Bacterial Evasion of Host Defense Mechanisms
Immunological Aspects of Microbial Host Interaction
Connective Tissue Alterations:Tissue Destruction in Periodontitis
BONE RESORPTION
Porphyromonas gingivalis belongs to the phylum Bacteroidetes and is a nonmotile, Gram-negative, rod-shaped, anaerobic, pathogenic bacterium. It forms black colonies on blood agar.
It is found in the oral cavity, where it is implicated in certain forms of periodontal disease, as well as in the upper gastrointestinal tract, the respiratory tract, and the colon. It has also been isolated from women with bacterial vaginosis. Collagen degradation observed in chronic periodontal disease results in part from the collagenase enzymes of this species. It has been shown in an in vitro study that P. gingivalis can invade human gingival fibroblasts and can survive in them in the presence of considerable concentrations of antibiotics.P. gingivalis also invades gingival epithelial cells in high numbers, in which cases both bacteria and epithelial cells survive for extended periods of time. High levels of specific antibodies can be detected in patients harboring P. gingivalis. Dr Harshavardhan Patwal , explains the various enzymes enzyme peptidyl-arginine deiminase, which is involved in citrullination.[4] Patients with rheumatoid arthritis have an increased incidence of periodontal disease, and antibodies against the bacterium are significantly more common in these patients.
P. gingivalis is divided into K-serotypes based upon capsular antigenicity of the various types.
Inflammation and Immunity in periodontitis pptPerio Files
Local destruction of periodontium occurs mostly by activation of immune and inflammatory response, initiated by plaque. First innate immune response is activated followed by specific immune response.
Useful for BDS and MDS students
Periodontitis is a chronic infectious inflammatory disease caused by microbes; however the presence of microbes is not enough for the cause of its complex nature of disease. Inflammation is the prime cause of periodontal disease. It commences with the aggregation of pathogenic microbes that induce the host to stimulate a cascade of inflammatory response reactions which in-turn leads to the destruction of the host tissues itself. There is a complex interplay of innate and adaptive immune responses which fights against the pathogens by direct interaction or by release of certain molecules including cytokines.
Cytokines are cell signalling molecules that aid cell to cell communication in immune responses and stimulate the movement of cells towards sites of inflammation, infection and trauma. Cytokine biology reveals that there are some subsets of cytokines which are pro-inflammatory cytokines which stimulate the inflammatory responses and cause tissue destruction.
A periodontist is expected to have a sound basis of the cytokine profile to understand the pathogenesis of periodontitis and also to discover the new treatment modality of anti-cytokine therapy.
Porphyromonas gingivalis belongs to the phylum Bacteroidetes and is a nonmotile, Gram-negative, rod-shaped, anaerobic, pathogenic bacterium. It forms black colonies on blood agar.
It is found in the oral cavity, where it is implicated in certain forms of periodontal disease, as well as in the upper gastrointestinal tract, the respiratory tract, and the colon. It has also been isolated from women with bacterial vaginosis. Collagen degradation observed in chronic periodontal disease results in part from the collagenase enzymes of this species. It has been shown in an in vitro study that P. gingivalis can invade human gingival fibroblasts and can survive in them in the presence of considerable concentrations of antibiotics.P. gingivalis also invades gingival epithelial cells in high numbers, in which cases both bacteria and epithelial cells survive for extended periods of time. High levels of specific antibodies can be detected in patients harboring P. gingivalis. Dr Harshavardhan Patwal , explains the various enzymes enzyme peptidyl-arginine deiminase, which is involved in citrullination.[4] Patients with rheumatoid arthritis have an increased incidence of periodontal disease, and antibodies against the bacterium are significantly more common in these patients.
P. gingivalis is divided into K-serotypes based upon capsular antigenicity of the various types.
Inflammation and Immunity in periodontitis pptPerio Files
Local destruction of periodontium occurs mostly by activation of immune and inflammatory response, initiated by plaque. First innate immune response is activated followed by specific immune response.
Useful for BDS and MDS students
Periodontitis is a chronic infectious inflammatory disease caused by microbes; however the presence of microbes is not enough for the cause of its complex nature of disease. Inflammation is the prime cause of periodontal disease. It commences with the aggregation of pathogenic microbes that induce the host to stimulate a cascade of inflammatory response reactions which in-turn leads to the destruction of the host tissues itself. There is a complex interplay of innate and adaptive immune responses which fights against the pathogens by direct interaction or by release of certain molecules including cytokines.
Cytokines are cell signalling molecules that aid cell to cell communication in immune responses and stimulate the movement of cells towards sites of inflammation, infection and trauma. Cytokine biology reveals that there are some subsets of cytokines which are pro-inflammatory cytokines which stimulate the inflammatory responses and cause tissue destruction.
A periodontist is expected to have a sound basis of the cytokine profile to understand the pathogenesis of periodontitis and also to discover the new treatment modality of anti-cytokine therapy.
The mouth, like all external surfaces of the body and the gut,
has a substantial microflora living in symbiosis with a healthy
host.
• The microflora of the mouth contains hundreds of species of
aerobic and anaerobic bacteria.
• Cultural studies indicate that more than 500 distinct microbial
species can be found in dental plaque.
5
• Although bacteria are necessary for periodontal disease to
take place, a susceptible host is also needed.
• The immune-inflammatory response that develops in the
gingival and periodontal tissues in response to the chronic
presence of plaque bacteria results in destruction of
structural components of the periodontium leading,
ultimately, to clinical signs of periodontitis.
6
• The host response is essentially protective, but both
hyporesponsiveness and hyper-responsiveness of certain
pathways can result in enhanced tissue destruction (Bruce
Pihlstrom 2005 ).
• Closer investigations of the destructive pathway of periodontal
disease began to focus on the relation-ship between bacteria
and the host response in the initiation and progression of
periodontal disease.
7
• This shift in etiological theory produced a paradigm that
called attention to the fact that although microorganisms are
the cause of periodontitis, the clinical expression of the disease
depends on how the host responds to the extent and virulence
of the microbial burden.
• It was found that degradation of host tissue results from this
bacterial-host interaction.
Blood supply,nerve supply and lymphatic drainage of the periodontium finalDr. Neha Pritam
Discussion of the various basic topics required to understand in the subject of periodontics. Periodontium being the tooth supporting tissue ,it is necessary to know the blood supply, nerve supply and the lymphatic drainage of the same in dentistry
Non Surgical Periodontal Therapy by Dr Santosh Martandesantoshmds
Review and Essay Material on Non Surgical Periodontal Therapy. Illustrative Contents for proper presentation on all aspects of NSPT. The Presentation helps in drafting A to Z of NSPT. Readers are encouraged to add newer studies and ideas under each aspect of NSPT.
