The study examines apoptosis in mouse splenic T cell and B cell populations during infection with Plasmodium chabaudi chabaudi AS malaria. High levels of apoptosis were found to correlate with high parasitemia and splenomegaly, particularly in CD4+ T cells. Apoptosis levels decreased as parasitemia was cleared but remained elevated compared to normal mice, with CD8+ T cells and B cells returning to basal apoptosis levels while CD4+ T cells remained higher.
The document discusses the immune system and its response to parasitic diseases. It introduces basic concepts of the immune system, including the innate and acquired responses. The innate response acts as a non-specific barrier, while the acquired response involves humoral and cell-mediated immunity. T helper cells can differentiate into Th1 or Th2 subsets, determining the type of response. Th1 supports cell-mediated immunity against intracellular pathogens, while Th2 induces antibody production against extracellular pathogens. CD8+ T cells and natural killer cells directly kill infected cells. Activated macrophages also have microbicidal functions. The balance between protective and pathological immune responses is important for host-parasite interactions.
This document provides an overview of the immunology of parasitic diseases. It discusses the immune system and its response to parasitic infections, including the roles of innate immunity, acquired immunity, T helper cells, macrophages, B cells, and antibodies. It also covers immunopathogenesis, immunodiagnosis, and approaches to immunization against parasitic diseases.
Protozoan parasites cause diseases like malaria, leishmaniasis, and trypanosomiasis. Both the innate and adaptive immune systems play crucial roles in defending against protozoan infections. The innate immune system includes mechanisms like cytokines, complement proteins, macrophages, and neutrophils. The adaptive immune system involves antibody production and T cell responses. Protozoan parasites have evolved ways to evade or subvert the host immune response, such as antigenic variation and inhibiting immune cell function, enabling chronic or recurrent infections. An effective immune response against protozoa involves a balance of pro-inflammatory cytokines, T cell subsets, and effector cells and molecules.
Parasitic infection and immunomodulation: A possible explanation for the hygi...Apollo Hospitals
This document discusses the hygiene hypothesis in autoimmune and allergic disease. It proposes that reduced incidence of parasitic infections in developed countries due to improved sanitation may be linked to increased rates of autoimmune and allergic diseases. Parasitic infections induce regulatory immune responses that help the parasites survive while also reducing inflammation. Specific parasite molecules modulate the immune system by suppressing Th1 and Th17 responses and inducing Th2 and regulatory T cell responses. Understanding these immunomodulatory mechanisms could help develop new treatments for inflammatory and allergic conditions.
There are two main types of immunity against parasitic infections: innate and acquired. The innate immune system provides initial defenses through barriers like skin and secretions, as well as cells like macrophages. Acquired immunity develops through antibody production by B cells and cellular responses by T cells. However, parasites have evolved strategies to evade the immune system, such as living intracellularly, antigenic variation, immunosuppression, migration, and producing enzymes. This makes the immune response less effective against parasites compared to other pathogens.
This document discusses the immune response to helminth infections in three parts. It begins by describing the innate and adaptive immune responses that lead to rejection of helminths, including the roles of cytokines, antibodies, granulocytes, and T cells. It then explains how helminths evade and modulate the immune system to establish chronic infections, such as through regulatory T cells, alternatively activated macrophages, and cytokines like IL-10 and TGF-β that suppress inflammation. Finally, it concludes that while immunomodulation benefits the host by reducing immune-mediated damage, it can also increase susceptibility to other pathogens.
Mechanism of immunoevasion in parasites 2018 06-17Rasika Deshmukh
The document summarizes mechanisms of immune evasion in various parasites. It discusses how parasites like malaria, trypanosomes, leishmania, toxoplasma, entamoeba, giardia, schistosomes, trichomonas, and helminths evade the host immune system. Some key strategies parasites use include antigenic disguise, molecular mimicry, immunosuppression through cytokines, inhibiting host immune signaling pathways, disrupting complement pathways, shedding surface antigens, and phenotypic variation. Understanding these immune evasion mechanisms provides insights into host-parasite interactions and disease pathogenesis.
Immunity against Helminths:role of InterleukinsIshfaq Maqbool
The document summarizes key aspects of the immune response against helminth parasites. It notes that helminths typically induce a type 2 immune response characterized by cytokines like IL-4, IL-5, and IL-13. This non-inflammatory response involves alternatively activated macrophages, eosinophils, and other effector cells that work to expel and kill parasites while repairing tissue damage. The response differs from bacterial and viral immunity, with Th1 responses only occurring during early larval migration stages.
The document discusses the immune system and its response to parasitic diseases. It introduces basic concepts of the immune system, including the innate and acquired responses. The innate response acts as a non-specific barrier, while the acquired response involves humoral and cell-mediated immunity. T helper cells can differentiate into Th1 or Th2 subsets, determining the type of response. Th1 supports cell-mediated immunity against intracellular pathogens, while Th2 induces antibody production against extracellular pathogens. CD8+ T cells and natural killer cells directly kill infected cells. Activated macrophages also have microbicidal functions. The balance between protective and pathological immune responses is important for host-parasite interactions.
This document provides an overview of the immunology of parasitic diseases. It discusses the immune system and its response to parasitic infections, including the roles of innate immunity, acquired immunity, T helper cells, macrophages, B cells, and antibodies. It also covers immunopathogenesis, immunodiagnosis, and approaches to immunization against parasitic diseases.
Protozoan parasites cause diseases like malaria, leishmaniasis, and trypanosomiasis. Both the innate and adaptive immune systems play crucial roles in defending against protozoan infections. The innate immune system includes mechanisms like cytokines, complement proteins, macrophages, and neutrophils. The adaptive immune system involves antibody production and T cell responses. Protozoan parasites have evolved ways to evade or subvert the host immune response, such as antigenic variation and inhibiting immune cell function, enabling chronic or recurrent infections. An effective immune response against protozoa involves a balance of pro-inflammatory cytokines, T cell subsets, and effector cells and molecules.
Parasitic infection and immunomodulation: A possible explanation for the hygi...Apollo Hospitals
This document discusses the hygiene hypothesis in autoimmune and allergic disease. It proposes that reduced incidence of parasitic infections in developed countries due to improved sanitation may be linked to increased rates of autoimmune and allergic diseases. Parasitic infections induce regulatory immune responses that help the parasites survive while also reducing inflammation. Specific parasite molecules modulate the immune system by suppressing Th1 and Th17 responses and inducing Th2 and regulatory T cell responses. Understanding these immunomodulatory mechanisms could help develop new treatments for inflammatory and allergic conditions.
There are two main types of immunity against parasitic infections: innate and acquired. The innate immune system provides initial defenses through barriers like skin and secretions, as well as cells like macrophages. Acquired immunity develops through antibody production by B cells and cellular responses by T cells. However, parasites have evolved strategies to evade the immune system, such as living intracellularly, antigenic variation, immunosuppression, migration, and producing enzymes. This makes the immune response less effective against parasites compared to other pathogens.
This document discusses the immune response to helminth infections in three parts. It begins by describing the innate and adaptive immune responses that lead to rejection of helminths, including the roles of cytokines, antibodies, granulocytes, and T cells. It then explains how helminths evade and modulate the immune system to establish chronic infections, such as through regulatory T cells, alternatively activated macrophages, and cytokines like IL-10 and TGF-β that suppress inflammation. Finally, it concludes that while immunomodulation benefits the host by reducing immune-mediated damage, it can also increase susceptibility to other pathogens.
Mechanism of immunoevasion in parasites 2018 06-17Rasika Deshmukh
The document summarizes mechanisms of immune evasion in various parasites. It discusses how parasites like malaria, trypanosomes, leishmania, toxoplasma, entamoeba, giardia, schistosomes, trichomonas, and helminths evade the host immune system. Some key strategies parasites use include antigenic disguise, molecular mimicry, immunosuppression through cytokines, inhibiting host immune signaling pathways, disrupting complement pathways, shedding surface antigens, and phenotypic variation. Understanding these immune evasion mechanisms provides insights into host-parasite interactions and disease pathogenesis.
Immunity against Helminths:role of InterleukinsIshfaq Maqbool
The document summarizes key aspects of the immune response against helminth parasites. It notes that helminths typically induce a type 2 immune response characterized by cytokines like IL-4, IL-5, and IL-13. This non-inflammatory response involves alternatively activated macrophages, eosinophils, and other effector cells that work to expel and kill parasites while repairing tissue damage. The response differs from bacterial and viral immunity, with Th1 responses only occurring during early larval migration stages.
This document summarizes the immune response to HIV infection. It discusses how CD4 T-cells, cytotoxic T-cells, B-cells, and antigen presenting cells respond to HIV. It notes that while cytotoxic T-cells develop against most HIV proteins, they ultimately fail to control the virus due to epitope escape, exhaustion, or suboptimal responses. Antibody responses face challenges in neutralizing HIV due to the glycosylation and structure of the viral envelope proteins. Overall, the immune system fails to clear HIV because the virus can integrate into genes, mutate to escape responses, and impair the functions of immune cells.
Immunity to bacteria and related organisms in animalPakawadee Tie
The document discusses various aspects of acquired immunity to bacteria, viruses, protozoa, and helminths. It describes the mechanisms of both innate and adaptive immunity. For bacteria, the key immune responses are neutralization of toxins, killing bacteria through antibodies and complement, and opsonization leading to phagocytosis. Viruses can evade the immune response through antigenic variation and by inhibiting interferons and antibodies. Immunity to protozoa and helminths involves both humoral and cell-mediated responses, though parasites have developed mechanisms to avoid these defenses.
The document summarizes evasion mechanisms used by viruses to avoid the host immune system. It discusses two main mechanisms used by influenza viruses: antigenic drift which involves point mutations in surface proteins, and antigenic shift which involves reassortment of RNA segments between animal and human influenza viruses. It also describes how herpes simplex viruses prevent the transport of viral peptides to the ER through the protein ICP-47, inhibiting antigen presentation through MHC class I molecules on infected cells.
This document discusses the host protective roles of type 2 immunity in response to parasitic infections. It summarizes that type 2 immunity involves both innate and adaptive immune cells that work together to kill parasites and repair tissue damage through mechanisms like alternate macrophage activation. Key cells involved include ILC2s, eosinophils, mast cells, and alternatively activated macrophages that secrete molecules like IL-4, IL-5, IL-13, and arginase to expel parasites and promote wound healing.
Viruses are obligatory intracellular pathogens that infect cells by utilizing cell surface receptors. The innate immune system responds to viruses through induction of type I interferons like IFN-α and IFN-β, which are produced by infected cells and activate natural killer cells. The adaptive immune system mounts both humoral and cell-mediated responses against viruses. However, viruses have evolved multiple mechanisms to evade the host immune response, such as inhibiting interferon activity, blocking antigen presentation, and inhibiting apoptosis of infected cells.
HCV has evolved multiple mechanisms to evade the immune system and establish chronic infection. It interferes with pattern recognition receptor signaling through cleavage of adaptor proteins by NS3/4A. NS3/4A and NS5A also block RIG-I signaling and JAK/STAT interferon pathways. HCV impairs dendritic cell function and induces T cell exhaustion. The high mutation rate allows escape from neutralizing antibodies and cytotoxic T cells. Combined, these immune evasion strategies enable HCV to overcome host defenses and persist long-term in most infected individuals.
