This document describes a case study of a 5-year-old female Argentine patient with a mutation in the CD25 gene resulting in CD25 deficiency. Key findings include chronic inflammatory lung disease (follicular bronchiolitis), eczema, infections, extremely low levels of regulatory T cells, and a homozygous missense mutation (c.122a>c; p.Y41S) in the CD25αR gene. The mutation is predicted to compromise protein function and cause immune dysregulation similar to IPEX syndrome. CD25 deficiency should be considered in patients presenting with these clinical and laboratory features to facilitate early diagnosis and treatment.
1) The peptide antimicrobials retrocyclin (RC-100) and protegrin-1 (PG-1) were found to activate human mast cells by inducing calcium mobilization and degranulation.
2) While RC-100 and PG-1 activated mast cells, only PG-1 displayed antimicrobial activity against bacteria, suggesting dissociation between mast cell activation and antimicrobial function for RC-100.
3) Mast cell activation by RC-100 and PG-1 occurred independently of the formyl peptide receptor FPRL1 but likely through the G protein coupled receptor MrgX2, similarly to other antimicrobial peptides.
In vivo effects of Interleukin 2 on Lymphocyte Subpopulations in a Patient wi...Elke Stein
This document describes a clinical trial using interleukin-2 (IL-2) to treat a 17-month-old boy with combined immunodeficiency. IL-2 was purified from leukocytes and administered subcutaneously over 50 days. Within 3 weeks, IL-2 treatment normalized the patient's lymphocytosis and improved his eosinophilia. Most striking was the normalization of the patient's abnormal OKT4/OKT8 ratio and increase in OKT3+ cells. Infectious episodes decreased during treatment. Some effects were transient, returning to pathological levels after treatment ended.
This study investigated the role of the cellular protein annexin 2 (Anx2) in human immunodeficiency virus type 1 (HIV-1) particle production and infectivity. The researchers knocked down Anx2 expression by 98% in various cell types using lentiviruses encoding short hairpin RNAs against Anx2. They found that knocking down Anx2 did not reduce HIV-1 virus-like particle production in COS-1, 293T, Jurkat T cells, or primary human macrophages. Similarly, murine cells lacking Anx2 produced normal levels of particles. However, supernatants from Anx2-depleted primary human macrophages exhibited decreased infectivity, indicating Anx2 plays a
This document discusses the role of dendritic cells (DCs) in autoimmune diseases. It begins by introducing DCs as professional antigen presenting cells that are involved in both inducing immune responses and maintaining peripheral tolerance. The review then examines the different DC subsets and their potential roles in tolerance induction. It discusses factors that influence the generation of tolerogenic DCs, including their maturation status, intrinsic characteristics, interactions with other immune cells, and the tissue microenvironment. The review challenges the traditional view that immature DCs induce tolerance, presenting evidence that both immature and mature DCs can induce tolerance depending on other factors. It highlights the need to better define the features of DC subsets that induce tolerance.
This study aimed to differentiate between invasive squamous cell carcinoma (SCC) and carcinoma-in-situ (CIS) of the uterine cervix using immunohistochemical markers. Tissue samples from 37 patients were stained for CD3, CD4, CD8, CD20, and CD138. Scoring showed decreased expression of CD8, CD20, and CD138 in invasive SCC compared to CIS, indicating differences in immune cell infiltration between invasive and non-invasive lesions. The results provide potential markers for differentiating invasive SCC from CIS of the cervix.
This document summarizes a study comparing CD8+ T cell responses targeting the KK10 epitope of HIV-1 Gag protein in elite controllers and progressors expressing HLA-B*2705. The study found:
1) Controllers and progressors had similar frequencies and antigen sensitivity of KK10-specific CD8+ T cells, despite large differences in viral load.
2) KK10-specific CD8+ T cells in controllers and progressors differed in their polyfunctional profiles, with some subsets being more frequent in one group versus the other.
3) KK10-specific CD8+ T cells in controllers and progressors showed considerable diversity in T cell receptor usage,
The document discusses HLA typing and its implications. It begins with a brief history of the discovery of the major histocompatibility complex (MHC) in mice and humans. It then describes the structure and functions of the MHC, including the class I, class II, and class III regions. The document discusses methods of HLA typing, including serological testing using microcytotoxicity and molecular methods. It notes some implications of HLA typing, such as its role in organ transplant matching and susceptibility to autoimmune disease.
This document summarizes 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.
1) The peptide antimicrobials retrocyclin (RC-100) and protegrin-1 (PG-1) were found to activate human mast cells by inducing calcium mobilization and degranulation.
2) While RC-100 and PG-1 activated mast cells, only PG-1 displayed antimicrobial activity against bacteria, suggesting dissociation between mast cell activation and antimicrobial function for RC-100.