The mouth, like all external surfaces of the body and the gut,
has a substantial microflora living in symbiosis with a healthy
host.
• The microflora of the mouth contains hundreds of species of
aerobic and anaerobic bacteria.
• Cultural studies indicate that more than 500 distinct microbial
species can be found in dental plaque.
5
• Although bacteria are necessary for periodontal disease to
take place, a susceptible host is also needed.
• The immune-inflammatory response that develops in the
gingival and periodontal tissues in response to the chronic
presence of plaque bacteria results in destruction of
structural components of the periodontium leading,
ultimately, to clinical signs of periodontitis.
6
• The host response is essentially protective, but both
hyporesponsiveness and hyper-responsiveness of certain
pathways can result in enhanced tissue destruction (Bruce
Pihlstrom 2005 ).
• Closer investigations of the destructive pathway of periodontal
disease began to focus on the relation-ship between bacteria
and the host response in the initiation and progression of
periodontal disease.
7
• This shift in etiological theory produced a paradigm that
called attention to the fact that although microorganisms are
the cause of periodontitis, the clinical expression of the disease
depends on how the host responds to the extent and virulence
of the microbial burden.
• It was found that degradation of host tissue results from this
bacterial-host interaction.
Blood supply,nerve supply and lymphatic drainage of the periodontium finalDr. Neha Pritam
Discussion of the various basic topics required to understand in the subject of periodontics. Periodontium being the tooth supporting tissue ,it is necessary to know the blood supply, nerve supply and the lymphatic drainage of the same in dentistry
Non Surgical Periodontal Therapy by Dr Santosh Martandesantoshmds
Review and Essay Material on Non Surgical Periodontal Therapy. Illustrative Contents for proper presentation on all aspects of NSPT. The Presentation helps in drafting A to Z of NSPT. Readers are encouraged to add newer studies and ideas under each aspect of NSPT.
Microbiology of Endodontic Infection.Mechanisms of MicrobialPathogenicity and Virulence Factors
Biofilm and Community-Based Microbial Pathogenesis
Biofilm and Bacterial Interactions
Biofilm Community Lifestyle
Quorum Sensing—Bacterial Intercommunication
Methods for Microbial Identification
Diversity of the Endodontic Microbiota
Primary Intraradicular Infection
Spatial Distribution of the Microbiota
Microbial Ecology and the Root Canal Ecosystem
Secondary/Persistent Infectionsand Treatment Failure
Similar to Host microbial interaction in periodontal disease (20)
Role of genetics in periodontal diseasesAnushri Gupta
Terminologies in Genetics
Genetic study design
genetic syndrome and disease associated with periodontal diseases, heretibility of periodontal disease, gene library, gene therapy
Stress is defined as a state of physiological or psychological strain caused by an adverse stimuli , physical, mental, or emotional, internal or external that tend to disturb the functioning of an organism and which the organism naturally desires to avoid.
Cementum is the calcified, avascular mesenchymal tissue that forms the outer covering of the anatomic root.
it describes the development of cementum and its various types.
about pathophysiology behind endo perio lesion and various methods for it. it also explains various complications related to it, dental anomalies associated.
The study of how genes and gene products interact with dietary chemicals to alter phenotype and, conversely, how genes and their products metabolize nutrients is called nutritional genomics or “Nutrigenomics”.
Peizosurgery: A boon in modern periodonticsAnushri Gupta
Piezoelectricity is the electricity resulting from pressure. It is effective in precise bone cutting. It spares soft tissue and hence less blood loss is seen.
describes the vascular and cellular events of acute inflammation. The process involves diapedesis and phagocytosis. The various chemical mediators involved in the process have been discussed. Fate of acute inflammation and conversion into chronic inflammation is described.
LOCAL ANESTHESIA AND ANATOMICAL LANDMARKSAnushri Gupta
Local anesthesia is the topic generally used in the field of dentistry. its composition, function of various components, mode of application, different anatomical landmarks and its comlications have been described in this presentation.
Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journeygreendigital
Tom Selleck, an enduring figure in Hollywood. has captivated audiences for decades with his rugged charm, iconic moustache. and memorable roles in television and film. From his breakout role as Thomas Magnum in Magnum P.I. to his current portrayal of Frank Reagan in Blue Bloods. Selleck's career has spanned over 50 years. But beyond his professional achievements. fans have often been curious about Tom Selleck Health. especially as he has aged in the public eye.
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Introduction
Many have been interested in Tom Selleck health. not only because of his enduring presence on screen but also because of the challenges. and lifestyle choices he has faced and made over the years. This article delves into the various aspects of Tom Selleck health. exploring his fitness regimen, diet, mental health. and the challenges he has encountered as he ages. We'll look at how he maintains his well-being. the health issues he has faced, and his approach to ageing .
Early Life and Career
Childhood and Athletic Beginnings
Tom Selleck was born on January 29, 1945, in Detroit, Michigan, and grew up in Sherman Oaks, California. From an early age, he was involved in sports, particularly basketball. which played a significant role in his physical development. His athletic pursuits continued into college. where he attended the University of Southern California (USC) on a basketball scholarship. This early involvement in sports laid a strong foundation for his physical health and disciplined lifestyle.
Transition to Acting
Selleck's transition from an athlete to an actor came with its physical demands. His first significant role in "Magnum P.I." required him to perform various stunts and maintain a fit appearance. This role, which he played from 1980 to 1988. necessitated a rigorous fitness routine to meet the show's demands. setting the stage for his long-term commitment to health and wellness.
Fitness Regimen
Workout Routine
Tom Selleck health and fitness regimen has evolved. adapting to his changing roles and age. During his "Magnum, P.I." days. Selleck's workouts were intense and focused on building and maintaining muscle mass. His routine included weightlifting, cardiovascular exercises. and specific training for the stunts he performed on the show.
Selleck adjusted his fitness routine as he aged to suit his body's needs. Today, his workouts focus on maintaining flexibility, strength, and cardiovascular health. He incorporates low-impact exercises such as swimming, walking, and light weightlifting. This balanced approach helps him stay fit without putting undue strain on his joints and muscles.