The document provides an overview of innate immunity, including:
- Innate immunity is the first line of defense and includes physical, chemical, and biological barriers as well as cellular and humoral components.
- Cellular components include phagocytes such as macrophages and granulocytes that recognize, engulf, and kill pathogens through receptors and cellular responses.
- Humoral components include cytokines, chemokines, and the complement system.
- Innate immunity helps stimulate the adaptive immune response through antigen presentation and release of inflammatory signals.
The document summarizes immunity against various protozoan diseases. It discusses that immunity against protozoa depends on the location of the parasite, with humoral immunity most effective for bloodstream parasites and cell-mediated responses for intracellular parasites. Effector cells like macrophages, neutrophils, and eosinophils can kill protozoa and worms. Immunity against specific protozoa involves both innate and acquired responses, including antibodies, B cells, plasma cells, memory cells, macrophages, NK cells, cytokines and effector T cells playing roles in protection.
This document provides an overview of the immune system and how it responds to microbial infections. It discusses both the innate and adaptive immune responses. The innate response involves inflammation, complement activation, NK cells, and activation of antigen presenting cells. The adaptive response involves activation of naive T lymphocytes, polarization of T cells into Th1 and Th2 subsets, roles of Th1 and Th2 cells, and roles of memory B and T cells in providing long-term protective immunity. The document also briefly discusses some methods microbes use to evade the immune system.
Dysregulation of macrophage signal transduction by ToxoplasmaIshfaq Maqbool
A brief account of mechanism adopted by Toxoplasma gondii to evade the immune response of the host immune cells particularly macrophages by disruption of macrophage signal transduction
This document discusses the immune system and its defenses against pathogens. It describes both nonspecific (innate) immunity and specific (adaptive) immunity. Nonspecific defenses include mechanical and chemical barriers that defend against any pathogen. Specific immunity involves antibody and lymphocyte responses that are targeted to specific antigens. The roles of B cells, T cells, antibodies, cytokines, complement system, inflammation and fever are summarized.
The document discusses the immunology of tuberculosis. It covers the stages of pathogenesis of M. tuberculosis infection, the host immune response including innate and acquired immunity, and the pro-inflammatory and anti-inflammatory mediators involved in tuberculosis. The key points are:
1) M. tuberculosis is an intracellular pathogen that infects the lungs and can spread to other organs. The host immune response involves phagocytosis by alveolar macrophages and recruitment of other immune cells.
2) Both the innate and acquired immune responses are involved in the host defense against M. tuberculosis. Important components include neutrophils, NK cells, TLR signaling, and the cell-mediated immune response involving CD4 and CD8 T cells.
Dr. ihsan edan abdulkareem alsaimary
PROFESSOR IN MEDICAL MICROBIOLOGY AND MOLECULAR IMMUNOLOGY
ihsanalsaimary@gmail.com
mobile : 009647801410838
university of basrah - college of medicine - basrah -IRAQ
The document discusses innate immunity and its mechanisms. It describes:
1. Innate immunity provides non-specific defenses like physical and chemical barriers that recognize pathogens. This includes epithelial barriers and secretions containing antimicrobial factors.
2. The innate immune system recognizes pathogens via pattern recognition receptors (PRRs) on immune cells that detect pathogen-associated molecular patterns. This triggers responses like phagocytosis, complement activation, and cytokine production.
3. Toll-like receptors are a major class of PRRs that recognize distinct microbial components and signal intracellular pathways leading to inflammation and antimicrobial defenses. Cross-talk between innate and adaptive immunity occurs via antigen presentation by dendritic cells to T-cells.
This document summarizes immune evasion strategies used by flaviviruses. It discusses how flaviviruses evade innate immune responses such as type I interferon responses and complement system activation. It also describes adaptive immune evasion mechanisms, including antigenic variation, antibody-dependent enhancement of infection, and inhibition of antigen presentation. The document provides diagrams illustrating key concepts and cites related studies on flavivirus immune evasion and modulation of host inflammatory responses.
Dr. ihsan edan abdulkareem alsaimary
PROFESSOR IN MEDICAL MICROBIOLOGY AND MOLECULAR IMMUNOLOGY
ihsanalsaimary@gmail.com
mobile : 009647801410838
university of basrah - college of medicine - basrah -IRAQ
Exploring the First Line of Defense - Research Tools for Innate Immnity: Host...QIAGEN
The innate immune system executes crucial and unique functions for host defense against infection. This slidedeck provides an overview of the most important cellular and molecular components of innate immunity and discusses their functions in a variety of disease states. Research technologies are also introduced for exploring innate immune activity in your system through profiling of gene expression, cytokine production and signal transduction pathway analysis, all in the context of current literature.
This document discusses gene vaccines and DNA vaccines specifically for toxoplasmosis. It explains that DNA vaccines work by injecting genetically engineered DNA that causes host cells to produce the introduced gene products, which stimulates an immune response. For toxoplasmosis, several surface antigens have been identified that could be used in a DNA vaccine, but current vaccines do not provide full protection. The key to immunity is the cytokine IFN-γ and CD4+ and CD8+ T cells, which help activate macrophages and kill infected cells. Research is ongoing into developing an effective DNA vaccine for toxoplasmosis.
Mechanisms of innate immunity in invertebrates (hemocytes)Abhijeet2509
The document summarizes the mechanisms of innate immunity in invertebrates, focusing on hemocytes in insects. There are several types of hemocytes that carry out different immune functions. Plasmatocytes represent 95% of circulating hemocytes and are responsible for phagocytosis. Crystal cells are involved in melanization by encapsulating microbes in a gel. Lamellocytes form capsules around foreign organisms through multilayer binding. The innate immune system uses physical barriers, humoral responses, and cellular responses like nodulation, encapsulation, and phagocytosis carried out by hemocytes to protect insects from infection.
As a periodontist, I have included the basics of immunity from the periodontist point of view that will help in understanding the immunological basis of periodontal disease...
Este documento describe el proceso para registrar una patente ante la IMPI (Instituto Mexicano de la Propiedad Industrial) en México. Explica los requisitos y documentos necesarios como la descripción de la invención, reivindicaciones, resumen y dibujo. También cubre los pasos del proceso incluyendo la presentación de la solicitud y los formatos requeridos. El objetivo es informar a los lectores sobre cómo proteger legalmente una invención mediante el registro de una patente.
Vitamin D analogs enhance the anticancer activity of 5-fluorouracil in an in ...Enrique Moreno Gonzalez
Active vitamin D analogs that are less toxic than calcitriol can be useful in the combined treatment of patients suffering from colon cancer. In the present study we demonstrate, for the first time in an in vivo model system, the biological effect of combined therapy using 5-fluorouracil (5-FU) along with vitamin D analog PRI-2191 (tacalcitol, 1,24-dihydroxyvitamin D3) or PRI-2205 (5,6-trans-isomer of calcipotriol) on colon cancer.
This document summarizes the immune response to HIV infection. It discusses how CD4 T-cells, cytotoxic T-cells, B-cells, and antigen presenting cells respond to HIV. It notes that while cytotoxic T-cells develop against most HIV proteins, they ultimately fail to control the virus due to epitope escape, exhaustion, or suboptimal responses. Antibody responses face challenges in neutralizing HIV due to the glycosylation and structure of the viral envelope proteins. Overall, the immune system fails to clear HIV because the virus can integrate into genes, mutate to escape responses, and impair the functions of immune cells.
Immunity to bacteria and related organisms in animalPakawadee Tie
The document discusses various aspects of acquired immunity to bacteria, viruses, protozoa, and helminths. It describes the mechanisms of both innate and adaptive immunity. For bacteria, the key immune responses are neutralization of toxins, killing bacteria through antibodies and complement, and opsonization leading to phagocytosis. Viruses can evade the immune response through antigenic variation and by inhibiting interferons and antibodies. Immunity to protozoa and helminths involves both humoral and cell-mediated responses, though parasites have developed mechanisms to avoid these defenses.
The document summarizes evasion mechanisms used by viruses to avoid the host immune system. It discusses two main mechanisms used by influenza viruses: antigenic drift which involves point mutations in surface proteins, and antigenic shift which involves reassortment of RNA segments between animal and human influenza viruses. It also describes how herpes simplex viruses prevent the transport of viral peptides to the ER through the protein ICP-47, inhibiting antigen presentation through MHC class I molecules on infected cells.
This document discusses the host protective roles of type 2 immunity in response to parasitic infections. It summarizes that type 2 immunity involves both innate and adaptive immune cells that work together to kill parasites and repair tissue damage through mechanisms like alternate macrophage activation. Key cells involved include ILC2s, eosinophils, mast cells, and alternatively activated macrophages that secrete molecules like IL-4, IL-5, IL-13, and arginase to expel parasites and promote wound healing.
Viruses are obligatory intracellular pathogens that infect cells by utilizing cell surface receptors. The innate immune system responds to viruses through induction of type I interferons like IFN-α and IFN-β, which are produced by infected cells and activate natural killer cells. The adaptive immune system mounts both humoral and cell-mediated responses against viruses. However, viruses have evolved multiple mechanisms to evade the host immune response, such as inhibiting interferon activity, blocking antigen presentation, and inhibiting apoptosis of infected cells.
HCV has evolved multiple mechanisms to evade the immune system and establish chronic infection. It interferes with pattern recognition receptor signaling through cleavage of adaptor proteins by NS3/4A. NS3/4A and NS5A also block RIG-I signaling and JAK/STAT interferon pathways. HCV impairs dendritic cell function and induces T cell exhaustion. The high mutation rate allows escape from neutralizing antibodies and cytotoxic T cells. Combined, these immune evasion strategies enable HCV to overcome host defenses and persist long-term in most infected individuals.
The document provides an overview of innate immunity, including:
- Innate immunity is the first line of defense and includes physical, chemical, and biological barriers as well as cellular and humoral components.
- Cellular components include phagocytes such as macrophages and granulocytes that recognize, engulf, and kill pathogens through receptors and cellular responses.
- Humoral components include cytokines, chemokines, and the complement system.
- Innate immunity helps stimulate the adaptive immune response through antigen presentation and release of inflammatory signals.
The document summarizes immunity against various protozoan diseases. It discusses that immunity against protozoa depends on the location of the parasite, with humoral immunity most effective for bloodstream parasites and cell-mediated responses for intracellular parasites. Effector cells like macrophages, neutrophils, and eosinophils can kill protozoa and worms. Immunity against specific protozoa involves both innate and acquired responses, including antibodies, B cells, plasma cells, memory cells, macrophages, NK cells, cytokines and effector T cells playing roles in protection.
This document provides an overview of the immune system and how it responds to microbial infections. It discusses both the innate and adaptive immune responses. The innate response involves inflammation, complement activation, NK cells, and activation of antigen presenting cells. The adaptive response involves activation of naive T lymphocytes, polarization of T cells into Th1 and Th2 subsets, roles of Th1 and Th2 cells, and roles of memory B and T cells in providing long-term protective immunity. The document also briefly discusses some methods microbes use to evade the immune system.
