The complement system is comprised of over 30 circulating and membrane-bound proteins that act in a cascade to help mediate innate and acquired immunity. It functions through three main pathways - classical, lectin, and alternative - that involve a chain of enzymes cleaving complement proteins and forming complexes that activate other proteins in the cascade. The final steps are identical for all three pathways and allow the complement system to help clear pathogens or immune complexes through lysis, opsonization, and inflammatory responses. Tight regulation is needed since complement is nonspecific and can damage host cells - regulatory mechanisms include short half-lives of proteins and inhibitors that block activity.
1) Streptococcus pneumoniae is a significant cause of morbidity and mortality worldwide. The main virulence factor is the capsular polysaccharide.
2) The study explored the reported restricted gene usage in response to polysaccharide antigens. One variable heavy chain specific for PPS23F was paired with alternative PPS-specific variable light chains to test structural and functional limitations.
3) Analysis found the antibodies maintained specificity for PPS23F but had unique binding characteristics. In contrast to Hib PS, no essential amino acid sequence was identified in the VL CDR3 for PPS23F binding.
This document reviews 8 papers on the structure-function relationships of human antibodies to polysaccharide antigens. The papers show that: (1) Different conjugate vaccines induce different variable region expression in anti-Hib antibodies; (2) Specific residues in the light chain determine expression of the HibId-1 idiotype; (3) Transgenic mice with human immunoglobulin loci can be used to study human antibody responses to pneumococcal polysaccharides. The papers also analyze the molecular ontogeny of infant antibody responses to Hib polysaccharide and how codon insertions contribute to antibody repertoire diversity.
This study investigated the interaction between estrogen receptors (ERs) and caveolin proteins. HEK 293 cells were transfected with either ERα and caveolin-1 (CAV1) or a mutated ERα where a palmitoylation site was altered. Co-immunoprecipitation and western blotting were performed using antibodies that recognize different ERα epitopes. The results showed co-immunoprecipitation between ERα and CAV1 with both antibodies, and similar co-immunoprecipitation between the mutated ERα and CAV1. This preliminary evidence suggests that palmitoylation of cysteine on ERα may not be required for its interaction with CAV1.
This document discusses oxidoreductases, enzymes that catalyze the formation of disulfide bonds, in Neisseria meningitidis. N. meningitidis contains three oxidoreductases, NmDsbA1, NmDsbA2, and NmDsbA3, which share varying levels of amino acid homology. While NmDsbA1 and NmDsbA3 can catalyze disulfide bonds in some substrates like PilE and PilQ, NmDsbA3 cannot catalyze bonds in these substrates. The document examines the structures and functions of the three oxidoreductases to better understand their differing substrate specificities.
This document describes a new method for specifically regulating genes between bacterial species using the CRISPR interference (CRISPRi) system. Researchers engineered a CRISPRi system on a conjugative plasmid to target and repress a fluorescent reporter gene (mRFP) in a recipient E. coli strain. The CRISPRi plasmid was transferred from a donor E. coli strain to the recipient strain through bacterial conjugation. When induced in the recipient, the CRISPRi system specifically repressed mRFP expression by 330-fold without affecting expression of another fluorescent reporter (sfGFP), demonstrating targeted gene regulation between bacterial cells via a natural horizontal gene transfer mechanism.
CRISPR- Trap: a clean approach for the generation of gene knockouts and gene replacements in human cells.- a paper is taken for lab presentation. A very good technique having advantages over conventional KO approaches and allow for the generation of clean CRISPR/ Cas9- based KOs.
The document describes an experiment using CRISPR/Cas9 to introduce mutations into the PNPLA3 gene in HepG2 cells. Sequencing of genomic DNA and mRNA from the cells showed the presence of SNP1, which changes an amino acid, but not SNP2. The researcher will use this sequence as a template to generate four combinations of the SNPs in order to study their effects on fat accumulation when transfected into HepG2 cells. This could provide insight into how genetic variants influence susceptibility to NAFLD in different ethnic groups.
Treatment for lysosomal storage diseases using crispr cas9limchloe
CRISPR/Cas9 gene editing shows promise for treating Lysosomal Storage Diseases (LSDs) by correcting mutations in patient-derived induced pluripotent stem cells (iPSCs). LSDs result from mutations rendering lysosomal enzymes nonfunctional. CRISPR/Cas9 can introduce targeted changes to correct mutations and restore enzyme function. Edited iPSCs could then be differentiated into cell types for transplantation. However, challenges include off-target effects, disease heterogeneity, and ensuring corrected cells effectively treat the disease in vivo. Future work aims to overcome these challenges and develop downstream methods to fully address LSD pathology.
1) Streptococcus pneumoniae is a significant cause of morbidity and mortality worldwide. The main virulence factor is the capsular polysaccharide.
2) The study explored the reported restricted gene usage in response to polysaccharide antigens. One variable heavy chain specific for PPS23F was paired with alternative PPS-specific variable light chains to test structural and functional limitations.
3) Analysis found the antibodies maintained specificity for PPS23F but had unique binding characteristics. In contrast to Hib PS, no essential amino acid sequence was identified in the VL CDR3 for PPS23F binding.
This document reviews 8 papers on the structure-function relationships of human antibodies to polysaccharide antigens. The papers show that: (1) Different conjugate vaccines induce different variable region expression in anti-Hib antibodies; (2) Specific residues in the light chain determine expression of the HibId-1 idiotype; (3) Transgenic mice with human immunoglobulin loci can be used to study human antibody responses to pneumococcal polysaccharides. The papers also analyze the molecular ontogeny of infant antibody responses to Hib polysaccharide and how codon insertions contribute to antibody repertoire diversity.
This study investigated the interaction between estrogen receptors (ERs) and caveolin proteins. HEK 293 cells were transfected with either ERα and caveolin-1 (CAV1) or a mutated ERα where a palmitoylation site was altered. Co-immunoprecipitation and western blotting were performed using antibodies that recognize different ERα epitopes. The results showed co-immunoprecipitation between ERα and CAV1 with both antibodies, and similar co-immunoprecipitation between the mutated ERα and CAV1. This preliminary evidence suggests that palmitoylation of cysteine on ERα may not be required for its interaction with CAV1.
This document discusses oxidoreductases, enzymes that catalyze the formation of disulfide bonds, in Neisseria meningitidis. N. meningitidis contains three oxidoreductases, NmDsbA1, NmDsbA2, and NmDsbA3, which share varying levels of amino acid homology. While NmDsbA1 and NmDsbA3 can catalyze disulfide bonds in some substrates like PilE and PilQ, NmDsbA3 cannot catalyze bonds in these substrates. The document examines the structures and functions of the three oxidoreductases to better understand their differing substrate specificities.
This document describes a new method for specifically regulating genes between bacterial species using the CRISPR interference (CRISPRi) system. Researchers engineered a CRISPRi system on a conjugative plasmid to target and repress a fluorescent reporter gene (mRFP) in a recipient E. coli strain. The CRISPRi plasmid was transferred from a donor E. coli strain to the recipient strain through bacterial conjugation. When induced in the recipient, the CRISPRi system specifically repressed mRFP expression by 330-fold without affecting expression of another fluorescent reporter (sfGFP), demonstrating targeted gene regulation between bacterial cells via a natural horizontal gene transfer mechanism.
CRISPR- Trap: a clean approach for the generation of gene knockouts and gene replacements in human cells.- a paper is taken for lab presentation. A very good technique having advantages over conventional KO approaches and allow for the generation of clean CRISPR/ Cas9- based KOs.
The document describes an experiment using CRISPR/Cas9 to introduce mutations into the PNPLA3 gene in HepG2 cells. Sequencing of genomic DNA and mRNA from the cells showed the presence of SNP1, which changes an amino acid, but not SNP2. The researcher will use this sequence as a template to generate four combinations of the SNPs in order to study their effects on fat accumulation when transfected into HepG2 cells. This could provide insight into how genetic variants influence susceptibility to NAFLD in different ethnic groups.
Treatment for lysosomal storage diseases using crispr cas9limchloe
CRISPR/Cas9 gene editing shows promise for treating Lysosomal Storage Diseases (LSDs) by correcting mutations in patient-derived induced pluripotent stem cells (iPSCs). LSDs result from mutations rendering lysosomal enzymes nonfunctional. CRISPR/Cas9 can introduce targeted changes to correct mutations and restore enzyme function. Edited iPSCs could then be differentiated into cell types for transplantation. However, challenges include off-target effects, disease heterogeneity, and ensuring corrected cells effectively treat the disease in vivo. Future work aims to overcome these challenges and develop downstream methods to fully address LSD pathology.
Homology modeling and functional testing of an abca1Pram Priyanca
The document discusses homology modeling and functional testing of an ABCA1 mutation that causes Tangier disease. Key points:
1. A homology model of the ABCA1 protein was constructed and found that the R1068 residue interacts with nearby residues important for ATP binding.
2. Cholesterol efflux assays showed that fibroblasts from Tangier disease patients had reduced efflux compared to wildtype, which increased with LXR stimulation.
3. While the R1068H mutation did not affect ABCA1 expression levels, confocal microscopy revealed defective trafficking of the mutant protein to the plasma membrane.