Importance of Flexibility and Mobility
In recent years, Selleck has emphasized the importance of flexibility and mobility in his fitness regimen. Understanding the natural decline in muscle mass and joint flexibility with age. he includes stretching and yoga in his routine. These practices help prevent injuries, improve posture, and maintain mobilit
These simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
micro teaching on communication m.sc nursing.pdfAnurag Sharma
Microteaching is a unique model of practice teaching. It is a viable instrument for the. desired change in the teaching behavior or the behavior potential which, in specified types of real. classroom situations, tends to facilitate the achievement of specified types of objectives.
Recomendações da OMS sobre cuidados maternos e neonatais para uma experiência pós-natal positiva.
Em consonância com os ODS – Objetivos do Desenvolvimento Sustentável e a Estratégia Global para a Saúde das Mulheres, Crianças e Adolescentes, e aplicando uma abordagem baseada nos direitos humanos, os esforços de cuidados pós-natais devem expandir-se para além da cobertura e da simples sobrevivência, de modo a incluir cuidados de qualidade.
Estas diretrizes visam melhorar a qualidade dos cuidados pós-natais essenciais e de rotina prestados às mulheres e aos recém-nascidos, com o objetivo final de melhorar a saúde e o bem-estar materno e neonatal.
Uma “experiência pós-natal positiva” é um resultado importante para todas as mulheres que dão à luz e para os seus recém-nascidos, estabelecendo as bases para a melhoria da saúde e do bem-estar a curto e longo prazo. Uma experiência pós-natal positiva é definida como aquela em que as mulheres, pessoas que gestam, os recém-nascidos, os casais, os pais, os cuidadores e as famílias recebem informação consistente, garantia e apoio de profissionais de saúde motivados; e onde um sistema de saúde flexível e com recursos reconheça as necessidades das mulheres e dos bebês e respeite o seu contexto cultural.
Estas diretrizes consolidadas apresentam algumas recomendações novas e já bem fundamentadas sobre cuidados pós-natais de rotina para mulheres e neonatos que recebem cuidados no pós-parto em unidades de saúde ou na comunidade, independentemente dos recursos disponíveis.
É fornecido um conjunto abrangente de recomendações para cuidados durante o período puerperal, com ênfase nos cuidados essenciais que todas as mulheres e recém-nascidos devem receber, e com a devida atenção à qualidade dos cuidados; isto é, a entrega e a experiência do cuidado recebido. Estas diretrizes atualizam e ampliam as recomendações da OMS de 2014 sobre cuidados pós-natais da mãe e do recém-nascido e complementam as atuais diretrizes da OMS sobre a gestão de complicações pós-natais.
O estabelecimento da amamentação e o manejo das principais intercorrências é contemplada.
Recomendamos muito.
Vamos discutir essas recomendações no nosso curso de pós-graduação em Aleitamento no Instituto Ciclos.
Esta publicação só está disponível em inglês até o momento.
Prof. Marcus Renato de Carvalho
www.agostodourado.com
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by Dr. Kami Maddocks, Professor-Clinical in the Division of Hematology and
Associate Division Director for Ambulatory Operations
The Ohio State University Comprehensive Cancer Center, will provide insight into new directions in targeted therapeutic approaches for older adults with mantle cell lymphoma.
STATEMENT OF NEED
Mantle cell lymphoma (MCL) is a rare, aggressive B-cell non-Hodgkin lymphoma (NHL) accounting for 5% to 7% of all lymphomas. Its prognosis ranges from indolent disease that does not require treatment for years to very aggressive disease, which is associated with poor survival (Silkenstedt et al, 2021). Typically, MCL is diagnosed at advanced stage and in older patients who cannot tolerate intensive therapy (NCCN, 2022). Although recent advances have slightly increased remission rates, recurrence and relapse remain very common, leading to a median overall survival between 3 and 6 years (LLS, 2021). Though there are several effective options, progress is still needed towards establishing an accepted frontline approach for MCL (Castellino et al, 2022). Treatment selection and management of MCL are complicated by the heterogeneity of prognosis, advanced age and comorbidities of patients, and lack of an established standard approach for treatment, making it vital that clinicians be familiar with the latest research and advances in this area. In this activity chaired by Michael Wang, MD, Professor in the Department of Lymphoma & Myeloma at MD Anderson Cancer Center, expert faculty will discuss prognostic factors informing treatment, the promising results of recent trials in new therapeutic approaches, and the implications of treatment resistance in therapeutic selection for MCL.
Target Audience
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with mantle cell lymphoma (MCL).
Learning Objectives
1.) Identify clinical and biological prognostic factors that can guide treatment decision making for older adults with MCL
2.) Evaluate emerging data on targeted therapeutic approaches for treatment-naive and relapsed/refractory MCL and their applicability to older adults
3.) Assess mechanisms of resistance to targeted therapies for MCL and their implications for treatment selection
ARTIFICIAL INTELLIGENCE IN HEALTHCARE.pdfAnujkumaranit
Artificial intelligence (AI) refers to the simulation of human intelligence processes by machines, especially computer systems. It encompasses tasks such as learning, reasoning, problem-solving, perception, and language understanding. AI technologies are revolutionizing various fields, from healthcare to finance, by enabling machines to perform tasks that typically require human intelligence.
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Ve...kevinkariuki227
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
Couples presenting to the infertility clinic- Do they really have infertility...Sujoy Dasgupta
Dr Sujoy Dasgupta presented the study on "Couples presenting to the infertility clinic- Do they really have infertility? – The unexplored stories of non-consummation" in the 13th Congress of the Asia Pacific Initiative on Reproduction (ASPIRE 2024) at Manila on 24 May, 2024.
These lecture slides, by Dr Sidra Arshad, offer a quick overview of physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar leads (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
Knee anatomy and clinical tests 2024.pdfvimalpl1234
This includes all relevant anatomy and clinical tests compiled from standard textbooks, Campbell,netter etc..It is comprehensive and best suited for orthopaedicians and orthopaedic residents.
Prix Galien International 2024 Forum ProgramLevi Shapiro
June 20, 2024, Prix Galien International and Jerusalem Ethics Forum in ROME. Detailed agenda including panels:
- ADVANCES IN CARDIOLOGY: A NEW PARADIGM IS COMING
- WOMEN’S HEALTH: FERTILITY PRESERVATION
- WHAT’S NEW IN THE TREATMENT OF INFECTIOUS,
ONCOLOGICAL AND INFLAMMATORY SKIN DISEASES?