Dysregulation of macrophage signal transduction by ToxoplasmaIshfaq Maqbool
A brief account of mechanism adopted by Toxoplasma gondii to evade the immune response of the host immune cells particularly macrophages by disruption of macrophage signal transduction
This document discusses the immune system and its defenses against pathogens. It describes both nonspecific (innate) immunity and specific (adaptive) immunity. Nonspecific defenses include mechanical and chemical barriers that defend against any pathogen. Specific immunity involves antibody and lymphocyte responses that are targeted to specific antigens. The roles of B cells, T cells, antibodies, cytokines, complement system, inflammation and fever are summarized.
The document discusses the immunology of tuberculosis. It covers the stages of pathogenesis of M. tuberculosis infection, the host immune response including innate and acquired immunity, and the pro-inflammatory and anti-inflammatory mediators involved in tuberculosis. The key points are:
1) M. tuberculosis is an intracellular pathogen that infects the lungs and can spread to other organs. The host immune response involves phagocytosis by alveolar macrophages and recruitment of other immune cells.
2) Both the innate and acquired immune responses are involved in the host defense against M. tuberculosis. Important components include neutrophils, NK cells, TLR signaling, and the cell-mediated immune response involving CD4 and CD8 T cells.
Dr. ihsan edan abdulkareem alsaimary
PROFESSOR IN MEDICAL MICROBIOLOGY AND MOLECULAR IMMUNOLOGY
ihsanalsaimary@gmail.com
mobile : 009647801410838
university of basrah - college of medicine - basrah -IRAQ
The document discusses innate immunity and its mechanisms. It describes:
1. Innate immunity provides non-specific defenses like physical and chemical barriers that recognize pathogens. This includes epithelial barriers and secretions containing antimicrobial factors.
2. The innate immune system recognizes pathogens via pattern recognition receptors (PRRs) on immune cells that detect pathogen-associated molecular patterns. This triggers responses like phagocytosis, complement activation, and cytokine production.
3. Toll-like receptors are a major class of PRRs that recognize distinct microbial components and signal intracellular pathways leading to inflammation and antimicrobial defenses. Cross-talk between innate and adaptive immunity occurs via antigen presentation by dendritic cells to T-cells.
This document summarizes immune evasion strategies used by flaviviruses. It discusses how flaviviruses evade innate immune responses such as type I interferon responses and complement system activation. It also describes adaptive immune evasion mechanisms, including antigenic variation, antibody-dependent enhancement of infection, and inhibition of antigen presentation. The document provides diagrams illustrating key concepts and cites related studies on flavivirus immune evasion and modulation of host inflammatory responses.
Dr. ihsan edan abdulkareem alsaimary
PROFESSOR IN MEDICAL MICROBIOLOGY AND MOLECULAR IMMUNOLOGY
ihsanalsaimary@gmail.com
mobile : 009647801410838
university of basrah - college of medicine - basrah -IRAQ
Exploring the First Line of Defense - Research Tools for Innate Immnity: Host...QIAGEN
The innate immune system executes crucial and unique functions for host defense against infection. This slidedeck provides an overview of the most important cellular and molecular components of innate immunity and discusses their functions in a variety of disease states. Research technologies are also introduced for exploring innate immune activity in your system through profiling of gene expression, cytokine production and signal transduction pathway analysis, all in the context of current literature.
This document discusses gene vaccines and DNA vaccines specifically for toxoplasmosis. It explains that DNA vaccines work by injecting genetically engineered DNA that causes host cells to produce the introduced gene products, which stimulates an immune response. For toxoplasmosis, several surface antigens have been identified that could be used in a DNA vaccine, but current vaccines do not provide full protection. The key to immunity is the cytokine IFN-γ and CD4+ and CD8+ T cells, which help activate macrophages and kill infected cells. Research is ongoing into developing an effective DNA vaccine for toxoplasmosis.
Mechanisms of innate immunity in invertebrates (hemocytes)Abhijeet2509
The document summarizes the mechanisms of innate immunity in invertebrates, focusing on hemocytes in insects. There are several types of hemocytes that carry out different immune functions. Plasmatocytes represent 95% of circulating hemocytes and are responsible for phagocytosis. Crystal cells are involved in melanization by encapsulating microbes in a gel. Lamellocytes form capsules around foreign organisms through multilayer binding. The innate immune system uses physical barriers, humoral responses, and cellular responses like nodulation, encapsulation, and phagocytosis carried out by hemocytes to protect insects from infection.
As a periodontist, I have included the basics of immunity from the periodontist point of view that will help in understanding the immunological basis of periodontal disease...
Este documento describe el proceso para registrar una patente ante la IMPI (Instituto Mexicano de la Propiedad Industrial) en México. Explica los requisitos y documentos necesarios como la descripción de la invención, reivindicaciones, resumen y dibujo. También cubre los pasos del proceso incluyendo la presentación de la solicitud y los formatos requeridos. El objetivo es informar a los lectores sobre cómo proteger legalmente una invención mediante el registro de una patente.
Vitamin D analogs enhance the anticancer activity of 5-fluorouracil in an in ...Enrique Moreno Gonzalez
Active vitamin D analogs that are less toxic than calcitriol can be useful in the combined treatment of patients suffering from colon cancer. In the present study we demonstrate, for the first time in an in vivo model system, the biological effect of combined therapy using 5-fluorouracil (5-FU) along with vitamin D analog PRI-2191 (tacalcitol, 1,24-dihydroxyvitamin D3) or PRI-2205 (5,6-trans-isomer of calcipotriol) on colon cancer.
Este documento describe el proceso de patentamiento en Colombia. La Superintendencia de Industria y Comercio es la entidad encargada de otorgar patentes de invención, modelos de utilidad y diseños industriales. Para solicitar una patente, se debe completar un formato con información sobre el solicitante, la invención y comprobar el pago. El proceso puede durar hasta dos años mientras se verifica la novedad internacional de la invención.
PicBadges es un sitio web que ofrece cientos de insignias o prendedores para agregar a las fotos de perfil de Facebook con el fin de mostrar apoyo a causas benéficas, derechos, ideologías políticas u otros intereses. Los usuarios pueden visitar la dirección PicBadges.com para encontrar una insignia que refleje sus creencias y agregarla fácilmente a su foto de perfil de Facebook.
Blue badge reform assessments - event - 28 march 2012 - presentation - itpNeil-Weston
The document summarizes the findings of an independent review of blue badge eligibility assessment practices in England. It describes the background and objectives of the review. Key findings included that independent mobility assessments (IMAs) conducted by healthcare professionals reduced costs and appeal rates compared to GP assessments. As a result, new legislation was introduced requiring the use of IMAs for assessing most applicants. The review identified core principles for local authorities to follow in developing desk-based assessment and IMA processes, including the appropriate roles and qualifications of assessors.
Este documento compara brevemente los entornos de desarrollo integrados (IDE) para PHP. Define un IDE como un entorno de programación que incluye un editor de código, compilador, depurador y constructor de interfaz gráfica. Explica que los componentes clave de un IDE son el editor de texto, compilador, intérprete, herramientas de automatización, depurador y posibilidad de control de versiones. Además, ofrece directrices para elegir un IDE PHP indicando que debe tener resaltado de sintaxis, autocompletado,
This document discusses an approach to science education that emphasizes hands-on, active learning through discussion, probing questions, and inquiry-based learning. The approach also incorporates internet research, real-life applications of science, current events, and time spent outdoors. The teacher takes on the role of a coach or mentor to guide student learning.
miRNAs in the spotlight: Making 'silent' mutations speak up.David W. Salzman
This document discusses the role of microRNAs (miRNAs) in disease. It describes two studies: 1) A human study showing that a silent mutation impairs miRNA binding, increasing Crohn's disease risk. This provides evidence that silent mutations can functionally impact miRNA regulation and cause disease. 2) A mouse study demonstrating tumor dependence on miR-21, highlighting the role of miRNAs as disease drivers. Targeting these miRNA drivers may help develop new drugs. The document argues that further investigation is needed into how genetic variants alter miRNA regulation and contribute to disease.
Phase ii study of temozolomide and thalidomideseayat1103
This study evaluated the combination of temozolomide and thalidomide in patients with metastatic neuroendocrine tumors. The results showed an objective response rate of 25% and a biochemical response rate of 40%. However, over half of patients discontinued treatment early due to toxicities such as neuropathy and infection. Further study is needed to better understand the efficacy and safety profile of this drug combination.
The document discusses two types of parasitic immunity: sterilizing immunity and non-sterilizing immunity. Sterilizing immunity completely wipes out parasites and provides long-term resistance to reinfection, but is rare. Non-sterilizing immunity eliminates most parasites but not all, is more common, and immunity only lasts while parasites are present.
HIV induces apoptosis in both infected and uninfected CD4+ T cells through multiple pathways. Several viral proteins (Tat, Nef, Vpr, Vpu, gp160) and host proteins (TNF, FasL, TRAIL, IFNα) can have either pro-apoptotic or anti-apoptotic effects depending on their concentration levels. The extrinsic pathway, involving death receptors like TNF, FasL and TRAIL, dominates over the intrinsic mitochondrial pathway in inducing apoptosis. However, the specific mechanisms of bystander apoptosis, such as the role of gp41-mediated hemifusion, remain uncertain. Understanding how HIV manipulates these various pro-apoptotic and anti-
This slide covers briefly how intracellular and extracellular bacteria elicits an immune response, how bacteria evade from the immune system, what complement system is, opsonization, neutralisation, septic shock, sepsis, superantigens, phagocytosis, interleukins, Toll-like receptors, a list of diseases caused by bacterias and their names etc.
The document summarizes different types of cell death including programmed cell death (PCD), apoptosis, necrosis, and autophagy. It describes key aspects of apoptosis such as the intrinsic and extrinsic pathways, the role of caspases and Bcl-2 proteins, mitochondrial involvement, and morphological changes cells undergo during apoptosis. Necrosis is described as unprogrammed cell death caused by external factors like trauma or infection. Autophagy is noted as another form of programmed cell death.
CAR-T cells are genetically modified T cells that are designed to target and destroy cancer cells. They contain chimeric antigen receptors (CARs) that allow them to recognize specific antigens on tumor cells independently of the normal T cell receptor. The CAR is composed of an extracellular antigen recognition domain attached to transmembrane and co-stimulatory domains, allowing the modified T cells to directly bind and kill cancer cells upon antigen recognition and initiate an immune response against the tumor.
The document discusses apoptosis, or programmed cell death. It defines apoptosis and describes the morphological changes that occur during apoptosis, including cell shrinkage, nuclear fragmentation, and chromatin condensation. It then explains the role of caspases in apoptosis, the intrinsic and extrinsic pathways that initiate apoptosis, and the common pathway involving caspase activation that leads to apoptosis. The document concludes by discussing disorders related to improper apoptosis and references several sources for further information.
