1. The study characterized antibody responses to Plasmodium falciparum invasion ligands EBA-140 and EBA-181 in individuals from malaria-endemic areas of Brazil and Cameroon.
2. Responses differed between populations, with African individuals strongly reacting to most EBA fragments while Brazilian individuals from Mato Grosso reacted weakly and those from the Amazon had elevated but lower responses than Africans.
3. When compared to responses against other malaria proteins, the Brazilian population appeared to have more variable ability to recognize P. falciparum invasion ligands, distinct from the African population.
This document discusses the role of somatic mutagenesis in the development of autoimmunity, specifically in systemic lupus erythematosus (SLE). It argues that:
1) Antinuclear antibodies (ANA) that arise in SLE predominantly originate from non-autoreactive B cells that undergo somatic hypermutation (SHM) and are transformed into autoreactive cells, rather than arising from autoreactive B cells escaping central tolerance.
2) SHM may create antigenic peptides in the B cell receptor that provide a route for unregulated T cell help to autoreactive B cells.
3) Spontaneous somatic mutagenesis of genes regulating B cell survival and activation may be a stochastic rate-
This Masters thesis defense presentation summarizes research identifying MH class IIβ alleles that may confer resistance or susceptibility to Bacterial Cold Water Disease (BCWD) in rainbow trout. The study genotyped MH class IIβ alleles in six families of trout that had been experimentally infected with the BCWD pathogen. Results found five alleles present among the families. The DAB*1001/DAB*0801 genotype had the lowest hazard ratio, suggesting an association with resistance to BCWD, although results were not statistically significant. Future work could examine MH class I alleles and innate immunity genes to better understand resistance in trout.
HLA BASICS AND ROLE IN TRANSPLANT IMMUNOLOGYravi jaiswal
George Snell and Jean Dausset were awarded the 1980 Nobel Prize in Physiology or Medicine for their discoveries concerning the HLA system and its role in organ and histocompatibility. The HLA system refers to human leukocyte antigens, which are proteins found on most cells that help the immune system distinguish the body's own cells from foreign cells. HLA genes are highly polymorphic and play a crucial role in matching donors and recipients in organ transplantation to minimize immune rejection. A closer match between a donor's and recipient's HLA types results in better outcomes after transplantation.
Genome-wide survey and characterization of AP2/ERF and HSP 90 gene family in ...ICRISAT
APETALA2/Ethylene Response Factor (AP2/ERF) and Heat Shock Protein 90 (HSP90) are important classes of transcription factor and chaperone proteins known to play a significant role under stress. Productivity and yield of legume crops are severely affected by environmental and pathogen stresses.
23 Jan 2015
- The naive follicular B-cell pool in mice lacking the surrogate light chain is enriched for B cells expressing antibody heavy chains with prototypic autoreactive CDR3 sequences.
- These mice spontaneously form germinal centers in the spleen that are enriched with B cells expressing prototypic autoreactive heavy chains.
- Peripheral tolerance is maintained by selection thresholds, as evidenced by the exclusion of intrinsically autoreactive VH81X-expressing B cells from the memory B-cell and plasma cell pools.
The document discusses a study on MRSA 252, a methicillin-resistant Staphylococcus aureus strain. It aims to construct a prophage-free host strain of MRSA 252 that can propagate lytic bacteriophages. 31 mutant strains of MRSA 252 were created using mitomycin C to induce prophages. Prophage screening using PCR found that mutations 7 and 8 did not contain the φSa2 and φSa3 prophages. Most mutant strains were susceptible to lytic phages in spot tests, but were resistant to some phages and high dilutions of others. Mutations 7 and 8 were resistant to all tested phages. The attempt to mobilize prophages from M
EcoTILLING is a method for identifying natural mutations and polymorphisms in populations using TILLING techniques. It allows for the detection of point mutations and small insertions/deletions in DNA in a high-throughput but low-cost manner using gel electrophoresis. EcoTILLING has been used to identify allelic variants in genes related to powdery mildew resistance (mlo and Mla) in barley. It has also been applied to identify natural variation in 196 Arabidopsis ecotypes and 41 cottonwood trees. The method shows potential for discovering alleles relevant to salt tolerance in rice varieties and resistance to potato virus Y in pepper varieties.
Bordetella Pertussis Review Paper - Schumacher(1)Scott Schumacher
The document reviews Bordetella pertussis, the bacteria that causes whooping cough. It discusses the bacteria's virulence factors and how they help the bacteria infect cells and evade the immune system. As the bacteria mutates, vaccines are becoming less effective. Comparing the genomes of B. pertussis strains provides insights into how the bacteria has adapted to humans and reveals diversity in its virulence genes. Understanding the mutations may help develop more effective vaccines to better protect public health.
This document discusses the role of somatic mutagenesis in the development of autoimmunity, specifically in systemic lupus erythematosus (SLE). It argues that:
1) Antinuclear antibodies (ANA) that arise in SLE predominantly originate from non-autoreactive B cells that undergo somatic hypermutation (SHM) and are transformed into autoreactive cells, rather than arising from autoreactive B cells escaping central tolerance.
2) SHM may create antigenic peptides in the B cell receptor that provide a route for unregulated T cell help to autoreactive B cells.
3) Spontaneous somatic mutagenesis of genes regulating B cell survival and activation may be a stochastic rate-
This Masters thesis defense presentation summarizes research identifying MH class IIβ alleles that may confer resistance or susceptibility to Bacterial Cold Water Disease (BCWD) in rainbow trout. The study genotyped MH class IIβ alleles in six families of trout that had been experimentally infected with the BCWD pathogen. Results found five alleles present among the families. The DAB*1001/DAB*0801 genotype had the lowest hazard ratio, suggesting an association with resistance to BCWD, although results were not statistically significant. Future work could examine MH class I alleles and innate immunity genes to better understand resistance in trout.
HLA BASICS AND ROLE IN TRANSPLANT IMMUNOLOGYravi jaiswal
George Snell and Jean Dausset were awarded the 1980 Nobel Prize in Physiology or Medicine for their discoveries concerning the HLA system and its role in organ and histocompatibility. The HLA system refers to human leukocyte antigens, which are proteins found on most cells that help the immune system distinguish the body's own cells from foreign cells. HLA genes are highly polymorphic and play a crucial role in matching donors and recipients in organ transplantation to minimize immune rejection. A closer match between a donor's and recipient's HLA types results in better outcomes after transplantation.
Genome-wide survey and characterization of AP2/ERF and HSP 90 gene family in ...ICRISAT
APETALA2/Ethylene Response Factor (AP2/ERF) and Heat Shock Protein 90 (HSP90) are important classes of transcription factor and chaperone proteins known to play a significant role under stress. Productivity and yield of legume crops are severely affected by environmental and pathogen stresses.
23 Jan 2015
- The naive follicular B-cell pool in mice lacking the surrogate light chain is enriched for B cells expressing antibody heavy chains with prototypic autoreactive CDR3 sequences.
- These mice spontaneously form germinal centers in the spleen that are enriched with B cells expressing prototypic autoreactive heavy chains.
- Peripheral tolerance is maintained by selection thresholds, as evidenced by the exclusion of intrinsically autoreactive VH81X-expressing B cells from the memory B-cell and plasma cell pools.
The document discusses a study on MRSA 252, a methicillin-resistant Staphylococcus aureus strain. It aims to construct a prophage-free host strain of MRSA 252 that can propagate lytic bacteriophages. 31 mutant strains of MRSA 252 were created using mitomycin C to induce prophages. Prophage screening using PCR found that mutations 7 and 8 did not contain the φSa2 and φSa3 prophages. Most mutant strains were susceptible to lytic phages in spot tests, but were resistant to some phages and high dilutions of others. Mutations 7 and 8 were resistant to all tested phages. The attempt to mobilize prophages from M
EcoTILLING is a method for identifying natural mutations and polymorphisms in populations using TILLING techniques. It allows for the detection of point mutations and small insertions/deletions in DNA in a high-throughput but low-cost manner using gel electrophoresis. EcoTILLING has been used to identify allelic variants in genes related to powdery mildew resistance (mlo and Mla) in barley. It has also been applied to identify natural variation in 196 Arabidopsis ecotypes and 41 cottonwood trees. The method shows potential for discovering alleles relevant to salt tolerance in rice varieties and resistance to potato virus Y in pepper varieties.
Bordetella Pertussis Review Paper - Schumacher(1)Scott Schumacher
The document reviews Bordetella pertussis, the bacteria that causes whooping cough. It discusses the bacteria's virulence factors and how they help the bacteria infect cells and evade the immune system. As the bacteria mutates, vaccines are becoming less effective. Comparing the genomes of B. pertussis strains provides insights into how the bacteria has adapted to humans and reveals diversity in its virulence genes. Understanding the mutations may help develop more effective vaccines to better protect public health.
The document discusses HLA typing and its implications. It begins with a brief history of the discovery of the major histocompatibility complex (MHC) in mice and humans. It then describes the structure and functions of the MHC, including the class I, class II, and class III regions. The document discusses methods of HLA typing, including serological testing using microcytotoxicity and molecular methods. It notes some implications of HLA typing, such as its role in organ transplant matching and susceptibility to autoimmune disease.
This document summarizes research on the Scr74 gene family in Phytophthora infestans and how different variants of this gene are recognized in potato genotypes. The key points are:
1. 27 variants of the Scr74 effector gene were identified from 12 P. infestans isolates. 4 novel variants were cloned.
2. 13 amino acid sites in Scr74 were found to be under positive diversifying selection, indicating these sites are important for pathogen recognition.
3. 17 Scr74 variants were screened using PVX assays on 12 potato genotypes. Some genotypes had strong cell death responses to specific Scr74 variants, suggesting recognition of these variants.
