This document provides an overview of the host immune response to microbial pathogens, focusing on periodontal bacteria. It discusses how microbe-associated molecular patterns (MAMPs) from bacteria are recognized by pattern recognition receptors (PRRs) like Toll-like receptors (TLRs) and Nucleotide-binding oligomerization domain-like receptors (NLRs). TLR2, TLR4, and TLR9 recognize bacterial lipoproteins, lipopolysaccharide, and CpG-DNA, respectively. NLRs like NOD1 and NOD2 detect peptidoglycan. This interaction stimulates proinflammatory cytokine production and activates innate and adaptive immunity. Recognition of MAMPs is important for the host
Peroxisomes are intracellular organelles that contain enzymes involved in important metabolic processes like lipid metabolism. They produce hydrogen peroxide and affect cell signaling and proliferation. The peroxisome proliferator-activated receptors (PPARs) are nuclear receptors that regulate peroxisome functions and modulate gene transcription. PPARs are expressed in skin cells and tissues and play roles in epidermal differentiation, inflammation, wound healing, sebum production, and disorders like psoriasis. Activation of PPARs has effects on conditions and diseases through regulation of metabolic and immune pathways.
Peroxisome proliferator-activated receptors (PPARs) are transcription factors that regulate genes involved in cell proliferation, differentiation, and inflammation. The three PPAR subtypes - α, β/δ, and γ - are expressed in keratinocytes. PPARβ/δ is most prominent in human keratinocytes and increases with differentiation, while PPARα and γ increase at lower levels. PPARβ/δ also upregulates in proliferating keratinocytes and wound healing. PPARs play important roles in skin barrier function, inhibiting growth, promoting terminal differentiation, and modulating inflammation, making them key regulators of conditions like psoriasis involving hyperproliferation and aberrant
Toll-like receptors are a class of proteins that play a key role in the innate immune system by recognizing structurally conserved molecules from microbes. There are multiple Toll-like receptors that recognize different microbial components. Upon activation, Toll-like receptors recruit adaptor proteins to initiate signaling pathways that result in immune responses. The major histocompatibility complex is a set of genes that code for cell surface proteins essential for the adaptive immune system. Major histocompatibility complex molecules are involved in antigen presentation and discriminating between self and non-self.
This document discusses the immunological aspects of oral cancer. It begins with definitions of key immunological terms like immunity, immune, and antigen presenting cells. It then describes the major cells of the immune system like lymphocytes, dendritic cells, and macrophages. It discusses concepts like MHC, tumor antigens, oncogenes, tumor suppressor genes, and how tumors can evade the immune system. It provides an overview of the immune response against tumors and immunotherapy approaches.
- Toll-like receptors are a family of pattern recognition receptors that play a key role in triggering inflammatory responses to microbial invasion. They recognize structurally conserved molecules derived from microbes.
- TLRs act as a bridge between innate and adaptive immunity by mediating dendritic cell maturation and activation of pathogen-specific T lymphocytes. On interaction with microbial ligands, TLRs signal through intracellular pathways to activate innate immune cells.
- There are 10 human TLRs that recognize distinct microbial ligands. TLR signaling leads to inflammation through cytokine production and helps direct the development of adaptive immune responses.
The document discusses arginine methylation, which is a common posttranslational modification that occurs on both nuclear and cytoplasmic proteins. It focuses on the roles of arginine methylation of histone tails by protein arginine methyltransferases (PRMTs) in regulating chromatin function and the histone code. Specifically, it describes the nine PRMT enzymes that catalyze methylation of histone tails, including their classification and substrates. It also discusses potential mechanisms of arginine demethylation and sites of arginine methylation on histone tails.
This document discusses Toll-like receptors (TLRs), which are a family of pattern recognition receptors that play a key role in the innate immune system. It provides information on TLR structure, tissue expression, ligands, signaling pathways, and the 13 known human TLR family members. TLRs recognize pathogen-associated molecular patterns and damage-associated molecular patterns, and signal through either the MyD88-dependent or MyD88-independent pathway to induce inflammatory responses and activate immune cells. They are involved in initiating inflammation during various disorders and diseases.
Peroxisomes are intracellular organelles that contain enzymes involved in important metabolic processes like lipid metabolism. They produce hydrogen peroxide and affect cell signaling and proliferation. The peroxisome proliferator-activated receptors (PPARs) are nuclear receptors that regulate peroxisome functions and modulate gene transcription. PPARs are expressed in skin cells and tissues and play roles in epidermal differentiation, inflammation, wound healing, sebum production, and disorders like psoriasis. Activation of PPARs has effects on conditions and diseases through regulation of metabolic and immune pathways.
Peroxisome proliferator-activated receptors (PPARs) are transcription factors that regulate genes involved in cell proliferation, differentiation, and inflammation. The three PPAR subtypes - α, β/δ, and γ - are expressed in keratinocytes. PPARβ/δ is most prominent in human keratinocytes and increases with differentiation, while PPARα and γ increase at lower levels. PPARβ/δ also upregulates in proliferating keratinocytes and wound healing. PPARs play important roles in skin barrier function, inhibiting growth, promoting terminal differentiation, and modulating inflammation, making them key regulators of conditions like psoriasis involving hyperproliferation and aberrant
Toll-like receptors are a class of proteins that play a key role in the innate immune system by recognizing structurally conserved molecules from microbes. There are multiple Toll-like receptors that recognize different microbial components. Upon activation, Toll-like receptors recruit adaptor proteins to initiate signaling pathways that result in immune responses. The major histocompatibility complex is a set of genes that code for cell surface proteins essential for the adaptive immune system. Major histocompatibility complex molecules are involved in antigen presentation and discriminating between self and non-self.
This document discusses the immunological aspects of oral cancer. It begins with definitions of key immunological terms like immunity, immune, and antigen presenting cells. It then describes the major cells of the immune system like lymphocytes, dendritic cells, and macrophages. It discusses concepts like MHC, tumor antigens, oncogenes, tumor suppressor genes, and how tumors can evade the immune system. It provides an overview of the immune response against tumors and immunotherapy approaches.
- Toll-like receptors are a family of pattern recognition receptors that play a key role in triggering inflammatory responses to microbial invasion. They recognize structurally conserved molecules derived from microbes.
- TLRs act as a bridge between innate and adaptive immunity by mediating dendritic cell maturation and activation of pathogen-specific T lymphocytes. On interaction with microbial ligands, TLRs signal through intracellular pathways to activate innate immune cells.
- There are 10 human TLRs that recognize distinct microbial ligands. TLR signaling leads to inflammation through cytokine production and helps direct the development of adaptive immune responses.
The document discusses arginine methylation, which is a common posttranslational modification that occurs on both nuclear and cytoplasmic proteins. It focuses on the roles of arginine methylation of histone tails by protein arginine methyltransferases (PRMTs) in regulating chromatin function and the histone code. Specifically, it describes the nine PRMT enzymes that catalyze methylation of histone tails, including their classification and substrates. It also discusses potential mechanisms of arginine demethylation and sites of arginine methylation on histone tails.