Cell-mediated and humoral immunity are the two main branches of the immune system. Cell-mediated immunity involves T cells that directly recognize and kill infected cells or activate other immune cells like macrophages. Humoral immunity involves B cells that produce antibodies, which circulate in bodily fluids and help neutralize pathogens or mark them for destruction. Both branches work together to protect the body from pathogens through mechanisms like activating cytotoxic T cells, stimulating macrophage and natural killer cell action, and initiating antibody production and complement activation.
1) The document discusses apoptosis and necrosis, two types of cell death. Apoptosis is programmed cell death where cells shrink and fragment in an orderly process. Necrosis is unprogrammed cell death caused by external injury or damage where cells swell and leak.
2) Apoptosis can be triggered internally through mitochondrial pathways or externally through death receptor pathways and leads to caspase activation and cell fragmentation. Cancer cells develop ways to avoid apoptosis like inhibiting proteins in these pathways.
3) Necrosis occurs when cells are damaged by external factors like toxins and involves cell and organelle swelling without fragmentation. Cancer cells and viruses can interfere with apoptosis to allow cancer progression.
The immune system protects the body from infection through innate and adaptive responses. The innate system provides immediate defense through physical barriers, chemicals, and cells. It is not antigen-specific. The adaptive system provides highly specific defenses that improve upon reexposure through immunological memory. Both systems work through cellular and humoral components. The innate system includes neutrophils, macrophages, and natural killer cells that phagocytose pathogens. It also utilizes chemical factors like complement proteins. Together these defenses provide protection until the adaptive response can mount an antigen-specific response.
Mast cells (MCs) play a broad role in both physiology and disease beyond just allergy. MCs originate from bone marrow progenitor cells and develop in tissues where they exist in different phenotypes. MCs can be activated through various stimuli to degranulate and release mediators that impact wound healing, homeostasis, the nervous system, host defense against parasites, bacteria, viruses, and venoms, as well as diseases like allergy, asthma, vascular disease, and fibrosis. MCs contribute to inflammation in conditions such as inflammatory bowel disease and some autoimmune/autoinflammatory diseases.
Immuno microbial pathogenesis of periodontal diseaseGanesh Nair
The document provides an overview of the inflammatory response in periodontal disease. It discusses how bacterial virulence factors like lipopolysaccharide activate the host immune system through toll-like receptors and pro-inflammatory cytokines like IL-1β and TNF-α are released, leading to tissue damage. It also describes other microbial products like fimbriae, DNA, and enzymes that stimulate inflammation and host mediators that perpetuate the inflammatory response and cause bone resorption and tissue destruction.
1) Apoptosis is a tightly regulated form of programmed cell death that occurs as a normal physiological process or in pathological conditions. It is characterized by cell shrinkage, chromatin condensation, DNA fragmentation, and formation of membrane-bound apoptotic bodies that are phagocytosed without inflammation.
2) The intrinsic and extrinsic pathways regulate apoptosis through a cascade of caspase activation. The intrinsic pathway involves mitochondrial permeabilization and cytochrome c release in response to cellular stress. This activates caspase-9 and downstream executioner caspases like caspase-3. The extrinsic pathway is triggered via death receptors engaging caspase-8 and -10. Both pathways converge on caspase activation and cell dismantling.
3)
The immune system functions to eliminate non-self molecules like microbes, cancer cells, and transplanted tissues. It contains central organs like the bone marrow and thymus that produce immune cells, secondary lymphoid tissues that develop these cells, and soluble factors like cytokines. The innate immune system provides non-specific defenses like physical barriers and phagocytes. The adaptive immune system mounts specific responses through B cells and antibodies or T cells. Antibodies mediate humoral immunity against pathogens.
The document discusses the role of phagocytes, specifically macrophages and neutrophils, in the innate immune response against infection. It describes how neutrophils are recruited from the bloodstream to sites of infection through endothelial activation, rolling, arrest, and migration in response to inflammatory signals. It also outlines the mechanisms phagocytes use to kill pathogens, including enzymatic degradation within phagosomes that fuse with lysosomes/granules, and reactive oxygen and nitrogen species produced during respiratory bursts. Phagocytes play a key role in the early innate immune response by removing pathogens, infected cells, and cellular debris.
1) Bacteria that normally live in the gut can have either symbiotic or pathogenic relationships with their human host. Pathogenic bacteria produce virulence factors that subvert the host's immune defenses, while symbiotic bacteria may secrete regulatory molecules that modulate immunity.
2) The human microbiota interacts with multiple organ systems beyond the gut, influencing metabolism, inflammation, and other physiological processes through molecular signals. Understanding these host-microbiota interactions could lead to new treatments.
3) Studies on the bacterial effector proteins secreted by pathogens like Shigella provide insights into how innate and adaptive immune responses are activated or suppressed. This knowledge may help design new antimicrobials and vaccines.
Survivin is a recently discovered protein that is implicated in controlling cell proliferation and apoptosis. It is overexpressed in most human cancers. Survivin belongs to the inhibitor of apoptosis family and has a unique structure with a single baculovirus IAP repeat. It functions to inhibit caspase activity and apoptosis. Survivin is regulated through the cell cycle and peaks in expression during mitosis, localizing to microtubules of the mitotic spindle. Due to its role in inhibiting apoptosis and promoting cell proliferation, survivin may provide insights into cancer diagnosis and treatment.
Central tolerance mechanisms aim to eliminate self-reactive immune cells in the thymus through clonal deletion and anergy. Peripheral tolerance mechanisms such as clonal anergy, antigen blockade, and immunologically privileged sites help maintain unresponsiveness to self-antigens outside the thymus. A breakdown of tolerance leads to autoimmunity, where the immune system attacks the body's own tissues and organs.
Origin and migration of T and B cells. Hemopoietic stem cells originating in the yolk sac, fetal liver, or bone
marrow migrate through the blood to the thymus, where they differentiate into T lymphocytes. Others
differentiate within the bone marrow in mammals, or the bursa of Fabricius in birds, to produce B cells.
Mature T and B cells circulate in the blood and lymph and colonize the T and B cell compartments
of the lymphoid tissues
1) Acute rejection of a transplanted organ is characterized by intense inflammation within the graft. Prostanoids, which are classic mediators of inflammation such as prostaglandins and thromboxane, modulate inflammation and alloimmune responses during graft rejection but their role has been overlooked.
2) Local production of prostanoids increases within the allograft during an episode of acute rejection. Prostanoids can interfere with graft function by modulating vascular tone, capillary permeability, and platelet aggregation.
3) Experimental evidence also suggests prostanoids may participate in alloimmune responses by directly modulating T lymphocyte and antigen-presenting cell function. The paper provides an overview of alloimmune responses,
The document summarizes key aspects of apoptosis including:
- The origins and definition of the term apoptosis from Greek meaning "falling leaves".
- The significance of apoptosis in development and maintenance of tissues by removing excess or damaged cells.
- The morphological features of apoptosis including membrane blebbing, nuclear fragmentation, and formation of apoptotic bodies.
- The molecular mechanisms including caspase signaling pathways like the intrinsic pathway involving mitochondria and the extrinsic pathway involving death receptors.
- Regulatory mechanisms involving proteins like Bcl-2 that balance survival and death signals.
- Dysregulation of apoptosis can lead to diseases like cancer, autoimmune disorders, and HIV infection.
Autophagy plays multifaceted roles in both the innate and adaptive immune system. In innate immunity, autophagy aids in the recognition of pathogens by pattern recognition receptors like TLRs, NLRs, and RLRs. It also facilitates the handling and destruction of intracellular bacteria by phagocytosis and lysosomal fusion. Autophagy regulates the production of cytokines as well. In adaptive immunity, autophagy contributes to antigen presentation on MHC class I and II molecules and is important for the homeostasis and functions of lymphocytes like T cells and B cells. However, the precise mechanisms in some cases require further clarification.
2011 repeated restraint stress reduces the ig a producing cells in peyers pat...LUVIA ENID SANCHEZ TORRES
1. The study examined the effects of repeated restraint stress on Peyer's patches (PPs), which are lymphoid tissues in the intestine that play a key role in immune responses.
2. It found that repeated restraint stress did not modify the morphological structure of PPs, but it did reduce the total number of lymphocytes, CD8+ T cells, B cells, and plasma cells in PPs.
3. Specifically, restraint stress reduced the number of IgA-producing plasma cells in the dome region of PPs, where these cells are usually most numerous. Since IgA protects against intestinal infections, repeated stress may increase susceptibility to pathogens.
This article examines the effects of repeated restraint stress on the structure and function of the nasal-associated lymphoid tissue (NALT) in mice. The study found that 4 days of restraint stress decreased the percentage of CD3+ and CD4+ T cells in the NALT as well as IgA+ cells and nasal IgA levels, while 8 days of stress increased the numbers of these cells and IgA levels compared to the control group. Repeated restraint stress was found to selectively affect immune cells in the nasal mucosa and basal IgA production.
Este documento presenta la información de contacto y las líneas de investigación de la Dra. Luvia Enid Sánchez Torres en el Posgrado de Inmunología de la Escuela Nacional de Ciencias Biológicas. Sus líneas de investigación incluyen la respuesta inmunológica a la malaria, la participación de la apoptosis en diferentes patologías y la evaluación de la actividad antineoplásica de fitoquímicos y compuestos sintéticos. También incluye cinco de sus publicaciones más recientes sobre estos temas.
Cas IIgly induces apoptosis in glioma C6 cells through both caspase-dependent and caspase-independent pathways. When exposed to Cas IIgly, glioma C6 cells showed inhibited proliferation, increased reactive oxygen species formation, and induced apoptosis in a dose-dependent manner. Both the mitochondria-nuclear translocation of apoptosis induction factor and endonuclease G, as well as the fragmentation of nucleosomal DNA and caspase-3 activation were involved in the apoptotic effects of Cas IIgly. Reactive oxygen species formation induced by Cas IIgly may also contribute to its apoptotic effects. Administration of Cas IIgly to glioma-bearing rats reduced tumor size and increased apoptosis.
This document summarizes research testing the ability of eight diindolylmethane derivatives to induce apoptosis in murine L5178Y lymphoma cells. The derivatives were synthesized with different substituted phenyl groups attached to the methane carbon. Testing found compound 3a, with a meta-hydroxyl group, was the most active, inhibiting 93% of cell growth and inducing 71.04% apoptosis. In general, substituents able to form hydrogen bonds and in the meta position were most effective at arresting the cell cycle. The preliminary results provide insight into how the substituent and position impact potency against lymphoma cells.
This article examines the cytotoxic effects of perezone and its isomer isoperezone on human leukemia cells. The key findings are:
1. Both perezone and isoperezone induce cytotoxicity in a concentration-dependent manner through both caspase-dependent and caspase-independent mechanisms.
2. The compounds cause changes in cell size, granularity, phosphatidylserine translocation, mitochondrial membrane potential disruption, and do not induce apoptosis inducing factor.
3. Perezone showed greater cytotoxic effects than isoperezone, but the mechanisms of cell death induction differed between the two compounds depending on concentration.