3) Mast cell activation by RC-100 and PG-1 occurred independently of the formyl peptide receptor FPRL1 but likely through the G protein coupled receptor MrgX2, similarly to other antimicrobial peptides.
In vivo effects of Interleukin 2 on Lymphocyte Subpopulations in a Patient wi...Elke Stein
This document describes a clinical trial using interleukin-2 (IL-2) to treat a 17-month-old boy with combined immunodeficiency. IL-2 was purified from leukocytes and administered subcutaneously over 50 days. Within 3 weeks, IL-2 treatment normalized the patient's lymphocytosis and improved his eosinophilia. Most striking was the normalization of the patient's abnormal OKT4/OKT8 ratio and increase in OKT3+ cells. Infectious episodes decreased during treatment. Some effects were transient, returning to pathological levels after treatment ended.
This study investigated the role of the cellular protein annexin 2 (Anx2) in human immunodeficiency virus type 1 (HIV-1) particle production and infectivity. The researchers knocked down Anx2 expression by 98% in various cell types using lentiviruses encoding short hairpin RNAs against Anx2. They found that knocking down Anx2 did not reduce HIV-1 virus-like particle production in COS-1, 293T, Jurkat T cells, or primary human macrophages. Similarly, murine cells lacking Anx2 produced normal levels of particles. However, supernatants from Anx2-depleted primary human macrophages exhibited decreased infectivity, indicating Anx2 plays a
This document discusses the role of dendritic cells (DCs) in autoimmune diseases. It begins by introducing DCs as professional antigen presenting cells that are involved in both inducing immune responses and maintaining peripheral tolerance. The review then examines the different DC subsets and their potential roles in tolerance induction. It discusses factors that influence the generation of tolerogenic DCs, including their maturation status, intrinsic characteristics, interactions with other immune cells, and the tissue microenvironment. The review challenges the traditional view that immature DCs induce tolerance, presenting evidence that both immature and mature DCs can induce tolerance depending on other factors. It highlights the need to better define the features of DC subsets that induce tolerance.
This study aimed to differentiate between invasive squamous cell carcinoma (SCC) and carcinoma-in-situ (CIS) of the uterine cervix using immunohistochemical markers. Tissue samples from 37 patients were stained for CD3, CD4, CD8, CD20, and CD138. Scoring showed decreased expression of CD8, CD20, and CD138 in invasive SCC compared to CIS, indicating differences in immune cell infiltration between invasive and non-invasive lesions. The results provide potential markers for differentiating invasive SCC from CIS of the cervix.
This document summarizes a study comparing CD8+ T cell responses targeting the KK10 epitope of HIV-1 Gag protein in elite controllers and progressors expressing HLA-B*2705. The study found:
1) Controllers and progressors had similar frequencies and antigen sensitivity of KK10-specific CD8+ T cells, despite large differences in viral load.
2) KK10-specific CD8+ T cells in controllers and progressors differed in their polyfunctional profiles, with some subsets being more frequent in one group versus the other.
3) KK10-specific CD8+ T cells in controllers and progressors showed considerable diversity in T cell receptor usage,
The document discusses HLA typing and its implications. It begins with a brief history of the discovery of the major histocompatibility complex (MHC) in mice and humans. It then describes the structure and functions of the MHC, including the class I, class II, and class III regions. The document discusses methods of HLA typing, including serological testing using microcytotoxicity and molecular methods. It notes some implications of HLA typing, such as its role in organ transplant matching and susceptibility to autoimmune disease.
This document summarizes 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.
This document provides information on MHC class I and class II molecules, including their structure, function, and role in antigen presentation. It discusses that MHC class I molecules are expressed on all nucleated cells and present intracellular antigens to CD8+ T cells. MHC class II molecules are expressed primarily on antigen presenting cells and present extracellular antigens to CD4+ T cells. The peptide binding grooves of MHC class I and II molecules differ in their structure and the size of peptides they can bind.
This document contains lecture notes on major histocompatibility complex (MHC) and related topics from a biotechnology course. It discusses antigen-presenting cells, the structure and function of MHC class I and II molecules, similarities and differences between the two classes, MHC-associated genes, and important immune signaling molecules like cytokines, interleukins, interferons, and chemokines. Diagrams are included to illustrate MHC pathway and types of interferons. The notes provide an overview of key concepts in MHC and immunology for students in the biotechnology course.
CD antigens, also known as clusters of differentiation, are cell surface proteins that are used to identify and characterize cell types. Over 371 CD markers have been identified that serve important functions like cell signaling. CD markers are analyzed using techniques like flow cytometry and help diagnose diseases like leukemia by identifying abnormal levels of specific CD antigens. Key CD markers have been identified for important immune cells like T cells, B cells, granulocytes, and stem cells. Immunophenotyping using CD markers is an important application in diagnosing diseases and monitoring treatment responses.