- ARTIFICIAL INTELLIGENCE AND ETHICS
- GENE THERAPY
- BEYOND BORDERS: GLOBAL INITIATIVES FOR DEMOCRATIZING LIFE SCIENCE TECHNOLOGIES AND PROMOTING ACCESS TO HEALTHCARE
- ETHICAL CHALLENGES IN LIFE SCIENCES
- Prix Galien International Awards Ceremony
2. INTRODUCTION
• The mouth, like all external surfaces of the body and the gut, has a
substantial microflora living in symbiosis with a healthy host.
• The microflora of the mouth contains hundreds of species of aerobic
and anaerobic bacteria.
• Cultural studies indicate that more than 500 distinct microbial
species can be found in dental plaque.
•Although bacteria are necessary for periodontal disease to take
place, a susceptible host is also needed.
• The immune-inflammatory response that develops in the gingival and
periodontal tissues in response to the chronic presence of plaque
bacteria results in destruction of structural components of the
periodontium leading, ultimately, to clinical signs of periodontitis.
3. •The host response is essentially protective, but both
hyporesponsiveness
and hyper-responsiveness of certain pathways can
result in enhanced tissue destruction.
• Closer investigations of the destructive pathway of periodontal
disease began to focus on the relation-ship between bacteria and
the
host response in the initiation and progression of periodontal
disease..
• This shift in etiological theory produced a paradigm that called
attention to the fact that although microorganisms are the cause of
periodontitis, the clinical expression of the disease depends on how
the host responds to the extent and virulence of the microbial
burden.
• It was found that degradation of host tissue results from this
bacterial-host interaction.
4. • A dynamic equilibrium exists between dental plaque bacterium and
innate host defense system.
• Dental plaque bacteria have adapted survival strategies favoring
growth, while the host limits growth by combination of
innate and adaptive immune responses.
• This interaction represents a highly evolved interaction between
bacteria and host.
5. WHAT IS HOST ?
•An organism which harbors the parasite
WHAT IS BACTERIA?
• Extremely small—usually 0.3 to 2.0
micrometers in diameter—and relatively
simple microorganisms possessing the
prokaryotic type of cell construction.
INTERACTION
• The combined effect of two or more
independent variables acting
simultaneously on a dependent variable.
6. DIFFERENT TYPES OF INTERACTIONS
• Symbiosis: It is an association in which both host and parasite are
so
dependent upon each other that cannot live without the help of other
and none of them suffers any harm from the association.
• Commensal: Is a non disease forming organism; which is a part of
the resident flora.
• Commensalisms: is an association in which parasite is deriving
benefits
without causing injury to its host.
• Parasitism: is an association where parasites gets benefits and the
host gets harmful effects.
• Mutualism: is an association where parasite and host both are
benefited.
7. PATHOGEN
• Pathogen is an organism that causes disease.
• Opportunistic pathogens: are normally not
pathogenic , but are able to become so if their
local environment is changed
• They can overgrow and the microbial load can cause disease.
• Virulence : ability of a microorganisms to cause the disease.
To function as pathogen, bacteria must:
1. Colonize at appropriate host tissue site.
2. Cause destruction of the host tissues.
• Toxins : Anything that is injurious, destructive, or fatal
or
A poisonous substance, especially a protein, that is produced
by living
cells or organisms and is capable of causing disease when
introduced
into the body tissues but is often also capable of inducing
neutralizing
8. Bacterial Adherence in Periodontal Environment
• Attachment to Acquired pellicle or onto the saliva coated tooth
surfaces.
Gingival
Crevice
First site for
contact &
attachment of
bacteria
Mechanical
cleansing by
saliva and GCF
Inhibits
bacterial
growth by
antibody and
phagocytic
secretion.
Gingival
Epithelium
Bacterial
Invasion
Antimicrobial
peptides (AMPs)
that kill bacteria.
IL8 attracts
PMNs and
Macrophages to
reduce microbial
IL-1b to enhance
local
inflammatory
action.
Barrier Function
9. Host Tissue Invasion
Mode of entry of bacteria:
• Through the ulceration in the epithelium
• Through gingival sulcus
• Through periodontal pockets
• Direct penetration of microorganisms
Organisms capable of invading tissues directly:
• Actinibacillus actinomycetum comitans
• P. gingivilis
• Fusobacterium nucleatum
• Trepanoma denticola
• This ability of the bacteria to invade the host tissue is one of the key
characteristic in distinguishing pathogenic from non pathogenic
strains.
• Localization of bacteria in the tissues provides an ideal position from
which the bacteria can deliver toxic molecules and enzymes to the host
tissue cells and this may be the significance of invasion as a virulence
factor.
10. •The bursts of disease activity in periodontal diseases may be
related to active phases of bacterial invasion of the tissues.
• Bacteria in the tissue may enable persistence of the species in the
pocket by providing a reservoir for colonization.
Advantages of tissue invasion:
• Tissues can provide reservoir for colonization
• Can not be eliminated easily by mechanical methods.
• Systemic antibodies are required to eliminate bacteria
• The presence of bacteria within the tissue makes periodontitis
more resistance to the treatment
11. Bacterial Evasion of Host Defense Mechanisms
Periodontal diseases provide a unique situation for the study of
microbial-host interactions. More than 500 different microbial species
can be found in the oral biofilm; however, only a few of those are
associated with periodontal disease.
Direct damage to polymorph nuclear leucocytes and
macrophages
Reduced PMN chemotaxis
Degradation of immunoglobulins
Degradation of fibrin
Altered lymphocyte function
Damage to crevicular epithelium
Production of volatile sulphur compounds
Degradation of periodontal tissues by bacterial enzyme .
13. Immunological Aspects of
Microbial Host Interaction
• Well characterized interactions involve release of:
1. IL-1,6,8
2. TNF
3. Prostaglandins
From monocytes,
macrophages and PMNs
exposed to bacterial
endotoxin (LPS)
14.
15. Innate Responses (Non-specific)
• Innate reactions include the inflammatory response and do not
involve immunological mechanisms.
Adaptive Responses (Specific)
• Adaptive reactions that include immunological responses tend to
be very effective as the host response is specifically “tailored” to the
offending
pathogen(s).
Host Defense Processes
16. •Although adaptive and innate immune responses are traditionally
distinguished, in vivo they are integral parts of the host defenses
against infections (i.e., innate immunity is not inactivated after the
adaptive response is initiated).
• Innate immunity is required for the activation of a more specific
adaptive immune response, but it also plays an important role in the
management of host-microbial interactions.
• The innate immune system is rapidly activated (within minutes),
and it is responsible for the defense during the initial hours and
days of the infection.
• Alternatively, adaptive immunity requires at least 7 to 10 days
before an adequate cellular or humoral response occurs.