This document discusses Toll-like receptors (TLRs), which are a family of pattern recognition receptors that play a key role in the innate immune system. It provides information on TLR structure, tissue expression, ligands, signaling pathways, and the 13 known human TLR family members. TLRs recognize pathogen-associated molecular patterns and damage-associated molecular patterns, and signal through either the MyD88-dependent or MyD88-independent pathway to induce inflammatory responses and activate immune cells. They are involved in initiating inflammation during various disorders and diseases.
This document summarizes key information about Toll-like receptors (TLRs):
- TLRs are pattern recognition receptors that recognize pathogens and activate immune responses. They play a role in both innate and adaptive immunity.
- TLRs recognize specific microbial ligands and signal through either MyD88-dependent or MyD88-independent pathways to induce inflammatory responses.
- Genetic variations in TLRs have been linked to susceptibility or resistance to various diseases like leprosy, tuberculosis, and cancer. Targeting TLR pathways may offer therapeutic approaches for neurological diseases like Alzheimer's disease.
Toll-like receptors (TLRs) are a family of proteins that play a key role in the innate immune system by recognizing molecular patterns from microbes. They are expressed on immune cells like neutrophils, macrophages, and dendritic cells as well as non-immune cells. Most TLRs are located on the cell surface but TLR9 is intracellular. Stimulation of different TLRs induces distinct patterns of gene expression to activate innate immunity and instruct the development of acquired immunity. The first human TLR was discovered in 1994 and TLRs were shown to induce adaptive immune responses in 1997. TLR signaling involves intracellular adapter proteins and transcription factors that trigger inflammatory responses.
This document discusses different human therapies including Tissue Plasminogen Activator (tPA), Interferons, and Antisense molecules. It provides details on tPA such as its function in catalyzing the conversion of plasminogen to plasmin to dissolve blood clots. It describes the three types of Interferons, their roles in the immune response against viruses, and how viruses can develop resistance against Interferons. It also defines the main classes of Antisense molecules that inhibit target RNA functions through complementary base pairing, including their advantages and applications in reducing expression of disease-associated proteins.
cell communications and cellular signalling systems vishnuvishnu priya
This document provides a seminar report on cell communications and cellular signaling systems. It contains an introduction to cellular communication and signaling, different forms of communication between cells, types of signaling, targets of drug action including receptors, ion channels, enzymes and carriers. It discusses cellular aspects related to excitation, contraction and secretion involving calcium regulation and release mechanisms. Finally, it covers conclusions and references. The document provides a comprehensive overview of the key topics in cellular communication and signaling in 3 pages with figures and content organized under headings.
MAJOR HISTOCOMPATIBILITY COMPLEX AND HEAT SHOCK PROTEINSiva Ramakrishnan
The document discusses major histocompatibility complex (MHC) and heat shock proteins (HSP) in chickens. MHC genes encode proteins that present antigens and are involved in immune response and recognition. HSPs help proteins fold correctly and prevent aggregation. Both MHC and HSP play important roles in immune function, disease resistance, and stress response in chickens. Manipulation of these genes may help improve production traits and resistance to disease.
The sources of wastewater from municipal and different industries act as a substantial pressure on the surrounding environment, so the waste management is ordinarily required before drainage.
This document discusses damage-associated molecular patterns (DAMPs) which include pathogen-associated molecular patterns (PAMPs) and alarmins. PAMPs are molecules from pathogens that are recognized by the immune system, while alarmins are endogenous molecules released during cell damage or death that activate similar immune responses. One example of an alarmin discussed is high mobility group box 1 (HMGB1) protein, which is rapidly released during nonprogrammed cell death and activates immune cells like dendritic cells and monocytes. The document argues that both PAMPs and alarmins constitute DAMPs, signaling molecules that activate immune responses to damage from pathogens or trauma.
TLRs are a category of pattern recognition receptors that play an important role in innate immunity. Each TLR detects a distinct subset of pathogens. TLRs have an extracellular domain containing leucine-rich repeats for ligand binding and an intracellular TIR domain for signaling. Engagement of TLRs by microbial ligands initiates signaling cascades involving adaptor proteins like MyD88 that ultimately activate transcription factors such as NF-κB and induce inflammatory responses that promote pathogen clearance.
The major histocompatibility complex (MHC) is a cluster of genes found in mammals that plays a key role in the immune system by helping the body distinguish self from non-self. The MHC was discovered through studies of inbred mouse strains and includes polymorphic glycoproteins divided into three main classes. MHC Class I and II are best known for presenting antigen peptides and interacting with T-cell receptors. Genes in the MHC are highly polymorphic, linked, and inherited as haplotypes from each parent. This polymorphism allows recognition of a diverse range of antigens and is advantageous for the immune system.
Genetic variation in drug transportersDeepak Kumar
This document discusses various transporter proteins involved in drug transport. It describes two main superfamilies - ATP-binding cassette (ABC) transporters and Solute-carrier (SLC) transporters. ABC transporters such as P-glycoprotein, MRP1, and BCRP act as efflux pumps and influence the bioavailability and toxicity of various drugs like irinotecan. Genetic variants in these transporters affect individual responses to drugs. SLC transporters import substances and influence drug absorption and distribution. Variations in transporter expression across tissues and individuals impact drug pharmacokinetics and treatment outcomes.
GPCRs are the most dynamic and most abundant all the receptors. The G protein-coupled receptor (GPCR) superfamily comprises the largest and most diverse group of proteins in mammals. GPCRs are responsible for every aspect of human biology from vision, taste, sense of smell, sympathetic and parasympathetic nervous functions, metabolism, and immune regulation to reproduction. GPCRs interact with a number of ligands ranging from photons, ions, amino acids, odorants, pheromones, eicosanoids, neurotransmitters, peptides, proteins, and hormones.
Nevertheless, for the majority of GPCRs, the identity of their natural ligands is still unknown, hence remain orphan receptors.
The simple dogma that underpins much of our current understanding of GPCRs, namely,
one GPCR gene− one GPCR protein− one functional GPCR− one G protein −one response
is showing distinct signs of wear.
Chemokines are small proteins that direct the movement of white blood cells to sites of injury or infection. They are classified based on structural characteristics like the positioning of conserved cysteine residues. The four main classes are CC, CXC, C, and CX3C chemokines. Chemokines bind to G protein-coupled receptors on cells and signal through G proteins and secondary messengers to induce cell migration. Chemokines play roles in processes like inflammation, immunity, and cancer and are implicated in diseases like HIV, arthritis, and transplant rejection.