4. Scr74 variants Scr74-A
This research aimed to study the relationship between the hypothetical VDBG_07494 gene in Verticillium alfalfae and its dark resting mycelia (DRM) pathway. A series of techniques were used including designing primers for the gene, performing homologous recombination to create a knockout version, extracting DNA, and running PCR and gel electrophoresis. The results showed growth of V. alfalfae cultures, presence of DRM structures, successful DNA extraction and amplification of the target region by PCR. However, gel electrophoresis suggested ectopic rather than homologous insertion of the knockout sequence occurred.
This document provides an overview of transplantation immunology. It defines key terms like transplantation, donor, recipient, graft, and alloantigens. It discusses that transplantation between non-identical individuals leads to rejection by the adaptive immune system. It describes the direct and indirect pathways of alloantigen recognition by T cells. It also outlines the activation and effector functions of alloreactive T lymphocytes, including their role in rejection through direct killing of graft cells or production of cytokines. Costimulation is also noted as important for full activation of alloreactive T cells.
The document discusses the Major Histocompatibility Complex (MHC) and its role in organ transplantation and immune response. It covers MHC genetics and polymorphism, allorecognition of T cells, mechanisms of graft rejection, immunosuppressive agents used to prevent rejection, and the use of tissue typing to match donors and recipients to improve graft survival.
1) Malaria vaccines aim to prevent infection, decrease disease severity, and reduce transmission. However, developing an effective malaria vaccine is challenging due to the parasite's high mutation rate and ability to evade the immune system.
2) Most research focuses on P. falciparum since it causes the most mortality. Potential vaccine candidates target different stages of the parasite's life cycle and include antigens like CSP, AMA1, MSP1, and Pfs25.
3) SPf66 was the first malaria vaccine tested in humans but showed limited efficacy. RTS,S is the most advanced candidate vaccine and has demonstrated up to 50% efficacy in clinical trials. However, more research is still needed to develop
Reduced Antimony Accumulation in ARM58-Overexpressing Leishmania infantumCarola Schäfer
1. The study identified ARM58, a novel antimony resistance marker gene in Leishmania infantum.
2. Overexpression of ARM58 in L. infantum reduces intracellular accumulation of antimony (Sb) by over 70%, indicating its role in Sb extrusion pathways.
3. A small putative transmembrane domain within one of ARM58's four conserved domains was found to be critical for its function in reducing Sb accumulation.
This document summarizes a study investigating the evolution of high-level resistance to the tuberculosis drug ethambutol in Mycobacterium tuberculosis. The key findings are:
1) M. tuberculosis strains selected in vitro for ethambutol resistance accumulated mutations in genes involved in decaprenylphosphoryl-β-d-arabinose (DPA) biosynthesis and utilization, including Rv3806c, Rv3792, embB and embC, resulting in a range of ethambutol minimum inhibitory concentrations depending on mutation type and number.
2) Multistep selection was required for M. tuberculosis to develop high-level ethambutol resistance over 32 μg/ml
The document summarizes the process of producing monoclonal antibodies (mAbs) through hybridoma technology. It involves immunizing an animal, usually a mouse, to elicit an immune response. B cells from the animal's spleen are then fused with myeloma cells to generate immortal hybridoma cells. These hybridoma cells are screened and selected in HAT medium to identify clones that produce the desired mAb. The selected clones are then subjected to further characterization and mass production methods.
- The document discusses research on the cotton root-knot nematode (Meloidogyne incognita), an endoparasitic nematode that infects thousands of plant species and causes billions in crop damage worldwide.
- The research uses Arabidopsis thaliana plants, including mutant strains, to study the nematode's infection process. Mutant plants have mutations in an ABC transporter gene (At4g15320) involved in secreting chemicals that nematodes use to locate host plants.
- The goal is to see if the mutant transporter gene affects nematode infection rates compared to wild-type Arabidopsis. Results found the mutant was actually not a true mutant and showed similar nematode infection to the
This document discusses Plasmodium vivax, the parasite that causes benign tertian malaria. It focuses on the reticulocyte binding protein 1a (RBP1a) of P. vivax. The study aimed to characterize RBP1a functionally and immunologically. Recombinant RBP1a fragments were produced and used to immunize animals. The antibodies produced bound to RBP1a as shown by ELISA. Different RBP1a antigen fragments were tested for binding to human reticulocytes. RBP1a was found to bind trypsin and chymotrypsin sensitive receptors on reticulocytes in a sialic acid independent manner. This study supports the
- B cell development begins with stem cells in the bone marrow, where they undergo a series of differentiation stages defined by immunoglobulin gene rearrangement under the influence of cytokines and contact with stromal cells.
- Successful rearrangement of the heavy and light chain genes leads to expression of a B cell receptor (BCR) and selection of clones that do not recognize self-antigens through deletion, anergy or receptor editing.
- Mature B cells that pass self-tolerance checkpoints are exported from the bone marrow to the peripheral immune system.
This document describes a study that used polymerase chain reaction (PCR) to amplify 16S ribosomal DNA (rDNA) from various bacterial species for phylogenetic analysis. The researchers designed universal primers that could amplify nearly full-length 16S rDNA from many bacterial genera. They demonstrated that this method allowed phylogenetic analysis of fastidious or pathogenic bacteria directly from lyophilized cultures without requiring cultivation. As an example, they amplified, cloned, sequenced and phylogenetically analyzed the 16S rDNA of Anaplasma marginale, placing it within the genera Rickettsia and Ehrlichia.
The Kell blood group system consists of 35 antigens that are carried on the Kell glycoprotein. The Kell glycoprotein is encoded by the KEL gene and is an enzyme involved in cleaving endothelin-3. The two major Kell antigens are K and k, which differ by a single amino acid. Anti-K antibodies can cause severe hemolytic disease of the fetus and newborn as well as hemolytic transfusion reactions by destroying red blood cells. Testing for Kell antigens and antibodies is important for blood transfusions and pregnancies.
1. Organ transplantation is used to treat organs that are severely malformed or damaged, with rejection by the host immune system being a major obstacle.
2. There are different types of transplants based on how similar the donor and recipient are genetically, ranging from autographs within an individual to xenographs between species.
3. The most common form of allograft is blood transfusion.
This document summarizes HLA tissue typing techniques used in transplantation. It discusses that transplantation involves transferring cells, tissue or organs from one person to another. The first successful human kidney transplant was between identical twins in 1954. Tissue typing procedures like microcytotoxicity testing and mixed lymphocyte reaction were developed to identify histocompatible and histoincompatible antigens between donor and recipient, encoded by the major histocompatibility complex (MHC). Microcytotoxicity testing uses antibodies specific for MHC alleles to detect cytotoxicity when donor and recipient white blood cells are mixed. Mixed lymphocyte reaction quantifies MHC class II compatibility by measuring proliferation of recipient T cells when mixed with irradiated donor cells. These techniques help screen donor
This study examined the interaction between maize lipoxygenase mutants (lox3-3, lox3-4, lox5-2, lox5-3) and Aspergillus flavus oxygenase mutants (Δlox, ΔppoA, ΔppoC, ΔppoD) to understand the role of oxylipin signaling. Kernel bioassays showed that lox3-4 and lox5-3 mutants supported increased fungal growth and conidiation compared to wild-type maize. The A. flavus mutants displayed variable interactions with the plant mutants, indicating specific functions of individual plant and fungal oxygenases in the interaction. This research aims to elucidate
The document discusses B cell development in the bone marrow. Key points:
- B cell development starts in the fetal liver and continues in the bone marrow post-birth, where it undergoes various stages defined by immunoglobulin gene rearrangements.
- Ligation of the pre-B cell receptor by an unknown ligand is essential, as it ensures each cell expresses only one antibody specificity via allelic exclusion and drives proliferation of pre-B cells.
- Mature B cells exit the bone marrow with the ability to bind antigen, and mechanisms exist to ensure tolerance by deleting or anergizing self-reactive B cells.
Distribution of aminoglycoside resistance mediatedAlexander Decker
This study investigated aminoglycoside resistance and the presence of 16S rRNA methylase genes in 100 clinical isolates of Escherichia coli and Pseudomonas aeruginosa in Iraq. Minimum inhibitory concentration testing showed high resistance to kanamycin and low resistance to amikacin. Polymerase chain reaction detected seven 16S rRNA methylase genes in the isolates, with ArmA being the most common in E. coli. The study also found a high frequency of blaCTX-M extended-spectrum beta-lactamase genes, suggesting a relationship between 16S rRNA methylation and beta-lactam resistance. This research provides the first report of 16S rRNA methylase genes in E. coli and P. aeruginosa
The document discusses five theories of antibody production: the side chain theory, direct template theory, indirect template theory, natural selection theory, and clonal selection theory. It provides details on each theory and explains why the earlier four theories were disproven. The document concludes that the currently accepted universal theory is the clonal selection theory proposed by Frank Macfarlane Burnet in 1957.
This study evaluated antibody responses to the Pv200L fragment of Plasmodium vivax merozoite surface protein-1 (PvMSP-1) in individuals from 4 malaria-endemic regions in Brazil. Plasma samples from 261 P. vivax infected individuals were tested for antibodies to Pv200L by ELISA. The frequency of antibody responders ranged from 71.9-98.7% between regions and correlated with malaria transmission intensity. Higher antibody levels were also associated with greater past exposure to malaria parasites. Results provide evidence that Pv200L elicits naturally acquired antibodies and could be a potential vaccine candidate.