This document describes the creation of an anti-CD33 antibody targeting Acute Myeloid Leukemia. The researchers used the Pichia Pastoris yeast expression system to produce a single-chain variable fragment (scFv) of the anti-CD33 antibody. Gel electrophoresis and SDS-PAGE analysis showed the successful production and purification of the anti-CD33 scFv protein. While further studies are still needed, the researchers were able to successfully generate an anti-CD33 antibody that may have potential therapeutic applications for Acute Myeloid Leukemia patients.
The roles of the white blood cell subset γδ t cells within the human body are yet to be fully described.
Current literature has detailed several critical functions that vary dramatically between different γδ t cells.
Understanding how these elusive cells influence our immune systems will provide an opportunity to utilise their functions to assist medical treatments for a range of pathologies including cancer, diabetes, and bacterial infections.
Please send correspondence to Philip Voyias at P.D.Voyias@Warwick.ac.uk.
NK cells play important roles in both innate and adaptive immunity. As part of the innate immune system, NK cells help control viral infections through cytotoxic killing of infected cells and by secreting cytokines like IFNγ and TNFα that activate macrophages. NK cells express activating and inhibitory receptors that allow them to distinguish healthy "self" cells from infected or abnormal cells. The balance of signals through these receptors determines whether an NK cell mounts an immune response. NK cells also contribute to adaptive immunity by developing a form of immunological memory, responding more rapidly upon secondary exposure to pathogens.
Human Leukocyte Antigens (HLA) are human MHC antigens located on chromosome 6p that show polymorphism and co-dominant expression. There are two main types of HLA antigens - HLA class I and II. HLA molecules present antigenic peptides to initiate immune responses through interactions with T-cell receptors. Certain diseases like ankylosing spondylitis are associated with particular HLA antigens due to increased relative risk, though most carriers of risk alleles do not develop diseases. Cytokines play important regulatory roles in immune responses through effects on cells like macrophages, granulocytes, and lymphocytes.
A. AGEN1884 and AGEN2041 are fully human anti-CTLA-4 antibodies that block CTLA-4 binding to CD80 and CD86, enhancing T cell activation. AGEN1884 mediates FcγRIIIA signaling while AGEN2041 mediates FcγRIIA signaling.
B. In reporter cell and PBMC assays, both antibodies potentiate IL-2 production in response to suboptimal T cell receptor stimulation. AGEN1884 combines effectively with anti-LAG3 and anti-PD-1 antibodies.
C. In animal studies, both antibodies enhanced vaccine responses and AGEN1884 combined effectively with an autologous tumor vaccine in a
This is a journal club presentation where we present good quality papers from leading journals of the world. This particular paper deals with new biomarkers for Rheumatoid Arthritis.
Transplantation involves transferring cells or tissues between individuals and can be lifesaving but also carries immunological risks. Major histocompatibility complex (MHC) proteins encoded by HLA genes are the main targets recognized by the recipient's immune system, leading to graft rejection. Careful HLA typing and screening for antibodies is crucial before transplantation to minimize immunological incompatibility between donor and recipient. Immunosuppressive drugs are used to reduce the immune response and prevent rejection after transplantation.
1) Mice lacking the gene encoding miR-122a (Mir122a-/- mice) developed steatohepatitis, fibrosis, and hepatocellular carcinoma at a high frequency and in a sex-dependent manner similar to humans.
2) Mir122a-/- mice exhibited impaired lipid metabolism including reduced expression of the microsomal triglyceride transfer protein MTTP, contributing to steatosis.
3) Restoring MTTP or miR-122a expression in Mir122a-/- mice reduced disease manifestations by reversing steatosis, inflammation, and fibrosis and improving liver function.
An antigen is any substance that reacts with lymphocytes, while immunogens generate immune responses. Haptens are small molecules that require coupling to carriers to induce responses. Antibody-antigen binding depends on weak interactions between sites on antibodies and epitopes on antigens. Antibodies are produced with a wide variety of binding sites to recognize different antigenic determinants. Factors like foreignness, size, structure, and route of administration influence a substance's immunogenicity.