This article examines the effects of repeated restraint stress on the structure and function of the nasal-associated lymphoid tissue (NALT) in mice. The study found that 4 days of restraint stress decreased the percentage of CD3+ and CD4+ T cells in the NALT as well as IgA+ cells and nasal IgA levels, while 8 days of stress increased the numbers of these cells and IgA levels compared to the control group. Repeated restraint stress was found to selectively affect immune cells in the nasal mucosa and basal IgA production.
La Dra. Luvia Enid Sánchez Torres es una investigadora de nivel SNI I en el Laboratorio de Inmunología Celular y de Inmunología de los Microorganismos. Sus líneas de generación y aplicación del conocimiento incluyen la inmunología de las enfermedades infecciosas, vacunas e inmunoterapia. Algunas de sus líneas de investigación son la muerte celular, la evaluación de compuestos naturales y sintéticos, y la respuesta inmune contra parásitos.
বাংলাদেশের অর্থনৈতিক সমীক্ষা ২০২৪ [Bangladesh Economic Review 2024 Bangla.pdf] কম্পিউটার , ট্যাব ও স্মার্ট ফোন ভার্সন সহ সম্পূর্ণ বাংলা ই-বুক বা pdf বই " সুচিপত্র ...বুকমার্ক মেনু 🔖 ও হাইপার লিংক মেনু 📝👆 যুক্ত ..
আমাদের সবার জন্য খুব খুব গুরুত্বপূর্ণ একটি বই ..বিসিএস, ব্যাংক, ইউনিভার্সিটি ভর্তি ও যে কোন প্রতিযোগিতা মূলক পরীক্ষার জন্য এর খুব ইম্পরট্যান্ট একটি বিষয় ...তাছাড়া বাংলাদেশের সাম্প্রতিক যে কোন ডাটা বা তথ্য এই বইতে পাবেন ...
তাই একজন নাগরিক হিসাবে এই তথ্য গুলো আপনার জানা প্রয়োজন ...।
বিসিএস ও ব্যাংক এর লিখিত পরীক্ষা ...+এছাড়া মাধ্যমিক ও উচ্চমাধ্যমিকের স্টুডেন্টদের জন্য অনেক কাজে আসবে ...
Reimagining Your Library Space: How to Increase the Vibes in Your Library No ...Diana Rendina
Librarians are leading the way in creating future-ready citizens – now we need to update our spaces to match. In this session, attendees will get inspiration for transforming their library spaces. You’ll learn how to survey students and patrons, create a focus group, and use design thinking to brainstorm ideas for your space. We’ll discuss budget friendly ways to change your space as well as how to find funding. No matter where you’re at, you’ll find ideas for reimagining your space in this session.
ISO/IEC 27001, ISO/IEC 42001, and GDPR: Best Practices for Implementation and...PECB
Denis is a dynamic and results-driven Chief Information Officer (CIO) with a distinguished career spanning information systems analysis and technical project management. With a proven track record of spearheading the design and delivery of cutting-edge Information Management solutions, he has consistently elevated business operations, streamlined reporting functions, and maximized process efficiency.
Certified as an ISO/IEC 27001: Information Security Management Systems (ISMS) Lead Implementer, Data Protection Officer, and Cyber Risks Analyst, Denis brings a heightened focus on data security, privacy, and cyber resilience to every endeavor.
His expertise extends across a diverse spectrum of reporting, database, and web development applications, underpinned by an exceptional grasp of data storage and virtualization technologies. His proficiency in application testing, database administration, and data cleansing ensures seamless execution of complex projects.
What sets Denis apart is his comprehensive understanding of Business and Systems Analysis technologies, honed through involvement in all phases of the Software Development Lifecycle (SDLC). From meticulous requirements gathering to precise analysis, innovative design, rigorous development, thorough testing, and successful implementation, he has consistently delivered exceptional results.
Throughout his career, he has taken on multifaceted roles, from leading technical project management teams to owning solutions that drive operational excellence. His conscientious and proactive approach is unwavering, whether he is working independently or collaboratively within a team. His ability to connect with colleagues on a personal level underscores his commitment to fostering a harmonious and productive workplace environment.
Date: May 29, 2024
Tags: Information Security, ISO/IEC 27001, ISO/IEC 42001, Artificial Intelligence, GDPR
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How to Setup Warehouse & Location in Odoo 17 InventoryCeline George
In this slide, we'll explore how to set up warehouses and locations in Odoo 17 Inventory. This will help us manage our stock effectively, track inventory levels, and streamline warehouse operations.
This presentation includes basic of PCOS their pathology and treatment and also Ayurveda correlation of PCOS and Ayurvedic line of treatment mentioned in classics.
How to Make a Field Mandatory in Odoo 17Celine George
In Odoo, making a field required can be done through both Python code and XML views. When you set the required attribute to True in Python code, it makes the field required across all views where it's used. Conversely, when you set the required attribute in XML views, it makes the field required only in the context of that particular view.
How to Build a Module in Odoo 17 Using the Scaffold MethodCeline George
Odoo provides an option for creating a module by using a single line command. By using this command the user can make a whole structure of a module. It is very easy for a beginner to make a module. There is no need to make each file manually. This slide will show how to create a module using the scaffold method.
This document provides an overview of wound healing, its functions, stages, mechanisms, factors affecting it, and complications.
A wound is a break in the integrity of the skin or tissues, which may be associated with disruption of the structure and function.
Healing is the body’s response to injury in an attempt to restore normal structure and functions.
Healing can occur in two ways: Regeneration and Repair
There are 4 phases of wound healing: hemostasis, inflammation, proliferation, and remodeling. This document also describes the mechanism of wound healing. Factors that affect healing include infection, uncontrolled diabetes, poor nutrition, age, anemia, the presence of foreign bodies, etc.
Complications of wound healing like infection, hyperpigmentation of scar, contractures, and keloid formation.
Chapter wise All Notes of First year Basic Civil Engineering.pptxDenish Jangid
Chapter wise All Notes of First year Basic Civil Engineering
Syllabus
Chapter-1
Introduction to objective, scope and outcome the subject
Chapter 2
Introduction: Scope and Specialization of Civil Engineering, Role of civil Engineer in Society, Impact of infrastructural development on economy of country.
Chapter 3
Surveying: Object Principles & Types of Surveying; Site Plans, Plans & Maps; Scales & Unit of different Measurements.
Linear Measurements: Instruments used. Linear Measurement by Tape, Ranging out Survey Lines and overcoming Obstructions; Measurements on sloping ground; Tape corrections, conventional symbols. Angular Measurements: Instruments used; Introduction to Compass Surveying, Bearings and Longitude & Latitude of a Line, Introduction to total station.
Levelling: Instrument used Object of levelling, Methods of levelling in brief, and Contour maps.
Chapter 4
Buildings: Selection of site for Buildings, Layout of Building Plan, Types of buildings, Plinth area, carpet area, floor space index, Introduction to building byelaws, concept of sun light & ventilation. Components of Buildings & their functions, Basic concept of R.C.C., Introduction to types of foundation
Chapter 5
Transportation: Introduction to Transportation Engineering; Traffic and Road Safety: Types and Characteristics of Various Modes of Transportation; Various Road Traffic Signs, Causes of Accidents and Road Safety Measures.
Chapter 6
Environmental Engineering: Environmental Pollution, Environmental Acts and Regulations, Functional Concepts of Ecology, Basics of Species, Biodiversity, Ecosystem, Hydrological Cycle; Chemical Cycles: Carbon, Nitrogen & Phosphorus; Energy Flow in Ecosystems.
Water Pollution: Water Quality standards, Introduction to Treatment & Disposal of Waste Water. Reuse and Saving of Water, Rain Water Harvesting. Solid Waste Management: Classification of Solid Waste, Collection, Transportation and Disposal of Solid. Recycling of Solid Waste: Energy Recovery, Sanitary Landfill, On-Site Sanitation. Air & Noise Pollution: Primary and Secondary air pollutants, Harmful effects of Air Pollution, Control of Air Pollution. . Noise Pollution Harmful Effects of noise pollution, control of noise pollution, Global warming & Climate Change, Ozone depletion, Greenhouse effect
Text Books:
1. Palancharmy, Basic Civil Engineering, McGraw Hill publishers.
2. Satheesh Gopi, Basic Civil Engineering, Pearson Publishers.
3. Ketki Rangwala Dalal, Essentials of Civil Engineering, Charotar Publishing House.
4. BCP, Surveying volume 1
Exploiting Artificial Intelligence for Empowering Researchers and Faculty, In...Dr. Vinod Kumar Kanvaria
Exploiting Artificial Intelligence for Empowering Researchers and Faculty,
International FDP on Fundamentals of Research in Social Sciences
at Integral University, Lucknow, 06.06.2024
By Dr. Vinod Kumar Kanvaria
1. Parasite Immunology, 2001: 23: 617±626
Mouse splenic CD41 and CD81 T cells undergo extensive apoptosis
during a Plasmodium chabaudi chabaudi AS infection
LUVIA SANCHEZ-TORRES, ANDREA RODRIGUEZ-ROPON, MARIBEL AGUILAR-MEDINA
& LUIS FAVILA-CASTILLO
Department of Immunology, National School of Biological Sciences, IPN, Mexico City , Mexico
SUMMARY INTRODUCTION
The presence and phenotype of apoptotic lymphocytes was Apoptosis is a natural mechanism of cell death, which
studied in spleen cell suspensions taken from CB6F1 mice involves membrane cell blebbing, cell shrinkage, chromatin
infected with Plasmodium chabaudi chabaudi AS. High condensation, nuclear fragmentation and DNA degradation
levels of apoptotic cells were found, associated with high (1). This mechanism, which has been also called pro-
parasitaemias and splenomegaly. This was also accompa- grammed cell death, is essential for the homeostasis of the
nied by expansion and disarray of spleen white pulp. whole organism and has a central role from development to
Apoptosis levels lowered when parasitaemia was cleared, the maintenance of body shape and function. There has
but were still higher than in normal mice. At this time, the been major advances in the understanding of the biochem-
spleen was diminishing in size and the white pulp was ical events that underlie the apoptotic process (2).
contracting and rearranging. When parasitaemia was Apoptosis is triggered by a variety of both internal and
patent, the cells most affected by apoptosis were CD41 T external signals. Most of the morphological changes
cells followed by CD81 T cells, and to a lesser extent observed in a cell that is undergoing apoptosis are caused
B2201 B cells. When parasitaemia was cleared, CD81 T by a family of cystein proteases which are activated in
cells and B2201 B cells returned to basal levels of cascade and are known as caspases. These enzymes have
apoptosis, while CD41 T cells still had higher apoptosis restricted protein targets which are normally inactivated
levels than normal mice. A similar pattern of lymphocyte after the caspase exerts its action. In some cases, the target
subpopulation apoptosis was found in infected BALB/c of a caspase is an enzyme inhibitor so the final action of the
mice, despite the fact that, for this mouse model, it has been caspases is the activation of the enzyme.
reported that B cells are the cells that are most affected by Inside the cell, there are proteins which facilitates the
apoptosis. We consider that the high levels of apoptosis in apoptotic process (pro-apoptotic) and others which suppress
CD41 T cells when parasitaemias are still high are not it (anti-apoptotic). The relative amount of pro- and anti-
easily explained by a normal mechanism of down regulation apoptotic proteins determines if a cell is sensitive or
of the immune response. resistant to apoptotic signals. One of the first identified
anti-apoptotic proteins was called Bcl-2, which was
Keywords apoptosis, mouse malaria, CD41 T cells, discovered in a B-cell lymphoma. Now we know that
CD81 T cells, B cells, Plasmodium chabaudi there is a family of these proteins and some of them, such as
Bax and Bak, are in fact pro-apoptotic. Many proteins of
the Bcl-2 family work at the mitochondria membrane level.