This study investigated the relationship between variants of the glycophorin B (GPB) gene and susceptibility to Plasmodium falciparum infection in the Brazilian Amazon. The researchers found that individuals carrying the GYPB*S allele were more likely to be infected with P. falciparum than those without this allele. Sequence analysis of GYPB also suggested it has been under natural selection due to malaria. This study provides evidence that genetic variation in GPB receptor influences the ability of P. falciparum to invade red blood cells in this population.
The document discusses HLA typing and its implications. It begins with a brief history of the discovery of the major histocompatibility complex (MHC) in mice and humans. It then describes the structure and functions of the MHC, including the class I, class II, and class III regions. The document discusses methods of HLA typing, including serological testing using microcytotoxicity and molecular methods. It notes some implications of HLA typing, such as its role in organ transplant matching and susceptibility to autoimmune disease.
This document summarizes research on the Scr74 gene family in Phytophthora infestans and how different variants of this gene are recognized in potato genotypes. The key points are:
1. 27 variants of the Scr74 effector gene were identified from 12 P. infestans isolates. 4 novel variants were cloned.
2. 13 amino acid sites in Scr74 were found to be under positive diversifying selection, indicating these sites are important for pathogen recognition.
3. 17 Scr74 variants were screened using PVX assays on 12 potato genotypes. Some genotypes had strong cell death responses to specific Scr74 variants, suggesting recognition of these variants.
4. Scr74 variants Scr74-A
This research aimed to study the relationship between the hypothetical VDBG_07494 gene in Verticillium alfalfae and its dark resting mycelia (DRM) pathway. A series of techniques were used including designing primers for the gene, performing homologous recombination to create a knockout version, extracting DNA, and running PCR and gel electrophoresis. The results showed growth of V. alfalfae cultures, presence of DRM structures, successful DNA extraction and amplification of the target region by PCR. However, gel electrophoresis suggested ectopic rather than homologous insertion of the knockout sequence occurred.
This document provides an overview of transplantation immunology. It defines key terms like transplantation, donor, recipient, graft, and alloantigens. It discusses that transplantation between non-identical individuals leads to rejection by the adaptive immune system. It describes the direct and indirect pathways of alloantigen recognition by T cells. It also outlines the activation and effector functions of alloreactive T lymphocytes, including their role in rejection through direct killing of graft cells or production of cytokines. Costimulation is also noted as important for full activation of alloreactive T cells.
The document discusses the Major Histocompatibility Complex (MHC) and its role in organ transplantation and immune response. It covers MHC genetics and polymorphism, allorecognition of T cells, mechanisms of graft rejection, immunosuppressive agents used to prevent rejection, and the use of tissue typing to match donors and recipients to improve graft survival.
1) Malaria vaccines aim to prevent infection, decrease disease severity, and reduce transmission. However, developing an effective malaria vaccine is challenging due to the parasite's high mutation rate and ability to evade the immune system.
2) Most research focuses on P. falciparum since it causes the most mortality. Potential vaccine candidates target different stages of the parasite's life cycle and include antigens like CSP, AMA1, MSP1, and Pfs25.
3) SPf66 was the first malaria vaccine tested in humans but showed limited efficacy. RTS,S is the most advanced candidate vaccine and has demonstrated up to 50% efficacy in clinical trials. However, more research is still needed to develop
Reduced Antimony Accumulation in ARM58-Overexpressing Leishmania infantumCarola Schäfer
1. The study identified ARM58, a novel antimony resistance marker gene in Leishmania infantum.
2. Overexpression of ARM58 in L. infantum reduces intracellular accumulation of antimony (Sb) by over 70%, indicating its role in Sb extrusion pathways.
3. A small putative transmembrane domain within one of ARM58's four conserved domains was found to be critical for its function in reducing Sb accumulation.
This document summarizes a study investigating the evolution of high-level resistance to the tuberculosis drug ethambutol in Mycobacterium tuberculosis. The key findings are:
1) M. tuberculosis strains selected in vitro for ethambutol resistance accumulated mutations in genes involved in decaprenylphosphoryl-β-d-arabinose (DPA) biosynthesis and utilization, including Rv3806c, Rv3792, embB and embC, resulting in a range of ethambutol minimum inhibitory concentrations depending on mutation type and number.
2) Multistep selection was required for M. tuberculosis to develop high-level ethambutol resistance over 32 μg/ml
The document summarizes the process of producing monoclonal antibodies (mAbs) through hybridoma technology. It involves immunizing an animal, usually a mouse, to elicit an immune response. B cells from the animal's spleen are then fused with myeloma cells to generate immortal hybridoma cells. These hybridoma cells are screened and selected in HAT medium to identify clones that produce the desired mAb. The selected clones are then subjected to further characterization and mass production methods.
- The document discusses research on the cotton root-knot nematode (Meloidogyne incognita), an endoparasitic nematode that infects thousands of plant species and causes billions in crop damage worldwide.
- The research uses Arabidopsis thaliana plants, including mutant strains, to study the nematode's infection process. Mutant plants have mutations in an ABC transporter gene (At4g15320) involved in secreting chemicals that nematodes use to locate host plants.
- The goal is to see if the mutant transporter gene affects nematode infection rates compared to wild-type Arabidopsis. Results found the mutant was actually not a true mutant and showed similar nematode infection to the
This document discusses Plasmodium vivax, the parasite that causes benign tertian malaria. It focuses on the reticulocyte binding protein 1a (RBP1a) of P. vivax. The study aimed to characterize RBP1a functionally and immunologically. Recombinant RBP1a fragments were produced and used to immunize animals. The antibodies produced bound to RBP1a as shown by ELISA. Different RBP1a antigen fragments were tested for binding to human reticulocytes. RBP1a was found to bind trypsin and chymotrypsin sensitive receptors on reticulocytes in a sialic acid independent manner. This study supports the
- B cell development begins with stem cells in the bone marrow, where they undergo a series of differentiation stages defined by immunoglobulin gene rearrangement under the influence of cytokines and contact with stromal cells.
- Successful rearrangement of the heavy and light chain genes leads to expression of a B cell receptor (BCR) and selection of clones that do not recognize self-antigens through deletion, anergy or receptor editing.
- Mature B cells that pass self-tolerance checkpoints are exported from the bone marrow to the peripheral immune system.
This document describes a study that used polymerase chain reaction (PCR) to amplify 16S ribosomal DNA (rDNA) from various bacterial species for phylogenetic analysis. The researchers designed universal primers that could amplify nearly full-length 16S rDNA from many bacterial genera. They demonstrated that this method allowed phylogenetic analysis of fastidious or pathogenic bacteria directly from lyophilized cultures without requiring cultivation. As an example, they amplified, cloned, sequenced and phylogenetically analyzed the 16S rDNA of Anaplasma marginale, placing it within the genera Rickettsia and Ehrlichia.
The Kell blood group system consists of 35 antigens that are carried on the Kell glycoprotein. The Kell glycoprotein is encoded by the KEL gene and is an enzyme involved in cleaving endothelin-3. The two major Kell antigens are K and k, which differ by a single amino acid. Anti-K antibodies can cause severe hemolytic disease of the fetus and newborn as well as hemolytic transfusion reactions by destroying red blood cells. Testing for Kell antigens and antibodies is important for blood transfusions and pregnancies.
1. Organ transplantation is used to treat organs that are severely malformed or damaged, with rejection by the host immune system being a major obstacle.
2. There are different types of transplants based on how similar the donor and recipient are genetically, ranging from autographs within an individual to xenographs between species.
3. The most common form of allograft is blood transfusion.
This document summarizes HLA tissue typing techniques used in transplantation. It discusses that transplantation involves transferring cells, tissue or organs from one person to another. The first successful human kidney transplant was between identical twins in 1954. Tissue typing procedures like microcytotoxicity testing and mixed lymphocyte reaction were developed to identify histocompatible and histoincompatible antigens between donor and recipient, encoded by the major histocompatibility complex (MHC). Microcytotoxicity testing uses antibodies specific for MHC alleles to detect cytotoxicity when donor and recipient white blood cells are mixed. Mixed lymphocyte reaction quantifies MHC class II compatibility by measuring proliferation of recipient T cells when mixed with irradiated donor cells. These techniques help screen donor
This study examined the interaction between maize lipoxygenase mutants (lox3-3, lox3-4, lox5-2, lox5-3) and Aspergillus flavus oxygenase mutants (Δlox, ΔppoA, ΔppoC, ΔppoD) to understand the role of oxylipin signaling. Kernel bioassays showed that lox3-4 and lox5-3 mutants supported increased fungal growth and conidiation compared to wild-type maize. The A. flavus mutants displayed variable interactions with the plant mutants, indicating specific functions of individual plant and fungal oxygenases in the interaction. This research aims to elucidate
The document discusses B cell development in the bone marrow. Key points:
- B cell development starts in the fetal liver and continues in the bone marrow post-birth, where it undergoes various stages defined by immunoglobulin gene rearrangements.
- Ligation of the pre-B cell receptor by an unknown ligand is essential, as it ensures each cell expresses only one antibody specificity via allelic exclusion and drives proliferation of pre-B cells.
- Mature B cells exit the bone marrow with the ability to bind antigen, and mechanisms exist to ensure tolerance by deleting or anergizing self-reactive B cells.
Distribution of aminoglycoside resistance mediatedAlexander Decker
This study investigated aminoglycoside resistance and the presence of 16S rRNA methylase genes in 100 clinical isolates of Escherichia coli and Pseudomonas aeruginosa in Iraq. Minimum inhibitory concentration testing showed high resistance to kanamycin and low resistance to amikacin. Polymerase chain reaction detected seven 16S rRNA methylase genes in the isolates, with ArmA being the most common in E. coli. The study also found a high frequency of blaCTX-M extended-spectrum beta-lactamase genes, suggesting a relationship between 16S rRNA methylation and beta-lactam resistance. This research provides the first report of 16S rRNA methylase genes in E. coli and P. aeruginosa
The document discusses five theories of antibody production: the side chain theory, direct template theory, indirect template theory, natural selection theory, and clonal selection theory. It provides details on each theory and explains why the earlier four theories were disproven. The document concludes that the currently accepted universal theory is the clonal selection theory proposed by Frank Macfarlane Burnet in 1957.