Market research report on G-Protein Coupled Receptors (GPCR) covers the types of GPCR Families and the various ligands targeting GPCR. The GPCR families covered include Rhodopsin, Secretin, Metabotropic glutamate and Other. The Ligands targeting GPCRs include Peptides or Proteins, Biogenic Amines, Lipids and Other. The report provides market analysis of each of the Families and ligands targeting GPCRs by their respective categories. The study includes estimations and predictions for the total global GPCR Drug targets market and also key regional markets that include North America, Europe, Asia-Pacific and Rest of World. Estimations and predictions (2005-2020) are illustrated graphically with 35 exhibits. Business profiles of 10+ major companies engaged in developing GPCR targeted drugs, GPCR cell lines and GPCR Assays are discussed in the report. The report serves as a guide to global GPCR ?Drug Targets industry, covering more than 100 companies that are engaged in the development of GPCR Targeted Drugs, GPCR Assays Information related to recent product releases, Assay developments, partnerships, collaborations, and mergers and acquisitions is also covered in the report. Compilation of Worldwide Patents and Research related to GPCR Drug Targets is also provided.
Robert J. Lefkowitz and Brian K. Kobilka won the 2012 Nobel Prize in Chemistry for their groundbreaking work studying G-protein–coupled receptors (GPCRs). Their research revealed key insights into how GPCRs function at the molecular level to transmit signals from outside to inside of cells. Specifically, Lefkowitz and Kobilka were able to clone and sequence the first GPCR, detect their binding properties, determine their three-dimensional structure, and elucidate the allosteric mechanism of signal transduction, establishing GPCRs as a family of related receptors. Their seminal findings provided a deeper understanding of the intricate signaling mechanisms of GPCRs and laid the foundation for advancing research and drug development targeting
Polymorphism affecting drug metabolism .heenakazi4
This document discusses genetic polymorphisms that affect drug metabolism. It begins by defining genetic polymorphism and describing the main types, including single nucleotide polymorphisms, insertions and deletions, and nucleotide repeat polymorphisms. It then discusses how genetic polymorphisms can alter drug metabolism through variations in metabolic enzyme activity and discusses specific examples of polymorphisms in key drug metabolizing enzymes like CYP2D6, CYP2C9, and N-acetyltransferases. The document emphasizes how understanding genetic variations in drug metabolism is important for predicting inter-individual differences in drug responses.
The document discusses the major histocompatibility complex (MHC), including its discovery through transplantation experiments in mice, serologic studies in humans, and the structure and function of MHC molecules. MHC molecules present antigen fragments to T cells and play a key role in the immune system by distinguishing self from non-self. There are two major classes of MHC molecules: Class I presents intracellular peptides to cytotoxic T cells, while Class II presents extracellular peptides to helper T cells.
GPCR dimers are ubiquitous in nature and mediate many physiological processes. While evidence suggests most GPCRs function as dimers, criticism remains that not all receptors dimerize under physiological conditions. Techniques like co-immunoprecipitation, FRET, and BRET are used to study dimers, but overexpression models may produce non-physiological dimers. Research now focuses on identifying physiologically relevant dimers expressed together in native cell types. The drug development paradigm is also shifting from single molecular targets to pathway-based models using in vivo screening of primary cell cultures and stem cells to better represent human biology.
1 (2013) role of the gut microbiota in immunity and inflammatory diseaseDaniel Chan
The gut microbiota plays an important dual role in both immunity and inflammatory disease. It helps develop gut-associated lymphoid tissues and regulates the development of T helper 17 cells and regulatory T cells, which are important for host defense and maintaining gut homeostasis. The microbiota also influences IgA-producing B cells and plasma cells in the intestine. Breakdown of the normal microbiota increases the risk of pathogen infection and inflammatory disease. Understanding the complex interactions between the microbiota, pathogens, and the immune system may provide insights into disease pathogenesis and new treatment approaches.
ROLE OF PATHOGEN ASSOCIATED MOLECULAR PATTERN IN PERIODONAL DISEASE.pptxDrPOOJAMAGAJIKONDI
1. Pathogen-associated molecular patterns (PAMPs) produced by bacteria in dental plaque activate pattern recognition receptors like Toll-like receptors (TLRs) which initiate innate immune responses involved in periodontal disease.
2. TLRs recognize specific PAMPs like lipopolysaccharide, lipoproteins, peptidoglycan, and CpG DNA. Activation of TLRs leads to proinflammatory cytokine production and tissue destruction if the immune response is not regulated.
3. In periodontal health, commensal bacteria predominate and tolerance mechanisms limit immune activation, while periodontal disease involves dysbiotic microbiota containing pathogens that strongly activate TLR-mediated inflammation through their PAMPs
Toll-like receptors (TLRs) play a key role in the innate immune system by recognizing pathogen-associated molecular patterns (PAMPs) from bacteria, viruses, and parasites. TLRs activate signaling pathways that launch immune responses. Membrane-bound TLRs recognize bacterial components, while endosomal TLRs recognize nucleic acids from viruses and bacteria. TLR activation leads to production of cytokines and inflammatory responses. TLR signaling on dendritic cells, macrophages, and mast cells initiates innate responses and also links innate and adaptive immunity by activating T cells. Polymorphisms in TLRs impact susceptibility to various infections.
This document summarizes key information about Toll-like receptors (TLRs):
- TLRs are pattern recognition receptors that recognize pathogens and activate immune responses. They play a role in both innate and adaptive immunity.
- TLRs recognize specific microbial ligands and signal through either MyD88-dependent or MyD88-independent pathways to induce inflammatory responses.
- Genetic variations in TLRs have been linked to susceptibility or resistance to various diseases like leprosy, tuberculosis, and cancer. Targeting TLR pathways may offer therapeutic approaches for neurological diseases like Alzheimer's disease.
Toll-like receptors (TLRs) are a family of proteins that play a key role in the innate immune system by recognizing molecular patterns from microbes. They are expressed on immune cells like neutrophils, macrophages, and dendritic cells as well as non-immune cells. Most TLRs are located on the cell surface but TLR9 is intracellular. Stimulation of different TLRs induces distinct patterns of gene expression to activate innate immunity and instruct the development of acquired immunity. The first human TLR was discovered in 1994 and TLRs were shown to induce adaptive immune responses in 1997. TLR signaling involves intracellular adapter proteins and transcription factors that trigger inflammatory responses.
This document discusses different human therapies including Tissue Plasminogen Activator (tPA), Interferons, and Antisense molecules. It provides details on tPA such as its function in catalyzing the conversion of plasminogen to plasmin to dissolve blood clots. It describes the three types of Interferons, their roles in the immune response against viruses, and how viruses can develop resistance against Interferons. It also defines the main classes of Antisense molecules that inhibit target RNA functions through complementary base pairing, including their advantages and applications in reducing expression of disease-associated proteins.
cell communications and cellular signalling systems vishnuvishnu priya
This document provides a seminar report on cell communications and cellular signaling systems. It contains an introduction to cellular communication and signaling, different forms of communication between cells, types of signaling, targets of drug action including receptors, ion channels, enzymes and carriers. It discusses cellular aspects related to excitation, contraction and secretion involving calcium regulation and release mechanisms. Finally, it covers conclusions and references. The document provides a comprehensive overview of the key topics in cellular communication and signaling in 3 pages with figures and content organized under headings.