If pro-apoptotic proteins predominate, the mitochondria
releases several molecules, including cytochome C, which
promote the apoptotic process.
During the course of an immune response, T-cell clones
Correspondence: Luis Favila-Castillo, Department of Immunology,
National School of Biological Sciences, IPN, Carpio y Plan de Ayala,
responding to the antigen undergo extensive proliferation.
  Â
Colonia Santo Tomas, Mexico DF 11340, Mexico. When the antigen is eliminated, the number of T-cells must
Received: 4 January 2001 be down regulated and this is achieved by inducing
Accepted for publication: 29 June 2001 apoptosis in the responding T-cells, a process termed
q 2001 Blackwell Science Ltd 617
2. L.Sanchez-Torres et al. Parasite Immunology
activation-induced cell death. The apoptotic signal is in different malaria mouse models, in humans and in other
received by the T-cell through a membrane receptor called animal models, where the infection becomes chronic (15±
CD95 or Fas, which is a type I transmembrane receptor. 17). In these latter two situations, apoptosis of lymphoid
The death signal is provided by the ligand of CD95 (CD95L cells might help explain the development of immunosup-
or FasL), which is expressed on lymphoid cells in the late pression and chronicity.
phases of the immune response. The elimination of The organ most affected in malaria is the spleen. Besides
responding cells is considered a normal mechanism to suffering changes in size and function, the spleen is also
turn off an ongoing immune response and to avoid self closely related to the development and maintenance of a
damage (3). There are other signals which contribute to protective immune response (18). Using a spleen transplant
activation-induced cell death, such as a receptor for tumour technique in a malaria rat model, it has been shown that,
necrosis factor (TNF)R2 which transmits apoptotic signals after primary infection, the spleen develops all the required
when bound to its ligand TNF-a. Finally, apoptotic cells are elements to protect itself against reinfection (19).
engulfed by phagocytic cells, eliminating them without One way to understand the role of lymphoid cell
causing tissue inflammation or alterations in tissue apoptosis in malaria is to study the presence of apoptotic
morphology or function. lymphoid cells during different stages of infection, and to
The idea that parasitic microorganisms might tamper with relate any changes to other physiological alterations in the
apoptotic signals or biochemical processes and hence use immune system. In this respect, it is also useful to
them to their advantage is attractive as it could help explain, determine how different lymphoid cell populations are
at least in part, how parasites can become established in affected by apoptosis. A recent study (20) investigated
their host and how infection becomes chronic. apoptosis in mouse spleen cells infected with P. chabaudi
An increase in apoptosis of lymphoid cells has been chabaudi AS. It was found that the frequency and absolute
described during mouse infection with microorganisms numbers of apoptotic cells in the spleen increased during
such as viruses (4,5), ricketssia (6), bacteria (7,8), protozoa primary infection, reached a peak around 4 days following
(9,10) and helminths (11). The relevant questions in these peak parasitaemia and then descended to almost normal
systems are: (i) does the parasitic microorganism use levels after the parasite was cleared. The findings also
apoptotic signals to interfere with the immune response and demonstrated that apoptosis involves T cells (CD41 and
become established in its host or (ii) is the increase in CD81), B cells and macrophages and that the majority of
apoptosis during the infection associated with the normal apoptotic cells are B cells.
silencing of the immune response against the parasite? A Here, we carried out a similar study using the same
third possibility is that the increase in apoptosis is an parasite, and, in general, confirmed the previous results
epiphenomenon, which is not relevant to the host±parasite (20). We also describe changes in spleen size and histology
interaction. during the infection, and correlate these changes with
In mice infected with the lymphocytic choriomeningitis apoptosis of spleen cells. Finally, it should be noted that we
virus (4) or with Listeria monocytogenes (7), lymphocyte studied apoptosis in lymphocyte subpopulations using a
apoptosis has been associated with silencing of the immune different experimental approach to the previous study (20).
response. Whereas, in mice infected with Trypanosoma We therefore conclude that when apoptosis is expressed as
cruzi, lymphocyte apoptosis has been interpreted as a way the percentage of apoptotic cells within a particular
to limit host tissue damage by the immune response, but lymphocyte subpopulation, the cells most affected by
which collaterally promotes the establishment of a chronic apoptosis are CD41 T cells, followed by CD81 T cells,
infection (10). On the other hand, a protein that induces while B2201 B cells are proportionally less affected. With
apoptosis in macrophages has been identified in Yersinia, this information, the possible role of apoptosis at the
and it has been shown that when Yersinia is inoculated into different stages of infection is discussed.
mice the expression of this protein is an important virulent
factor (12).
MATERIALS AND METHODS
In malaria, there are several phenomena in which
apoptosis of lymphoid cells could be involved. There is a
Mice
very intense proliferation of lymphoid cells (13,14) and
severe splenomegaly, and these events are subdued when Female (BALB/cXC57Bl/6) F1 hybrids or BALB/c 14±22-
parasitaemia is controlled. In both cases, apoptosis could be week-old mice were used for all experiments. The parents
part of a normal mechanism to reduce the number of were originally purchased from the Jackson Laboratory
lymphoid cells and, as a consequence, spleen size. On the (Bar Harbor, ME, USA) and hybrids or BALB/c mice were
other hand, general immunosuppression has been described bred in our facilities at the Department of Immunology, in
618 q 2001 Blackwell Science Ltd, Parasite Immunology, 23, 617±626
3. Volume 23, Number 12, December 2001 T cell apoptosis in P. chabaudi malaria
the National School of Biological Sciences, IPN, Mexico Determination of apoptotic cells by cytofluorometry
City. Experimental mice were maintained in a reversed 12-h
The presence of apoptotic cells was determined in cell
light-dark cycle from 07.00 h to 19.00 h.
suspensions by their ability to bind Annexin V (21). The
Apodetect Annexin V-fluorescein-isothiocyanate (FITC) kit
Parasite and infection (Zymed Laboratories, San Francisco, CA, USA) was used,
according to the manufacturer's instructions. Briefly: spleen
Plasmodium chabaudi chabaudi AS was kindly donated by cells, obtained as described above, were adjusted to
Dr David Walliker (University of Edinburgh, Edinburgh, 5 Â 105 per ml in binding buffer and 10 ml of FITC-
UK), and is a cloned and mosquito-transmitted line. The Annexin V were added to a 190-ml sample of the cell
parasite has been syringe passaged from the original suspension. The mixture was incubated for 10 min at room
material no more than eight times and reference populations temperature. After centrifugation, cells were resuspended in
are cryopreserved in liquid nitrogen. For all experiments, 190 ml of binding buffer and 10 ml of propidium iodide
parasites from frozen material were inoculated into young (20 mg/ml) were added. Cells were analysed in a
mice (8±10 weeks old) and when parasitaemias were FACScalibur cytofluorometer (Becton Dickinson, San
patent, experimental mice were inoculated intraperitoneally Jose, CA, USA) using the Cell Quest program (version
with 5 Â 104 parasitized red blood cells. Control mice were 2´0), and 10 000 events per sample were recorded. Cells
inoculated with the same amount of normal red blood cells that were positive for both propidium iodide and Annexin V
as the total amount of red cells received by the infected were considered as necrotic cells, and were excluded from
mice. The parasite causes a synchronical infection and the analysis. The results are expressed as the percentage of
undergoes schizogony every 24 h between 09.00 h and apoptotic cells (^ SD).
11.00 h. Parasitaemia was determined by light microscopy
of methanol-fixed, Giemsa-stained thin blood films, and
was expressed as percent parasitaemia. Determination of apoptotic cells in sections
Apoptotic cells were detected by the TUNEL reaction (22).
An in situ cell death detection kit (Boehringer Mannheim
Determination of splenomegaly
GmbH, Mannheim, Germany) was used according to the
A group of mice was infected with P. chabaudi, as manufacturer's instructions. Briefly, wax was removed
described above, and was only used for the determination from sections, they were rehydrated and treated with
of splenomegaly. At different times following infection, proteinase K. The sections were then incubated with
groups of three mice were sacrificed, their spleens extracted terminal deoxinucleotidyl transferase and FITC-labelled
and weighed. At each experimental point, one normal, age nucleotides, which were detected using an alkaline
matched mouse was also killed and its spleen weight phosphatase conjugated anti-FITC antibody, using nitroblue
recorded. A total of eight normal mice were sacrificed tetrazolium as the substrate. Apoptotic cells were stained
during the experiment and all resulting data were pooled. blue and sections were then counterstained with nuclear
red, dehydrated and mounted in synthetic resin.
Processing of spleens from infected and control mice
Purification of lymphocyte subpopulations by magnetic
A group of mice was infected with the parasite, and at
beads
different times following infection, groups of infected or
control mice were sacrificed, their spleens extracted CD41 or CD81 T cells or B2201 B cells were purified
(always between 13.00 h and 14.00 h) and cut in half. from total spleen cell suspensions, prepared as described
From one half, a cell suspension was prepared by above. Spleen cells (107) were resuspended in 90 ml of PBS
expressing the spleen through nylon mesh with the help (containing 2 mm ethylenediaminetetraacetic acid and
of a plastic syringe plunger. The spleen cells were collected 0´5% bovine seric albumin) and 10 ml of the respective
in cold phosphate-buffered saline (PBS), centrifuged, paramagnetic bead bound antibody (Miltenyi Biotec,
resuspended in PBS, counted and used for the determina- Aarhus, Denmark) were added. Cells were incubated on
tion of apoptotic cells by cytofluorometry (see below). The ice for 15 min, washed twice, resuspended in 500 ml of
other spleen half was fixed in 10% formalin in PBS, PBS and loaded onto a positive selection column (MS1/
embedded in paraffin-wax and processed by standard RS1 MACS column, Miltenyi). The column was then
histological techniques used to prepare and stain 4 mm exposed to a strong magnetic field (VarioMacs, Miltenyi).
sections with haematoxilin and eosin (H&E). Negative cells were eluted with 1´5 ml of PBS and were
q 2001 Blackwell Science Ltd, Parasite Immunology, 23, 617±626 619
4. L.Sanchez-Torres et al. Parasite Immunology
collected. The column was removed from the magnetic 21±38 p.i., when parasitaemia had been cleared. During
field and positive cells were eluted with 1´5 ml of PBS and this time, the level of apoptosis, although low, was still
collected. The purification procedure was repeated using significantly higher than in normal mice (16´7% apoptotic
the positive cells. The purity of the cells was assessed by cells, day 38 p.i., P , 0´001).
cytofluorometry using FITC-conjugated anti-CD4 or anti- Changes in spleen size were determined in a different
CD8 monoclonal antibodies and PE-conjugated anti-B220 group of infected mice, which gave a parasitaemia curve
monoclonal antibody. The percentage of apoptotic cells was very similar to the one shown in Figure 1(a) (data not
determined in the purified cells by cytofluorometry, as shown). The spleen started to increase in size early in
described above. ascending parasitaemia. At day 4 p.i., the spleen was
already significantly bigger than in normal mice (Figure 1c,
P , 0´05). The spleen size increased sharply after this time
Statistical analysis
and at peak parasitaemia it was around 12-fold higher than
Student's t-test was used to assess statistical significance. a normal spleen (12X, P , 0´001). The spleen size reached
P , 0´05 was considered statistically significant. a peak at day 14 p.i. (17X, P , 0´001) which was 4 days
later than the peak of apoptosis (Figure 1b) and 6 days later
than peak parasitaemia, when descending parasitaemia was
RESULTS
around 0´01% (Figure 1a). After this time, the size of the
spleen decreased sharply to become 6´5X at day 16 p.i.