4. The results suggest the mutation disrupts the ABCA1 monomer structure around the
The document summarizes the complement system, which consists of over 20 proteins that work together to eliminate pathogens. It operates through three pathways - the classical, lectin, and alternative pathways. The classical pathway requires antibodies, while the alternative pathway can be activated independently of antibodies by pathogens. All three pathways involve a cascade of proteins that activate each other, ultimately forming the membrane attack complex that lyses the target cell membrane. The complement system also has roles beyond direct lysis, such as opsonization, inflammation, and activation of the immune response.
This paper describes a regulatory pathway controlling expression of Borrelia burgdorferi OspC and DbpA proteins. The study found that in B. burgdorferi strain 297, the alternative sigma factor RpoN controls expression of the alternative sigma factor RpoS. RpoS then governs expression of the outer surface lipoproteins OspC and DbpA. This regulatory network was determined through targeted gene disruption of rpoN and rpoS, followed by genetic complementation. The findings provide insight into key regulatory networks that impact B. burgdorferi pathogenesis, host range, and virulence.
This document summarizes research investigating the biosynthesis and processing of succinate dehydrogenase (SDH) subunits in cultured mammalian cells. The key points are:
1. Antisera were produced against purified bovine heart SDH and its large and small subunits, which detected precursor and mature forms of the subunits in rat, pig, and bovine cell lines.
2. In pig kidney cells, newly synthesized precursors of the large and small SDH subunits were detected that were 1000-2000 and 4000-5000 Da larger than the mature forms, respectively.
3. Pulse-chase experiments showed the precursor forms were fully processed to the mature subunits within 45 minutes when uncouplers of
This study used CRISPR Cas9 to knockout the KDM6A gene in human pancreatic cancer cell lines to investigate the clinical and biological impacts of KDM6A deficiency. The knockout of KDM6A led to increased cell proliferation, migration, and invasion compared to wild type cells. It also decreased the enrichment of H3K27ac at tumor suppressor genes. Therefore, KDM6A acts as a tumor suppressor in pancreatic cancer by activating tumor suppressor genes through H3K27 demethylation and acetylation. Targeting KDM6A deficiency with HDAC inhibitors may be a potential therapeutic strategy for this cancer subtype.
Modulation of MMP and ADAM gene expression in human chondrocytes by IL-1 and OSMpjtkoshy
The document examines the effects of interleukin-1 (IL-1) and oncostatin M (OSM) on the expression of matrix metalloproteinase (MMP), ADAM, and ADAM-TS genes in human chondrocytes. The study finds that IL-1 and OSM synergistically induce expression of the collagen-degrading enzymes MMP-1, MMP-8, MMP-13, and MMP-14 as well as the aggrecan-degrading enzyme ADAM-TS4. In particular, MMP-1, MMP-3, and MMP-13 expression is induced early, while MMP-8 expression occurs later. IL-1 and OSM also synergistically induce MMP
The document describes research identifying a small molecule called BRD7389 that induces insulin expression in pancreatic α-cells. Key findings include:
1) BRD7389 was identified in a high-throughput screen as inducing insulin expression in mouse α-cells. It also increased expression of the β-cell marker genes Pdx1, Pax4, Iapp, and Npy.
2) Treatment with BRD7389 caused α-cells to take on a clustered morphology resembling β-cells and to express low levels of insulin protein.
3) Profiling and biochemical assays identified BRD7389 as an inhibitor of RSK kinases, and knockdown experiments supported a role for RSK kin
Correction IARS syndrome using CRISPR/Cas9 in Japanese Black CattleBoon Keat Ngan
1. CRISPR/Cas9 was used to repair a mutation in the IARS gene that causes growth retardation and death in Japanese Black cattle calves.
2. The mutation site was targeted using a sgRNA and Cas9 nuclease, and a donor DNA template was used to introduce the correct sequence.
3. Analysis of genome-edited fibroblast cell lines showed that the IARS mutation was precisely repaired without additional DNA changes.
This document summarizes Federica Campana's doctoral thesis on investigating drug-cell membrane interactions using molecular dynamics simulations. The thesis examines how membrane composition influences the effects of membrane fluidizers and heat shock protein co-inducers. It also analyzes the binding of anti-inflammatory molecules like hydroxyarachidonic acid to cyclooxygenase enzymes. The overall goal is to better understand how drug molecules interact with and modulate lipid bilayer properties at a molecular level.
Characterization of the human HCN1 channel and its inhibition by capsazepineShahnaz Yusaf
1. The human hyperpolarization-activated cyclic nucleotide-gated 1 (hHCN1) subunit was expressed in mammalian cell lines and its electrophysiological properties were characterized using patch-clamp recordings.
2. Activation of hHCN1 generated a slowly activating, non-inactivating inward current similar to native hyperpolarization-activated currents (Ih). Ih was blocked by known blockers Cs+, ZD 7288, and zatebradine.
3. The VR1 receptor antagonist capsazepine inhibited hHCN1-mediated currents in a concentration-dependent, reversible manner by shifting the activation curve and slowing current activation kinetics.
This study aimed to identify the site of ubiquitination on Activation-Induced Cytidine Deaminase (AID) by the ubiquitin ligase RING Finger Protein 126 (RNF126). Using site-directed mutagenesis, the researchers found that mutating all lysine residues (K0 mutant) prevented ubiquitination, suggesting ubiquitination occurs on a lysine. Analysis of single lysine mutants revealed the K22 mutant still showed ubiquitination, indicating K22 is the main site. However, RNF126 can ubiquitinate AID at other residues as well. Together, this suggests RNF126 favors K22 as the primary ubiquitination site on AID, though it can modify AID at additional
The document provides an overview of the complement system including:
1) It describes the three pathways of complement activation - the classical, lectin, and alternative pathways. It explains the proteins involved in each pathway and their functions.
2) Regulatory mechanisms of complement activation are discussed including factors and receptors that inhibit inappropriate complement activation on host cells.
3) The biological functions of complement activation are summarized including opsonization, initiation of inflammation, and direct lysis of pathogens.
4) Complement-related disorders are briefly mentioned including those associated with deficiencies in early classical pathway components.
This study analyzed epigenomic and transcriptomic regulation in human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs) using an integrated approach with ChIP-seq, RNA-seq, and BS-seq data. The results showed that iPSCs were not fully reprogrammed to an hESC-like state at the epigenetic level. Specifically, certain epigenetic regulators like KDM2B and DNMT3B exhibited different chromatin positioning and methylation in iPSCs compared to hESCs. KDM2B, which promotes iPSC generation, was not expressed and highly methylated in iPSCs. This suggests that iPSC reprogramming
This document summarizes an RNA project focused on inhibition of Dipeptidyl peptidase-IV (DPP-IV), a treatment for Type 2 Diabetes. Key components included:
1) An Internal Ribosome Entry Site (IRES) to allow translation of multiple protein coding regions. Two IRES sequences from EMCV and NKRF were characterized.
2) A neomycin gene to confer antibiotic resistance for selection.
3) An aptazyme as an RNA "kill switch" activated by theophylline.
4) siRNA targeting the 3' untranslated region of DPP-IV mRNA for cleavage.
5) An RNA-dependent RNA polymerase (
The Efficiency and Ethics of the CRISPR System in Human EmbryosStephen Cranwell
This document summarizes research on the CRISPR/Cas9 system for genome editing in human embryos. It discusses efforts to understand DNA repair mechanisms after inducing double-strand breaks, reduce off-target mutations, and improve the specificity and efficiency of editing. While the technology shows promise, significant issues around off-target effects, mosaicism, and ethical concerns must still be addressed before any clinical applications. The document concludes that further basic research is needed to advance the field while also having open discussions on societal implications.
Taxol and 10-deacetylbaccatinIII induce distinct changesNeesar Ahmed
The document summarizes a study comparing the effects of Taxol, 10-deacetylbaccatinIII (10-DAB), and BaccatinIII (BacIII) on caveolae dynamics in HeLa cells expressing GFP-Caveolin-1. The key findings are:
1) Taxol treatment caused a transient recruitment of Caveolin-1 to the cell surface followed by internalization, while 10-DAB increased the "kiss and run" dynamics of caveolae.
2) Sustained Caveolin-1 phosphorylation was observed with both Taxol and 10-DAB treatments, with Taxol also inducing phosphorylation of Raf-1, ERK1/2,
1. The document analyzes a serine protease gene found in QPX, a pathogen of quahogs. It was found to belong to the subtilase family and contain the catalytic triad of amino acids.
2. Expression of the serine protease gene varied across QPX strains and was temperature dependent, being significantly upregulated during contact with host tissue.
3. A serine protease inhibitor gene was found in quahogs that likely plays a role in the immune response against QPX infection. Expression of this gene varied across quahog strains.
This study examines the degradation pathway of the thiazide-sensitive NaCl cotransporter (NCC) in yeast and mammalian cells. The authors show that NCC is a substrate of endoplasmic reticulum-associated degradation (ERAD) in yeast. Using yeast strains with mutations in ERAD components, they identify the E3 ubiquitin ligase Hrd1 and the cytoplasmic Hsp70 chaperone Ssa1/Hsp70 as important for NCC ubiquitination and degradation. Expression of NCC in mammalian kidney cells reveals similar polyubiquitination and proteasome-dependent degradation. Cytoplasmic Hsp70 preferentially associates with immature glycosylated NCC, indicating its role
1. Researchers administered an AAV9 gene therapy vector expressing CLN3 to a mouse model of CLN3 disease via tail vein or retro-orbital injections.
2. Viral genome copy numbers were measured in various tissues 7 days later, ranging from 2.80x10^3 to 1.56x10^7 copies per microgram of DNA.