MAJOR HISTOCOMPATIBILITY COMPLEX AND HEAT SHOCK PROTEINSiva Ramakrishnan
The document discusses major histocompatibility complex (MHC) and heat shock proteins (HSP) in chickens. MHC genes encode proteins that present antigens and are involved in immune response and recognition. HSPs help proteins fold correctly and prevent aggregation. Both MHC and HSP play important roles in immune function, disease resistance, and stress response in chickens. Manipulation of these genes may help improve production traits and resistance to disease.
The sources of wastewater from municipal and different industries act as a substantial pressure on the surrounding environment, so the waste management is ordinarily required before drainage.
This document discusses damage-associated molecular patterns (DAMPs) which include pathogen-associated molecular patterns (PAMPs) and alarmins. PAMPs are molecules from pathogens that are recognized by the immune system, while alarmins are endogenous molecules released during cell damage or death that activate similar immune responses. One example of an alarmin discussed is high mobility group box 1 (HMGB1) protein, which is rapidly released during nonprogrammed cell death and activates immune cells like dendritic cells and monocytes. The document argues that both PAMPs and alarmins constitute DAMPs, signaling molecules that activate immune responses to damage from pathogens or trauma.
TLRs are a category of pattern recognition receptors that play an important role in innate immunity. Each TLR detects a distinct subset of pathogens. TLRs have an extracellular domain containing leucine-rich repeats for ligand binding and an intracellular TIR domain for signaling. Engagement of TLRs by microbial ligands initiates signaling cascades involving adaptor proteins like MyD88 that ultimately activate transcription factors such as NF-κB and induce inflammatory responses that promote pathogen clearance.
The major histocompatibility complex (MHC) is a cluster of genes found in mammals that plays a key role in the immune system by helping the body distinguish self from non-self. The MHC was discovered through studies of inbred mouse strains and includes polymorphic glycoproteins divided into three main classes. MHC Class I and II are best known for presenting antigen peptides and interacting with T-cell receptors. Genes in the MHC are highly polymorphic, linked, and inherited as haplotypes from each parent. This polymorphism allows recognition of a diverse range of antigens and is advantageous for the immune system.
Genetic variation in drug transportersDeepak Kumar
This document discusses various transporter proteins involved in drug transport. It describes two main superfamilies - ATP-binding cassette (ABC) transporters and Solute-carrier (SLC) transporters. ABC transporters such as P-glycoprotein, MRP1, and BCRP act as efflux pumps and influence the bioavailability and toxicity of various drugs like irinotecan. Genetic variants in these transporters affect individual responses to drugs. SLC transporters import substances and influence drug absorption and distribution. Variations in transporter expression across tissues and individuals impact drug pharmacokinetics and treatment outcomes.
GPCRs are the most dynamic and most abundant all the receptors. The G protein-coupled receptor (GPCR) superfamily comprises the largest and most diverse group of proteins in mammals. GPCRs are responsible for every aspect of human biology from vision, taste, sense of smell, sympathetic and parasympathetic nervous functions, metabolism, and immune regulation to reproduction. GPCRs interact with a number of ligands ranging from photons, ions, amino acids, odorants, pheromones, eicosanoids, neurotransmitters, peptides, proteins, and hormones.
Nevertheless, for the majority of GPCRs, the identity of their natural ligands is still unknown, hence remain orphan receptors.
The simple dogma that underpins much of our current understanding of GPCRs, namely,
one GPCR gene− one GPCR protein− one functional GPCR− one G protein −one response
is showing distinct signs of wear.
Chemokines are small proteins that direct the movement of white blood cells to sites of injury or infection. They are classified based on structural characteristics like the positioning of conserved cysteine residues. The four main classes are CC, CXC, C, and CX3C chemokines. Chemokines bind to G protein-coupled receptors on cells and signal through G proteins and secondary messengers to induce cell migration. Chemokines play roles in processes like inflammation, immunity, and cancer and are implicated in diseases like HIV, arthritis, and transplant rejection.
Market research report on G-Protein Coupled Receptors (GPCR) covers the types of GPCR Families and the various ligands targeting GPCR. The GPCR families covered include Rhodopsin, Secretin, Metabotropic glutamate and Other. The Ligands targeting GPCRs include Peptides or Proteins, Biogenic Amines, Lipids and Other. The report provides market analysis of each of the Families and ligands targeting GPCRs by their respective categories. The study includes estimations and predictions for the total global GPCR Drug targets market and also key regional markets that include North America, Europe, Asia-Pacific and Rest of World. Estimations and predictions (2005-2020) are illustrated graphically with 35 exhibits. Business profiles of 10+ major companies engaged in developing GPCR targeted drugs, GPCR cell lines and GPCR Assays are discussed in the report. The report serves as a guide to global GPCR ?Drug Targets industry, covering more than 100 companies that are engaged in the development of GPCR Targeted Drugs, GPCR Assays Information related to recent product releases, Assay developments, partnerships, collaborations, and mergers and acquisitions is also covered in the report. Compilation of Worldwide Patents and Research related to GPCR Drug Targets is also provided.
Robert J. Lefkowitz and Brian K. Kobilka won the 2012 Nobel Prize in Chemistry for their groundbreaking work studying G-protein–coupled receptors (GPCRs). Their research revealed key insights into how GPCRs function at the molecular level to transmit signals from outside to inside of cells. Specifically, Lefkowitz and Kobilka were able to clone and sequence the first GPCR, detect their binding properties, determine their three-dimensional structure, and elucidate the allosteric mechanism of signal transduction, establishing GPCRs as a family of related receptors. Their seminal findings provided a deeper understanding of the intricate signaling mechanisms of GPCRs and laid the foundation for advancing research and drug development targeting
Polymorphism affecting drug metabolism .heenakazi4
This document discusses genetic polymorphisms that affect drug metabolism. It begins by defining genetic polymorphism and describing the main types, including single nucleotide polymorphisms, insertions and deletions, and nucleotide repeat polymorphisms. It then discusses how genetic polymorphisms can alter drug metabolism through variations in metabolic enzyme activity and discusses specific examples of polymorphisms in key drug metabolizing enzymes like CYP2D6, CYP2C9, and N-acetyltransferases. The document emphasizes how understanding genetic variations in drug metabolism is important for predicting inter-individual differences in drug responses.
The document discusses the major histocompatibility complex (MHC), including its discovery through transplantation experiments in mice, serologic studies in humans, and the structure and function of MHC molecules. MHC molecules present antigen fragments to T cells and play a key role in the immune system by distinguishing self from non-self. There are two major classes of MHC molecules: Class I presents intracellular peptides to cytotoxic T cells, while Class II presents extracellular peptides to helper T cells.
GPCR dimers are ubiquitous in nature and mediate many physiological processes. While evidence suggests most GPCRs function as dimers, criticism remains that not all receptors dimerize under physiological conditions. Techniques like co-immunoprecipitation, FRET, and BRET are used to study dimers, but overexpression models may produce non-physiological dimers. Research now focuses on identifying physiologically relevant dimers expressed together in native cell types. The drug development paradigm is also shifting from single molecular targets to pathway-based models using in vivo screening of primary cell cultures and stem cells to better represent human biology.
