Perio/Immunology/Research Flashcards
Prevalence and severity of periodontal disease
Gingivitis of varying severity is almost universal in children and adolescents
Prevalence of severe attachment loss is less than 1% in young patients
Epidemiology of gingivitis
Developed countries 73% of children 6-11 years old
Gingivitis prevalence rises with age
Prevalence rises with puberty
Less in girls than boys (likely related to oral hygine)
Normal pediatric periodontium features
Smooth, slightly stippled surface
Sulcus depth 2mm average
Rounded or rolled contour
Firm and resilient tissue
Is attached gingiva in adults or children narrower?
Children
Wider in the maxilla
Gingiva is more red compared to adults due to thinner epithelium
PDL in children versus adults
Wider in children
Less dense and fewer fibers per unit area
Increased hydration with greater blood and lymph supply
Cementum in children versus adults
Thinner and less dense than adults
Tendency to hyperplasia
Alveolar bone in children versus adults
Lamina dura is thinner
Fewer trabecular and large marrow spaces
Smaller amount of calcification
Greater blood and lymph supply
Dental Plaque Induced Gingivitis in Pediatric Population
Less severe than in adults with similar plaque levels
Gingival inflammation without loss of attachment or bone
Reversible
Contributing factors: crowding, ortho, mouth breathing, eruption, calculus
Chronic periodontitis adults versus children
More common in adults
Overview Aggressive Periodontitis
Localized or generalized
Rapid attachment and bone loss with familial aggregation
PHagocyte abnormalities and hyperresponsive macrophage phenotype
Definition of Localized Aggressive Periodontitis
Interproximal attachment los on at least 2 permanent first molars and incisors with attachment loss on NO more than 2 teeth other than first molars and incisors
Features of LAgP
No evidence of systemic disease Can be associated with chromosome 4 gene Inflammation not prominent feature Children otherwise healthy More in African Americans
Bacteria in LAgP
Actinobacillus actinomycetemcomintans
Bacterioides-like species
Eubacterium in some populations
Functional defects in neutrophils - Susceptibility to LAgP
- anomalies in chemotaxis
- anomalies in phagocytosis
- anomalies in bactericidal activity
- anomalies in superoxide production
What is a molecular marker of LAgP?
Low numbers of chemoattractant receptors
Low glycoprotein GP-110
Adherence receptors on neutrophils and monocytes like LFA-1 and MAC-1 are normal
Treatment for LAgP?
Surgical and-nonsurgical root debridement
Antibiotics (tetracyclines, tetracyclines + metronidazole, metronidazole + amoxicillin)
Maintenance every 4 months
Generalized Aggressive Periodontitis
Marked periodontal inflammation with heavy accumulation of plaque
Consequences of GAgP
Severe generalized attachment loss
Premature exfoliation of primary teeth
Presence in gingival clefts and severe recession
Suppressed chemotaxis in neutrophils
What antibody has alterations in patients with GAgP?
IgG
Microbes of GAgP
Non-motile, facultative anaerobic gram negative rods
P gingivalis, T denticola
Treatment of GAgP
Use of antibiotics and debridement is not very successful
Lab test to identify specific pathogens
Features of periodontitis as a manifestation of systemic disease
Occurs with erupting of primary teeth up to age4-5
Localized or generalized
Neutrophils have abnormalities in surface glycoproteins
Leukocyte adhesion deficiency
Bacteria include AA, P intermedia, Eikenella and others
Syndromes associated with periodontitis
Papillon-Lefevre Hypophosphatasia Cyclic neutropenia Down syndrome Leukocyte adherence deficiency Agranulocytosis
NOT diabetes
Areas endemic for necrotizing periodontal disease
NPD is seen with greater frequency in certain populations of children and adolescents from Africa, sia, and South America (developing areas)
2 most significant findings in necrotizing periodontal disease
Presence of interproximal necrosis and ulceration
Rapid onset o gingival pain
Bacteria in necrotizing periodontal disease
Spirochetes
P intermedia
Causes of necrotizing periodontal disease
Viral infections Malnutrition Emotional stress Lack of sleep Systemic diseases
Treatment for necrotizing periodontal disease
Local debridement, oral hygiene instructions, follow up
Antibiotics (metronidazole and penicillin) only if patient is febrile
Which organ is important in immune system function that decreases in size?
Thymus
Innate Immunity Components
Skin Phagocytes Complement NK cells Macrophages Antigen-presenting cells
Adaptive Immunity Components
B lymphocytes and T lymphocytes
Which immunoglobulin is found in the highest concentration in the oral cavity?
IgA
Which system (innate or adaptive) has immunologic memory?