This document summarizes a study examining the effect of molecules secreted by the probiotic bacterium Lactobacillus acidophilus La-5 on the ability of enterohemorrhagic Escherichia coli O157:H7 (EHEC O157) to colonize the gastrointestinal tract. Fractions of L. acidophilus La-5 cell-free spent medium inhibited the ability of EHEC O157 to adhere to epithelial cells in vitro and reduced colonization of the gastrointestinal tract and fecal shedding in a mouse model. Certain fractions remarkably reduced attaching and effacing lesions in HeLa cells and significantly inhibited bacterial adhesion to Hep-2 cells. This suggests molecules from L. acid
This study investigated the effects of cigarette smoke (CS) on the immune response to vimentin, a joint protein, in transgenic mice carrying either the rheumatoid arthritis (RA)-susceptible HLA DRB1*0401 or RA-resistant DRB1*0402 gene. The study found that CS enhanced the immune response to citrullinated vimentin in DRB1*0401 mice by increasing T cell response, antibody production, and expression of peptidyl arginine deiminase enzymes involved in citrullination. In DRB1*0402 mice, CS augmented a Th2 response and regulatory T cell numbers. The results suggest CS alters the immune response to v
Impact of MHC class I diversity on immune control of Immuno-deficiency virus ...Ramesh Pothuraju
This document summarizes a presentation on the impact of MHC class I diversity on immune control of HIV replication. It discusses how MHC class I molecules present antigens to T cells, and their role in distinguishing self from non-self. It then focuses on the central role of MHC class I molecules, particularly HLA-B alleles, in controlling HIV viral loads through CD8+ T cell responses targeting conserved HIV proteins like Gag. Polyfunctional and HLA-B restricted CD8+ T cell responses targeting Gag seem to be most effective at control of HIV replication.
The document discusses interleukin-17 (IL-17) and its role in psoriasis. It describes how IL-17 is produced by T-helper 17 cells and promotes neutrophil recruitment and defense against extracellular pathogens. Blocking IL-17 has shown efficacy in clinical trials for the treatment of psoriasis. The document also reviews the IL-17 family of cytokines and their functions, receptors, and role in immune responses.
Antigen specific T cell activation assay is one of the technologies we can provide during the one-stop service which can activate CAR-T cells for further downstream research or clinical trials. T cell activation requires at least two signals to be fully activated. The first signal is provided by the interaction of T cell antigen-specific receptor and the antigen-major histocompatibility complex (MHC).
https://www.creative-biolabs.com/car-t/antigen-specific-t-cell-activation-assay.htm
T-Cell Activation
• Concept of immune response
• T cell-mediated immune response
• B cell-mediated immune response
I. Concept of immune response
• A collective and coordinated response to the introduction of foreign substances in an individual mediated by the cells and molecules in the immune system.
II. T cell-mediated immune response
• Cell-mediated immunity is the arm of the adaptive immune response whose role is to combat infection of intracellular pathogens, such as intracellular bacteria (mycobacteria, listeria monocytogens), viruses, protozoa, etc.
Pells et al [2015] PLoS ONE 10[7] e0131102Steve Pells
This research article identifies novel human embryonic stem cell regulators based on their conserved and distinct CpG island methylation patterns. The researchers analyzed CpG island methylation in four human embryonic stem cell lines using a CpG island array and identified 1,111 CpGs that were methylated in all stem cell lines. They compared the methylation profiles to somatic tissues and mRNA expression data to identify stem cell-specific methylation patterns associated with gene expression. Genes related to transcriptional repression and activation were overrepresented among genes associated with methylated or unmethylated CpGs specifically in stem cells. Knockdown experiments confirmed that some candidate regulators induced stem cell differentiation, while overexpression modulated induced pluripotent stem cell formation
El sistema inmune innato se compone de una serie diversa de tipos de células hematopoyéticas evolutivamente antiguas, incluyendo células dendríticas, monocitos, macrófagos y granulocitos. Estas poblaciones de células colaboran entre sí, con el sistema inmune adaptativo y con las células no hematopoyéticas para promover la inmunidad, inflamación y reparación de tejidos. células linfoides innatas son los constituyentes más recientemente identificados del sistema inmune innato y han sido objeto de intensa investigación en los últimos cinco años. Resumimos los estudios que identifican formalmente células linfoides innatas y ponemos de relieve sus roles emergentes para el control de la homeostasis del tejido en el contexto de la infección, la inflamación crónica, enfermedades metabólicas y cáncer.
This document summarizes a study examining the use of biodegradable nanoparticles loaded with TGF-β and IL-2 cytokines and targeted to CD4+ cells for inducing and maintaining regulatory T cells (Tregs). The nanoparticles were able to induce CD4+ Tregs in vitro and expand their numbers in vivo. Nanoparticle-induced Tregs demonstrated enhanced stability and retained their suppressive phenotype even in inflammatory conditions, highlighting the potential of this nanoparticle approach for stabilizing Tregs to treat autoimmune disease and inflammation.