Innate Immunity in Periodontal Disease
17. •The host may respond through inflammation to a range of challenges, from bacteria to cholesterol.
• However, the nature of the response differs and its character depends on the microbial triggering of
specific receptors, the signal transduction pathways, and the way cells and tissues respond to these signals
in terms of cytokine and defensive protein production.
• Innate immunity represents the inherited resistance to microbial infection, which is detected by Pattern
Recognition Receptors (PRRs).
• PRRs are strategically located at the interface between the mammalian host and the microbes, and have
evolved to recognize conserved microbial motifs, known as Microbe Associated Molecular Patterns
(MAMPs) OR Pathogen Associated Molecular Patterns (PAMPs)
• Toll Like Receptors (TLRs) constitute an evolutionarily ancient PRR family, which plays a central role in the
induction of innate immune and inflammatory responses and act as bridge b/w the innate and acquired
immune systems.
18. •TLRs are single-pass transmembrane proteins with N-terminals that
present leucine-rich repeats that are responsible for the recognition of
their ligands and with C-terminal cytoplasmic domains that are very
similar to the cytoplasmic region of the interleukin-1 receptor, which
are called Toll/IL-1 receptor domains (TIR domains).
• Thus, subsequent to the recognition of a ligand by TLRs, the signal
generated makes use of pathways similar to those used by the IL-1
receptor
STRUCTURE OF TLR
20. • Within periodontal tissues, TLR2 and TLR4 expression appears to
be severely increased in diseased states.
• TLR-4 is expressed in equal levels by gingival and periodontal
fibroblasts.
• TLR-2 is expressed in higher levels by PDL fibroblasts.
• Human gingival and periodontal fibroblasts are known to produce
various inflammatory cytokines such as IL-1,6,8 when stimulated by
bacterial LPS.
• CD-14 is responsible for pattern recognition of common bacterial cell
surface components such LPS and PGN (peptidoglycan).
• Cementoblasts also express TLR-2,4 as well as CD-14
• It has been suggested that TLR4 mediates the response to LPS
while TLR2 is involved in response to other bacterial cell wall
components.
TLR Expression and Microbial Recognition in Periodontal Tissues
21. • TLRs are expressed predominantly in cells which mediate first-line
defense,
such as neutrophils, monocytes/ macrophages, and dendritic cells, as
well as
epithelial cells.
• Distinct members of the TLR family respond to different types of
MAMPs, endowing the innate response with a relative specificity.
Nucleotide-binding
oligomerization
domain-containing
protein 1
23. Epithelial Cells
• Epithelial cell express TLR-2, 9.
• LPS from Aac increases expression of ICAM-1 (Intercellular
Adhesion Molecule 1) and LFA-1 (Lymphocyte function-associated
antigen 1) due to bacterial LPS.
• However, P.gingivalis LPS down regulates ICAM1 and LFA1
secretion.
• There is increased PMN migration towards the pocket.
• Increased IL-8 production in response to LPS production by
various pathogens.
• It also activate endothelial cells, macrophages, dendritic cells
and PMNs to produce MMPs.
24. Dendritic Cells or Langerhans Cells
• DCs express TLR-9.
• Recognize MAMPs and initiate maturation process.
• Mature DCs present antigens to (major histocompatibility complex)
MHC Class-II.
• Produce cytokines and co-stimulatory molecules (CD- 36,40,54,80,86)
that induce activation of T-lymphocytes
• DCs + P.gingivalis fimbriae + T lymphocytes = Th1 type response.
• DCs + P.gingivalis LPS = Th2 type response.
25. Macrophages
• Act as professional phagocytes with the primary function of engulfing
and destroying microbes.
• Produce cytokines and MMP-1, NO when stimulated by LPS by
periodontal pathogens.
Cementoblasts
• Stimulated by LPS exhibit decreased levels of expression of RANKL
(Receptor Activator Of Nuclear Factor-kappa Beta ligand) and similar
to gingival fibroblasts, increase expression of both OPG
(osteoprotegrin) and OPN (Osteopontin).
26. Fibroblast
• Gingival fibroblast:
• Produces proinflammatory cytokines and also express adhesion
molecules in
response to PAMPs such as LPS, PGN and DNA of various pathogens.
• PDL fibroblast :
• Produces Alkaline Phosphatase activity similar to osteoblasts.
• These cells can also liberate proteinases causing tissue destruction.
• The capsular polysaccharide from Aac can inhibit expression of IL-6
and IL-8 induction in gingival fibroblasts by LPS from the same micro-
organism
and modulate an immune response in blocking bone resorption which
is supported by an increase in OPG expression by LPS stimulated
Gingival
fibroblasts.
• On stimulation with PGN, PDL fibroblasts express higher levels of IL-
8 than gingival fibroblasts, perhaps because of more TLR-2
expression.
27. • May be stimulated by IL-8 secreted by other cells and also directly by
LPS through TLR-4 ultimately leading to activation and increased
adhesion of monocytes.
• This is due to the induction of cytokine production and increased
expression of adhesion molecules like ICAMs (Intercellular Adhesion
Molecule) and VCAM-1 (Vascular Cell Adhesion Molecule 1) by MAMPs.
• Also function as APCs (Antigen-presenting cells ).
Endothelial cells
28. Osteoblasts
• P. intermedia LPS inhibits osteoblast differentiation and mineralization.
• Capsular polysaccharide from Aac promote osteoclast differentiation of
bone marrow cells.
• In absence of stromal cells and osteoblasts, LPS inhibits RANKL
(Receptor Activator Of Nuclear Factor-kappa Beta ligand) induced
differentiation of osteoclast precursors as a result of decreased M-CSF
(macrophage colony-stimulating factor) and RANK receptor.
• If osteoclast precursors are primed with RANKL, LPS synergistically
increases differentiation influenced by autocrine stimulation with LPS,
induced TNFa and
PGE2.
29. Monocytes
• Stimulated by MAMPs produce inflammatory cytokines and also
increase proliferation and adhesion to endothelial cells.
• LPS induced differentiation of monocytes into osteoclasts even in
absence of osteoblasts and the induction of RANKL expression is the key
mechanism in it.
• In the presence of IL-12, P.gingivalis LPS significantly increases
Interferon gamma production by T cells and also augments production of
IL-12 by monocytes.
• Without co-stimulatory factors, P.g LPS fails to induce proinflammatory
cytokines on monocytes ; on the contrary, it induces expression of anti-
inflammatory IL-10 that can down regulate IL-12 levels.