This study evaluated antibody responses to the Pv200L fragment of Plasmodium vivax merozoite surface protein-1 (PvMSP-1) in individuals from 4 malaria-endemic regions in Brazil. Plasma samples from 261 P. vivax infected individuals were tested for antibodies to Pv200L by ELISA. The frequency of antibody responders ranged from 71.9-98.7% between regions and correlated with malaria transmission intensity. Higher antibody levels were also associated with greater past exposure to malaria parasites. Results provide evidence that Pv200L elicits naturally acquired antibodies and could be a potential vaccine candidate.
This study investigated the relationship between variants of the glycophorin B (GPB) gene and susceptibility to Plasmodium falciparum infection in the Brazilian Amazon. The researchers found that individuals carrying the GYPB*S allele were more likely to be infected with P. falciparum than those without this allele. Sequence analysis of GYPB also suggested it has been under natural selection due to malaria. This study provides evidence that genetic variation in GPB receptor influences the ability of P. falciparum to invade red blood cells in this population.
This study investigated the relationship between variants of the glycophorin B (GPB) gene and susceptibility to Plasmodium falciparum infection in the Brazilian Amazon. The researchers found that individuals carrying the GYPB*S allele were more likely to be infected with P. falciparum than those without this allele. Additionally, population genetics analysis suggested that natural selection has shaped patterns of genetic diversity at the GYPB locus. This study provides evidence that genetic variation in GPB influences susceptibility to P. falciparum infection in this population.
1) Field isolates of Plasmodium falciparum from Colombia and Peru were found to invade red blood cells through an atypical pathway that was resistant to all enzyme treatments, unlike what is typically seen.
2) The invasion pathways and ligand polymorphisms differed between Colombian, Peruvian, and Brazilian isolates, with Peruvian isolates showing a combination of Colombian and Brazilian characteristics.
3) The atypical resistant pathway was associated with specific variants of PfRh2a, PfRh5 and EBA-181, which may be major players in this pathway based on expression levels.
1. Researchers studied Plasmodium falciparum field isolates from Colombia, Peru, and Brazil to determine the invasion pathways and ligand polymorphisms used.
2. They found that most isolates from Colombia and Peru invade red blood cells through an atypical pathway that is resistant to all enzyme treatments, unlike known pathways.
3. This unusual pathway was associated with specific variants of PfRh2a, PfRh5, and EBA-181 ligands, suggesting these proteins play a major role in this pathway. The study demonstrates diversity in invasion mechanisms between regions.
My presentation in the "CME on Sickle Cell Disease" at Government Medical College, Akola, Maharashtra, India on 19th December 2012 organized by MMC-CME Committee of GMC, Akola and the Department of Pediatrics, GMC, Akola.
This document summarizes a study that analyzed Duffy blood group genotypes in Plasmodium vivax malaria patients and blood donors in four areas of the Brazilian Amazon region. The study found:
1) A high frequency of the FYA/FYB genotype in both patients and donors, followed by FYB/FYB.
2) Some Duffy genotypes showed significant differences in frequency between patients and donors.
3) Individuals with the FYA/FYB genotype may have higher susceptibility to malaria, while the presence of the FYB-33 allele could provide resistance.
This document summarizes information about malaria vaccines. It discusses how malaria is caused by Plasmodium parasites and transmitted by mosquitoes. Four species can infect humans. Current vaccines target different stages of the parasite's life cycle, including pre-erythrocytic, blood, and sexual stages. Challenges to vaccine development include the parasite's ability to evade the immune system through antigenic variation. Several candidate vaccines are discussed that target different stages, but none have achieved high levels of efficacy and durability.
This study characterized 10 novel human monoclonal antibodies (Mabs) against PfCelTOS, a Plasmodium falciparum protein important for malaria parasite infection. The Mabs were produced using Kymouse technology. Initial tests using western blot and dot blot assessed antibody reactivity to full length PfCelTOS and its termini. Enzyme-linked immunosorbent assays (ELISAs) then provided quantitative results and determined fine specificity mapping of the Mabs. Cross-reactivity between other Plasmodium species was also examined. Immunofluorescent assays found that a few Mabs strongly bound epitopes in the C and N terminus regions of PfCelTOS on sporozoite surfaces. Further examination of
This document summarizes a study that investigated the influence of HLA-DRB1 alleles on the production of antibodies against malaria antigens in individuals naturally infected with Plasmodium vivax in Brazil. The study found an association between HLA-DR3 and HLA-DR5 alleles and lack of antibody response to the amino terminal region of the circumsporozoite protein (CSP). It also found an association between HLA-DR3 and higher antibody response to merozoite surface protein 1 (MSP1). No significant associations were found between HLA-DRB1 alleles and antibody responses to other malaria antigens tested.
This document summarizes a study that investigated the influence of HLA-DRB1 alleles on the production of antibodies against malaria antigens in individuals naturally infected with Plasmodium vivax in Brazil. The study found an association between HLA-DR3 and HLA-DR5 alleles and lack of antibody response to the amino terminal region of the circumsporozoite protein (CSP). It also found an association between HLA-DR3 and higher antibody response to merozoite surface protein 1 (MSP1). No significant associations were found between HLA-DRB1 alleles and antibody responses to other malaria antigens tested.
Expression and Purification of the Plasmodium berghei Apical Membrane Antigen-1Nathan Jones
This document summarizes the production and purification of the Plasmodium berghei Apical Membrane Antigen-1 (PbAMA-1) protein for use as a vaccine candidate in mice. The PbAMA-1 gene was amplified from P. berghei genomic DNA and cloned into an expression vector. This plasmid was transformed into E. coli cells for protein expression. The expressed PbAMA-1 protein was purified using nickel affinity and size-exclusion chromatography. Analysis by SDS-PAGE and western blot confirmed the purified protein had the correct size and identity. The purified PbAMA-1 protein is now being tested in mice for its ability to protect against blood stage and sporozoite stage
This document compares the allele frequencies of 15 Plasmodium falciparum merozoite antigen genes in malaria infections sampled in Kenya in 2007 and 2008. It finds fluctuating allele frequencies in codons 147 and 148 of the reticulocyte-binding homologue 5 (Rh5) gene over this period in uncomplicated malaria infections. However, the dominant YH haplotype was stable over multiple years in asymptomatic and complicated infections. A regression analysis found the chance of the less common HD haplotype decreased over time from 2007 to 2009 in uncomplicated and asymptomatic infections.
This study evaluated four recombinant proteins representing the 19 kDa C-terminal region of the Plasmodium vivax merozoite surface protein-1 (MSP119) for detecting P. vivax antibodies in human serum samples. The sensitivity of an ELISA using the recombinant proteins to detect antibodies in 200 samples from individuals with P. vivax infection ranged from 90-93.5%. Specificity using control samples without P. vivax exposure was 98.3-100%. The study demonstrates the potential of an ELISA using recombinant MSP119 proteins for serological detection of P. vivax infection.
This study examined the immune response in patients with early cutaneous leishmaniasis (ECL), defined as illness duration of 60 days or less, compared to those with late cutaneous leishmaniasis (LCL) of over 12 months. The results showed that in ECL, 32% of patients had absent or low lymphoproliferative responses to Leishmania antigens and 41% had an absence of interferon (IFN)-γ production. IFN-γ levels were significantly lower in ECL compared to LCL, while interleukin (IL)-10 levels were significantly higher in ECL. The addition of anti-IL-10 or anti-IL-12 antibodies restored lymphoprolifer
arabidopsis thaliana a model plant for studying plant pathogen interactionsKanthraj Kanthu
This document discusses the use of Arabidopsis thaliana as a model organism for studying plant-pathogen interactions. It notes that A. thaliana is well-suited for such studies because it is small, has a short lifecycle, can be easily grown in the lab, and was the first plant to have its genome sequenced. The document outlines several key findings from research using A. thaliana, including the identification of R-gene loci that mediate gene-for-gene resistance to pathogens and the characterization of defense response genes induced during infection. It also discusses how A. thaliana exhibits similar physiological responses as crop plants when challenged by pathogens, such as phytoalexin production and systemic acquired resistance.
Molecular Biology - Bachelor of Science in Biological Sciences by Slidesgo (2...manuelag1702
This study examined the interaction between the AraC/XylS-like transcriptional activator InvF of Salmonella Typhimurium, the RNA polymerase alpha subunit, and the chaperone SicA. The researchers used RT-qPCR, dimerization assays, Western blot, and ELISA methods. The results demonstrated that InvF binds to the alpha subunit and SicA can independently contact both proteins. Molecular dynamics simulations also supported the interaction between InvF and the alpha subunit. The conclusions were that further research on these protein interactions is important for understanding gene regulation and virulence mechanisms in pathogens like Salmonella Typhimurium.
Five attenuated Francisella novicida transposon mutants (with mutations corresponding to dsbB, FTT0742, pdpB, fumA, and carB in F. tularensis) were identified that provided protection against challenge with over 8 x 105 CFU of wild-type F. novicida in mice. The mutants were screened by examining their ability to grow in mouse macrophages and their virulence in mice. These attenuated mutants were then tested for their ability to protect mice against challenge with high doses of wild-type bacteria. The findings from this study could be useful in the design of a vaccine against tularemia.