1 (2013) role of the gut microbiota in immunity and inflammatory diseaseDaniel Chan
The gut microbiota plays an important dual role in both immunity and inflammatory disease. It helps develop gut-associated lymphoid tissues and regulates the development of T helper 17 cells and regulatory T cells, which are important for host defense and maintaining gut homeostasis. The microbiota also influences IgA-producing B cells and plasma cells in the intestine. Breakdown of the normal microbiota increases the risk of pathogen infection and inflammatory disease. Understanding the complex interactions between the microbiota, pathogens, and the immune system may provide insights into disease pathogenesis and new treatment approaches.
ROLE OF PATHOGEN ASSOCIATED MOLECULAR PATTERN IN PERIODONAL DISEASE.pptxDrPOOJAMAGAJIKONDI
1. Pathogen-associated molecular patterns (PAMPs) produced by bacteria in dental plaque activate pattern recognition receptors like Toll-like receptors (TLRs) which initiate innate immune responses involved in periodontal disease.
2. TLRs recognize specific PAMPs like lipopolysaccharide, lipoproteins, peptidoglycan, and CpG DNA. Activation of TLRs leads to proinflammatory cytokine production and tissue destruction if the immune response is not regulated.
3. In periodontal health, commensal bacteria predominate and tolerance mechanisms limit immune activation, while periodontal disease involves dysbiotic microbiota containing pathogens that strongly activate TLR-mediated inflammation through their PAMPs
Toll-like receptors (TLRs) play a key role in the innate immune system by recognizing pathogen-associated molecular patterns (PAMPs) from bacteria, viruses, and parasites. TLRs activate signaling pathways that launch immune responses. Membrane-bound TLRs recognize bacterial components, while endosomal TLRs recognize nucleic acids from viruses and bacteria. TLR activation leads to production of cytokines and inflammatory responses. TLR signaling on dendritic cells, macrophages, and mast cells initiates innate responses and also links innate and adaptive immunity by activating T cells. Polymorphisms in TLRs impact susceptibility to various infections.
The document discusses host microbial interactions and the innate immune response. It describes how pattern recognition receptors (PRRs) like Toll-like receptors (TLRs) recognize pathogen associated molecular patterns (PAMPs) from bacteria. TLRs activate signaling pathways that induce inflammation and the production of cytokines and antimicrobial peptides. The document outlines TLR expression and function in various periodontal tissues and resident cells, and how periodontal pathogens can stimulate inflammatory responses through PRRs, potentially contributing to periodontal disease.
The innate immune response is the first line of defense against infection and predates the adaptive immune response. It uses germline-encoded pattern recognition receptors (PRRs) to recognize pathogen-associated molecular patterns (PAMPs) and initiate a proinflammatory response. The major PRR families are Toll-like receptors (TLRs), RIG-I-like receptors (RLRs), NOD-like receptors (NLRs), and C-type lectin receptors (CLRs). TLRs recognize bacteria and viruses at the cell surface and within endosomes, and signal through either the MyD88 or TRIF adaptor pathways to induce inflammatory cytokines and type I interferons. NLRs and RLRs function
Toll-like receptors (TLRs) are immune sensors that detect pathogen-associated molecular patterns and induce inflammatory responses. TLRs activate signaling cascades that lead to the production of cytokines and immune cell activation through adaptor proteins and kinases. Dysregulation of TLR signaling can cause or contribute to immune deficiencies, autoimmune diseases, and cancers. The document discusses TLR structure and function, downstream signaling pathways, regulation of the response, and diseases associated with TLR signaling abnormalities.
This document provides an overview of the molecular biology of the host-microbe interaction in periodontal disease. It discusses how the innate immune system recognizes microbes via pattern recognition receptors like TLRs. It also describes how innate immunity initiates and modulates the adaptive immune response. Key aspects of the pathogenesis of periodontal disease are explained, including the roles of pro-inflammatory cytokines, RANKL signaling, and MMPs in degrading periodontal tissues. Host genetic variations and intracellular signaling pathways are also discussed in modulating susceptibility to periodontal disease.
The document discusses innate immunity and inflammation. It describes the innate immune system, including macrophages and their polarization. Macrophages are primary phagocytic cells that can be polarized into M1 and M2 phenotypes. The document also discusses phagocytosis, inflammation, acute and chronic inflammation, and the inflammatory response mechanism involving pathways such as TLR and NF-κB. Pattern recognition receptors activate these pathways to trigger innate and inflammatory responses.
Host microbial interactions in periodontal diseasesDr Heena Sharma
The document summarizes host microbial interactions in periodontal diseases. It describes how the junctional epithelium initiates the innate immune response through neutrophils and macrophages. The innate response includes neutrophil response, complement system, and toll-like receptors. The adaptive response involves antigen presentation and generation of T-cell and B-cell responses. Key components of the innate response discussed are epithelial antimicrobial peptides, complement pathways, and toll-like receptor signaling and roles.
Evaluation and importance of innate & adaptive immunity Dr. ihsan edan ab...dr.Ihsan alsaimary
Dr. ihsan edan abdulkareem alsaimary
PROFESSOR IN MEDICAL MICROBIOLOGY AND MOLECULAR IMMUNOLOGY
ihsanalsaimary@gmail.com
mobile : 009647801410838
university of basrah - college of medicine - basrah -IRAQ
This document discusses host modulation therapies for the treatment of periodontal disease. It first introduces concepts of host modulation and describes how therapies aim to downregulate destructive aspects of the host inflammatory response. A major focus is on matrix metalloproteinases (MMPs), which degrade connective tissue during periodontal disease. The document outlines various stages of MMP inhibition that could be targeted therapeutically, including inhibiting MMP induction, activation of latent MMPs, and upregulating natural MMP inhibitors. It provides extensive details on the mechanisms and clinical studies of sub-antimicrobial doses of doxycycline, one of the few approved host modulation drugs for treating periodontitis.
The document summarizes Toll-like receptors (TLRs) and their role in innate immunity. It discusses how TLRs were first discovered in invertebrates and then found to have vertebrate homologs. TLRs recognize pathogen-associated molecular patterns and trigger signaling pathways that induce antimicrobial responses. There are 10 TLRs in humans that recognize distinct microbial ligands. TLR signaling involves adaptor proteins and transcription factors that activate genes encoding inflammatory cytokines, chemokines, and interferons.
THE ROLE OF MACROPHAGE IN PERIODONTICS.pptxPrasanthThalur
The document discusses the role of macrophages and innate immunity in periodontitis. It describes how macrophages recognize pathogens via pattern recognition receptors like toll-like receptors and NLR inflammasomes. This activation of these receptors triggers signaling cascades that promote inflammation and the secretion of cytokines. Overactivation of these pathways can lead to excessive inflammation and tissue damage. The document also explains that macrophages can polarize into pro-inflammatory M1 or anti-inflammatory M2 states, and their plasticity and different states influence periodontitis development.