30. B Lymphocytes
• They are Directly stimulated by MAMPs specifically CpG (Cytosine
phosphate Guanine) DNA because they lack TLR-2 while simultaneously
expressing TLR-9.
• This leads to proliferation, antibody production and production of
proinflammatory cytokines.
31. T Lymphocytes
• It play role in cell-mediated immunity.
• It gets activation by LPS is species specific.
• LPS from E.coli was shown to induce both CD4+ and CD8+ T cells to
produce interferon gamma.
• P.gingivalis LPS was shown to induce Th2 cells to produce Th2 type
cytokines.
• CpG DNA induces differentiation and activation of T cells
• Also inhibits CD4+ apoptosis.
32. ROLE OF GINGIPAIN
• Pick et al. (1994) separated the trypsin-like activity in P. Gingivalis
culture supernatants called 'gingipain' and found that there were two
separate cysteine proteinase activities, one with arginine and one with
lysine specificity
• Arg-gingipain have been found potently to enhance vascular
permeability.
• These enzymes increase gingival crevicular fluid production and thus
provide
a continuous supply of nutrients for the bacterium, enhancing its growth
and
virulence.
• Arg-gingipain has also been found to be a very efficient enzyme for the
production of the potent chemotactic factor C5a by directly cleaving the
C5
component of complement.
• These enzyme also degrades C3,and in this way eliminates the
creation of
C3-derived opsonins.
• This render sp. Gingivalis more resistant to phagocytosis by
33. ROLE OF GINGIPAIN
• Fibrinogen is a major target for lys-gingipain and it thus increases the
local clotting time, leading to gingival bleeding.
• The bleeding of periodontal sites is of primary importance for the
growth
of P. Gingivalis, since it ensures the rich source of haem and iron that it
requires for survival.
• Gingipains act as adhesins and have a strong binding affinity for
fibrinogen , fibronectin and laminin.
• It inhibits haemagglutination.
• Since these complexes are present on the surfaces of both the vesicles
and membranes of P. Gingivalis , they may play an important role in the
attachment of this bacterium to host cells.
34.
35. Connective Tissue Alterations:
Tissue Destruction in Periodontitis
• Remodeling of connective tissues that leads to a net loss of
local soft tissues, bone and periodontal attachment apparatus.
• The fundamental event in the transition from gingivitis to
periodontitis is the loss of soft tissue attachment to the tooth and
subsequent
loss of alveolar bone.
• Mediators produced as part of host response contribute to tissue
destruction include Proteinase,Cytokines, Prostaglandins
37. BACTERIAL PRODUCTS
• Degrade basement membrane and extracellular
matrix proteins including collagen, proteoglycans, and
glycoproteins. This would destroy periodontal
connective tissue and facilitates bacterial invasion.
• Interferes with tissue repair by inhibiting clot
formation or lysing the fibrin matrix in periodontal
lesions.
• Activates latent host tissue collagenase which would
enhance host tissue enzyme mediated tissue
destruction.
• Inactivates proteins important in host defense.
38. Neutrophils / Polymorphonuclear
Leukocytes
• Elastase, a serine protease, is contained in the primary granules of
the PMN; may cause tissue breakdown and is present with increased
activity
at sites of gingival inflammation.
• Lactoferrin is contained in the secondary granules of the PMN, and
is released during PMN migration and is associated with PMN
activation.
• A greater proportion of lactoferrin to elastase was found in advanced
periodontitis lesions than in gingivitis sites.
• TNF – Alpha plays a major role in development of inflammation by
stimulating the release of cytokines, including IL-1B from neutrophils.
• Lipoxin A4 is a cytokine regulating lipid mediator that can reduce the
inflammation induced by TNF – A.
• P.gingivalis impedes transendothelial migration of neutrophils and
prevents epithelial cells from secreting IL-8 in response to bacterial
challenge.
39. PROTEINASES
•Proteinases (collagenase, elastase - like and trypsinlike, as well as
serine and cysteine proteinases) cleave proteins by hydrolyzing
peptide bonds.
• Depending on the location of activity of the enzyme on its substrate:
1. Endopeptidases
2. Exopeptidases,
Proteinase Inhibitors:
Alpha-2
macroglobulin(A2-
M)
• Inhibits gingival
collagenase
Alpha1 antitrypsin
(A1-AT)
• Inhibits PMN
collagenase
40. • Matrix metalloproteinases (MMPs) are considered to be primary
proteinases involved in periodontal tissue destruction by degradation of
extracellualr matrix molecules.
• MMPs are a family of proteolytic enzymes found in neutrophils,
macrophages, fibroblasts, epithelial cells, osteoblasts and osteoclasts
that degrade matrix molecules such collagen, elastin and gelatin.
• MMP1 and MMP8, both are collagenases and are elevated in tissues
and GCF
associated with periodontitis.
• MMP 8 is released by infiltrating neutrophils whereas MMP1 is
expressed by resident cells including fibroblasts,
monocytes/macrophages and epithelial cells.
• Neutrophil (PMN) Collagenase is found in higher concentrations in
inflamed gingival specimens than in clinically healthy gingiva.
• Their increase during experimental gingivitis and decrease after
periodontal treatment suggest that MMPs from PMNs are involved in
periodontal tissue breakdown.
41. • MMPs are also produced by Aac and Pg which is not considered
a major factor in disease progression.
• MMPs are secreted in the inactive/latent form.
• Activation by proteolytic cleavage of a portion of the latent
enzyme.
• Proteases capable of MMP activation:
1. Chymotrypsin like protease by T. denticola
2. Neutrophil Cathepsin G by Host cell enzyme
• MMPs are inactivated by:
1. Alpha-macroglobulins found in serum and GCF.
2. Tissue Inhibitors of MMPs produced by cells of host tissue and
fluid.
3. Tetracycline appears to inactivate neutrophil MMP
Other Proteinases
1. Elastase degrades elastin, collagen, fibronectin.
2. Cathepsin – G: MMP – 8 activation.
42. Cytokines
• Cytokines are soluble proteins, secreted by cells involved in both the
innate and adaptive host response, and act as messenger molecules
that transmit signals to other cells.
• Actions:
1. Initiation and maintenance of immune and inflammatory responses.
2. Regulation of growth and differentiation of cells.
• Interleukins are important members of the cytokine group and are
primarily involved in communication between leukocytes and other
cells, such as epithelial cells, endothelial cells, and fibroblasts engaged
in the inflammatory process.