3. No significant differences were found between the injection methods, supporting the use of tail vein injections for future efficacy and toxicology studies in mice to enable human clinical trials for this fatal pediatric disease.
Comparing internalization in cells expressing the wild-type andAndalus Ayaz
This study investigated the internalization of wild-type and mutant forms of the VSV-G protein in cells. The researchers mutated basic amino acids in the cytoplasmic tail of VSV-G to neutral amino acids to see if this affected internalization. They found that lower expressing cells internalized wild-type VSV-G faster, and that wild-type and mutant VSV-G were expressed at the same level on the plasma membrane but the mutant was expressed at a significantly lower level within cells overall. Further studies are needed to understand why and investigate if mutant VSV-G transport or degradation is impaired.
The complement system is comprised of over 30 circulating and membrane-bound proteins that act in a cascade to help mediate innate and acquired immunity. It functions through three main pathways - classical, lectin, and alternative - that involve a chain of enzymes cleaving complement proteins and forming complexes that activate other proteins in the cascade. The final steps are identical for all three pathways and allow the complement system to help clear pathogens through mechanisms like opsonization, inflammation, and lysis. Tight regulation is needed since complement is nonspecific and can damage host cells - regulatory proteins inhibit activity and many components have short half-lives.
This document provides an overview of the content covered in a health and social care course over the period of one week. It discusses key topics like different types of health and social care provision including statutory, private and voluntary services. It also covers important values and legislation related to working in the health and social care sector. Various class activities are outlined like discussing the role of informal carers and demonstrating care values through practical examples. Learners' objectives and outcomes are also stated for the topics discussed.
Homology modeling and functional testing of an abca1Pram Priyanca
The document discusses homology modeling and functional testing of an ABCA1 mutation that causes Tangier disease. Key points:
1. A homology model of the ABCA1 protein was constructed and found that the R1068 residue interacts with nearby residues important for ATP binding.
2. Cholesterol efflux assays showed that fibroblasts from Tangier disease patients had reduced efflux compared to wildtype, which increased with LXR stimulation.
3. While the R1068H mutation did not affect ABCA1 expression levels, confocal microscopy revealed defective trafficking of the mutant protein to the plasma membrane.
4. The results suggest the mutation disrupts the ABCA1 monomer structure around the
The document summarizes the complement system, which consists of over 20 proteins that work together to eliminate pathogens. It operates through three pathways - the classical, lectin, and alternative pathways. The classical pathway requires antibodies, while the alternative pathway can be activated independently of antibodies by pathogens. All three pathways involve a cascade of proteins that activate each other, ultimately forming the membrane attack complex that lyses the target cell membrane. The complement system also has roles beyond direct lysis, such as opsonization, inflammation, and activation of the immune response.
This paper describes a regulatory pathway controlling expression of Borrelia burgdorferi OspC and DbpA proteins. The study found that in B. burgdorferi strain 297, the alternative sigma factor RpoN controls expression of the alternative sigma factor RpoS. RpoS then governs expression of the outer surface lipoproteins OspC and DbpA. This regulatory network was determined through targeted gene disruption of rpoN and rpoS, followed by genetic complementation. The findings provide insight into key regulatory networks that impact B. burgdorferi pathogenesis, host range, and virulence.
This document summarizes research investigating the biosynthesis and processing of succinate dehydrogenase (SDH) subunits in cultured mammalian cells. The key points are:
1. Antisera were produced against purified bovine heart SDH and its large and small subunits, which detected precursor and mature forms of the subunits in rat, pig, and bovine cell lines.
2. In pig kidney cells, newly synthesized precursors of the large and small SDH subunits were detected that were 1000-2000 and 4000-5000 Da larger than the mature forms, respectively.
3. Pulse-chase experiments showed the precursor forms were fully processed to the mature subunits within 45 minutes when uncouplers of
This study used CRISPR Cas9 to knockout the KDM6A gene in human pancreatic cancer cell lines to investigate the clinical and biological impacts of KDM6A deficiency. The knockout of KDM6A led to increased cell proliferation, migration, and invasion compared to wild type cells. It also decreased the enrichment of H3K27ac at tumor suppressor genes. Therefore, KDM6A acts as a tumor suppressor in pancreatic cancer by activating tumor suppressor genes through H3K27 demethylation and acetylation. Targeting KDM6A deficiency with HDAC inhibitors may be a potential therapeutic strategy for this cancer subtype.
Modulation of MMP and ADAM gene expression in human chondrocytes by IL-1 and OSMpjtkoshy
The document examines the effects of interleukin-1 (IL-1) and oncostatin M (OSM) on the expression of matrix metalloproteinase (MMP), ADAM, and ADAM-TS genes in human chondrocytes. The study finds that IL-1 and OSM synergistically induce expression of the collagen-degrading enzymes MMP-1, MMP-8, MMP-13, and MMP-14 as well as the aggrecan-degrading enzyme ADAM-TS4. In particular, MMP-1, MMP-3, and MMP-13 expression is induced early, while MMP-8 expression occurs later. IL-1 and OSM also synergistically induce MMP
The document describes research identifying a small molecule called BRD7389 that induces insulin expression in pancreatic α-cells. Key findings include:
1) BRD7389 was identified in a high-throughput screen as inducing insulin expression in mouse α-cells. It also increased expression of the β-cell marker genes Pdx1, Pax4, Iapp, and Npy.
2) Treatment with BRD7389 caused α-cells to take on a clustered morphology resembling β-cells and to express low levels of insulin protein.
3) Profiling and biochemical assays identified BRD7389 as an inhibitor of RSK kinases, and knockdown experiments supported a role for RSK kin
Correction IARS syndrome using CRISPR/Cas9 in Japanese Black CattleBoon Keat Ngan
1. CRISPR/Cas9 was used to repair a mutation in the IARS gene that causes growth retardation and death in Japanese Black cattle calves.
2. The mutation site was targeted using a sgRNA and Cas9 nuclease, and a donor DNA template was used to introduce the correct sequence.
3. Analysis of genome-edited fibroblast cell lines showed that the IARS mutation was precisely repaired without additional DNA changes.
This document summarizes Federica Campana's doctoral thesis on investigating drug-cell membrane interactions using molecular dynamics simulations. The thesis examines how membrane composition influences the effects of membrane fluidizers and heat shock protein co-inducers. It also analyzes the binding of anti-inflammatory molecules like hydroxyarachidonic acid to cyclooxygenase enzymes. The overall goal is to better understand how drug molecules interact with and modulate lipid bilayer properties at a molecular level.
Characterization of the human HCN1 channel and its inhibition by capsazepineShahnaz Yusaf
1. The human hyperpolarization-activated cyclic nucleotide-gated 1 (hHCN1) subunit was expressed in mammalian cell lines and its electrophysiological properties were characterized using patch-clamp recordings.
2. Activation of hHCN1 generated a slowly activating, non-inactivating inward current similar to native hyperpolarization-activated currents (Ih). Ih was blocked by known blockers Cs+, ZD 7288, and zatebradine.
3. The VR1 receptor antagonist capsazepine inhibited hHCN1-mediated currents in a concentration-dependent, reversible manner by shifting the activation curve and slowing current activation kinetics.
This study aimed to identify the site of ubiquitination on Activation-Induced Cytidine Deaminase (AID) by the ubiquitin ligase RING Finger Protein 126 (RNF126). Using site-directed mutagenesis, the researchers found that mutating all lysine residues (K0 mutant) prevented ubiquitination, suggesting ubiquitination occurs on a lysine. Analysis of single lysine mutants revealed the K22 mutant still showed ubiquitination, indicating K22 is the main site. However, RNF126 can ubiquitinate AID at other residues as well. Together, this suggests RNF126 favors K22 as the primary ubiquitination site on AID, though it can modify AID at additional
The document provides an overview of the complement system including:
1) It describes the three pathways of complement activation - the classical, lectin, and alternative pathways. It explains the proteins involved in each pathway and their functions.
2) Regulatory mechanisms of complement activation are discussed including factors and receptors that inhibit inappropriate complement activation on host cells.
3) The biological functions of complement activation are summarized including opsonization, initiation of inflammation, and direct lysis of pathogens.
4) Complement-related disorders are briefly mentioned including those associated with deficiencies in early classical pathway components.
This study analyzed epigenomic and transcriptomic regulation in human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs) using an integrated approach with ChIP-seq, RNA-seq, and BS-seq data. The results showed that iPSCs were not fully reprogrammed to an hESC-like state at the epigenetic level. Specifically, certain epigenetic regulators like KDM2B and DNMT3B exhibited different chromatin positioning and methylation in iPSCs compared to hESCs. KDM2B, which promotes iPSC generation, was not expressed and highly methylated in iPSCs. This suggests that iPSC reprogramming
This document summarizes an RNA project focused on inhibition of Dipeptidyl peptidase-IV (DPP-IV), a treatment for Type 2 Diabetes. Key components included:
1) An Internal Ribosome Entry Site (IRES) to allow translation of multiple protein coding regions. Two IRES sequences from EMCV and NKRF were characterized.
2) A neomycin gene to confer antibiotic resistance for selection.
3) An aptazyme as an RNA "kill switch" activated by theophylline.
4) siRNA targeting the 3' untranslated region of DPP-IV mRNA for cleavage.
