICULAR FLUID
3) neutrophils present with Few lymphocytes and macrophages are evident in the junctional epithelium.
4) PMN migrate into the gingival crevice via the junctional and sulcular epithelium.
Early lesion
What occurs in the early lesion?
What happens?
Which cells are present?
GCF flow rate?
4-7 days
1)
- Localised proliferation of Junctional epithelium, and sulcular epithelium
- some loss of collagen subjacent to the junctional and sulcular epithelium
2) vasodilation continues - bringing IgG, complement, fibrin and more PMN into the tissues. PMN migration occurs in response to IL-8 (same as initial lesion)
PMN still present in the crevice and within the periodontal tissue.
Neutrophils present
There is local accumulation of lymphocytes, most of which are T cells.
This is called Early gingivitis
There is an increase in GCF flow rate
Established lesion
What occurs during the established lesion?
What cells present?
GCF flow rate?
2-3 weeks
Proliferation of Junctional epithelium and sulcular epithelium, further loss of collagen within the gingiva, but NO LOA (NO LOSS OF ATTACHMENT ).
New vessel formation
Plasma cells are found adjacent to the vessels and gingival lesion. There is mainly IgG and IgA, but very little IgM present.
Neutrophils present
PMN persist
T cells may dominate the lesion
Maximal increase in GCF flow rate
Advanced lesion
What is advanced lesion?
What occurs here ?
PERIODONTITIS
Pocket formation, LOA, collagen destruction within the periodontal ligament and bone loss
In the advanced lesion of periodontitis, the following characteristics are found;
- Loss of connective tissue attachment
- Apical migration of the junctional epithelium and formation of a true periodontal pocket
- Loss of alveolar bone
An imbalance in the host-microbial interaction heralds the transition from a successful defense to a destructive pathological reaction. There is also a reparative fibrotic response, which becomes more evident with time
GCF, IgG, IgA, IgM, Complement
New vessel formation Plasma cells are found adjacent to the vessels and gingival lesion. There is IgG, IgA, IgM
Neutrophils
Increase in GCF flow
What cell is present in all lesions
Neutrophils
But in advanced lesions the neutrophils form a wall within the juncitonal epitheilium
Do all plaque induced gingivitis convert into periodontitis
NO
Most cases of plaque induced gingivitis do not convert into periodontitis
Factors responsible for progression are unknown - 2 theories :
1. Host response could have changed
2. Change in nature of bacterial plaque
What is complement
Made of around 20 proteins
What are the three different ways complement can be activated
Classical pathway
Lectin pathway
Alternative pathway
What are each of the pathways?
What do they all lead to the production of?
What do c3a and c5a do?
What does c3b do?
What does c5b, c6, c7, c8, c9 do?
Role of neutrophils
Phagocytosis
Activation of bacterial mechanisms
(Respond first in acute inflammation)
What are the stages of neutrophils migrating into cells
Role of macrophages
As macrophages are capable of presenting antigens to T cells what does this promote
Adaptive immune response
In what cells are TLRs present in?
Immune cells
Epithelial cells
PMNs
Macrophages
Dendritic cells
TLR important in innate immmunity
What do TLR assist in
Microbial recognition
What TLR recognise gram negative organisms
TLR4 and TLR5
What TLR recognise gram positive organisms
TLR2 and TLR5
TLR
Which TLRs are found on cell surface and which are found intracellular?
Cell surface
TLR-2, TLR-4, TLR-5, TLR-6
Intracellular
TLR-3, TLR-7, TLR- 9
What are cytokines
What cytokines do macrophage secrete? (5)
What are the local and potentially systemic effects of each cytokine?
Which cause systemic effects (of fever )and local effects ?
Which cytokines are linked to bone resorption
(3)
Adaptive immunity
What are the 2 groups of adaptive immunity
What cells do they contain
Antibodies
What are 3 ways antibodies protect the host?
1) Neutralisation
-by receptors binding to bacterial toxins, leads to ingestion by macrophages
2) Opsonisation
AB can bind to microbial surface directly therefore enables macrophage to recognise microbe - leads to opsonisation and then phagocytosis
3) Complement activation
-non antigen specific AB allow complement to be activated is immune complexes involving IgG and IgM can activate compliment and lead to microbial lysis
Clonal selection
Clonal selection is a fundamental concept in immunology that describes the process by which the immune system selects and amplifies specific lymphocytes
Adaptive immunity - T cells
1) what type of T cells can we have
2) what are T cells either ———— or ———— ?
3) types of t helper cells and what do they do?
4) what do tregs do?
Mutual antagonism
What cells are involved in antigen presentation
Dendritic cell
Macrophage
B lymphocyte
How do t helper cells activate B cells
How do t helper cells activate macrophages
Innate and adaptive work together
How many basal lamina does junctional epithelium have
2
But In periodontitis once starts to be more like oral epithelium - loses ability to form double basal lamina
Neutrophils and macrophages have phagocytic functions
Macrophages also have additional ability to present to T cells
Gamma delta cells in epithelium - precise roles unknown but have functionality of t helper cells and cytotoxic cells