• Interleukin (IL)-1a, IL-1b, and tumor necrosis factor (TNF)-alpha
stimulate bone resorption and inhibit bone formation.
43. • IL-1, IL-6 and TNF-alpha have the central role in periodontal
destruction.
• IL1a and IL1b are the 2 active forms.
• Main factor of IL-1 : Osteoclast Activating Factor.
• IL-1 is produced by activated macrophages or lymphocytes but may
also be produced by mast cells, fibroblasts, keratinocytes and
endothelial cells.
• Bacterial LPS is a potent activator of macrophage IL-1 and TNF-a
secretion.
• TNF-a and IL-1 can upregulate their own production.
• IL-6 also results in Bone remodeling.
• TNF-a and TNF-b are active forms.
• TNFa shares similar biologic activity of IL-1a including stimulation of
bone resorption.
• TNF-β is primarily produced by Th1 subset of CD4+ T cells that have
been activated by antigen or mitogen
44. • IL-1 is a potent stimulant of osteoclast proliferation,
differentiation, and activation
• TNF-ά have same effects on osteoclasts but less potent.
Proinflammatory effects of IL-1 and TNF-a:
1. Stimulation of endothelial cells to express selectins that
facilitate recruitment of leukocytes.
2. Activation of macrophage IL-1production.
3. Induction of PGE2 by macrophages and gingival fibroblasts.
45. Prostaglandins
• Prostaglandins are arachidonic acid metabolites generated by
cyclooxygenases (COX-I, COX-2).
• Arachidonic acid is a 20-carbon polyunsaturated fatty acid found in plasma
membrane of most cells.
• COX-2 is upregulated by IL-1β, TNF-β and bacterial LPS leading to
formation of
PGE2 associated with inflammation
• PGE2 is increased in periodontal sites demonstrating inflammation and
attachment loss.
• PGE2 also induces MMPs and osteoclastic Bone Resorption.
• PGE2 is elevated in gingivitis and Periodontitis in active disease.
• PGE2 is partly responsible for bone loss associated with periodontitis
46. Elevated prostaglandin E2 levels are detected in the gingiva and
gingival crevicular fluid of patients with periodontal diseases,
compared to periodontally healthy subjects in 1974, Goodson Et
Al. reported a 10-fold increase of prostaglandin E2 levels in
inflamed gingival tissue, compared with healthy gingival tissue.
Macrophages produce prostaglandin E (PGE) and (IL-1)
and
lymphocytes produce Interleukin-1 (IL-1) which activate
Osteoclasts.
47. REACTIVE OXYGEN SPECIES
• Any species capable of independent existence that contain one or more
unpaired electrons.
• Inflammatory cells and in particular PMN once stimulated produce
reactive oxygen species via metabolic pathway of the respiratory burst,
which occurs in the process of phagocytosis.
• These includes superoxide anion, hydrogen peroxide, hydroxyl
radicle and hyperchlorus acid.
ROS can
cause
Protein
damage
Lipid
Peroxidation
DNA
damage
48. COLLAGEN DEGRADATION IN HOST BACTERIAL
INTERACTION
• Tissue remodeling is usually tightly regulated by a complex interplay of
cell-cell and cell-matrix interactions involving the production of
enzymes, activators, inhibitors and regulatory molecules such as
cytokines and growth factors.
• The accelerated breakdown of connective tissues occurring in
pathological situations, such as periodontal diseases.
• The endopeptidases (or proteinases) are key enzymes in tissue
degradative processes, since the protein components of most matrices
are the predominant determinants of tissue structure and function.
49. • Collagenase :
• Collagenase 1 or MMP 1 or fibroblast collagenase can hydrolyses
collagen type 1,2,3,6,8,and 10
• Collagenase 11 or MMP 8 or PMN’s collagenase can hydrolyze
collagen
type 1 and 3
• Elastase :
• MMP 2 and MMP 9 can degrade collagen type 4, 7, 10 and 11 and
Elastin.
• Stromeolysin :
• Stromeolysin 1
• Stromeolysin 2
• Stromeolysin 3
Degrade proteoglycans, basement membrane , laminin and
fibronectin.
50. • Higher levels of antibodies to collagen type I were found in the
peripheral blood of patients with periodontitis than in healthy controls.
• In addition to antibodies to collagen type-1 there are several other
types of auto reactive components.
• Increased reactions of IgG auto antibodies to desmosomal
proteins were observed in sera from individuals with periodontitis in
comparison to sera from healthy individuals.
• Two regulators of MMP expression are IL-1 AND TGF-β. These
substance are present in inflamed tissue
• In macrophages MMP production is stimulated by LPS and inhibited
by
INF-γ, IL-4 and IL-10.
51. MEDIATORS AFFECTING COLLAGEN
Increase in collagen synthesis:
• PDGF
• TGFβ
• FGF
• IGF
Decrease In Collagen Synthesis:
• Cytokines
• IL-1α, β
• INF γ
• TNF α
• Hormones like Glucocorticoids
• Others like PGE2
52. BONE RESORPTION
• Bone resorption is mediated by osteoclasts.
• Concomitant with the breakdown of the connective tissue
attachment during disease progression.
• The mechanisms involved in bone resorption respond to
signals from inflammatory cells in the lesion and initiate
degradation of bone in order to maintain a “safety” distance to
the periphery of the inflammatory cell infiltrate.
55. •Bone loss in periodontal disease are listed by Haussmann in
1974
• Direct action of plaque products on bone progenitor cells induce
their differentiation into osteoclasts.
• Plaque products acts directly on bone destroying it through a
noncellular mechanism.
• Plaque products stimulate gingival cells, causing them to release
mediators which in turn trigger bone progenitor cells to
differentiate
into osteoclasts.
• Plaque products cause gingival cells to release agents that can
act as
co-factor in bone resorption.
• Plaque products can cause gingival cells to release agents that
destroy
bone by direct chemical action without osteoclasts.
56. Osteoclasts:
• Osteoclasts are multinucleated cells that develop from osteoclast
progenitor
cells/macrophages.
• Mediators such as IL-1 beta, PGE2 and TNF alpha, IL-6, IL-11 and IL-
17 may act as activators of osteoclasts.
58. OSTEOBLAST INDUCED
• All systemic and local bone resorbing factors exert their influence
by stimulating osteoblasts.
• Osteoblasts are involved in the regulation of osteoclasts function
because they have receptors for systemic factors such as
parathromone and 125-OH2 (Vitamin D) and locally produced
factors such as prostaglandins, leukotrienes and cytokines which
effects local changes and exert their influence by stimulating
osteoblasts.