5) An RNA-dependent RNA polymerase (
The Efficiency and Ethics of the CRISPR System in Human EmbryosStephen Cranwell
This document summarizes research on the CRISPR/Cas9 system for genome editing in human embryos. It discusses efforts to understand DNA repair mechanisms after inducing double-strand breaks, reduce off-target mutations, and improve the specificity and efficiency of editing. While the technology shows promise, significant issues around off-target effects, mosaicism, and ethical concerns must still be addressed before any clinical applications. The document concludes that further basic research is needed to advance the field while also having open discussions on societal implications.
Taxol and 10-deacetylbaccatinIII induce distinct changesNeesar Ahmed
The document summarizes a study comparing the effects of Taxol, 10-deacetylbaccatinIII (10-DAB), and BaccatinIII (BacIII) on caveolae dynamics in HeLa cells expressing GFP-Caveolin-1. The key findings are:
1) Taxol treatment caused a transient recruitment of Caveolin-1 to the cell surface followed by internalization, while 10-DAB increased the "kiss and run" dynamics of caveolae.
2) Sustained Caveolin-1 phosphorylation was observed with both Taxol and 10-DAB treatments, with Taxol also inducing phosphorylation of Raf-1, ERK1/2,
1. The document analyzes a serine protease gene found in QPX, a pathogen of quahogs. It was found to belong to the subtilase family and contain the catalytic triad of amino acids.
2. Expression of the serine protease gene varied across QPX strains and was temperature dependent, being significantly upregulated during contact with host tissue.
3. A serine protease inhibitor gene was found in quahogs that likely plays a role in the immune response against QPX infection. Expression of this gene varied across quahog strains.
This study examines the degradation pathway of the thiazide-sensitive NaCl cotransporter (NCC) in yeast and mammalian cells. The authors show that NCC is a substrate of endoplasmic reticulum-associated degradation (ERAD) in yeast. Using yeast strains with mutations in ERAD components, they identify the E3 ubiquitin ligase Hrd1 and the cytoplasmic Hsp70 chaperone Ssa1/Hsp70 as important for NCC ubiquitination and degradation. Expression of NCC in mammalian kidney cells reveals similar polyubiquitination and proteasome-dependent degradation. Cytoplasmic Hsp70 preferentially associates with immature glycosylated NCC, indicating its role
1. Researchers administered an AAV9 gene therapy vector expressing CLN3 to a mouse model of CLN3 disease via tail vein or retro-orbital injections.
2. Viral genome copy numbers were measured in various tissues 7 days later, ranging from 2.80x10^3 to 1.56x10^7 copies per microgram of DNA.
3. No significant differences were found between the injection methods, supporting the use of tail vein injections for future efficacy and toxicology studies in mice to enable human clinical trials for this fatal pediatric disease.
Comparing internalization in cells expressing the wild-type andAndalus Ayaz
This study investigated the internalization of wild-type and mutant forms of the VSV-G protein in cells. The researchers mutated basic amino acids in the cytoplasmic tail of VSV-G to neutral amino acids to see if this affected internalization. They found that lower expressing cells internalized wild-type VSV-G faster, and that wild-type and mutant VSV-G were expressed at the same level on the plasma membrane but the mutant was expressed at a significantly lower level within cells overall. Further studies are needed to understand why and investigate if mutant VSV-G transport or degradation is impaired.
The complement system is comprised of over 30 circulating and membrane-bound proteins that act in a cascade to help mediate innate and acquired immunity. It functions through three main pathways - classical, lectin, and alternative - that involve a chain of enzymes cleaving complement proteins and forming complexes that activate other proteins in the cascade. The final steps are identical for all three pathways and allow the complement system to help clear pathogens through mechanisms like opsonization, inflammation, and lysis. Tight regulation is needed since complement is nonspecific and can damage host cells - regulatory proteins inhibit activity and many components have short half-lives.
This document provides an overview of the content covered in a health and social care course over the period of one week. It discusses key topics like different types of health and social care provision including statutory, private and voluntary services. It also covers important values and legislation related to working in the health and social care sector. Various class activities are outlined like discussing the role of informal carers and demonstrating care values through practical examples. Learners' objectives and outcomes are also stated for the topics discussed.
This document discusses hypersensitivity reactions, specifically focusing on Type 1 hypersensitivity reactions. It defines hypersensitivity as injurious consequences in a sensitized host following contact with a specific antigen. Type 1 reactions are immediate or anaphylactic hypersensitivities that involve IgE antibodies and mast cells or basophils. Upon re-exposure to an antigen, pre-bound IgE is crosslinked, causing degranulation and release of inflammatory mediators like histamine. This leads to symptoms of anaphylaxis such as hives, swelling, breathing difficulties, and low blood pressure. Food allergies, hay fever, and asthma are examples of Type 1 hypersensitivity reactions.
This document is a report card from Kelsey Park School for Boys summarizing student performance in the spring/summer term of 1916. It includes the student's name, form or grade level, ratings for effort and attainment in various subjects, comments from teachers, and signatures from the headmaster. The report provides performance assessments and feedback for individual students to communicate their progress to parents or guardians.
Este documento presenta el programa de estudio de Historia, Geografía y Ciencias Sociales para 5° año básico. Incluye orientaciones para la implementación del programa, como propósitos, habilidades, y sugerencias didácticas y de evaluación. El contenido se organiza en dos semestres, con cuatro unidades en total que abarcan los aprendizajes esperados para el año.
The document discusses several topics:
1. It provides a summary of key points from 6 documents, with highlights that include discussions around strengthening relationships, managing challenges, and improving communication.
2. A follow up is proposed with next steps that involve continuing conversations to solidify understanding and work towards mutually agreeable solutions.
3. Key action items are identified for various parties to address open issues and progress discussions in a collaborative manner.
El documento proporciona instrucciones sobre qué hacer si te roban el teléfono celular. Recomienda obtener el número de serie IMEI marcando *#06# y reportarlo a tu operador si ocurre un robo, para bloquear el dispositivo aunque cambien la tarjeta SIM. También menciona que el número de emergencia 112 funciona incluso si el teléfono está bloqueado.
Este documento presenta un resumen de los presidentes de Costa Rica entre 1914 y 1950. Durante este período, los presidentes establecieron instituciones clave como el Banco Nacional, la Caja Costarricense de Seguro Social y la Universidad de Costa Rica. También promovieron el desarrollo de infraestructura como carreteras, puertos y el aeropuerto internacional.
El documento presenta los resultados de la Evaluación Inicia 2011 realizada por el Ministerio de Educación de Chile. Los objetivos de la evaluación son entregar información a las instituciones de formación docente y a los egresados para mejorar la calidad de la formación inicial. Se aplicaron diferentes pruebas que miden conocimientos pedagógicos, disciplinarios, habilidades de comunicación escrita y uso de TIC. Los resultados muestran que la mitad de los egresados de educación básica y un tercio de parvularia logran un nivel aceptable,
La metodología PACIE permite el uso de las TIC como soporte para el aprendizaje y autoaprendizaje. Estructura las aulas virtuales en tres bloques: introducción, bloque académico y conclusión. El bloque académico contiene secciones para exposición de contenidos, actividades de autoevaluación, construcción de conocimientos a través de la discusión, y comprobación del aprendizaje mediante la síntesis y verificación.
1) La Web 2.0 permite a los usuarios crear y compartir contenido de forma dinámica y colaborativa en lugar de tener un papel pasivo. 2) Esto ofrece grandes posibilidades educativas como recopilar y compartir información usando canales RSS y favoritos, y crear y compartir contenido a través de blogs, wikis y otros formatos. 3) La Web 2.0 transforma la educación al facilitar la comunicación, colaboración y construcción colectiva del conocimiento.
Este documento resume los conceptos básicos de informática, incluyendo hardware, software, periféricos, unidad central de procesamiento y memoria. Explica que la informática es el tratamiento automático de información usando una computadora, que consta de elementos físicos (hardware) y lógicos (software). Describe los componentes principales de una computadora y sus funciones.
La taxonomía de Bloom clasifica los objetivos educativos en seis niveles jerárquicos que van desde el más básico al más complejo: 1) conocimiento, 2) comprensión, 3) aplicación, 4) análisis, 5) síntesis y 6) evaluación. Cada nivel requiere habilidades más avanzadas que el anterior y los educadores deben diseñar actividades que ayuden a los estudiantes a progresar a través de los diferentes niveles.
Este documento contiene una evaluación sobre conceptos básicos de Chile, incluyendo preguntas sobre el escudo nacional, la flor nacional, la patria, la bandera nacional y sus colores, los animales del escudo y una actividad para completar la bandera y oraciones sobre datos del país.
El documento resume los conceptos clave de Internet, la Web 2.0, dispositivos portátiles y redes. Explica que Internet permite el intercambio de información a nivel mundial y ha evolucionado a través de la Web 2.0, que facilita la comunicación y aplicaciones como redes sociales. También describe los dispositivos portátiles que permiten acceder a información de forma remota y cómo las redes conectan distintos sistemas informáticos para compartir recursos e información.
El documento analiza las estrategias de mercado de Zenith para la introducción de televisores HDTV. Propone identificar estratégicamente una nueva tecnología para innovar la televisión. Su misión es brindar apoyo a distribuidores para lanzar nuevos productos como los HDTV. Su visión es convertirse en líder mundial de productos digitales asegurando la satisfacción del cliente. Recomienda realizar análisis de mercado y competidores, y definir una estrategia de liderazgo en costos, diferenciación o en
The document describes a high-throughput screen that identified small molecule compounds that can enhance the pharmacological effects of oligonucleotides. Several "hit" compounds were discovered that potentiated the actions of splice-switching oligonucleotides, antisense oligonucleotides, and siRNAs in cell culture. The hit compounds preferentially caused the release of fluorescent oligonucleotides from late endosomes. Studies in transgenic mice indicated the hit compounds could enhance the in vivo effects of a splice-switching oligonucleotide without significant toxicity. The findings suggest selected small molecules may help advance oligonucleotide-based therapeutics by modulating intracellular trafficking and endosomal release.