Adaptive
Humoral arm versus Cellular arm of Adaptive Immunity
Humoral: antibodies
Cellular: cytotoxicity
Phagocytes (macrophages, granulocytes, dendritic cells)
First step of innate immune response
Engulf and digest pathogens
Recognize pathogen-specific patterns (PAMPs/MAMPs)
Regulate other cells
Lymphocytes (B and T cells)
Adaptive Immunity
Recognize antigens
B cell function
Recognize antigen directly and produce antibodies
T cell function
Recognize antigen in association with antigen-presenting cells
T helper: soluble mediators
T cytotoxic: kill infected cells
Antigen-presenting cells
Dendritic cells
Link the adaptive and innate immunity
Process antigen and present to T cells
Dendritic cells are phagocytic and motile - reside in epithelial surfaces and lymphoid tissues
Primary Organs of Immune System
Bone marrow (B cell maturation)
Bursa of Fabricius (B cell maturation)
Thymus (T cell maturation)
Secondary Organs of Immune System
Spleen
Lymph Nodes
Mucosa
Lymphoid tissue
Signaling molecules of Innate Immune System
Cytokines -> Complement
Signaling molecules of Adaptive Immune System
Cytokines
Interleukins
Cytokine definition
Low molecular weight proteins that stimulate or inhibit the differentiation, proliferation or function of cells
Produced by immune and non-immune cells
Interleukins
Subset of cytokines that communicate between leukocytes
Important Cytokines
TNFa: pro-inflammatory, produced by macrophages
IL-1: pro-inflammatory, produced by macrophages
IL-2: growth factor, produced by T cells
IFNg: pro-inflammatory, produced by T cells
C-reactive protein
Cytotoxic molecules
Enzymes
Reactive oxygen species
Chronology of Immune Response
Innate immunity: 0-4 hours
Infection -> recognition by preformed, non-specific and broadly specific effectors -> removal of infectious agent
Memory
Classification of research studies according to time
Looking back: retrospective, case control
Looking forward: prospective cohort, experimental
Looking now: cross-sectional
Classification of research studies according to intervention/control
Experimental Design (RCT) Observational (no control, no intervention)
Cross-sectional study
Used for questionnaires, surveys, prevalence estimates
Do not provide causative evidence
Advantages of cross-sectional studies
Quick
Low cost
Evaluate large number of variables
Enroll a large number of subjects
Disadvantages of cross-sectional studies
Subject selection may reflect selection bias
Difficult to identify cause-effect relationship
Case Control Study
Retrospective assessment of risk factors
Measures relative rates
Used for rare diseases, especially those with long latency (ex: cancer)
Advantages of case-control
Not dependent on natural frequency of disease
Well-suited to study diseases of long latency
Few cases
Allows study of multiple causes
Low cost
Quick
Ethical - disease has already occurred
Disadvantages of case-control
Case selection may be problematic
Controls may not be representative of same population
Investigators may be biased or subjects may be biased
Incidence, prevalence and RR can’t be calculated
Cohort study
Select 2 or more groups that are free of disease but differ in exposure status Allows for calculation of true rates Useful when exposure varies over time No intervention (observational)
Advantages of cohort
Allows risk to be expressed as incidence
Certain biases are reduced
Subject characteristics can be related to more than one outcome
Disadvantages of cohort
Inefficient for study of rare disease Assessment of relationships limited to those defined at beginning of study Selection bias not controlled Loss to follow up is common Subjects may change in satus (exposure) Expensive Time consuming
RCT
Prospective controlled experiment of human subjects to assess intervention of a specific disease
Asks important research question
Requires IRB and informed consent
Phases of Clinical Trials
1: Dose finding
2: efficacy at fixed dose
3: comparing treatment (RCT)
4: late/uncommon effects
Advantages of RCT
Investigator directly controls assignment to study groups
Investigator controls exposure to agent
Random assignment can control extraneous factors
Blinding of evaluators may be possible
Can establish causality
Disadvantages of RCT
Not immune to problems like other designs (noncompliance, biased observation)
May have low external validity
May not be feasible for studies of disease etiology
May not be feasible for effective disease prevention
Can be expensive
Efficacy versus Effectiveness
Efficacy: the potential to provide a clinical benefit (measured in clinical trial)
Effectiveness: benefit provided in the real world (measured in registrieds, market incident reports, etc.)
Problems with Dental RCTs
Difficult to randomize
Ethical concerns
Blinding usually not possible
Expensive and often lack sponsor
Principle of Equipoise
involves ethical treatment of human subjects in experimental conditions
Systematic Review definition
Comprehensively locates, evaluates, and synthesizes all the available literature on a given topic using a strict scientific design which must itself be reported in the review
Aim of systemic review
Systemic, explicit, reproducible
Provide summary and context of current state of knowledge
Systemic reviews and meta-analysis are top of pyramid
External Validity versus Internal Validity
External: do subjects represent a definable population of interest? (is it relevant?)
Internal: is the study reproducible, well-designed and analyzed?
Power
The ability of a test to detect a significant difference when one exists
-was the population large enough?
Important in negative studies (studies that do not find an association)
Placebo effect
Placebo should be as similar a possible to intervention
Effect can be up to 70%
Intra-rater versus Inter-rater reliability
IntRA-rater: same cases over time
IntER-rater: comparison of same case among raters
Categorical variables
Variables that have levels that are numeric or character
Examples: SES, probing depth ranges, stages of cancer
Continuous variables
Variables that have numeric values only
Examples: probing depth, BMI, viral load, etc.
Comparing continuous variables - statistics
T-test: difference between two group means
ANOVA: analysis of variance; difference between 2 or more groups
Linear regression also used for continuous variables
Statistics for dichotomous outcomes
Chi-Squared
Mantel-Haensel test
Logistic regression
P-value
Measures consistency between the results actually observed and the “pure chance” explanation of those results
Low p-value = very unlikely the null hypothesis is true
Null hypothesis
There is no difference
If the p value is very low, you can reject the null hypothesis and accept the study hypothesis
Confidence Intervals
Type of interval estimate o a population parameter and issued to indicate reliability of an estimate
95% CI: 95% confident that the true value of the parameter is in the confidence interval
Corresponds with level of significance - 95% CI reflects significance level of 0.05
Bias
Any systematic error in a study which results in incorrect estimate of the association between disease and exposure
Types of bias
Selection bias
Recall bias
Observation bias
Confounding
Results when there is a mixing of the effect of the exposure and disease with a “third factor”
-may be unknown to researchers
Sensitivity
Ability of a test to find positive when it is present (true positive)
Ex: 95% sensitive test would have 5% chance it is false negative
Specificity
Ability of a test to find negatives (true negatives)
Ex: 95% specific test would have 5% chance of false positive
Accuracy versus Precision
Accuracy: true value
Precision: obtaining the same values