Apoptosis of spleen cells and changes in spleen size
(parasitaemia cleared) and continued to decrease to reach a
during P. chabaudi primary infection
size of 2´5X at day 31 p.i. (Figure 1c, P , 0´001). The
The curve of parasitaemia caused by P. chabaudi infection spleen stays around this size for several months after
in CB6F1 mice has four distinct zones. Four days after infection (data not shown).
inoculation, parasites start to be detected by light micro-
scopy and numbers sharply increase (ascending parasitae-
Histological changes in the spleen during P. chabaudi
mia) to reach a maximum at day 8 p.i. (peak parasitaemia).
primary infection
Then parasitaemia starts to rapidly decline (descending
parasitaemia) and the parasite becomes undetectable by H&E stained sections were prepared from the spleens of
light microscopy around days 17±19 p.i., and stays this mice used to generate the parasitaemia curve shown in
way up to day 38 p.i. (parasitaemia cleared) (Figure 1a). In Figure 1(a). A section from a normal spleen is shown in
this study, parasitaemia has been considered to be cleared at Figure 2(a), where normal distribution and aspect of red
this time; however, the presence of the parasite can be and white pulp is observed. There were a few lymphoid
demonstrated by subinoculation of blood into normal mice cells with picnotic nuclei (0´2±0´5 per field, using a  40
up to days 60 or 70 p.i. After this time, parasites cannot be objective) which were considered to be apoptotic cells since
demonstrated in blood by subinoculation (data not shown). they were TUNEL positive (see below). At day 4 p.i., when
The percentage of apoptotic cells in the spleen was parasites just started to be detected, the white pulp was
determined during P. chabaudi primary infection in the organized and did not show obvious proliferative activity
same mice used to generate the parasitaemia curve (Figure 2b). In general, no differences in histology
(Figure 1a). Results are shown in Figure 1(b). In a group compared to normal spleens were detected, including the
of 13 normal mice, a background of 7´6% (^ 0´6) apoptotic amount of apoptotic cells. At day 8 p.i., the time of peak
cells was detected. In infected mice, the percentage of parasitaemia, cells in the white pulp had proliferated
apoptotic cells at the beginning of ascending parasitaemia considerably, such that white pulp had enlarged and the
(days 2 and 4 p.i.) was not different from normal controls. limits between white and red pulp started to disappear
When mice were approaching, or had reached peak (Figure 2c). At this time, the spleen had increased
parasitaemia (days 7 and 8 p.i.), there was a small but considerably in size, although it had not reached its peak.
statistically significant increase in apoptotic cells (15´2% The amount of apoptotic cells increased (2±3 per field) and
apoptotic cells, day 7 p.i., P , 0´001). After this time, the clusters of apoptotic cells started to appear. At day 10 p.i.,
percentage of apoptotic cells increased steadily to reach a which is the time when the peak in numbers of apoptotic
peak at day 10 p.i., when 53´1% of the spleen cells were cells was detected in cell suspensions, total tissue
found to be apoptotic (P , 0´01). At this time, descending disorganization was observed. This disorganization was
parasitaemia had already started, although parasitaemia was due mainly to hiperplasia of the lymphoid tissue, the red
still high (Figure 1a). After this peak of apoptotic cells, pulp had almost disappeared (Figure 2d) and apoptotic cells
apoptosis started to decline and reached a plateau from days were abundant (10±20 per field). Spleen size was increased,
620 q 2001 Blackwell Science Ltd, Parasite Immunology, 23, 617±626
5. Volume 23, Number 12, December 2001 T cell apoptosis in P. chabaudi malaria
but it was still not at its peak. The time of peak of apoptotic cells and clusters, although still high (around
splenomegaly is day 14 p.i., which is when parasitaemia 10 per field) was lower than at day 10 p.i. At day 38 p.i.,
is being resolved, and the white pulp has started to when parasitaemia has been controlled and splenomegaly
reorganize although it is still hyperplasic (Figure 2e). The was subdued, white and red pulp are clearly separated again
red pulp started to be distinguishable again and the amount and in the white pulp few individual apoptotic cells were
observed (2±3 per field). In addition, many discrete less
dense areas were easily recognizable at low magnification
(Figure 2f). These structures were not seen in normal
(a)
spleens and started to appear in the spleens of infected mice
100
until day 19 p.i. (not shown) but were much more abundant
at day 38 p.i. At higher magnification (Â 100 objective),
10 these structures were conglomerates of apoptotic cells,
bodies and cell debris, apparently inside a macrophage
% Parasitemia
1 (Figure 2g). All these structures were TUNEL positive, as
were individual cells with condensed chromatin which were
0·1
probably those recognized as apoptotic in H&E stained
sections (Figure 2h).
0·01
0·001 Apoptosis in lymphocytes subpopulations
0 5 10 15 20 25 30 35 40
Our results show that there is an increase in apoptotic cells
(b) in the spleen during P. chabaudi primary infection. We next
80 studied apoptosis at the level of lymphocyte subpopulation
at different stages of infection. For this, we determined the
70
percentage of apoptotic cells in CD41 and CD81 T cells
60 and B2001 B cells, purified by antibody coated magnetic
% Apoptotic cells
beads, as described in Materials and Methods.
50
We prepared a purified spleen cell subpopulation from
40 normal and infected CB6F1 or BALB/c mice at high
30 ascending parasitaemias, when the number of apoptotic
cells started to rise significantly (Figure 1b), from peak
20
parasitaemia or from descending parasitaemia. For CB6F1
10 mice, samples were also studied a few days following
parasitaemia clearance. For all experiments, the percentage
0
0 5 10 15 20 25 30 35 40 of apoptotic cells in the unseparated whole spleen cell
suspension was also determined, and it was found to be
(c) within the range predicted by the curve shown in
1·6 Figure 1(b) (data not shown). The percentage of each cell
1·4
1·2 Figure 1 CB6F1 mice were infected with P. chabaudi. (a) Resulting
Spleen weight (g)
parasitaemias were followed in six mice and expressed as percent
1·0 parasitaemia (mean ^ SD). (b) Apoptosis in spleen cell suspensions of
0·8 mice infected with P. chabaudi, determined by Annexin V binding. The
percentage of apoptotic cells was determined in mice from the same
0·6 group as in a at the indicated times (3±6 mice per experimental point).
The open triangle in day 1 is the result of 13 normal mice (mean ^ SD),
0·4 P , 0´01 from days 7±38 p.i. compared to normal mice. (c) The weight
of the spleen of three mice per experimental point was recorded at the
0·2
indicated times, in a different group of mice than in a (mean ^ SD). The
0·0 open triangle in day 1 is the mean weight of eight normal spleens.
0 5 10 15 20 25 30 35 40 Infected mice had significantly bigger spleens from days 4±31 p.i.
Days postinfection (P , 0´05 at day 4 p.i. and P , 0´001 from day 7 p.i. to day 31 p.i.).
q 2001 Blackwell Science Ltd, Parasite Immunology, 23, 617±626 621
7. Volume 23, Number 12, December 2001 T cell apoptosis in P. chabaudi malaria
CB6F1 mice BALB/c mice was 7±11% in the sampled mice) compared to 2´7% in
(a) (d)
60
+
60
+
normal BALB/c mice.
For CD81 T cells, there was also a significant increase in
CD4 T cells CD4 T cells
50 50
∗∗
40 ∗∗ 40 ∗∗ apoptotic cells in all the three stages of parasitaemia, both
30 30
∗ for CB6F1 and BALB/c mice. In CB6F1 mice, the level of
20 ∗∗ 20
10 10 ∗∗ CD81 apoptotic T cells approached normal levels when the
∗∗
0
NL ASC PEAK DESC CLD
0
NL ASC PEAK DESC
ND
CLD
parasite was cleared (Figure 3b,e). The increase in
apoptotic CD81 T cells was approximately one-half the
increase in apoptotic CD41 T cells. For CB6F1 mice,
(b) (e)
60 60
19´0% of CD81 T cells were apoptotic and, for BALB/c
+ +
CD8 T cells CD8 T cells
50 50
% Apoptotic cells
40 40 mice, 23´9% were apoptotic, both at peak parasitaemia,
30 30
compared to 2´6% in normal mice for both mouse strains.
∗
For B2201 B cells, although there was a tendency for the
20 20 ∗∗
∗∗ ∗ ∗∗
10 ∗∗ 10
0 0
ND percentage of apoptotic cells to increase during patent
NL ASC PEAK DESC CLD
parasitaemia for both CB6F1 and BALB/c mice; the
NL ASC PEAK DESC CLD
(c) (f ) difference was significant only at descending parasitaemia.
For CB6F1 mice, the percentage of apoptotic B2201 B
60 60
+ +
B220 B cells B220 B cells
50 50
40 40 cells returned to normal levels when parasitaemia was
30 30 cleared (Figure 3c,f).
20 20 The percentage of CD41 and CD81 T cells in the spleen
10
∗ 10
∗
ND diminished during infection, both in CB6F1 and in BALB/c
0 0
NL ASC PEAK DESC CLD NL ASC PEAK DESC CLD mice, following a similar pattern during the different stages
Figure 3 Apoptotic cells detected by Annexin V binding in of parasitaemia (Figure 4a,b,d,e). In CB6F1 mice, the
subpopulations of spleen lymphocytes purified by magnetic beads and percentage of both CD41 and CD81 T cells tended to
analysed by citofluorometry. The cells were determined in 3±6 CB6F1 return to normal levels when the parasitaemia has been
or BALB/c mice per group of normal mice (NL), infected mice with 5± cleared (Figure 4a,b).
15% of ascending parasitaemia (ASC), peak parasitaemia (PEAK), 2±
The percentage of B2201 B cells increased or stayed
18% desending parasitaemia (DESC) or mice 3 days after parasitaemia
had become undetectable by light microscopy (cleared, CLD). Bars are within normal range during the different stages of para-
1 SD; ND, not determined, *P , 0´05, **P , 0´01, compared to sitaemia, both in CB6F1 and BALB/c mice (Figure 4c,f).
normal mice.