This document provides information on MHC class I and class II molecules, including their structure, function, and role in antigen presentation. It discusses that MHC class I molecules are expressed on all nucleated cells and present intracellular antigens to CD8+ T cells. MHC class II molecules are expressed primarily on antigen presenting cells and present extracellular antigens to CD4+ T cells. The peptide binding grooves of MHC class I and II molecules differ in their structure and the size of peptides they can bind.
This document contains lecture notes on major histocompatibility complex (MHC) and related topics from a biotechnology course. It discusses antigen-presenting cells, the structure and function of MHC class I and II molecules, similarities and differences between the two classes, MHC-associated genes, and important immune signaling molecules like cytokines, interleukins, interferons, and chemokines. Diagrams are included to illustrate MHC pathway and types of interferons. The notes provide an overview of key concepts in MHC and immunology for students in the biotechnology course.
CD antigens, also known as clusters of differentiation, are cell surface proteins that are used to identify and characterize cell types. Over 371 CD markers have been identified that serve important functions like cell signaling. CD markers are analyzed using techniques like flow cytometry and help diagnose diseases like leukemia by identifying abnormal levels of specific CD antigens. Key CD markers have been identified for important immune cells like T cells, B cells, granulocytes, and stem cells. Immunophenotyping using CD markers is an important application in diagnosing diseases and monitoring treatment responses.
This document describes the creation of an anti-CD33 antibody targeting Acute Myeloid Leukemia. The researchers used the Pichia Pastoris yeast expression system to produce a single-chain variable fragment (scFv) of the anti-CD33 antibody. Gel electrophoresis and SDS-PAGE analysis showed the successful production and purification of the anti-CD33 scFv protein. While further studies are still needed, the researchers were able to successfully generate an anti-CD33 antibody that may have potential therapeutic applications for Acute Myeloid Leukemia patients.
The roles of the white blood cell subset γδ t cells within the human body are yet to be fully described.
Current literature has detailed several critical functions that vary dramatically between different γδ t cells.
Understanding how these elusive cells influence our immune systems will provide an opportunity to utilise their functions to assist medical treatments for a range of pathologies including cancer, diabetes, and bacterial infections.
Please send correspondence to Philip Voyias at P.D.Voyias@Warwick.ac.uk.
NK cells play important roles in both innate and adaptive immunity. As part of the innate immune system, NK cells help control viral infections through cytotoxic killing of infected cells and by secreting cytokines like IFNγ and TNFα that activate macrophages. NK cells express activating and inhibitory receptors that allow them to distinguish healthy "self" cells from infected or abnormal cells. The balance of signals through these receptors determines whether an NK cell mounts an immune response. NK cells also contribute to adaptive immunity by developing a form of immunological memory, responding more rapidly upon secondary exposure to pathogens.
Human Leukocyte Antigens (HLA) are human MHC antigens located on chromosome 6p that show polymorphism and co-dominant expression. There are two main types of HLA antigens - HLA class I and II. HLA molecules present antigenic peptides to initiate immune responses through interactions with T-cell receptors. Certain diseases like ankylosing spondylitis are associated with particular HLA antigens due to increased relative risk, though most carriers of risk alleles do not develop diseases. Cytokines play important regulatory roles in immune responses through effects on cells like macrophages, granulocytes, and lymphocytes.
A. AGEN1884 and AGEN2041 are fully human anti-CTLA-4 antibodies that block CTLA-4 binding to CD80 and CD86, enhancing T cell activation. AGEN1884 mediates FcγRIIIA signaling while AGEN2041 mediates FcγRIIA signaling.
B. In reporter cell and PBMC assays, both antibodies potentiate IL-2 production in response to suboptimal T cell receptor stimulation. AGEN1884 combines effectively with anti-LAG3 and anti-PD-1 antibodies.
C. In animal studies, both antibodies enhanced vaccine responses and AGEN1884 combined effectively with an autologous tumor vaccine in a
This is a journal club presentation where we present good quality papers from leading journals of the world. This particular paper deals with new biomarkers for Rheumatoid Arthritis.
Transplantation involves transferring cells or tissues between individuals and can be lifesaving but also carries immunological risks. Major histocompatibility complex (MHC) proteins encoded by HLA genes are the main targets recognized by the recipient's immune system, leading to graft rejection. Careful HLA typing and screening for antibodies is crucial before transplantation to minimize immunological incompatibility between donor and recipient. Immunosuppressive drugs are used to reduce the immune response and prevent rejection after transplantation.
1) Mice lacking the gene encoding miR-122a (Mir122a-/- mice) developed steatohepatitis, fibrosis, and hepatocellular carcinoma at a high frequency and in a sex-dependent manner similar to humans.
2) Mir122a-/- mice exhibited impaired lipid metabolism including reduced expression of the microsomal triglyceride transfer protein MTTP, contributing to steatosis.