- Malaria is caused by Plasmodium parasites and is a major tropical disease, especially in Africa. The most lethal species is P. falciparum.
- There are three main types of malaria vaccines targeting different life stages of the parasite: pre-erythrocytic (liver stage), blood stage, and transmission blocking vaccines.
- The leading and most advanced vaccine candidate is RTS,S/AS02, which targets the pre-erythrocytic stage and has reached phase III clinical trials. It consists of the CSP antigen fused to the hepatitis B surface antigen. Phase II trials demonstrated approximately 30% efficacy.
Malaria due to Plasmodium falciparum is a major public health concern in Cameroon and Africa, responsible for high rates of morbidity and mortality. While control measures have been effective, an effective vaccine is needed to achieve global malaria elimination goals. This study analyzed genetic diversity in the merozoite surface protein 1 (msp1) gene of P. falciparum isolates from Mount Cameroon. It found 45 distinct DNA fragments in samples from 81 of 173 infected individuals, indicating significant intragenic recombination contributing to parasite diversity. Understanding this diversity is important for vaccine development against P. falciparum.
Similar to 2007 differential antibodies responses p. falciparum (20)
This document analyzes the frequency of two polymorphisms (C282Y and H63D) in the HFE gene in malaria patients and blood donors from four states in the Brazilian Amazon region. The study found:
1) No individuals were homozygous for the C282Y polymorphism, and only 5 heterozygous individuals were detected, all from Pará State.
2) The most common genotype for the H63D polymorphism was heterozygous in both patient groups.
3) Allele frequencies for the H63D polymorphism were higher than for the C282Y polymorphism, consistent with other studies on Brazilian populations.
This study examined 51 Brazilian Plasmodium falciparum isolates for polymorphisms in the Pfmdr1 gene thought to be associated with chloroquine resistance. 49 of the isolates were found to be resistant to chloroquine in vitro, while all were sensitive to mefloquine, amodiaquine, and quinine. The isolates were analyzed for three Pfmdr1 polymorphisms: Asn86Tyr, Asn1042Asp, and Asp1246Tyr. Asn86Tyr was not detected in any isolates, while Asn1042Asp was found in 50 isolates and Asp1246Tyr was found in all 51 isolates. This provides support that As
This study evaluated the distribution of Plasmodium vivax variants (VK210, VK247, and P. vivax-like) in three areas of Brazil using a new GFM-PCR-ELISA technique. All variants were found in all three areas. VK210 was most commonly found as a single infection while the others occurred in mixed infections. VK210 was associated with the highest parasitemia levels while P. vivax-like had the lowest. Parasitemia clearance times did not differ based on variant or treatment schedule. The new technique was accurate for epidemiological surveys of the vivax complex.
This document analyzes genetic variation at the Pfs48/45 gene and microsatellite loci in 255 Plasmodium falciparum isolates from 5 populations. It finds:
1) Alleles and haplotypes of 5 SNPs in the Pfs48/45 gene varied extremely between populations, much more so than alleles at 11 neutral microsatellite loci.
2) Measurements of between-population allele frequency variation (FST) were 4-7 times higher for Pfs48/45 than microsatellites, both within and between continents.
3) The highly skewed Pfs48/45 patterns suggest divergent selection on the protein's amino acid sequence between populations, indicating it may determine game
This study compared ELISA and PCR-ELISA techniques for detecting human Plasmodium parasites in Anopheles mosquitoes from the Amazon region of Brazil. The PCR-ELISA technique confirmed all positive and negative ELISA results but detected additional Plasmodium species in 5 of the 32 positive mosquitoes that were not detected by ELISA alone. The PCR-ELISA is more sensitive than ELISA for detecting human malaria parasites in mosquitoes.
1) O documento analisa os casos de malária no estado de Santa Catarina entre 1996-2001, com 5,5% das 4.707 amostras sendo positivas.
2) Plasmodium vivax causou 69% dos casos, Plasmodium falciparum 25,6%, infecções mistas 5% e Plasmodium malariae 0,4%.
3) 67,4% dos casos foram importados e 32,6% autóctones, com aumento de casos importados nos anos subsequentes.
This study analyzed genetic diversity and population structure of Plasmodium falciparum in 5 populations in the Brazilian Amazon region. Microsatellite markers were analyzed in 196 parasite isolates. There was significant multilocus linkage disequificance within populations, particularly those with fewer mixed infections. However, most isolates had unique multilocus genotypes, indicating genetic diversity. Genetic divergence between populations was substantial but did not correlate simply with geographical distance. The findings suggest distinct population structures and minimal gene flow between foci in the region.
1) The study evaluated the performance of the OptiMal malaria rapid diagnostic test under different storage conditions of 25°C, 30°C, and 39°C for 24, 48, and 72 hours.
2) The test detected all 111 positive blood samples except for 2 low parasitemia Plasmodium malariae samples.
3) The study suggests that the OptiMal test can be used for malaria diagnosis in Brazilian regions, though further research is needed to evaluate its performance under different environmental conditions like humidity.
This study evaluated the frequency of asymptomatic Plasmodium carriers (APCs) among blood donors in four blood banks in the Brazilian Amazon region. Blood samples from 400 donors who passed screening were tested using PCR to detect Plasmodium DNA. The positivity rate varied from 1-3% between blood banks, with an overall rate of 2.3%. All positive samples contained mixed infections of P. vivax and P. falciparum. While screening methods used by the blood banks did not detect the infections, PCR revealed its superiority for detecting low levels of parasites. The results emphasize the need to improve screening for APCs in blood banks in malaria endemic areas to control transfusion-transmitted malaria.
This study investigated genetic mutations associated with chloroquine resistance in Plasmodium falciparum samples from the Brazilian Amazon region. The study analyzed 40 samples from 4 localities for mutations in the pfmdr1, cg2, and pfcrt genes. It found 100% of samples contained mutations in pfmdr1 codons 184, 1042, and the cg2 gamma region associated with chloroquine resistance. Most samples also contained the pfcrt K76T mutation, except some from Porto Velho which matched a Thai resistant genotype. This research contributes to understanding the molecular basis of widespread chloroquine resistance in this region.
1. The study developed a new PCR/RFLP technique to identify the 3 genotypes of Plasmodium vivax circumsporozoite protein (VK210, VK247, and P. vivax-like) using DNA extracted from blood samples.
2. The technique uses PCR amplification of the central immunodominant region of the CSP gene followed by restriction enzyme digestion and fragment analysis to distinguish the genotypes.
3. Testing demonstrated the technique could accurately identify the genotypes using plasmid controls for each variant, and that it had high sensitivity detecting parasitemia levels as low as 0.0069 parasites per microliter.
We present evidence of Plasmodium vivax infection in two homozygous FY*B-33 (Duffy-negative) individuals from the Brazilian Amazon region. Molecular analysis confirmed P. vivax infection through detection of P. vivax small subunit rRNA and circumsporozoite protein genes. One individual had a mixed infection of VK210 and P. vivax-like genotypes, while the other was infected with VK210. Both individuals also had antibodies to the P. vivax merozoite surface protein 1. This provides rare evidence that P. vivax may be capable of invading Duffy-negative red blood cells in some regions, though additional studies are needed to better understand this finding.
Mixed Plasmodium falciparum infections were common in four areas of the Brazilian Amazon region. Molecular diagnosis found 73% of infections were single P. falciparum infections, while 27% were mixed infections, mostly double infections. Mixed infections were associated with weaker clinical malaria symptoms like lower rates of fever and headache compared to single P. falciparum infections. The study highlights the need for improved malaria diagnosis to better understand mixed infections and their impact on disease severity.
This study aimed to investigate the presence of arboviruses like dengue virus in clinical samples from 111 malaria patients in the Amazon region of Brazil.
Dengue virus serotype 2 was detected in two patients from Novo Repartimento, Pará who also had active Plasmodium vivax malaria infections. Despite limited data, concurrent dengue and malaria infections are likely more common in the Amazon region than detected, as both diseases co-circulate and have similar transmission vectors and clinical presentations, making dual diagnosis possible. Further research is needed to better understand the frequency of co-infection in this region.
This study investigated the frequencies of ABO blood group genotypes and alleles in Plasmodium falciparum malaria patients and blood donors from the Brazilian Amazon region. The researchers found that over half of individuals had the ABO*O01O01 genotype. The ABO*AO01 genotype was the second most common. No significant differences were detected in genotype or allele frequencies between the malaria patients and blood donors. Analysis of O alleles found the O1 variant allele to be most frequent in both groups, with no evidence of the homozygous O2 allele.
1. A study analyzed genetic and immune response differences between P. vivax circumsporozoite (CS) genotypes VK210 and P. vivax-like.
2. Phylogenetic analysis of 18S rRNA and CytB genes found high similarity between the genotypes, with zero nucleotide diversity, placing them in the same clade.
3. Individuals infected with P. vivax-like had a lower antibody response against CS repetitive region peptides than those with VK210, suggesting variation is limited to the CS repetitive region.
This document describes the development of a PCR-RFLP assay to identify Plasmodium species and variants of P. vivax infecting Anopheles mosquitoes. Specific primers were designed that target regions of the circumsporozoite gene to distinguish P. falciparum, P. malariae, and P. vivax variants VK210, VK247, and P. vivax-like. The assay was tested on artificially infected mosquitoes and showed good agreement with nested PCR. The PCR-RFLP method provides a sensitive way to detect Plasmodium species and variants, which can help understand malaria transmission dynamics.
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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.