This document summarizes a study investigating the epigenetic changes that occur during the transdifferentiation of pancreatic acinar cells (HPACs) to hepatocyte-like cells. The study found that DNA methylation in HPACs peaks at 24 hours after treatment with dexamethasone, and the cells display phenotypic changes associated with hepatocytes after 7 days. The study also examined the promoter sequence of the SGK1 gene, which is involved in the transdifferentiation process. The results suggest therapeutic potential for producing hepatocytes from pancreatic cells to treat liver disease in a more cost-effective manner than current alternatives.
The complement system was discovered in 1894 and consists of over 30 proteins that contribute to the innate immune system. It has 3 major pathways of activation: the classical pathway activated by antibody-antigen binding, the alternative pathway activated by microbial surfaces independently of antibody, and the lectin pathway activated by mannose-binding lectin binding to pathogens. The complement system carries out important immune functions like opsonization to enhance phagocytosis, inflammation, lysis of foreign cells, and clearance of immune complexes.
This review article summarizes our current understanding of the complement system. It describes complement as an intricate immune surveillance system that distinguishes between healthy host cells, cellular debris, apoptotic cells, and foreign intruders. Complement acts through pattern recognition, activation, amplification, and regulation to eliminate microbes and cellular debris while also signaling immune responses. The review highlights the classical, lectin, and alternative pathways of complement activation and the roles of C3 convertases. It describes how complement contributes to homeostasis but can also attack healthy cells if not properly regulated.
A team of scientists developed an optimized peptide toxin derived from ShK, a peptide from sea anemone venom, for potential treatment of autoimmune diseases. They used a systematic approach called MAPS (Multi Attribute Positional Scan) analoging to chemically synthesize 132 variants of ShK with single amino acid substitutions throughout the peptide. These variants were tested for their ability to inhibit the Kv1.3 potassium ion channel while sparing the closely related Kv1.1 channel. Two lead variants showed improved selectivity for Kv1.3 over Kv1.1. One variant was further modified with a PEG polymer to improve its pharmacokinetic properties. In primate studies, the PEGylated peptide
The document discusses the complement system and immunoglobulins. It provides an overview of:
- The components and pathways of the complement system and its role in host defense.
- The structure and classes of immunoglobulins, including IgG, IgA, IgM, IgE, and IgD.
- Deficiencies in the complement system and immunoglobulins that can cause increased susceptibility to infection.
2 complemento receptores - segunda apresentaçãoufamimunologia
The document summarizes complement regulators and inhibitory proteins that control the complement system. It begins by explaining that the complement system helps remove microorganisms and modified self cells, but must be tightly regulated to prevent damage to healthy tissues. It then discusses the complement cascade and its initiation, amplification and progression. Finally, it focuses on the regulators that modify and control the complement system to ensure activation only occurs at the proper time and locations.
The complement system is made up of around 30 proteins that augment the immune response. It was first identified in the 1890s as heat-labile components of serum that helped antibodies kill bacteria. There are three pathways of complement activation: the classical pathway which is antibody-dependent, the lectin pathway which resembles the classical pathway, and the alternative pathway which is antibody-independent. All three pathways involve a cascade of complement components that ultimately form the membrane attack complex (MAC) which can lyse target cells. The complement system plays important roles in opsonization, chemotaxis, inflammation, and clearance of pathogens.
Complement system and its synthesis + activationVaisHali822687
Proteins normally found in serum in inactive form, but when activated they augment the immune responses.
Complements constitute about 5% of normal serum proteins.
Their level does not increase following either infection or vaccination.
There are four main stages in the activation of any of the complement pathways.
Initiation of the pathway
Formation of C3 convertase
Formation of C5 convertase
Formation of membrane attack complex (MAC)
This presentation summarizes the complement system. It discusses that complement proteins are part of the innate immune system and act as a bridge between innate and adaptive immunity. It describes the three pathways of complement activation - the classical, lectin, and alternative pathways. It also explains the components and functions of the complement system, including recognizing and marking pathogens, stimulating immune responses, and directly killing microbes via membrane attack complexes.
Mice lacking the integrin β3 gene (Itgb3-/-) were subjected to unpredictable chronic mild stress (UCMS) to examine their behavioral and neurochemical responses to stress compared to wild-type mice (Itgb3+/+). Itgb3-/- mice displayed increased anxiety-like behaviors and decreased activity in an open field test after UCMS compared to Itgb3+/+ mice. UCMS led to reductions in dopamine turnover in the midbrains of Itgb3+/+ mice but not Itgb3-/- mice, suggesting disrupted stress regulation of dopamine homeostasis. Chronic stress also altered synaptic expression of proteins in the midbrains of Itgb3-/- mice compared to Itgb3+/+
This presentation is organized with the help of other presentations, text book of immunology and some internet resources for better understanding of students.
The complement system consists of over 30 serum and cell surface proteins that play a key role in both innate and adaptive immunity. It can be activated through three pathways - the classical pathway triggered by antigen-antibody complexes, the lectin pathway activated by mannose-binding lectin, and the alternative pathway activated spontaneously by microbial surfaces. All three pathways converge on the formation of C3 and C5 convertases that activate downstream components, ultimately forming the membrane attack complex to lyse microbial cells. The complement system functions to opsonize pathogens, induce chemotaxis, activate the inflammatory response, and aid in immune clearance.
Notch signaling is essential to maintain skeletal muscle stem cells in quiescence. However, the
precise roles of different Notch receptors are incompletely defined. Here, we demonstrate a
role for Notch3 (N3) in the self-renewal of muscle stem cells. We found that N3 is active in quiescent C2C12 reserve cells (RCs), and N3 over-expression and knockdown studies in C2C12 and
primary satellite cells reveal a role in self-renewal.
This experiment aimed to identify genes that were overexpressed in BU.MPT cells resistant to apoptosis compared to normal BU.MPT cells. RNA from the two cell populations underwent subtractive hybridization to identify differences. Eight colonies were sequenced, with one gene of interest identified as cysteine and histidine rich protein 1 (Chrp). Chrp is known to bind specifically to galectin-3, keeping it localized in the cytoplasm where it can activate anti-apoptotic pathways and properties. This binding of Chrp to galectin-3 provides a potential explanation for the resistance to apoptosis in the selected BU.MPT cells.
The complement system refers to a series of >20 proteins that are normally inactive but become sequentially activated in an enzyme cascade in response to microorganisms. Complement activation can lead to cytolysis, opsonization, and stimulation of inflammation. The classical, lectin, and alternative pathways activate the complement cascade through different mechanisms but all lead to formation of the membrane attack complex. Complement proteins are regulated to prevent attack of host cells but deficiencies can lead to diseases like hereditary angioedema where swelling occurs.
The document summarizes programmed cell death or apoptosis. It describes apoptosis as a naturally occurring, genetically programmed process where a cell undergoes an organized breakdown. During apoptosis, cells shrink, break into membrane-bound fragments called apoptotic bodies, and are removed by phagocytes without causing inflammation. The document outlines the major pathways of apoptosis, including the intrinsic mitochondrial pathway and extrinsic death receptor pathway, and discusses the roles of caspase proteases and Bcl-2 family proteins in apoptosis signaling and regulation.
The document provides an overview of the complement system in fish. It discusses:
1) The complement system consists of soluble and membrane-bound proteins that play a critical role in the host defense through interactions with both the innate and adaptive immune systems.
2) The complement system has three pathways - classical, lectin, and alternative - that recognize pathogens and promote their clearance through lysis, opsonization, and inflammation.
3) Complement components are produced as inactive zymogens and activated through proteolytic cleavage in cascading reactions on pathogen surfaces to form the membrane attack complex, which lyses cells.
Kupffer Cells Mediate Leptin-Induced Liver Fibrosis.