• Stimulated osteoblasts stimulate osteoclast formation by secretion
of cytokines, growth factors in particular granulocyte macrophage
colony stimulating factors (GM-CSF) and macrophage colony
stimulating factor (M-CSF) and interleukin-6.
59. • IL-6 secretion is stimulated by IL-1 attachment to osteoblasts
receptor.
• All these secreted cytokine in presence of IL-3 can stimulate the
development of precursors cells in marrow , these precursors cells
are stimulated by IL-6 to become osteoclasts
• Bone resorbing agent such as PTH hormone stimulates osteoblast
to synthesize and collagenase and plasminogen activator which
digests the osteoid exposing the mineralizing matrix which may be
chemotactic to osteoclast
• Osteoblasts release short range soluble activators for osteoclasts
60. OSTEOCLAST MEDIATED
• The resorption area is defined beneath the ruffled border of osteoclast.
• This is highly specialized region of cytoplasmic infolding of plasma
membrane, t containing podosomes which are specialized protrusion of
the ventral surface of osteoclasts which adhere directly to the bone
surface on being broken down.
• Osteoclasts also produce ROS which may play a role in pathological
demineralization of bone during disease
• RANK (Receptor Activator Of Nuclear Factor-kappa Beta) is a receptor
expressed by osteoclast progenitor cells.
• RANKL and OPG are cytokines that belong to the TNF family and are
produced by osteoblasts and bone marrow stromal cells.
• While RANKL promotes activation of osteoclasts, OPG has the
opposite effect.
• Thus, the binding of RANKL to the RANK will result in the
differentiation of osteoclast progenitor cells into active osteoclasts,
while OPG that binds to RANKL will inhibit the differentiation process.
62. Schematic illustration presents hypothetical mechanisms
of immune intervention in the periodontal bone resorption
induced by RANKL-mediated osteoclastogenesis.
• In the presence of periodontopathic organisms CD4+ T cells
presents
increased expression of RANKL, triggering the activation of
osteoclasts and causing bone loss.
63. • A characteristic cytokine profile has been associated with each type
of periodontal disease (i.e., inflammation of marginal soft tissues
without active
bone resorption [gingivitis] or with active bone resorption
[periodontitis]).
• Thus expression of Th1-type cytokines has been associated with
gingivitis, whereas Th2-type cytokines were found in higher levels in
periodontitis-affected tissues.
• Even though this distinction was not clear because both Th1 and
Th2 cytokines were produced in gingivitis and periodontitis-affected
tissues; and the predominant profile may actually represent the
current activity of
tissue destruction.
64. ROLE OF NO IN BONE RESORPTION
• There is good evidence to suggest that NO (nitric oxide) has biphasic
effects on osteoclastic bone resorption.
• Low concentrations of no have been shown to potentiate IL-1 induced
bone resorption, based on the observation that NO inhibitors inhibit IL-1
induced bone resorption in vitro.
• Constitutive production of NO within osteoclasts has been suggested
to be essential for normal osteoclast function.
65. • The chronic immune system plays an important role in healing
process, which consists regeneration and repair:
Regeneration involves the replacement of tissue with new, identical
tissues that function same as the orignal tissue
Repair involves replacement of one tissue with another tissue, such
as fibrous connective tissue
• Under normal conditions, a platelet rich clot forms at the site of injury
which facilitates in healing.
• In periodontal infections, the platelet rich clot does not form.
• The periodontal healing cycle during the pathogenesis of periodontal
diseases is primarily post inflammatory and cellular elements other
than platelets provide important signals in this process.
• Periodontal repair occurs in overlapping phases of
1. Inflammation shutdown,
2. Angiogenesis
3. Fibrogenesis.
Healing Process in Periodontitis
66. Inflammation Shutdown
• In post inflammatory healing process, shut down of inflammatory
processes and initiation of post healing is orchestrated by leukocytes
• Anti inflammatory signals generated by leukocyte are:
IL-1 receptor antagonist (IL- 1ra)
Transforming growth factor-β (TGF-β)
• IL-4, IL-10, IL-11 also depress inflammatory response
• In the inflamed periodontal tissues:
• IL-1ra
Macrophages
• TGF-b
Mast cells
lymphocytes
Neutrophils
Macrophages
68. Angiogenesis and Fibrogenesis
• IL-1β and TNF-β participate both in inflammation and healing
• IL-1β are indirectly involved in inducing fibroblast proliferation and
collagen synthesis by stimulating the production of PGE2 or release of
secondary cytokines such as Platelet derived growth factor (PDGF)
• PDGF is a protein complex formed by different combinations of A,B, C
and D chains (PDGFAA, AB,BB,CC,DD)
• PDGF is structurally and functionally related to vascular endothelial
growth factor(VEGF), an important factor in endothelial proliferation
• PDGF activates fibroblasts and osteoblasts resulting induction of
protein synthesis.
69. • Also TGF-β promotes the elaboration of fibroblast extracellular
matrix adhesion
• TGF-β is potent inhibitor of osteoclast formation
• Osteoclast differentiation and activation are inhibited by interferon-
γ (INF- γ ) which is secreted by natural killer cells, Th1 cells and
macrophages
• The main effect of INF-γ appears to be inhibition IL-1 and TNF-ά
induced osteoclast activation.
• IL-1ra also effective in blocking IL-1 and TNF-ά induced osteoclast
activation
70. CONCLUSION
• The host-bacterial interaction theory may explain why otherwise healthy
individuals with moderate levels of plaque do not exhibit loss of periodontal
support.
• In these individuals, PMNS are effective in blocking invading pathogens without
destroying the collagen content
of the periodontium in the process.
• If these same pathogens attempted to invade the periodontium of people
predisposed to periodontal disease, it appears that impaired chemotaxis and
phagocytosis of defense cells may put these individuals at significantly greater risk
for progressive periodontal destruction.
71. REFERENCES
•Text book of periodontology: Carranza 12 edn
•Text book of microbiology: Ananthnarayana 7 edn
• Oringer rj. American academy of periodontology, research, science,
and therapy committee. Modulation of the host response in periodontal
therapy. J periodontol. 2002;73(4): 460-470.
• The role of reactive oxygen and antioxidant species in periodontal
tissue destruction periodontology 2000;2007;vol43
• Toll-like receptors and their role in periodontal health and disease.
Periodontology 2000;2007;vol43;41-50
• Robbinson's basic pathology 10 edition
• Harsh Mohan - Textbook of Pathology 6th Edition