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
- Video recording of this lecture in English language: https://youtu.be/Pt1nA32sdHQ
- Video recording of this lecture in Arabic language: https://youtu.be/uFdc9F0rlP0
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
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share - Lions, tigers, AI and health misinformation, oh my!.pptxTina Purnat
• Pitfalls and pivots needed to use AI effectively in public health
• Evidence-based strategies to address health misinformation effectively
• Building trust with communities online and offline
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Promoting Wellbeing - Applied Social Psychology - Psychology SuperNotesPsychoTech Services
A proprietary approach developed by bringing together the best of learning theories from Psychology, design principles from the world of visualization, and pedagogical methods from over a decade of training experience, that enables you to: Learn better, faster!
These lecture slides, by Dr Sidra Arshad, offer a simplified look into the mechanisms involved in the regulation of respiration:
Learning objectives:
1. Describe the organisation of respiratory center
2. Describe the nervous control of inspiration and respiratory rhythm
3. Describe the functions of the dorsal and respiratory groups of neurons
4. Describe the influences of the Pneumotaxic and Apneustic centers
5. Explain the role of Hering-Breur inflation reflex in regulation of inspiration
6. Explain the role of central chemoreceptors in regulation of respiration
7. Explain the role of peripheral chemoreceptors in regulation of respiration
8. Explain the regulation of respiration during exercise
9. Integrate the respiratory regulatory mechanisms
10. Describe the Cheyne-Stokes breathing
Study Resources:
1. Chapter 42, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 36, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 13, Human Physiology by Lauralee Sherwood, 9th edition
Kosmoderma Academy, a leading institution in the field of dermatology and aesthetics, offers comprehensive courses in cosmetology and trichology. Our specialized courses on PRP (Hair), DR+Growth Factor, GFC, and Qr678 are designed to equip practitioners with advanced skills and knowledge to excel in hair restoration and growth treatments.
5-hydroxytryptamine or 5-HT or Serotonin is a neurotransmitter that serves a range of roles in the human body. It is sometimes referred to as the happy chemical since it promotes overall well-being and happiness.
It is mostly found in the brain, intestines, and blood platelets.
5-HT is utilised to transport messages between nerve cells, is known to be involved in smooth muscle contraction, and adds to overall well-being and pleasure, among other benefits. 5-HT regulates the body's sleep-wake cycles and internal clock by acting as a precursor to melatonin.
It is hypothesised to regulate hunger, emotions, motor, cognitive, and autonomic processes.
2. 978 FORD AND OTHERS
Two study groups from hypoendemic regions for malaria in INKK) and EBA-175 region II (aa 145–760; 3D7 allele) were
Brazil were studied: The serum samples of the first group expressed in yeast and were a kind gift from D. Narum and L.
were collected in 1995 from 17 adult male individuals (median Miller (LMV, NIH). The 19-kDa processed fragment of the
age 52 סyears) living in Peixoto de Azevedo, a municipality merozoite surface protein 1, MSP-119, was obtained as a re-
of Mato Grosso state, located in the southern part of the combinant yeast protein from the MR4 (ATCC) and also
Amazon region in Brazil. The individuals were migrant gold corresponds to the 3D7 allele. These 3 recombinant proteins
mining workers without documented ethnicity who had come were properly folded.
to the local health service center, run by the Ministry of Measurement of antigen-specific antibody responses. Hu-
Health, and were found to be P. falciparum positive and P. man serum samples were analyzed for IgG1 and IgG3 reac-
vivax negative. These individuals resided in the endemic re- tivity to the recombinant malaria proteins by a defined en-
gion for only a few years and had no more than 1–3 malaria zyme-linked immunosorbent assay (ELISA), as described
episodes. The serum samples of the second group were col- previously.26 Sera were analyzed for IgG antibody isotypes.
lected in 2004 and originated from individuals who have lived The subclass of immunoglobulin determines antibody func-
in the Amazon regions (Macapá, Belém, Porto Velho, and tion (e.g., complement fixation or the activation of phago-
Rio Branco) of Brazil for most of their life and have reported cytes), and in humans, immunoglobulin G1 (IgG1) and IgG3
multiple episodes (range 1 to > 4 episodes) of P. falciparum are important mediators of malaria parasite clearance.27 To
malaria infection and were P. vivax-negative at the time of determine which E. coli-expressed EBA protein fragments
blood collection. This group consisted of 37 individuals (4 were antigenic, we performed an initial ELISA screen using
females and 33 males; median age 52 סyears, range 18–76 the various recombinant EBA fragments with a small group
years). of sera from Cameroon. Based on their antigenicity, for all
The serum samples from West Africa were collected in further experiments we focused on the antibody responses
1996 and 1997 and originated from individuals who live in generated to 3 EBA-140 protein fragments: portion of region
villages in the Kumba region, an area of hyperendemic ma- II, region VI and the C-terminal region, and to the C-terminal
laria in the southwest province of Cameroon. The individuals region fragment of EBA-181.
who participated in the study were born or had resided for Microtiter ELISA plates (Costar, Corning Life Sciences,
> 10 years in villages: Marumba I, Marumba II, Boa Bakundu, Corning, NY) were coated with 1 g/mL of recombinant pro-
Bombanda, and Bombele. The group consisted of individuals tein diluted in 0.05 M carbonate buffer, pH 9.6. After incu-
who were both P. falciparum blood smear positive and nega- bation overnight at 4°C, the plates were washed 5 times with
tive at the time of bleeding. The Cameroonian study group phosphate-buffered saline (PBS) with 0.05% Tween 20
comprised 180 individuals (118 males and 62 females; median (PBST) and blocked with blocking buffer (3% BSA in PBST)
age 71 סyears; range, 3–75 years). An age-matched subset of for 1.5 hr at 37°C. Serum samples were pre-incubated with E.
these individuals was selected (N ;82 סmedian age 23 ס coli extract prior to dilution and incubation with the bound
years; range 8–38 years) to compare their responses with antigen to remove antibodies to potential E. coli contami-
those from the individuals from Brazil. nants in the recombinant protein preparations. Serum
All blood samples were obtained from volunteers with in- samples, diluted 1:500 in blocking buffer, were reacted with
formed consent using protocols approved by both local and the bound antigens by incubating for 2 hr at 37°C, in duplicate
NYBC IRB committees. wells. The bound IgG1 and IgG3 antibodies were detected
Recombinant malaria protein expression and purifica- after incubation for 1 hr at 37°C with mouse monoclonal
tion. Recombinant malaria proteins were expressed in Es- antibodies against different human IgG subclasses (Hybri-
cherichia coli BL21 (DE3) (Sigma, St. Louis, MO) as fusion doma Reagent Laboratory, Baltimore, MD) diluted 1:1000 in
proteins with glutathione S-transferase (GST) using the blocking buffer, followed by incubation for 1 hr at 37°C with
pGEX vector (Amersham Biotech, Piscataway, NJ). horseradish peroxidase-conjugated goat anti-mouse IgG (H +
The 3D7 strain of P. falciparum was used as template to L) (Kirkegaard & Perry Laboratories, Inc., Gaithersburg,
derive the various fragments that were used for cloning and MD) diluted 1:1250 in blocking buffer. Tetramethylbenzi-
expression. Fragments of the erythrocyte-binding proteins dine (Sigma, St Louis, MO) was used as the substrate for all
EBA-140 and EBA-181 were expressed as soluble GST- ELISAs, and the optical density (OD) was read at 450 nm on
fusion proteins and corresponded to fragments within the fol- a SpectraMax 190 ELISA Reader (Molecular Devices,
lowing regions: portion (aa 350–440) of the Duffy binding-like Sunnyvale, CA).
domain (DBL) also known as region II, portions of region VI Each serum sample was tested against GST as a negative
(aa 799–963) and the C-terminal region (aa 967–1140) of control for the GST-fusion proteins. Positive responders were
EBA-140, and portions of the N-terminal (aa 33–171) and the defined as those that gave an OD value greater than the
C-terminal (aa 1235–1345) of EBA-181. These regions do not cut-off OD, which was defined as the mean plus 3 standard
exhibit sequence polymorphism among the various P. falci- deviations of OD values from control sera. If the cut-off was
parum strains. Recombinant proteins were purified by affinity < 0.1, positive responders were defined as those with an OD
chromatography on glutathione agarose (Sigma) as previ- value > 0.1. Control sera used were collected from 5 healthy
ously described.25 Control GST was purified from E. coli adult volunteers living in New York who had never been
BL21 transformed with the pGEX vector alone. Fusion pro- exposed to malaria. Samples from the different study sites
teins were assessed by Coomassie blue staining of SDS- were run in parallel to ensure reliable comparison of ODs.