3) Restoring MTTP or miR-122a expression in Mir122a-/- mice reduced disease manifestations by reversing steatosis, inflammation, and fibrosis and improving liver function.
An antigen is any substance that reacts with lymphocytes, while immunogens generate immune responses. Haptens are small molecules that require coupling to carriers to induce responses. Antibody-antigen binding depends on weak interactions between sites on antibodies and epitopes on antigens. Antibodies are produced with a wide variety of binding sites to recognize different antigenic determinants. Factors like foreignness, size, structure, and route of administration influence a substance's immunogenicity.
This document summarizes a study examining the effect of molecules secreted by the probiotic bacterium Lactobacillus acidophilus La-5 on the ability of enterohemorrhagic Escherichia coli O157:H7 (EHEC O157) to colonize the gastrointestinal tract. Fractions of L. acidophilus La-5 cell-free spent medium inhibited the ability of EHEC O157 to adhere to epithelial cells in vitro and reduced colonization of the gastrointestinal tract and fecal shedding in a mouse model. Certain fractions remarkably reduced attaching and effacing lesions in HeLa cells and significantly inhibited bacterial adhesion to Hep-2 cells. This suggests molecules from L. acid
This study investigated the effects of cigarette smoke (CS) on the immune response to vimentin, a joint protein, in transgenic mice carrying either the rheumatoid arthritis (RA)-susceptible HLA DRB1*0401 or RA-resistant DRB1*0402 gene. The study found that CS enhanced the immune response to citrullinated vimentin in DRB1*0401 mice by increasing T cell response, antibody production, and expression of peptidyl arginine deiminase enzymes involved in citrullination. In DRB1*0402 mice, CS augmented a Th2 response and regulatory T cell numbers. The results suggest CS alters the immune response to v
Impact of MHC class I diversity on immune control of Immuno-deficiency virus ...Ramesh Pothuraju
This document summarizes a presentation on the impact of MHC class I diversity on immune control of HIV replication. It discusses how MHC class I molecules present antigens to T cells, and their role in distinguishing self from non-self. It then focuses on the central role of MHC class I molecules, particularly HLA-B alleles, in controlling HIV viral loads through CD8+ T cell responses targeting conserved HIV proteins like Gag. Polyfunctional and HLA-B restricted CD8+ T cell responses targeting Gag seem to be most effective at control of HIV replication.
The document discusses interleukin-17 (IL-17) and its role in psoriasis. It describes how IL-17 is produced by T-helper 17 cells and promotes neutrophil recruitment and defense against extracellular pathogens. Blocking IL-17 has shown efficacy in clinical trials for the treatment of psoriasis. The document also reviews the IL-17 family of cytokines and their functions, receptors, and role in immune responses.
Antigen specific T cell activation assay is one of the technologies we can provide during the one-stop service which can activate CAR-T cells for further downstream research or clinical trials. T cell activation requires at least two signals to be fully activated. The first signal is provided by the interaction of T cell antigen-specific receptor and the antigen-major histocompatibility complex (MHC).
https://www.creative-biolabs.com/car-t/antigen-specific-t-cell-activation-assay.htm
T-Cell Activation
• Concept of immune response
• T cell-mediated immune response
• B cell-mediated immune response
I. Concept of immune response
• A collective and coordinated response to the introduction of foreign substances in an individual mediated by the cells and molecules in the immune system.
II. T cell-mediated immune response
• Cell-mediated immunity is the arm of the adaptive immune response whose role is to combat infection of intracellular pathogens, such as intracellular bacteria (mycobacteria, listeria monocytogens), viruses, protozoa, etc.
Pells et al [2015] PLoS ONE 10[7] e0131102Steve Pells
This research article identifies novel human embryonic stem cell regulators based on their conserved and distinct CpG island methylation patterns. The researchers analyzed CpG island methylation in four human embryonic stem cell lines using a CpG island array and identified 1,111 CpGs that were methylated in all stem cell lines. They compared the methylation profiles to somatic tissues and mRNA expression data to identify stem cell-specific methylation patterns associated with gene expression. Genes related to transcriptional repression and activation were overrepresented among genes associated with methylated or unmethylated CpGs specifically in stem cells. Knockdown experiments confirmed that some candidate regulators induced stem cell differentiation, while overexpression modulated induced pluripotent stem cell formation
El sistema inmune innato se compone de una serie diversa de tipos de células hematopoyéticas evolutivamente antiguas, incluyendo células dendríticas, monocitos, macrófagos y granulocitos. Estas poblaciones de células colaboran entre sí, con el sistema inmune adaptativo y con las células no hematopoyéticas para promover la inmunidad, inflamación y reparación de tejidos. células linfoides innatas son los constituyentes más recientemente identificados del sistema inmune innato y han sido objeto de intensa investigación en los últimos cinco años. Resumimos los estudios que identifican formalmente células linfoides innatas y ponemos de relieve sus roles emergentes para el control de la homeostasis del tejido en el contexto de la infección, la inflamación crónica, enfermedades metabólicas y cáncer.