GASTROENTEROLOGY 2009;137:713–723
JIANHUA WANG,* ISABELLE LECLERCQ,‡ JOANNE M. BRYMORA,* NING XU,* MEHDI RAMEZANI–MOGHADAM,* ROSLYN M. LONDON,* DAVID BRIGSTOCK,§ and JACOB GEORGE*
*Storr Liver Unit, Westmead Millennium Institute, University of Sydney and Westmead Hospital, Westmead, Australia; ‡Laboratory of Gastroenterology, Faculty of
Medicine, Université Catholique de Louvain, Brussels, Belgium; and §Center for Cell and Vascular Biology, Children’s Research Institute, Columbus, Ohio
瘦素(Leptin)是一由脂肪細胞(Adipocyte)所分泌之荷爾蒙,是調控體重及新陳代謝之重要因子。過去研究發現病態肥胖(Obese)、脂肪肝(Nonalcoholic steatohepatitis)及酒精性肝炎(Alcoholic liver disease)等病患之血液循環中,Leptin量有明顯增加。而近期研究報告指出leptin具有促進肝臟纖維化(Liver fibrosis)之能力,當中分子機理並未明確。
在肝纖維化過程中,肝臟星狀細胞(HSC)會被活化增生及促進胞外基質(ECM)產生,而鄰近之Kupffer細胞(KC)則已知可透過促發炎因子(Proinflammatory factor)和促纖維化因子(Profibrogenic factors)例如TGF-β1和ROS影響HSC表現。雖然HSC是肝纖維化過程中重要角色,前人研究卻發現leptin似對HSC無任何調控作用。故本篇作者針對Leptin是否透過間接作用於HSC鄰近之KC,刺激其產生促纖維化因子,以活化HSC。
為探討leptin直接或間接影響HSC之分子機理,本篇作者透過RT-PCR、Immunoblot等分子生物學方法,分別測定leptin刺激後HSC及KC中Collagen I、TIMP1等促纖維化因子基因及蛋白表現,發現leptin雖可促使HSC增生,但對其纖維化能力之影響甚微。而leptin可刺激KC中TGF-β1及CTGF/CCN2等肝纖維化中重要之cytokines表現。另發現Leptin-treated KC-conditioned培養液可刺激HSC增生及增加其中Collagen I、TIMP1等表現,得出了leptin是透過刺激KC來活化HSC之推論。作者亦於後續實驗中,透過磷酸化測定、EMSA等方法探討leptin訊號傳遞作用,發現leptin可活化KC中STAT3、ERK1/2、AKT等路徑,及下游因子AP-1、NF-κB,而此兩種蛋白具有增強TGF-β1及CTGF/CCN2基因表現之能力。
International Journal of Pharmaceutical Science Invention (IJPSI)inventionjournals
International Journal of Pharmaceutical Science Invention (IJPSI) is an international journal intended for professionals and researchers in all fields of Pahrmaceutical Science. IJPSI publishes research articles and reviews within the whole field Pharmacy and Pharmaceutical Science, new teaching methods, assessment, validation and the impact of new technologies and it will continue to provide information on the latest trends and developments in this ever-expanding subject. The publications of papers are selected through double peer reviewed to ensure originality, relevance, and readability. The articles published in our journal can be accessed online
This document provides definitions and information related to infection and infection control in dentistry. It begins with definitions of key terms like infection, disease, virulence, and modes of transmission. It then discusses the normal flora of humans and stages of infection. Virulence factors and toxins are explained. The objectives and types of infection control are outlined, including universal precautions, routes of spread, and measures for pretreatment, chairside, and post-treatment infection control.
Mycology is the study of fungi. Fungi are eukaryotic organisms that include molds, yeasts, and mushrooms. They obtain nutrients by absorbing organic compounds from dead or living organisms. Many fungi are harmless saprophytes, but some can cause diseases (mycoses) in humans and other animals. Common superficial fungal infections in humans include ringworm, athlete's foot, and yeast infections. Deeper fungal infections can also occur, especially in immunocompromised individuals. Proper identification of fungal species relies on examining their morphology and growth characteristics under the microscope and in culture.
This document discusses antibiotic sensitivity testing (AST), including the Kirby-Bauer disk diffusion method and minimum inhibitory concentration (MIC) method. It provides details on selecting media, control strains, preparing antibiotic discs and inoculum, and interpreting zone sizes. AST is useful but has limitations as it only measures in vitro drug activity, not in vivo effects. Proper technique and quality controls are important for accurate results. New automated methods can generate reports faster than traditional AST.
1. Bacteria are unicellular prokaryotes that vary in size from 0.5-10 micrometers. They have distinct cell shapes including cocci, bacilli, spirilla, and vibrios.
2. The bacterial cell contains a cell membrane, cell wall, cytoplasm, and varying structures like flagella, pili, capsules, and endospores. The cell wall structure differs between gram positive and gram negative bacteria.
3. Gram staining allows bacteria to be classified as either gram positive or gram negative based on differences in their cell wall structures. Specialized structures like flagella, pili and capsules serve functions like motility, adhesion and virulence.
This document provides information on culture media and methods used to culture bacteria. It discusses the requirements bacteria have for growth and how laboratory culture media aims to provide a captive environment for bacteria to grow. Various types of culture media are described, including solid, liquid and semi-solid media made with ingredients like agar. Special media like enriched, selective, differential and indicator media are also outlined. Common biochemical tests performed on cultured bacteria like TSI, oxidase, indole and citrate are briefly explained. The document provides an overview of basic microbiology laboratory techniques for culturing and identifying bacteria.
This document discusses Staphylococcus bacteria, including S. aureus and coagulase-negative species. S. aureus is a major human pathogen that can cause skin and soft tissue infections or serious infections like pneumonia, sepsis, and toxic shock syndrome by producing various exotoxins and virulence factors. Coagulase-negative Staphylococcus like S. epidermidis commonly reside on human skin and mucous membranes but can opportunistically cause infections associated with medical devices and in immunocompromised patients. The document covers taxonomy, microbiological characteristics, pathogenic mechanisms, diseases caused, diagnosis, treatment and prevention of Staphylococcus infections.
These lecture slides, by Dr Sidra Arshad, offer a quick overview of the 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 lead (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
6. Describe the flow of current around the heart during the cardiac cycle
7. Discuss the placement and polarity of the leads of electrocardiograph
8. Describe the normal electrocardiograms recorded from the limb leads and explain the physiological basis of the different records that are obtained
9. Define mean electrical vector (axis) of the heart and give the normal range
10. Define the mean QRS vector
11. Describe the axes of leads (hexagonal reference system)
12. Comprehend the vectorial analysis of the normal ECG
13. Determine the mean electrical axis of the ventricular QRS and appreciate the mean axis deviation
14. Explain the concepts of current of injury, J point, and their significance
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. Chapter 3, Cardiology Explained, https://www.ncbi.nlm.nih.gov/books/NBK2214/
7. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
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.
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.
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.
Osteoporosis - Definition , Evaluation and Management .pdfJim Jacob Roy
Osteoporosis is an increasing cause of morbidity among the elderly.
In this document , a brief outline of osteoporosis is given , including the risk factors of osteoporosis fractures , the indications for testing bone mineral density and the management of osteoporosis
Muktapishti is a traditional Ayurvedic preparation made from Shoditha Mukta (Purified Pearl), is believed to help regulate thyroid function and reduce symptoms of hyperthyroidism due to its cooling and balancing properties. Clinical evidence on its efficacy remains limited, necessitating further research to validate its therapeutic benefits.
Here is the updated list of Top Best Ayurvedic medicine for Gas and Indigestion and those are Gas-O-Go Syp for Dyspepsia | Lavizyme Syrup for Acidity | Yumzyme Hepatoprotective Capsules etc
TEST BANK For Basic and Clinical Pharmacology, 14th Edition by Bertram G. Kat...rightmanforbloodline
TEST BANK For Basic and Clinical Pharmacology, 14th Edition by Bertram G. Katzung, Verified Chapters 1 - 66, Complete Newest Version.
TEST BANK For Basic and Clinical Pharmacology, 14th Edition by Bertram G. Katzung, Verified Chapters 1 - 66, Complete Newest Version.
TEST BANK For Basic and Clinical Pharmacology, 14th Edition by Bertram G. Katzung, Verified Chapters 1 - 66, Complete Newest Version.
TEST BANK For Basic and Clinical Pharmacology, 14th Edition by Bertram G. Katzung, Verified Chapters 1 - 66, Complete Newest Version.
1. THE COMPLEMENT SYSTEM
• Important effector in both innate and
acquired immunity
• Over 30 circulating and membrane-bound
proteins (synthesized in liver and other
cells- immune and epithelial)
• Acts as a cascade (one event must occur before
another takes place)
Dr Reena Kulshrestha, M.Sc, PhD.
2. Cascade:
• Many of the components are enzymes
that become activated when cleaved into
two peptides
• The larger peptide (joins the cascade)
binds to the immune complex and
becomes a functional part of it
• The smaller peptide diffuses away and
can become an inflammatory mediator
(binds to a receptor)
Dr Reena Kulshrestha, M.Sc, PhD.
3. Complement is an acute phase protien.
It belongs to triggered enzyme cascade
system.
Every step has its own control
mechanism.
It is present in sera of all mammals.
Dr Reena Kulshrestha, M.Sc, PhD.
4. It is non-specific i.e. Complement of one species
can react with antibody of other species.
It constitute 5 % of normal serum protein & the
level rises during acute phase inflammation and is
not increased by immunization.
Fixation of complement is not influenced by nature
of antigen but class of immunoglobulin.
The complement binds on the fc part of
immunoglobulin CH2 (constant heavy domain) of
IgG & 4 of IgM.
Complement does not bind to free antigen &
antibody.
All classes of immunoglobulin do not fix
complement only IgM , IgG3 , IgG1 & IgG2 fix in
the respective order.
IgG4 , IgA , IgD & IgE do not fix complement.
Dr Reena Kulshrestha, M.Sc, PhD.
5. Four important functions:
• Lysis
• Opsonization
• Activation of inflammatory
response
• Clearance of immune
complexes
Dr Reena Kulshrestha, M.Sc, PhD.
11. Three pathways: Classical, Alternative, & Lectin
Final steps identical in all 3 pathways
1.Classical - Initiated by formation of an Ag- Ab
complex
2. Alternative - Antibody-independent
- Part of innate immunity
- Initiated by foreign cell
surfaces
3. Lectin - Initiated by host proteins binding
microbial surfaces
Dr Reena Kulshrestha, M.Sc, PhD.