PAGE gels, and protein concentrations were measured using Statistical analysis. The 2 test was used to compare pro-
the Bio-Rad protein assay (Bio-Rad, Hercules, CA) accord- portions of antibody responders in different groups, whereas
ing to the manufacturer’s instructions. the differences in the immunoglobulin levels between groups
Full length EBA-140 region II (aa 141–756; the 3D7 allele, were compared using the two-tailed nonparametric Mann–
3. ANTIBODY RESPONSES TO MALARIA INVASION LIGANDS 979
Whitney U test. Spearman’s rank correlation test was used to ing in Macapá, Belém, Porto Velho, and Rio Branco, the
test the significance of the correlation between the age of the antigen-specific antibody responses differed between the 2
individuals and their antibody responses, with the correlation endemic regions within Brazil (Figure 1B, C). The antibody
coefficient being expressed as r. A P value of < 0.05 was responses in these Amazonian individuals, to the same panel
considered statistically significant. Statistical analysis was per- of EBA proteins, were elevated (percent positive responders:
formed using GraphPad PRISM software (GraphPad Soft- IgG1, 7.7–30.8%; IgG3, 28.5–69.2%) when compared with
ware Inc., San Diego, CA). those from Mato Grosso, although lower in magnitude than
the responses in the Cameroonian sera (Table 1). Amazonian
individuals had significantly higher antibody responses than
RESULTS
individuals from Mato Grosso to EBA-181 C-terminal frag-
Differential antibody responses to EBA-140 and EBA-181 ment (P < 0.001 for both IgG1 and IgG3), EBA-140 region II
fragment proteins in individuals living in Brazil and in Cam- fragment (P < 0.001 IgG1 and P 7200.0 סIgG3), EBA-140
eroon. Analysis of the IgG1 and IgG3 responses to different region VI fragment (P 4230.0 סIgG1), and EBA-140 C-
fragments of EBA-140 and EBA-181 in individuals from terminal fragment (P 1500.0 סIgG3). Regardless, the anti-
Mato Grosso and the Amazon region, Brazil, and Cameroon body responses in the Amazon individuals was significantly
revealed a dramatic difference in both the prevalence and lower than the responses in the Cameroon individuals to
magnitude of responses between the populations (Figure 1; EBA-140 full-length region II (P < 0.001 for both IgG1 and
Table 1). Whereas the Cameroon individuals mounted an ef- IgG3), EBA-140 region II fragment (P 2610.0 סIgG1 and
ficient antibody response to most of the recombinant EBA- P 3000.0 סIgG3), EBA-140 region VI fragment (P 8800.0 ס
140 and EBA-181 proteins (percent positive responders: IgG3), and EBA-140 C-terminal fragment (P 6000.0 סIgG1
IgG1, 38.1–96.4%; IgG3, 65–100%), the antibody response to and P < 0.001 IgG3). Antibody responses to the EBA-181
the same panel of proteins in residents of Mato Grosso was C-terminal fragment in the Amazonian individuals were also
much lower (percent positive responders: IgG1, 5.9–29.4%; lower than in the Cameroon individuals; however, these dif-
IgG3, 5.9–29.4%) (Figure 1A,B; Table 1). Only 1 serum ferences were not statistically significant (P 541.0 סIgG1 and
sample from Mato Grosso in each assay showed a strong P 671.0 סIgG3).
response (OD > 0.3) to the EBAs. All of the IgG1 and IgG3 Antibody responses to MSP-119 and EBA-175 region II. To
responses in Mato Grosso, with the exception of the IgG1 determine if the low humoral response seen in the Mato
response mounted to a fragment within the EBA-140 region Grosso population against the EBA proteins was antigen-
II, were significantly lower than the responses in Cameroon specific, we examined the antibodies present in these endemic
(EBA-140 proteins—full-length region II P < 0.001 for both, populations to 2 other known highly antigenic malaria pro-
region II fragment P < 0.001 IgG3, region VI fragment P ס teins: the GPA-binding domain of EBA-175, EBA-175 region
0.0097 IgG1 and P 4330.0 סIgG3, C-terminal fragment P ס II, another member of the EBL family and the 19-kDa pro-
0.0087 IgG1 and P < 0.001 IgG3; EBA-181 C-terminal frag- cessed fragment of the merozoite surface protein 1 (MSP-119).
ment P < 0.001 for both). The EBA-140 proteins correspond- These results are presented in Table 1 and Figure 2. In both
ing to full-length region II, fragment of region VI, and frag- the Mato Grosso inhabitants and the individuals from Cam-
ment of the C-terminal were found to be the most antigenic eroon, the IgG3 responses to MSP-119 were prevalent (76.5%
ligands for the Mato Grosso population (11.8–29.4% positive IgG3-positive responders in Mato Grosso versus 95% IgG3-
responders), although the reactivity was much lower than positive responders in Cameroon; P 80.0 סusing 2 analysis).
found in the African population (80–100% positive respond- The prevalence of the IgG1 responses against MSP-119 was,
ers). In the African population, the full-length region II frag- however, significantly lower in Mato Grosso inhabitants than
ment, the RBC-binding domain of EBA-140, is the most im- in the individuals from Cameroon (70.6% IgG1-positive re-
munoreactive in all individuals, regardless of age. sponders in Mato Grosso versus 100% IgG1-positive re-
Interestingly, when we analyzed the profile of antibodies sponders in Cameroon, P 2 700.0 סtest) (Table 1). Both the
present in other populations of the Brazilian Amazon, resid- IgG1 and IgG3 antibody responses to MSP-119 by individuals
FIGURE 1. Comparison of isotype-specific antibody responses to EBA-140 and EBA-181 fragment proteins in age-matched individuals living
in (A) Kumba, Cameroon (N ( ,)82 סB) Mato Grosso, Brazil (N ,)71 סand (C) the Amazon, Brazil (N .)93 סMedian values are indicated by
horizontal bars.
4. 980 FORD AND OTHERS
TABLE 1
Prevalence and magnitude of antibody responses to EBA fragment proteins and MSP-119 from age-matched individuals living in Kumba,
Cameroon,* Mato Grosso, Brazil,† and the Amazon, Brazil‡ (measured by ELISA)
Kumba, Cameroon Mato Grosso, Brazil Amazon, Brazil
IgG1 IgG3 IgG1 IgG3 IgG1 IgG3
Positive Positive Positive Positive Positive Positive
sera Median OD sera Median OD sera Median OD sera Median OD sera Median OD sera Median OD
Antigen (%)§ (95% CI)¶ (%) (95% CI) (%) (95% CI) (%) (95% CI) (%) (95% CI) (%) (95% CI)
EBA-181 38.1 0.07 65.0 0.28 5.9 0.001 5.9 0.020 10.3 0.04 69.2 0.14
aa1235–1345 (0.02–0.51) (0.29–0.93) (0–0.07) (0–0.04) (0.03–0.11) (0.13–0.25)
EBA-140 96.4 1.23 100 1.17 11.8 0.014 29.4 0.042 25.6 0.02 38.5 0.08
aa141–756 (0.90–1.66) (1.07–1.69) (0–0.08) (0–0.24) (0.01–0.34) (0.10–0.34)
EBA-140 20.0 0 70.8 0.14 5.9 0.001 5.9 0.001 7.7 0.04 28.5 0.03
aa350–440 (0–0.05) (0.13–0.71) (0–0.01) (0–0.03) (0.04–0.06) (0.04–0.17)
EBA-140 80.0 0.14 80.0 1.33 11.8 0.001 23.5 0.001 30.8 0.06 30.8 0
aa799–963 (0–0.81) (0–2.50) (0–0.20) (0–0.43) (0.08–0.29) (0.01–0.13)
EBA-140 80.0 0.27 81.8 0.79 29.4 0.050 11.8 0.001 12.8 0.04 38.5 0.04
aa967–1140 (0.11–0.42) (0.63–1.16) (0.03–0.11) (0–0.07) (0.04–0.06) (0.06–0.13)
EBA-175 92.9 1.19 100 1.34 11.8 0.001 5.9 0.001 5.1 0 15.4 0.01
aa145–760 (0.90–1.46) (1.07–1.72) (0–0.04) (0–0.004) (0–0.08) (0.01–0.06)
MSP-119 100 1.42 95.2 1.59 70.6 0.84 76.5 0.30 38.5 0.03 33.3 0
(1.03–1.54) (1.19–1.89) (0.45–1.17) (0.29–0.96) (0.26–0.72) (0.10–0.34)
* 28 serum samples collected from Kumba, Cameroon.
† 17 serum samples collected from Mato Grosso, Brazil.
‡ 39 serum samples collected from Amazon, Brazil.
§ Percentage of positive responders (% positive sera) are defined as those with an OD value greater than the cut-off OD which was defined as the mean + 3 standard deviations for the ODs
of control sera or OD values > 0.1.
¶ Median ODs are shown with 95% confidence interval (CI).
in Mato Grosso were significantly lower than the responses Mato Grosso to EBA-175 region II (P < 0.001 for both IgG1
mounted by Cameroon individuals (P 2940.0 סfor IgG1 and and IgG3), the antibody response in the Amazon individuals
P 8000.0 סfor IgG3) (Figure 2). The antibody responses to to EBA-175 region II was also significantly lower than those
MSP-119 in the Amazon individuals were also significantly in the Cameroon individuals (P < 0.001 for both IgG1 and
lower than the responses in the Cameroon individuals (P < IgG3) (Figure 2).
0.001 for both IgG1 and IgG3) (Figure 2). Although the responses to the EBA proteins in the Ama-
Notably, we found a significantly lower prevalence of both zon individuals were elevated compared with those from
IgG1 and IgG3 responses to EBA-175 region II (11.8% IgG1- Mato Grosso (Figures 1 and 2), both IgG1 and IgG3 re-
positive responders and 5.9% IgG3-positive responders) in sponses to MSP-119 in individuals from the Amazon region
Mato Grosso, which was in sharp contrast to the 93% IgG1- were significantly lower than those in Mato Grosso (P ס
positive responders and 100% IgG3-positive response in 0.0438 IgG1 and P 6000.0 סIgG3) (Figure 2).
Cameroon (P < 0.0001 for both 2 test) (Table 1). Both the Antibody responses to the C-terminal regions of EBA-181
IgG1 and IgG3 antibody responses to EBA-175 region II by and EBA-140 in Cameroonians correlate with age. Screening
individuals in Mato Grosso were significantly lower than the a small sample of adult individuals from Cameroon (N = 28,
responses mounted by Cameroon individuals (P < 0.0001 for median age 23 סyears) revealed that the most antigenic
both) (Figure 2). Although the Amazonian individuals had fragments of the EBA proteins, in addition to EBA-140 re-
significantly higher antibody responses than individuals from gion II, were the C-terminal regions of both EBA-181 and
FIGURE 2. Comparison of isotype-specific antibody responses to EBA-175 region II and MSP19 in age-matched individuals living in living in
(A) Kumba, Cameroon (N ( ,)82 סB) Mato Grosso, Brazil (N ,)71 סand (C) the Amazon, Brazil (N .)93 סMedian values are indicated by
horizontal bars.