DISCUSSION
subpopulation in the unseparated cell suspension was also
determined. In this study, we investigated apoptosis of lymphocytes at
For CD41 T cells, we found an important and significant different stages of P. chabaudi infection in mice, and
increase in apoptotic cells in all three stages of para- related our findings to parasitaemia and changes in spleen
sitaemia, both for CB6F1 and BALB/c mice. In CB6F1 size and histology. When parasites just started to be
mice, the level of CD41 apoptotic T cells approached detectable by light microscopy there were no noticeable
normal levels when the parasitaemia was cleared (Fig- changes in spleen histology (Figure 2b), size (Figure 1c) or
ure 3a). At peak parasitaemia, 48´3% of CD41 T cells were percentage of apoptotic cells (Figure 1b). At peak para-
apoptotic in CB6F1 mice compared to 2´3% in normal sitaemia, the white pulp had expanded (Figure 2c) which
CB6F1 mice. For BALB/c mice, 43´3% of CD41 T cells correlates with an increase in spleen size (Figure 1c) and
were apoptotic at descending parasitaemia (parasitaemia the number of apoptotic cells had started to increase
Figure 2 Haematoxilin and eosin stained sections from: (A) normal spleen; (B) spleen from a mouse at day 4 p.i. with P. chabaudi where white and
red pulp are clearly separated; (C) spleen from a mouse at day 8 p.i. with P. chabaudi. Note that the separation between white and red pulp starts to
disappear; (D) spleen from a mouse at day 10 p.i. Note that the white pulp is not longer distinguished as cells from the white pulp appear to have
invaded most of the organ and there are only a few red blood cells; (E) spleen from a mouse at day 14 p.i. The white pulp is becoming rearrenged,
although it is larger than in a normal spleen. Groups of red blood cells can be seen again in the red pulp; (F) spleen from a mouse at day 38 p.i. The
white and red pulp are again clearly separated but the white pulp shows clusters of material sorrounded by a clear area (arrows); (G) Magnification of
the clusters seen in F, there are two kind of clusters, some are in fact formed by a single cell with a condensed nucleus which looks like an apoptotic
cell, and other clusters, which are larger, include apoptotic cells and cell debris (seven such clusters are shown); (H) TUNEL reaction of the clusters
shown in (G), both single cells and clusters are positive. Original magnification: (A) to (E) Â 200; (F) Â 100; (G±H) Â 1000.
q 2001 Blackwell Science Ltd, Parasite Immunology, 23, 617±626 623
8. L.Sanchez-Torres et al. Parasite Immunology
(a)
CB6F1 mice
(d)
BALB/c mice red pulp were seen to be clearly separated. However, we
60 CD4+ T cells 60 CD4+ T cells found clusters of apoptotic cells and bodies in the white
50 50
pulp, which were easily recognized since they were less
40 40
dense that the surrounding tissue. These structures, which
30 30
∗ are shown in more detail in Figure 2(g,h), have been
20 20 ∗∗
10
∗∗
∗∗ 10 ∗∗ described in other pathologies as tingible body macro-
∗∗ ∗∗
0 0
ND
phages, which are macrophages that have engulfed
NL ASC PEAK DESC CLD NL ASC PEAK DESC CLD
apoptotic cells and bodies (24). In this study, these
PERCENT OF LYMPHOCYTE SUBPOPULATION
structures were detected as being clearly TUNEL positive
(b) (e)
60 CD8+ T cells 60 CD8+ T cells
50 50 (Figure 2h). We do not know their significance, although it
40 40 is interesting that they started to appear rather late in the
30 30
infection (day 19 p.i.) and were very abundant at day 38 p.i.
20
∗∗
20
∗ (Figure 2f). We have observed the same structures in pig
10 ∗∗ 10 ∗∗
0 0
ND lymph nodes undergoing a viral infection; however, the
NL ASC PEAK DESC CLD NL ASC PEAK DESC CLD structures appeared much earlier (day 4 p.i) (25).
60
(c)
B220+ B cells 60
(f)
B220+ B cells
On the other hand, the identification of apoptotic
50 ∗∗ 50 cells by Annexin V binding, which detects an early change
∗∗
40 40
∗∗
in membrane structure preceding DNA fragmentation,
30 30 correlated well with the observation of picnotic nuclei, a
20 20 late stage of apoptosis, in H&E stained spleen sections.
10 10
ND We also investigated apoptosis in different lymphocyte
subpopulations. Cells were purified by antibody coated
0 0
NL ASC PEAK DESC CLD NL ASC PEAK DESC CLD
magnetic beads. This is an efficient procedure that takes
Figure 4 Percent of lymphocyte subpopulations in spleen cells from
approximately only 1 h to complete and the beads do not
normal mice (NL), infected mice with 5±15% of ascending
parasitaemia (ASC), peak parasitaemia (PEAK), 2±18% desending interfere with cytofluorometric analysis. At all the studied
parasitaemia (DESC) or mice 3 days after parasitaemia had become stages of patent parasitaemia, CD41 and CD81 T cells had
undetectable by light microscopy (cleared, CLD). Bars are 1 SD; ND, high percentages of apoptotic cells (Figure 3a,b). When
not determined, *P , 0´05, **P , 0´01, compared to normal mice. parasitaemia was cleared, the percentage of apoptotic
CD81 T cells returned to normal levels while apoptotic
moderately (Figure 1b). The peak of apoptotic cells was CD41 T cells, although diminished, were still significantly
found at day 10 p.i., when there was more than 50% greater in number compared to normal mice. The
apoptosis. Although parasite growth was already seen to be percentage of total CD41 and CD81 T cells was found to
under control, parasitaemia was still high (approximately diminish during patent parasitaemia (Figure 4a,b,d,e).
20%), we therefore do not believe that this peak of During patent parasitaemia, the percentage of apoptotic
apoptotic cells can be interpreted as a mechanism for B2201 B cells was not greatly modified (Figure 3c,f),
turning off the immune response. This is supported by the although there was an increase in the percentage of total
fact that splenomegaly had not reached its peak and the B2201 B cells (Figure 4c,f).
spleen histology was in total disarray (Figure 2d). One In conclusion, the population most affected by apoptosis
possible explanation for the presence of apoptotic cells at were T lymphocytes, particularly CD41 T cells, from
this time of the infection is that they are induced, at least in which approximately 50% were apoptotic at peak and
part, by parasite products, as has been described for descending parasitaemia, compared to approximately 2% in
P. falciparum malaria (23). Spleen size reached a peak at normal mice, while the least affected population comprised
day 14 p.i. and at this time parasitaemia was low, and the the B2201 B cells.
white and red pulp had started to reorganize (Figure 2e). In a previous study (20), apoptosis of spleen cells was
The percentage of apoptotic cells had diminished, although also studied in mice infected with the same Plasmodium
it was still high (approximately 30%, Figure 1b). We strain that we used, except that in that study BALB/c mice
believe that at this stage apoptosis is related to the turning were used instead of CB6F1 mice. Using Annexin V to
off of the antiparasite immune response, since after this detect apoptotic cells by cytofluorometry, these authors
time the spleen size diminished rapidly, red and white pulp reported results very similar to ours in terms of percentage
became clearly separated again and parasites became and kinetics of apoptotic cells during primary infection.
undetectable by light microscopy. When the spleen had However, they reach the conclusion that the majority of
reduced to a near normal size (day 38 p.i.), the white and apoptotic cells during patent parasitaemia are B cells, while
624 q 2001 Blackwell Science Ltd, Parasite Immunology, 23, 617±626
9. Volume 23, Number 12, December 2001 T cell apoptosis in P. chabaudi malaria
apoptosis in CD41 and CD81 T cells is only moderately Listeria monocytogenes (7) and Yersinia pseudotuberculosis
increased. At first sight, it seems that we reached opposite (12).
conclusions to their study; however, we believe that the It seems that an increase in apoptosis, in some or most of
difference lies in the different experimental approach that the lymphoid cells, is a general phenomenon in a variety of
we took. They analysed unseparated spleen cell suspensions infections. In principle, this can be explained as a normal
by double staining. Apoptotic cells were stained with homeostatic response involved in the termination of the
Annexin V labelled with one fluorochrome and the immune response induced by the microorganism (3).
lymphocyte subpopulation was marked with an anti-cell Nevertheless, in our mouse malaria model, we found that
surface marker antibody labelled with a second fluoro- the peak of apoptotic cells is reached when there are still
chrome. They performed a cytofluorometric analysis of the relatively high parasite loads, which, from our point of
sample using one label to identify and quantify the view, is still too early a time to terminate the immune
apoptotic cells and then, using the second label, determined response. On the other hand, it is well established that
within the apoptotic population the percentage of cells CD41 T cells are important in the control P. chabaudi
carrying a particular marker (i.e. CD41). In this way, they primary infection (26,27). Other authors working with
did not determine the percentage of cells with that another malaria mouse model (P. berghei) have described
particular marker that are not part of the nonapoptotic P. berghei specific CD41 T cells that are specifically
population. deleted when adoptively transferred into recipient mice
Our approach was to first purify a particular lymphocyte challenged with the same parasite. It is suggested that this
subpopulation and then determine the percentage of deletion is mediated by apoptosis (28). This, together with
apoptotic cells within that purified subpopulation. This our observation that approximately 50% of CD41 T cells
gave us an idea of how apoptosis affects a particular undergo apoptosis during P. chabaudi infection, provides
lymphocyte subpopulation. In this way, we could see that sufficient data to stimulate the study of lymphocyte
CD41 T cells comprise the lymphocyte subpopulation most apoptosis in malaria.
affected by apoptosis, and not B2201 B cells.
Furthermore, it is important to exclude the possibility
that the difference between ours and the previous study (20) ACKNOWLEDGEMENTS
is explained by the use of different mouse strains. We Â
This work was supported by Coordinacion General de
therefore infected BALB/c mice with P. chabaudi, and Â
Posgrado e Investigacion del IPN. Luis Favila-Castillo is
determined the percentage of apoptotic cells in purified fellow from COFAA-IPN, EDD-IPN and SNI-SEP. Luvia
lymphocyte subpopulations in the same way as we did for   Â
Sanchez-Torres, Andrea Rodrõguez-Ropon and Maribel
CB6F1 mice, as shown in Figure 3(d±f). Although there are Aguilar-Medina were supported by CONACYT Mexico.
some minor differences in the results between BALB/c and Luvia Sanchez-Torres received during part of this study a
CB6F1 mice, the conclusion is that in BALB/c mice the scholarship from the Von Behring and Kitasato Foundation,
cells most affected by apoptosis are also CD41 and Mexico City. We thank Dr Edith Ormerod for reviewing the
CD81 T cells. The variations in the percentage of spleen use of the English language.
CD41, CD81 T cells and B2201 B cells during
parasitaemia were also similar between BALB/c and
CB6F1 mice (Figure 4a±f). We therefore conclude that, REFERENCES
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