20. Classical pathway
• Classical was discovered first (but
actually evolved later)
• Initiated by:
-formation of a soluble Ag-Ab complex
-binding of antibody to a target such as
a bacterial cell
• Only certain antibodies can initiate this
(IgM, some classes of IgG)
Dr Reena Kulshrestha, M.Sc, PhD.
35. Activator e.g.
endotoxin
C3b (bound)
factor BMg++
C3bB
C3bBb
Ba factor D
+
C3b in
circulation
Free C3b
inactivated
by factors
H and I.
(C3 convertase)Dr Reena Kulshrestha, M.Sc, PhD.
37. C567
Binds to cell
membrane and
prepares the cells for
lysis by C8 and C9
It also sensitises
bystander cells to
make them
susceptible to
lysis.
C8
C9
C3bBb3b5b6789
Cell damage or lysis.
Dr Reena Kulshrestha, M.Sc, PhD.
38. Differences Between classical and alternative pathway
1) Activators
Antigen antibody complex Bacterial endotoxins
Retroviruses IgA & IgD
C Reactive protein Cobra Venom
DNA Nephritic Factor
Trypsin like Enzyme Zymogene
2) Starting component
C1q C3
C3 activation by PZ(Properdin zymogene complex)
Mg++ Proteinase enzyme
C3a
C3
C3b
3) Attachment to Fc No attachment.
C1q has 6 combining sites.
Recognizes Fc of IgM & IgG.
4) Components
11 components C3 factors BDPH ,5,6,7,8,9
C1q, r,s,2,3,4,5,6,7,8,9
5) C3 convertase
________ _ ____
C1 4b 2b C3b Bb
Dr Reena Kulshrestha, M.Sc,
PhD.
39. Lectin pathway
• Lectin is a protein that binds to carbohydrate
• MBL (mannose-binding lectin) binds to
mannose on many bacterial cells
- MBL is produced by liver in acute-phase
inflammatory reactions
• Once MBL binds to target cell, 2 serine
proteases (MASP-1, MASP-2) bind
• Acts like C1
Dr Reena Kulshrestha, M.Sc, PhD.
41. Lectin pathway (mannose binding pathway)
Macrophages ingenst virus bacteria other foreign material
Release chemicals which stimulates
Liver cells
Acute phase proteins released like ( Mannose binding protein)
Binds to pathogens
Opsonisation Binds to lectin Binds to MASP
Phagocytosis Alternative pathway Mannose associated serine esteraseDr Reena Kulshrestha, M.Sc,
PhD.
42. Dr Reena Kulshrestha, M.Sc, PhD.
The Complement CascadeThe Complement Cascade
C5
C5a
Ba Properidin
D
C3 P C3a
B
The Alternative Pathway
C3b C3bB C3bBb C3bBbP C3bBb3
b
B
C3C3iC3iB
Ba
C3iBb
C3
C3a
The Tick-over Activation
C5b
C4
C4a
C2 C2b C3 C3a
The Classical Pathway
Antibody +
C1qrs
C4b C4b2a C4b2a3
b
43. Regulation of complement system
• Because it is nonspecific, several
regulatory mechanisms are involved
(otherwise there would be a lot of
“collateral damage”)
• Many components are very labile
• Many regulatory proteins block activity
through binding to target
Dr Reena Kulshrestha, M.Sc, PhD.
44. REGULATON OF COMPLEMENT
ACTIVATOR
[A] INHIBITOR
(1). C1 ESTERASE
* INHIBIT CLR,CLS BY BINDING TO ACTIVE SITE.
*MURAMINOGLYCOPROTEIN
*HEAT LABILE
*PREVENTS NORMAL CASCADE
*CHECKS AUTOCATALYTIC PROLONGATION
Dr Reena Kulshrestha, M.Sc, PhD.
45. REGULATON OF COMPLEMENT
ACTIVATOR
(2).S PROTIEN
*BINDS TO C567
*MODULATES CYTOLYTIC
ACTION OF MEMBRANE
ATTATCH COMPLEX
[B] INACTIVATOR
(1) Fac1
*SERUM BETA GLOBULIN
*C3B,C4B ARE CLEAVED & IN
ACTIVATED
Dr Reena Kulshrestha, M.Sc, PhD.
46. REGULATON OF COMPLEMENT
ACTIVATOR
*HOMEOSTATIC CONTROL OF C3 ACTIVATION.
*ENDOPEPTIDASE WHICH CLEAVES C3b & C4b.
(2) FACTOR H
*REGULATES ALTERNATIVE PATH WAY BY
PREVENTION FACTOR B TO BOUND TO C3
*BETA GLOBULIN FACTOR
*ACTS ALONG WITH FACTOR 1 MODULATIG C3
ACTIVATION.
Dr Reena Kulshrestha, M.Sc, PhD.
47. REGULATON OF COMPLEMENT
ACTIVATOR
(3) ANAPHYLATOXIN INACTIVATORS
*ENZYMATICALLY DEGRADES C3a,C4a,C5a
(4) C4 BINDING PROTEIN
*CONTROLS ACTIVITY OF ALL BOUND C4b
*BINDS TIGHTLY TO C4b & ENHANCES C4b
DEGRADATION.
Dr Reena Kulshrestha, M.Sc, PhD.
48. REGULATION OF COMPLEMENT
ACTIVATOR
(5) FACTOR P OR PROPERDIN
*BINDS TO A STABILIZER THE ALTERNATIVE PATH
WAY C3 CONVERTASE
*ACTIVATED PROPERDIN BINDS DIRECTLY TO BOUND
& UNBOUND C3b
*STABILIZE C3 & C5 CONVERTASE
Dr Reena Kulshrestha, M.Sc, PhD.
49. REGULATION OF COMPLEMENT
ACTIVATOR
*INDUCE FURTHER ACTIVATION OF COMPLIMENT
COMPONENT INDIRECTLY BY EXTENDING THE
HALF LIFE OF C3bBb
(6)COBRA VENOM FACTOR (COVF)
*PROTEIN FOUND IN COBRA VENOM ACTIVATES
COMPLEMENT & LYSES ERYTHROCYTES
Dr Reena Kulshrestha, M.Sc, PhD.
50. REGULATION OF COMPLEMENT
ACTIVATOR
*CAN COMBINE TO FACTOR B TO FORM COVF-Bb
COMPLEX i.e. EQUIVALENT TO C5 CONVERTASE
*VENOM IS RESISTANT TO ACTION OF
INACTIVATORS OF ALTERNATIVE PATH WAY
FACTOR H & I
Dr Reena Kulshrestha, M.Sc, PhD.
51. BIOLOGICAL EFFECTS OF
COMPLEMENT SYSTEM
(1) INFLAMMATORY RESPONSE : C3a & C5a
*ANAPHYLATOXINS
*RELEASES HISTAMINE & OTHER MEDIATOR BY
DEGRANULATION OF MAST CELLS
*CHEMOTATICE-C567
*INCREASE VASCULAR PERMEABILITY,CONTRACTION
OF SMOOTH MUSCLE,VASODILATION,COLLECTION
OF INFLAMATORY CELLS,INCREASE IN PHAGOCYTIC
ACTIVITY
Dr Reena Kulshrestha, M.Sc, PhD.
52. BIOLOGICAL EFFECTS OF
COMPLEMENT SYSTEM
(2)HYPER SENSITIVITY:TYPE II & TYPE III
(3) ENDOTOXIC SHOCK:
ALTERNATIVE PATH WAY,EXCESSIVE C3
ACTIVATION,PLATELET ADERENCE
(4) COAGULATION C3
*LYSES PROTHROMBIN
*THROMBIN RELEASES LARGE AMOUNT OF PLATELET
FACTOR
Dr Reena Kulshrestha, M.Sc, PhD.
53. BIOLOGICAL EFFECTS OF
COMPLEMENT SYSTEM
DISSEMINATED INTRAVASCULOR COAGULATION &
THROMBOCYTOPENIA
(5) IMMUNE ADHERENCE :
*C3 & C4
*ANTIGEN ANTIBODY COMPLEXES + C
ADHERE TO ERYTHROCYTES OR PLATELETS
ENHANCED PHAGOCYTOSIS
*PHAGOCYTIC CELLS HAVE RECEPTORS FOR C3b
Dr Reena Kulshrestha, M.Sc, PhD.
54. BIOLOGICAL EFFECTS OF
COMPLEMENT SYSTEM
(6) OPSONIZATION : CR1,CR2,CR9,CR4,CCq ON
MACROPHGES,NEUTROPHILL,MONOCYTES ETC.CR2
PRESENT OF B CELL
(7) AUTO IMMUNE DISEASES
E.G.-SLE & ANGIONEUROTIC OEDEMA
-DUE TO DEFICIENCY OF DOME COMPLEMENT FACTORS
Dr Reena Kulshrestha, M.Sc, PhD.
55. BIOLOGICAL EFFECTS OF
COMPLEMENT SYSTEM
(8) SUSCEPTIBILITY
GRAM NEGATIVE BACTERIA – LYSIS
GRAM POSITIVE BACTERIA- WITHOUT LYSIS
(9) C3 & C6 PARTICIPATE IN COAGULATION PROCESS
Dr Reena Kulshrestha, M.Sc, PhD.
60. Regulation of the ComplementRegulation of the Complement
CascadeCascade
Short half-time ofShort half-time of
C3bC3b
C3bBbC3bBb
C5bC5b
C1 inhibitorC1 inhibitor
Inhibits the C1s activityInhibits the C1s activity
Protein S in SerumProtein S in Serum
Binds to C5b67Binds to C5b67
→ Inhibits Formation of the Membrane AttackInhibits Formation of the Membrane Attack
ComplexComplex
Dr Reena Kulshrestha, M.Sc, PhD.