5. ANTIBODY RESPONSES TO MALARIA INVASION LIGANDS 981
EBA-140 (Figure 1). We extended our study to a larger popu- Grosso individuals had detectable antibody responses. Thus,
lation (N ,081 סmedian age )71 סto perform an age cor- the Mato Grosso population had an apparently dichotomous
relation study in the Cameroonian population. Both the IgG3 response to the 2 sets of ligands, the MSPs versus the EBLs.
antibody responses to the C-terminal regions of both EBA- Further analysis of a second set of Brazilian individuals living
181 and EBA-140 were slightly increased with age (r ,391.0 ס in the Amazon revealed that the individuals from Mato
P 10.0 סand r ,681.0 סP ,210.0 סrespectively) (data not Grosso were not typical of the Brazilian immune response, as
shown). EBA-140 region II-specific IgG3 responses were elevated EBA-140 and EBA-181 antibody responses were
highly elevated in all Cameroon individuals, at a 1:500 dilu- found in other regions of the Amazon, although with much
tion, regardless of age (data not shown). lower responses than those found in the Cameroonian popu-
In addition, none of the antibody responses in Cameroon lation. Regardless, most of the Amazonian population was
were correlated to active infection with P. falciparum as in- still nonresponders to the EBA-175 region II protein similarly
dicated by a positive blood smear (data not shown). as those from Mato Grosso.
We put forward 2 hypotheses to explain these differences:
(1) Exposure to the parasite in terms of both overall years
DISCUSSION living in endemic areas and number of malaria infections has
a direct effect on antibodies to various parasite antigens. A
Malaria is a unique example of an infection where people careful look at the history of malaria in Brazil reveals many
exposed multiple times to the blood-stage parasite acquire epidemics associated with migration of a nonimmune popu-
immunity with age and/or number of episodes. This ability to lation to malaria-endemic areas.34–36 Malaria in Brazil, which
combat malaria is an important adaptive trait of populations accounts for 90% of the cases in South America, has in-
living in endemic areas. The detection of significant differ- creased 3-fold during the past decade, and nearly 631,000
ences in the expression of this trait and the identification of cases were reported in 2002. Of these infections, 80% are P.
the factors involved should improve the understanding of the vivax and 20% are P. falciparum infections. Almost all re-
host–parasite relationship and thus lead to advances in con- ported cases of malaria in Brazil originate in the Amazon
trol strategies. region, where migrant populations and poor access to diag-
This is the first study to examine the humoral response to nosis and treatment are major barriers to effective control of
the invasion ligands EBA-140 and EBA-181 induced by natu- malaria. Migrant populations help to spread parasites
ral infection. It is believed that effective immunity to P. fal- throughout the endemic regions and also contribute to the
ciparum blood-stage parasites involves the acquisition of in- spread of the disease in malaria-free areas, thus increasing the
hibitory antibodies targeted to various antigens of the inva- risk for malaria outbreaks. It is believed that malaria in Mato
sive merozoite. The obligatory interaction between invasion Grosso could have originated from such migrant populations
ligands and their cognate receptors on the RBC represents a and is characterized by a hypoendemic pattern of infection,
potential target for inhibition by vaccine-induced antibodies. due mainly to its low demographic index. Thus, in Mato
Some of the current most promising vaccine candidates are Grosso, antibodies against only the immunodominant anti-
indeed such invasion ligands as exemplified by MSP-1, AMA- gens like MSP-119 and other MSPs were found, as exposure to
1, and EBA-175.28 In this study, recombinant proteins repre- P. falciparum in these inhabitants would not be as high or
senting different fragments of P. falciparum EBA-140 and repeated as in the rest of the Amazon (relatively stable popu-
EBA-181 were used to analyze the profile of naturally ac- lation), whose inhabitants are subjected to multiple malaria
quired human antibodies to these proteins. The amino acid episodes in short periods of time. Malaria in the Brazilian
sequence homology between region II, which is the RBC- Amazon, on the other hand, was characterized by elevated
binding domain, or region VI of the 2 EBL proteins is very antibody responses to all parasite ligands, including both
low, < 25% and < 20%, respectively. The similarity between MSP-119 and the EBLs, although overall magnitudes were
the EBA members of the EBL family is attributed to their less than what was found in Africa. This substantial difference
conserved structures.29 Although we recognize that the tested in exposure levels to the parasite thus impacted antibody re-
recombinant proteins may not represent all the conforma- sponse to these 2 sets of ligands in these 2 Brazilian popula-
tional epitopes on the native EBLs, this study serves as a tions. Future studies in a larger population in the Brazilian
springboard for a future large-scale analysis of the antibody Amazon could confirm this hypothesis. (2) The repertoire of
responses in these two populations. host RBC receptors available in specific populations will,
We found that the Mato Grosso individuals did not mount over time, select for expression of specific parasite ligands
a strong humoral response against these two EBA ligands. that can mediate successful RBC invasion, and thus the im-
This was in contrast to the African individuals in whom, con- mune responses to such ligands may be differential, correlat-
siderable IgG1 and IgG3 antibodies were detectable to all the ing to their expression. In a recent study in Tanzania,37 it was
recombinant EBA-140 and 180 fragments tested. In addition shown that expression levels of some of EBA and PfRH
to the full-length region II of EBA-140, a fragment of the ligands correlated with the specific invasion pathway that the
C-terminus of both EBA-140 and EBA-181 was also the most corresponding parasites used for invasion. The authors also
antigenic in this Cameroonian population. However, both hypothesized that the ligand expression patterns may repre-
populations mounted equally robust responses to the various sent frequency-dependent selection either by polymorphic
MSPs (data not shown), which have been shown to be anti- host receptors or by immune responses. Therefore, our re-
genic in a variety of different endemic populations.30–33 When sults, showing differences in the immunoreactivity, could be
the same sera were analyzed for immunoreactivity to the also linked to RBC heterogeneity between these 2 popula-
GPA-binding domain of EBA-175 (EBA-175 region II), a tions which could have dictated parasite choice of invasion
dominant member of the EBL family, only a few Mato pathways and thus expression of specific EBLs. We have pre-
6. 982 FORD AND OTHERS
viously characterized the invasion pathways used by field iso- 2. Marsh K, 1992. Malaria—a neglected disease? Parasitology 104
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invasion pathways used by isolates from the regions of the project: a longitudinal study of natural malaria infection and
Amazon, the low anti-EBA-175 response we see in both Bra- the mechanisms of protective immunity in a community living
zilian populations could allude to a common low usage of the in a holoendemic area of Senegal. Am J Trop Med Hyg 51:
123–137.
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in Gambia found that invasion via GPA and EBA-175 was suphajaisiddhi T, Druilhe P, 1990. Antibodies that protect hu-
frequently used by field strains,23 and if this is reflective of mans against Plasmodium falciparum blood stages do not on
malaria on the whole in Africa, then the high anti-EBA-175 their own inhibit parasite growth and invasion in vitro, but act
in cooperation with monocytes. J Exp Med 172: 1633–1641.
reactivities that were observed in the Cameroonian popula-
5. Cohen S, McGregor IA, Carrington S, 1961. Gamma-globulin
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a grant from the NIH-P50 HL 54459 and in part by the New York pathways for invasion. J Clin Invest 80: 1190–1193.
Blood Center. The research of Ricardo Machado was supported by 14. Mitchell GH, Hadley TJ, McGinniss MH, Klotz FW, Miller LH,
Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) 1986. Invasion of erythrocytes by Plasmodium falciparum ma-
and Conselho Nacional de Pesquisa (CNPq). laria parasites: evidence for receptor heterogeneity and two
Authors’ addresses: Louise Ford, Cheryl A. Lobo, Marilis Rodriguez, receptors. Blood 67: 1519–1521.
and Sara Lustigman, Laboratory of Molecular Parasitology, Lindsley 15. Perkins ME, Holt EH, 1988. Erythrocyte receptor recognition
F. Kimball Research Institute, New York Blood Center, 310 East varies in Plasmodium falciparum isolates. Mol Biochem Para-
67th St., New York, NY 10065, Telephone: +1 (212) 570-3000, Fax: +1 sitol 27: 23–34.
(212) 570-3195, E-mail: slustigman@nybloodcenter.org. Mariano G. 16. Narum DL, Haynes JD, Fuhrmann S, Moch K, Liang H, Hoffman
Zalis, University Hospital, Federal University of Rio de Janeiro, 255 SL, Sim BK, 2000. Antibodies against the Plasmodium falci-
Rua Professor Rodolpho Paulo Rocco, Rio de Janeiro, 21949-900, parum receptor binding domain of EBA-175 block invasion
Brazil, Telephone: +55-21-2562-2617, Fax: + 55-21-2280-8193. pathways that do not involve sialic acids. Infect Immun 68:
Ricardo L.D. Machado, Andréa R.B. Rossit, and Carlos E. Cavasini, 1964–1966.
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Faria Lima, São José do Rio Preto, São Paulo, 15090-000, Brazil, Kashala LO, Ballou WR, Snellings NJ, Ockenhouse CF, Lanar
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Couto, SEAMA College, Macapa, 1201 Avenida Nacoes Unidas,
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Amapa 68908-170, Brazil, Telephone and Fax: +55-91-3223-7393. Pe-
´ their recognition by human antibodies. Infect Immun 65: 3631–
ter A. Enyong, Tropical Medicine Research Station, PO Box 55, 3637.
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