This document summarizes a study examining the use of biodegradable nanoparticles loaded with TGF-β and IL-2 cytokines and targeted to CD4+ cells for inducing and maintaining regulatory T cells (Tregs). The nanoparticles were able to induce CD4+ Tregs in vitro and expand their numbers in vivo. Nanoparticle-induced Tregs demonstrated enhanced stability and retained their suppressive phenotype even in inflammatory conditions, highlighting the potential of this nanoparticle approach for stabilizing Tregs to treat autoimmune disease and inflammation.
This study assessed regulatory T cells (Tregs) in patients with acute and recovered hepatitis E virus (HEV) infection compared to healthy controls. The study found elevated levels of Foxp3 mRNA and Foxp3+ Tregs in both patient groups compared to controls. Levels of the immunosuppressive cytokines IL-10 and TGF-β were also elevated in acute patients. Tregs from patients exhibited higher suppressive activity and expressed higher levels of immune inhibitory markers compared to controls. These findings suggest Tregs play an immunosuppressive role in self-limiting HEV infection through elevated Foxp3 expression and cytokine production.
1) WASp-deficient dendritic cells (DCs) show impaired activation of naive CD8+ T cells, especially at low antigen doses.
2) This is partly due to altered trafficking of antigen-bearing DCs from the periphery to lymph nodes. However, correcting DC migration does not fully rescue T cell activation.
3) In vitro and in vivo imaging revealed that cytoskeletal alterations in WASp-null DCs reduce their ability to form and maintain conjugates with naive CD8+ T cells in lymph nodes, contributing to defective T cell priming.
current understanding of the immunological changes and adaptations that occur in pregnancy enabling tolerance to the foreign paternal fetal antigens in the maternal uterus
In 3 sentences or less:
The document analyzes how anthrax and plague biowarfare vaccines interact with human dendritic cells. It finds that while the plague vaccine strongly induces dendritic cell maturation and stimulates immune responses, the anthrax vaccine is a poor stimulator of dendritic cell maturation and cytokine production. However, the anthrax vaccine can stimulate T cell responses when combined with an adjuvant like pertussis, supporting the use of adjuvants to enhance the immune response to suboptimal vaccines.
1) The document discusses tumor immunology and mechanisms of tumor immune evasion. It describes how tumors can downregulate MHC expression, secrete immunosuppressive factors, inhibit T cell function through checkpoint pathways like PD-1/PD-L1, and recruit immunosuppressive cells like Tregs.
2) Checkpoint pathways like CTLA-4 and PD-1 normally regulate T cell activation, but tumors can exploit these pathways to evade immune destruction by overexpressing ligands that bind these inhibitory receptors.
3) Several immunotherapies targeting CTLA-4 and PD-1/PD-L1 have been developed including ipilimumab, nivolumab, pembrol
This document summarizes combined immunodeficiency (CID), a disorder characterized by defects in the production or maturation of T cells and/or B cells, leaving the body without necessary immunity. There are two main types of CID - mutagenic defects due to genetic mutations and enzyme deficiencies from lack of enzymes. Mutagenic CIDs can be autosomal recessive or X-linked. Treatments discussed include bone marrow transplantation, gene therapy, passive antibody administration, and enzyme replacement.
Major histocompatibility complex (MHC) molecules display antigen peptides on the cell surface to be recognized by T cells, and MHC genes are a major genetic contributor to autoimmune diseases. MHC genes are highly polymorphic, expressed from both alleles, and mediate antigen presentation and interactions between immune cells. T cell receptors recognize antigen peptides presented by MHC to activate T cells and induce adaptive immune responses, including cell-mediated immunity which destroys intracellular pathogens. The five classes of antibodies - IgG, IgA, IgM, IgD, and IgE - vary in structure and function, with IgG being most prevalent and IgA protecting mucosal surfaces.
Regulatory T-cells (Tregs) help maintain self-tolerance and prevent autoimmunity by suppressing immune responses. They express FOXP3 and CD25 and function through various mechanisms like secreting inhibitory cytokines or metabolizing IL-2. Tregs are implicated in tumor immune escape by suppressing anti-tumor immunity. While Tregs are normally beneficial, in cancer high levels associate with poor prognosis by hindering immune response. Emerging immunotherapies aim to deplete or modulate Tregs to enhance anti-tumor immunity.