61. HRF or CD59HRF or CD59
Bind to C8Bind to C8
Inhibits C9 bindingInhibits C9 binding
Factor HFactor H
Binds to C3bBinds to C3b
→ Facilitates binding of Factor IFacilitates binding of Factor I
→ cleaves C3b to inactive iC3bcleaves C3b to inactive iC3b
→ cleaves C4b to inactive fragmentscleaves C4b to inactive fragments
Decay Accelerating FactorDecay Accelerating Factor
Increased dissociation ofIncreased dissociation of
C3 convertase (bothC3 convertase (bothDr Reena Kulshrestha, M.Sc, PhD.
62. Complement ActivationComplement Activation
GeneralGeneral
Hydrophobic surfacesHydrophobic surfaces
OxidesOxides
Strong binding of C3(b) to nucleophilicStrong binding of C3(b) to nucleophilic
groups (-NH2, -OH)groups (-NH2, -OH)
Higher absorption of C3 to crystalline TiOHigher absorption of C3 to crystalline TiO22
than to amorphousthan to amorphous
Kallikrein directly activates C5Kallikrein directly activates C5
Plasmin directly activates C5Plasmin directly activates C5
Dr Reena Kulshrestha, M.Sc, PhD.
63. Classical PathwayClassical Pathway
Antibodies IgM, IgG1, IgG2, IgG3Antibodies IgM, IgG1, IgG2, IgG3
Lectin via the mannan binding proteinLectin via the mannan binding protein
(MBP) “Lectin Pathway”(MBP) “Lectin Pathway”
Hageman Factor (F XIIa)Hageman Factor (F XIIa)
Rough surfacesRough surfaces
C-reactive protein (CRP)C-reactive protein (CRP)
(Zirkonium, transiently)(Zirkonium, transiently)
Dr Reena Kulshrestha, M.Sc, PhD.
65. Biological effects of complement
activation
• Complement fragments must bind to
complement receptors
expressed by various cells
Dr Reena Kulshrestha, M.Sc, PhD.
68. AnaphylatoxinsAnaphylatoxins
Fragments C5a, C3a, C4aFragments C5a, C3a, C4a
Degranulation of PhagocytesDegranulation of Phagocytes
Reactive oxygen speciesReactive oxygen species
ProstaglandinsProstaglandins
MonocytesMonocytes
→→ IL-1, IL-6IL-1, IL-6
Mast cellsMast cells
→→ HistamineHistamine
ChemotaxisChemotaxis
Only C5aOnly C5a
Dr Reena Kulshrestha, M.Sc, PhD.
69. Consequences in vitro
• Lysis of “innocent” neighbour cells
– Red blood cells
• Activation of phagocytic cells
– Release of reactive oxygen species
– Release of mediators
Dr Reena Kulshrestha, M.Sc, PhD.
70. ConsequencesConsequences in vivoin vivo
Factors of complement activation at revised hipFactors of complement activation at revised hip
implantsimplants
One single studyOne single study ((Tang L.Tang L. et al.et al. J Biomed Mater ResJ Biomed Mater Res 4141: 333-340 (1998)): 333-340 (1998))
Au-Mercaptoglycerol induces strong inflammatoryAu-Mercaptoglycerol induces strong inflammatory
response in control animals.response in control animals.
No reaction in Complement-depleted animals.No reaction in Complement-depleted animals.
Dr Reena Kulshrestha, M.Sc, PhD.
71. Amplifies humoral response
Destroys invading bacteria and viruses
(lysis by MAC)
Inflammatory response
Opsonization of antigen (enhances
phagocytosis)
Virus neutralization
Clearance of immune complexes
Dr Reena Kulshrestha, M.Sc, PhD.
72. Some bacteria can resist lysis
• Gram-positive bacteria
• Some microbes produce inactivating
enzymes
• Nucleated cells are harder to lyse
• Not particularly effective against tumor
cells (they can endocytose MAC and
repair damage)
Dr Reena Kulshrestha, M.Sc, PhD.
74. Inflammation
• many of the released fragments help
develop an inflammatory response
• C3a, C4a, C5a- anaphylotoxins
bind to receptors on mast cells and
basophils; degranulation
(smooth muscle contraction; capillary
dilation; fluid influx)
• also play a role in blood cell chemotaxis
Dr Reena Kulshrestha, M.Sc, PhD.
76. Viral neutralization
• Some viruses activate alternative or lectin
pathway
• Antibody-mediated (classical) pathway is
more common
• Causes aggregation of viruses; can’t infect
host cells; more vulnerable to phagocyte
• Enveloped viruses can be lysed
Dr Reena Kulshrestha, M.Sc, PhD.
78. Consequences of complement deficiency
• Early components of classical pathway (C1,
C4, C2)- immune complex disease
• can’t generate C3b, which is needed
for solubilization
• Recurrent Staph and Strep infections
(can’t lyse bacteria but seem to control
infections)
• Early components of alternative pathway-
not as serious; tendency to infections
by NeisseriaDr Reena Kulshrestha, M.Sc, PhD.
79. •C3 deficiencies (can’t activate C5 and form
MAC)
•Recurrent severe bacterial infections
•MAC deficiencies- recurrent Neisseria
infections
•Regulatory protein deficiencies
1.edema
2.RBC lysis
Dr Reena Kulshrestha, M.Sc, PhD.
80. Dr Reena Kulshrestha, M.Sc, PhD.
Methods for Investigation
General/Common pathway
– Lysis of sheep red blood cells
– Solid phase methods (ELISA, RIA)
• Products: C3a, C5a, sC5b-9
• Consumption of C3
– Ellipsometry
Classical Pathway
– Measurement of C1qrs
– Measurement of C2b or C4b2a
Alternative Pathway
– Measurement of Ba or C3bBb
– Measurement of Properidin
81. CLASSICALCLASSICAL ALTERNATIVEALTERNATIVE LECTINLECTIN
ACTIVATINGACTIVATING
SUBS.SUBS.
IMMUNEIMMUNE
COMPLEXESCOMPLEXES
(IgG OR IgM)(IgG OR IgM)
LPS (bacterialLPS (bacterial
capsule)capsule)
IgAIgA
MannoseMannose
groups ongroups on
microbial cellmicrobial cell
RECOGNITIONRECOGNITION
UNITUNIT
C1q, C1r, C1sC1q, C1r, C1s C3, Factor B,C3, Factor B,
Factor DFactor D
MBP, MASP-1,MBP, MASP-1,
MASP-2MASP-2
C3C3
CONVERTASECONVERTASE
C4b2aC4b2a C3bBbC3bBb C4b2aC4b2a
C5C5
CONVERTASECONVERTASE
C4b2a3bC4b2a3b C3bBb3bC3bBb3b C4b2a3bC4b2a3b
MACMAC
C5b6789C5b6789
END RESULTEND RESULT
CELL LYSISCELL LYSIS
Dr Reena Kulshrestha, M.Sc, PhD.
82. Biosynthesis of C
1) C1 - Intestinal epithelium
2) C2 C4 - Macrophages
3) C5 C8 - Spleen
4) C3 C6 C9 - Liver
5) C7 - Not known
6) Factors - Macrophages
B,D,P & I
Dr Reena Kulshrestha, M.Sc, PhD.
83. Compliment deficiency and associated diseases
1) C1, C2, C3 &C4 disorders - Immune and rheumatic
2) C5, C6,C7,C8 disorders - Recurrent infection (Neisseria)
3) C1q disorders - Combined immunodeficiency states
4) C1r disorder - Many infections and lupus like symptoms
5) C1s disorder - Systemic Lupus Erythematossis
6) C4 disorder - Lupus like symptoms
7) C2 disorder - Increased susceptibility to infection
8) C3 disorder - Severe Pyogenic infections
9) C5 disorder - Recurrent infection of GIT
10) C6 C7 &C8 disorder - Disseminated gonococcal infections and recurrent
Mieningococcal Meningitis
11) C9 disorder - Not more susceptible to disease than other
individual in general populations.
12) C1 Inhibitors - Hereditary angioneurotic oedema
13) C3b inactivator factor 1
& factor D Properdin -Recurrent infection
Dr Reena Kulshrestha, M.Sc,
PhD.
84. Key Facts
1. The complement system, a multi component triggered enzyme cascade, attracts
phagocytic cells to the microbes which engulf them.
2. Complement can be activated by classical and alternative pathways.
3. The amount of complement present in the serum cannot be increased by
immunization.
4. Complement participates in type II and type III Hypersensitivity.
5. Several serum compliment components are lowered in many auto immune
diseases such as systemic lupus erythematosus & Rheumatoid arthritis. They may,
therefore, be involved in the pathogenesis of auto immune diseases.
6. Complement mediates immunological membrane damage.
7. C fragments released during cascade reaction help in amplifying the inflammatory
response.
8. C3 and C4 mediate immune adherence.
9. C3 and C6 participate in Coagulation process
Dr Reena Kulshrestha, M.Sc,
PhD.
85. Summary
The complement system comprises a group
of serum proteins which, when activated,
plays an important role in antigen
clearance.
The classical, alternative and lectin pathways
have been described.
Elaborate regulatory mechanisms are required
to prevent damage to normal cells.
Dr Reena Kulshrestha, M.Sc, PhD.