The document summarizes key aspects of innate immunity and the complement system. It describes how the complement system recognizes microbes via three pathways: the classical, lectin, and alternative pathways. It also outlines the three main functions of complement in host defense: opsonization, chemotaxis, and formation of the membrane attack complex. The summary concludes by mentioning how deficiencies in complement proteins can increase susceptibility to certain infections.
This document discusses autoinflammatory diseases, which are characterized by dysregulation of the innate immune system leading to recurrent, unprovoked inflammation without high autoantibodies or T cells. Common autoinflammatory diseases are caused by mutations that activate the inflammasomes or interferon pathways. Autoinflammatory diseases typically begin in childhood and can cause fever, rash, and organ inflammation. The pathophysiology involves cytosolic pattern recognition receptors such as NLRs, RLRs, and DNA sensors that activate the inflammasomes or interferon response when mutated.
1. The document discusses fundamentals of host defense and innate immunity, focusing on physical and chemical defenses, the inflammatory response, and cellular defenses as part of the innate immune system.
2. Pattern recognition receptors (PRRs) play an important role in innate immunity by recognizing pathogen-associated molecular patterns (PAMPs) from microbes. Toll-like receptors (TLRs) are a major class of PRRs that signal the presence of various pathogens.
3. Innate immunity provides rapid response to infection prior to adaptive immunity and helps initiate adaptive immune responses through cytokines and antigen presentation. Therapeutic manipulation of TLRs may enhance or suppress immune responses.
This presentation answers the following questions!!
How Immune Cells communicate with each other?
Receptors of Immune System?
Receptors of Innate Immune System?
What are PRRS?
What are PAMPS?
What are DAMPS?
What is the structure of PRRS?
What is the mechanism of PRRS?
What are the types of PRRS?
What is the role of PRRS in Immunology?
RECEPTOR DIVERSITY OF INNATE IMMUNITY.pptxJustinMutua
- Innate immunity relies on pattern recognition receptors (PRRs) like Toll-like receptors (TLRs) and Nod-like receptors (NLRs) to recognize pathogens.
- TLRs and NLRs activate immune responses upon binding pathogen-associated molecular patterns. TLR4 recognizes LPS from gram-negative bacteria while TLR2 recognizes components from gram-positive bacteria.
- Nod1 and Nod2 are intracellular NLRs. Nod1 detects peptidoglycan fragments from gram-negative bacteria containing meso-diaminopimelic acid while Nod2 detects muramyl dipeptide found in peptidoglycan of most bacteria. Binding of ligands activates NF-kB and MAPK
Toll-like receptors (TLRs) play a key role in the innate immune system and recognize distinct pathogen molecules. TLRs signal through either a MyD88-dependent or TRIF-dependent pathway to activate pro-inflammatory genes. Dysregulation of TLR signaling contributes to inflammatory diseases like sepsis, atherosclerosis, and systemic lupus erythematosus. Inhibiting TLRs through small molecule inhibitors, antibodies, oligonucleotides, or lipid A analogs may help treat these diseases. However, few TLR antagonists have been approved for clinical use.
This course required us to present an article which prof gave us randomly. And my article is a review paper related to TLR signaling! I upload here just hope that it can be useful for someone who is interested in this approach for studyding TLR signaling dynamics based on Synthetic ligands!
Many thanks for your look at my presentation and leave some comments if I got mistakes inside!
Does Over-Masturbation Contribute to Chronic Prostatitis.pptxwalterHu5
In some case, your chronic prostatitis may be related to over-masturbation. Generally, natural medicine Diuretic and Anti-inflammatory Pill can help mee get a cure.
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Cell Therapy Expansion and Challenges in Autoimmune DiseaseHealth Advances
There is increasing confidence that cell therapies will soon play a role in the treatment of autoimmune disorders, but the extent of this impact remains to be seen. Early readouts on autologous CAR-Ts in lupus are encouraging, but manufacturing and cost limitations are likely to restrict access to highly refractory patients. Allogeneic CAR-Ts have the potential to broaden access to earlier lines of treatment due to their inherent cost benefits, however they will need to demonstrate comparable or improved efficacy to established modalities.
In addition to infrastructure and capacity constraints, CAR-Ts face a very different risk-benefit dynamic in autoimmune compared to oncology, highlighting the need for tolerable therapies with low adverse event risk. CAR-NK and Treg-based therapies are also being developed in certain autoimmune disorders and may demonstrate favorable safety profiles. Several novel non-cell therapies such as bispecific antibodies, nanobodies, and RNAi drugs, may also offer future alternative competitive solutions with variable value propositions.
Widespread adoption of cell therapies will not only require strong efficacy and safety data, but also adapted pricing and access strategies. At oncology-based price points, CAR-Ts are unlikely to achieve broad market access in autoimmune disorders, with eligible patient populations that are potentially orders of magnitude greater than the number of currently addressable cancer patients. Developers have made strides towards reducing cell therapy COGS while improving manufacturing efficiency, but payors will inevitably restrict access until more sustainable pricing is achieved.
Despite these headwinds, industry leaders and investors remain confident that cell therapies are poised to address significant unmet need in patients suffering from autoimmune disorders. However, the extent of this impact on the treatment landscape remains to be seen, as the industry rapidly approaches an inflection point.
Local Advanced Lung Cancer: Artificial Intelligence, Synergetics, Complex Sys...Oleg Kshivets
Overall life span (LS) was 1671.7±1721.6 days and cumulative 5YS reached 62.4%, 10 years – 50.4%, 20 years – 44.6%. 94 LCP lived more than 5 years without cancer (LS=2958.6±1723.6 days), 22 – more than 10 years (LS=5571±1841.8 days). 67 LCP died because of LC (LS=471.9±344 days). AT significantly improved 5YS (68% vs. 53.7%) (P=0.028 by log-rank test). Cox modeling displayed that 5YS of LCP significantly depended on: N0-N12, T3-4, blood cell circuit, cell ratio factors (ratio between cancer cells-CC and blood cells subpopulations), LC cell dynamics, recalcification time, heparin tolerance, prothrombin index, protein, AT, procedure type (P=0.000-0.031). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and N0-12 (rank=1), thrombocytes/CC (rank=2), segmented neutrophils/CC (3), eosinophils/CC (4), erythrocytes/CC (5), healthy cells/CC (6), lymphocytes/CC (7), stick neutrophils/CC (8), leucocytes/CC (9), monocytes/CC (10). Correct prediction of 5YS was 100% by neural networks computing (error=0.000; area under ROC curve=1.0).
Histololgy of Female Reproductive System.pptxAyeshaZaid1
Dive into an in-depth exploration of the histological structure of female reproductive system with this comprehensive lecture. Presented by Dr. Ayesha Irfan, Assistant Professor of Anatomy, this presentation covers the Gross anatomy and functional histology of the female reproductive organs. Ideal for students, educators, and anyone interested in medical science, this lecture provides clear explanations, detailed diagrams, and valuable insights into female reproductive system. Enhance your knowledge and understanding of this essential aspect of human biology.
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3. Introduction
The host response is defined as the defense
mechanism of the host against exogenous
microorganisms.
Periodontium is a dynamic remodelling tissue
challenged by bacterial biofilms colonizing
proximal odontogenic and mucosal surfaces.