The document provides an overview of the immune system, including its normal functions, divisions, components, cells, molecules, and regulation. The key points are:
- The immune system protects against pathogens and prevents reinfection through immunological memory. Its divisions are the innate and adaptive systems.
- The innate system provides first response via nonspecific defenses like skin, phagocytes, and natural killer cells. The adaptive system responds antigen-specifically via T and B cells.
- T cells recognize antigen via T cell receptors and MHC molecules and mediate cellular immunity. B cells recognize antigen directly and produce antibodies for humoral immunity.
- Cytokines mediate communication between immune cells, directing immune responses. Regulatory
The document discusses anti-cancer immunity from an immune perspective. It covers topics like cancer immunoediting, how cancer cells become resistant to immune elimination, and different anti-cancer immunotherapy strategies. Specifically:
1) Cancers evolve to escape immune detection through a process called immunoediting where immunogenic tumor cells are eliminated, leaving behind immune-resistant cells.
2) Tumor cells can become resistant by losing antigen expression or failing to present antigens on MHC molecules, allowing them to evade T cell attack.
3) Popular immunotherapies include immune checkpoint blockade, adoptive cell transfer, vaccines, and strategies that non-specifically stimulate the immune system.
This document outlines different types of regulatory T cells, including their identification, mechanisms of function, development processes, and properties. It discusses natural regulatory T cells that develop in the thymus and express high levels of CD25 and FoxP3, as well as induced regulatory T cells that develop in the periphery, including Tr1 cells that produce high levels of IL-10 and TGF-β, and Th3 cells that are induced following oral antigen administration and secrete TGF-β. The document also reviews CD8+ regulatory T cells and NKT regulatory cells, and compares the phenotypes, suppression mechanisms, targets, and roles of the different regulatory T cell subsets.
1) Dendritic cells can use IgE and the high-affinity IgE receptor FcεRI to uptake and cross-present soluble antigens to cytotoxic T cells at very low antigen doses.
2) This IgE/FcεRI-mediated cross-presentation pathway efficiently induces cytotoxic T cell proliferation and granzyme B production in response to soluble antigens.
3) Using tumor antigen-specific IgE and dendritic cell-based vaccination experiments in vivo, the authors demonstrate that IgE/FcεRI-mediated cross-presentation significantly improves anti-tumor immune responses and induces memory responses.
IMMUNOLOGICAL FUNTIONS OF LYMPHOCYTES AND ITS CLINICAL IMPLICATION final cop...satwat54
This document discusses the immunological functions of lymphocytes and their clinical implications. It begins by describing the different types of lymphoid precursor cells including T cells, B cells, natural killer cells, and plasmacytoid dendritic cells. It then discusses T cell and B cell maturation processes and the roles of different T cell and B cell subtypes. Key points covered include T cell stimulation pathways, memory T cell populations, immunoglobulin classes, and the functions of natural killer cells and plasmacytoid dendritic cells. The document concludes by examining disorders of lymphocytes including primary immunodeficiencies affecting T cells and B cells such as SCID, DiGeorge syndrome, and common variable immunodeficiency.
Combining Old and New: Sensitising Drugs and Other Vaccines To Augment Effica...NeuroAcademy
1) The document discusses combining existing drugs and vaccines like levamisole, BCG, imiquimod, mifamurtide, and dendritic cell vaccines to augment the efficacy of dendritic cell immunotherapy.
2) It provides details on the mechanisms and effects of these drugs, including how they stimulate immune responses and dendritic cell activation.
3) Experimental results are presented showing improved survival rates in cancer patients receiving combined immunotherapy and chemotherapy compared to immunotherapy alone.
Cytokines play an important role in regulating lymphocyte development and differentiation. The authors identified a cytokine-inducible protein called Cybr that binds to and regulates the activity of cytohesin-1. Cybr expression is increased by IL-2 and IL-12 and is most abundant in hematopoietic cells and tissues. Cybr physically interacts with cytohesin-1 through their coiled-coil domains and enhances cytohesin-1's ability to catalyze guanine nucleotide exchange on ARF GTPases. As Cybr modifies the activity of cytohesin-1, the authors designate it as a cytohesin binder and regulator.
This document summarizes a study that screened an antibody library to identify antibodies that could induce protective immune responses by targeting dendritic cells. The screening identified an antibody against CD36, a receptor expressed on CD8α+ dendritic cells. The antibody was linked to the model antigen OVA and shown to deliver the antigen for both MHC class I and II processing in vitro and in vivo. Immunization with the anti-CD36-OVA antibody induced robust activation of naive CD4+ and CD8+ T cells and differentiation of primed CD8+ T cells into long-term effector cytotoxic T lymphocytes. Vaccination protected against tumor growth in a tumor-specific antigen model. Targeting CD36 was qualitatively different than targeting DEC