Extensive molecular research has elucidated
that the host immune response is the primary
mediator of periodontal tissue destruction.
5. Evolutionary conserved molecular motifs
present in microorganisms. Found in higher
eukaryotes.
Include microbial cell wall macromolecules,
nucleic acids and flagellin which functions as
ligands.
Contributes to pathophysiologic tissue
destruction in chronic inflammatory disease
states such as periodontitis
12. Recognition of MAMPs by innate immune cells
stimulates the secretion of proinflammatory
cytokines
Examples: IL-1β, IL-6, TNF and type 1 interferons
(IFN-α ,IFN- β)
Upregulates the production of co-stimulatory
molecules.
PRRs are considered the bridge between the innate
and adaptive immune systems.
16. Plasma membrane TLR signalling induces the
expression of proinflammatory cytokines
Endolysosomal TLR signalling predominantly induces
the expression of type 1 IFNs.
TLRs localized to the plasma membrane recognize
extracellular microbial cell wall components (TLR 1,
TLR 2, TLR 4, TLR 6) or flagellin (TLR 5).
TLRs localized to the endolysosomal membrane
recognize microbial nucleic acids (TLR 3, TLR 7, TLR
8,TLR 9)
17. TLR 2 and TLR 4 recognises the extracellular
bacterial cell wall components at the cell surface
TLR 9 is addressed with regard to recognizing
bacterial nucleic acids within endosomes.
TLRs are single pass transmembrane proteins
characterized-
1. N-terminal leucine rich recognition domain
2. C-terminal (intracellular) Toll/IL1 receptor
signalling domain (TIR).
18. Myeloid
differentiation
primary response
protein 88 (MYD88)
TRIF related adaptor
molecule (TRAM)
MYD88 adaptor like
protein (MAL)
TIR domain
containing adaptor
protein inducing IFN-
β (TRIF)
TIR domain of TLRs act as a scaffold to recruit
various TIR domain containing adaptor proteins
19. Toll Like Receptor-4 Lipopolysaccharide
Recognition
Oral bacterial interactions with host TLRs are
largely dependent on the exposed macromolecules.
Lipoproteins are common constituents of the outer
membranes of both gram –ve and +ve bacteria.
LPS is the major macromolecule composing the
outer surface envelope of gram negative bacteria.
20. It induces a host immune response through recognition
of lipid A.
LPS is typically made up of three domains
Lipid A
O-Antigen
A short core
oligosaccharide
21. Mammalian cells recognize LPS through-
LBP processes and delivers LPS to CD14 which
sensitizes cells for LPS binding by MD2-TLR-4 receptor.
TLR-4
homodimer
protein
complex
consisting of
TLR-4
Coreceptor
myeloid
differentiati
on factor 2
(MD2)
Accessory
proteins
CD14 and
LBP
22. Toll Like Receptor-2- Lipoprotein/Lipoteichoic
Acid/Peptidoglycan Recognition
TLR-2 has the capacity to recognize diverse
microbial macromolecules.
Forms heterodimer protein complexes with other
TLR family members (TLR-1, TLR-6)
TLR-2 ligands are highly relevant to oral flora
interactions with host cells include lipoproteins,
LTA and peptidoglycan.
23. Triacylated lipoproteins are recognized by TLR-
2/TLR-1 heterodimer complex.
Diacylated lipoproteins are recognized by TLR-
2/TLR-6 heterodimer complex.
LTA and peptidoglycan are recognized by
incompletely characterized TLR-2/TLR-6
heterodimer complexes.
24. Toll Like Receptor-9-CpG-DNA
Recognition
TLR-9 is different from TLR-2 and TLR-4 and
recognizes MAMPs in endosomes.
TLR-9 is the endosomal TLR family member that
recognizes intracellular microbial nucleic acids.
During infection, microbe derived nucleic acids are
sensed by endosomal TLRs.
This sensing facilitates mounting a host immune
response to clear the invading microorganisms.
25. TLR-9 recognizes both viral and bacterial CpG-DNA.
CpG-DNA localized within lysosomal compartments
induces-
1. Trafficking of TLR-9 from the ER to the
endolysosome
2. Activates TLR-9 signal transduction.
26. Role Of Toll Like Receptors In
Periodontitis
Gram–ve bacteria-induced periodontal destruction
is mediated through TLR-2 signal transduction.
Gram–ve bacteria-induced catabolic actions are
1. Differential signalling at the TLR-2 receptor
2. Concomitant activation of TLR-4 receptor by LPS.
P. gingivalis has the ability to stimulate TLR signal
transduction through various MAMPs.
27. P. gingivalis coactivation of TLR-2 and TLR-4 is
critical in stimulating host immune response
mechanisms driving alveolar bone loss.
TLR-9 expression up regulates in clinical
periodontitis tissues when compared with gingivitis
tissues and healthy gingival biopsy samples.
28. Nucleotide Binding Oligomerization Domain
Like Receptors
Currently 22 family members comprise the
intracellularly expressed NLRs in humans.
Localized to the cytosol and play a critical role in
sensing invading microorganisms and prompting the
immune response.
Characterized by-
1. C-terminal leucine rich repeats that act as a
sensing domain(i.e., a NOD)
2. N-terminal effector domain that mediates
downstream signalling.
29. NOD1/NOD2-Peptidoglycan Recognition
NOD1 recognizes gamma-D-glutamyl-
mesodiaminopimelic acid (iE-DAP), a component of
peptidoglycan.
NOD2 recognizes muramyl dipeptide (MDP) which is
found in peptidoglycan.
Peptidoglycan binding at NOD1 and NOD2 receptors
causes their oligomerization.
30. This results in-
1. Recruitment of a serine/threonine kinase adapter
protein.
2. RIP-2/RICK to a caspase activation
3. Recruitment domain (CARD) at the N-terminus
RIP-2/RICK recruitment at the N-terminus
activates NF-κB and MAPK-dependent up
regulation of proinflammatory cytokine genes.
31. NLRP3-Inflammasome Complex
Inflammasomes are multiprotein complexes that-
1. Recognize diverse inflammation-inducing stimuli
including exogenous MAMPs and endogenous DAMPs
2. Control the production of proinflammatory
cytokines
3. Regulate pyroptosis (an inflammatory form of cell
death)
Several PRR families act as components in the
inflammasome complex
32. Recognition of cytosolic MAMPs and DAMPs induces
NLRP3 to act as a scaffold for inactive zymogen pro
caspase-1.
Pro caspase-1(which has a CARD)is recruited to
inflammasome complex through-
1. Homotypic binding of CARD via a pyrin domain
(PYD)
2. Adaptor apoptosis-associated speck like protein
containing a CARD (ASC).
33. Oligomerization of pro-caspase-1 proteins in the
inflammasome leads to their autoproteolytic
cleavage into active caspase-1.
Activated caspase-1 functions to cleave pro IL-1β
and pro-IL-18 into their biologically active form.
36. Role of NOD-Like Receptors in
Periodontitis
NOD1 and NOD2 are expressed in human oral
epithelium, gingival fibroblast cells and periodontal
ligament fibroblast cells.
The knockout mice models found-
1. Mice deficient in NOD2 showed comparable levels
of alveolar bone resorption.
2. Mice deficient in NOD1 demonstrated reduced
levels of alveolar bone loss
37. NOD1 knockout mice had fewer osteoclasts and
lower proinflammatory cytokine expression levels
in gingival tissue isolates.
Another experiment:
1. NOD1 had exacerbated alveolar bone loss,
increased osteoclast numbers.
2. Up-regulated proinflammatory cytokine
expression levels in cultured bone marrow
macrophages.
Hence it is unclear whether NOD1 or NOD2
critically regulates periodontal bone loss
38. MAMPs present in biofilm can activate TLRs and
NOD1/2 signalling which converge at the MAPK and
NF-κB signalling pathways.
NLRP3 and NLRP2 are found to be increased in
human gingival tissues.
IL-1β and IL-18 mRNA expression levels were
increased in gingival tissues affected by periodontal
disease states.
39. Complement System
Periodontal host immune response is dependent on
a functional complement system, which notably
coordinates the recruitment and activation of
immune cells, bacterial opsonisation, phagocytosis
and lysis.
40. Complement-Pattern-Recognition Receptor
Signalling
Some soluble PRR families are also secreted into the
plasma as humoral proteins.
Soluble PRRs represent the functional ancestors of
antibiotics including pentraxins, mannose-binding
lectin (MBL), ficolins and properdin
Soluble PRRs interact with circulating MAMPs and
DAMPs to activate the complement system
42. Classical Pathway:
1. Occurs in response to antigen-antibody complexes
that are recognized by the C1q subunit of C1.
2. C1q activates compliment by functioning as a PRR
to recognize distinct MAMPs and DAMPs
3. Activates through other soluble PRRs such as
pentraxins (i.e. C-reactive protein)
Lectin Pathway:
1. Similarly triggered through soluble PRRs, including
MBL and ficolins which predominantly recognize
carbohydrate groups.
43. Both the pathways then proceed through C4 and C2
cleavage for the generation of the classical/lectin
C3 convertase (C4bC2b)
Alternative Pathway:
1. Initiated by the hydrolysis of C3 to C3(H₂O) which
is a C3b analogue that forms the initial alternative
pathway for C3 convertase.
2. Possesses a PRR based initiation mechanism via
properdin which recognizes MAMPs and DAMPs.
3. Serves as a positive feedback loop for the other
two pathways.
44. Three pathways converge at the third component of
complement (C3)
On activation by pathway-specific C3 convertases
leads to the generation of key effector molecules.
Include C3a and C5a anaphylatoxins which activate
specific G-protein coupled receptor
Mediate the mobilization and activation of
leukocytes.
45. C3b opsonins which promote phagocytosis through
complement receptors
C5b-9 membrane attack complex which can lyse
targeted pathogens
46. Role Of Complement In Periodontitis
Dysregulation of complement activities may lead to
a failure to protect the host against pathogens.
Activated components are found-
1. Higher levels in the GCF of periodontitis patients.
2. Chronically inflammed gingiva
Complement components are non detectable at
lower levels in healthy gingival biopsy specimens.
47. Local complement activation may promote
periodontal inflammation predominantly via
1. C5a induced vasodilation
2. Increases vascular permeability
3. Flow of inflammatory exudate
4. Chemotactic recruitment of inflammatory cells,
especially neutrophils.
48. Antimicrobial Peptides
Components of the innate immune response in
eukaryotes.
Provides defence against a wide spectrum of
gram+ve and gram–ve bacteria, viruses and fungi.
In the oral cavity, 45 different antimicrobial
peptides are found in the saliva and GCF.
49. Defensins and Cathelicidin LL-37
Cationic peptides that bind to negatively charged
molecules on the microbial surfaces.
Examples: LPS in gram-ve bacteria and LTA in
gram+ve bacteria.
Depolarize the cell membrane and render it
permeable with resulting bacterial cell death.
Defensins are modulated by immune response
mediators
50. Based on structural distinctions in the connecting
patterns of three disulphide bonds and in the spacing of
cysteine residues, defensins are
α-Defensins
Β-Defensins
51. 6 human α-defensins and 4 human Β-defensins are
characterized
α-defensins (1-4) present in the oral cavity are
known as human neutrophil peptides due to their
expression in neutrophils.
α-defensins (5 and 6) are localised to the mucosal
Paneth cells of the small intestine.
52. Β-defensins 1-4 are:
1. Produced by a variety of epithelial cells throughout
the body.
2. Produced abundantly by epithelial tissues within the
oral cavity
3. Found in the GCF and saliva.
Cathelicidin LL-37 are
1. Human defense peptide residing in neutrophils
2. Found in the gingival epithelium.
53. Role of Antimicrobial Peptides in
Periodontitis
Specific Β-defensins are located in different
anatomic regions of the periodontal epithelium.
Β-defensins 1 and 2 are observed in :
1. Upper layers of the gingival and sulcular epithelium
2. Adjacent to the microbial biofilm and external
environment
3. Consistent with the innate immune “barrier”
function of the epithelium.
54. Neither Β-defensins 1 or 2 are found in the
junctional epithelium
Protection of JE provided by the higher
concentration of α-defensins 1-3 and LL-37.
Expression of neutrophil derived α-defensins 1-3 and
LL-37 are elevated in the GCF of chronic
periodontitis patients.
Expression of defensins induced by whole
periopathogenic bacteria is largely dependent on
TLR signalling.
55. Immunomodulatory Therapies
MMP inhibitors have been used in combination with
scaling and root planing or surgical therapy.
High risk patient(eg-diabetic patients) have
benefited from the systemic administration of MMP
inhibitors.
Use of soluble antagonists of TNF-α and IL-1β
delivered locally to periodontal tissues in non
human primates has shown good results.
56. Pharmacologic inhibitors of NF-κB and p38 MAPK
pathways are developed to manage rheumatoid
arthritis and inflammatory bone diseases
With the use of this novel strategy, inflammatory
mediators (eg- IL-1, TNF, IL-6) are necessary for
inflammatory gene expression or mRNA stability.
C3 is a central component of all three activation
pathways, blockade at this level is a reasonable
approach for treating periodontitis.
57. CR3 antagonism through topical small molecules
inhibitors has been shown to reduce P. gingivalis –
induced alveolar bone loss
C5a functions as a potent mediator of complement
signalling and neutrophil recruitment that may
protect and mediate excessive neutrophil activation
Has the potential to augment tissue damage during
periodontal disease progression
C5aR inhibitor is used for the treatment and
management of periodontal diseases.
58. Conclusion
Host response contributes to the progression
of the disease. Majority of periodontal
breakdown is caused by host derived
destructive enzymes & inflammatory
mediators. They are released during cascade
of destructive events of inflammatory
response. Paradoxically inflammatory response
which is essentially protective in design is
responsible for much of breakdown of the
periodontium.