The document discusses neuroimmunology and provides information on the immune system and its normal functions and disorders. It describes the innate and adaptive immune systems, including skin, phagocytes, natural killer cells, the complement system, antibodies, B cells, antigen presenting cells, major histocompatibility complex, toll-like receptors, T lymphocytes, cluster of differentiation markers, cytokines, chemokines, initiation and regulation of the immune response, termination of the immune response, self-tolerance, central tolerance, peripheral tolerance, anergy, regulatory T cells, immune privilege in the central nervous system, and several immune-mediated disorders of the nervous system including multiple sclerosis, myasthenia gravis, Guillain-Barré syndrome
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
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.
Immune tolerance is induced through central and peripheral mechanisms that eliminate or suppress self-reactive immune cells. Central tolerance occurs in the thymus and bone marrow where high-affinity self-reactive T and B cells undergo apoptosis or receptor editing. Peripheral tolerance includes anergy induction, suppression by regulatory T cells (Tregs), and inhibition by receptors like CTLA-4 and PD-1. Tregs expressing the transcription factor FoxP3 are critical for maintaining tolerance and preventing autoimmunity. Failure of these tolerance mechanisms can lead to autoimmune disease.
The document summarizes the major histocompatibility complex (MHC). It discusses how the MHC was discovered through studies of tissue transplantation in mice. The MHC locus contains genes that encode MHC class I and class II molecules that present antigens to T cells and play a key role in immune responses. MHC molecules are expressed on nearly all nucleated cells for class I and specifically on antigen presenting cells for class II. The genomic organization and structures of MHC class I and II molecules allow them to present peptides to CD8+ or CD4+ T cells, respectively.
An undergraduate lecture on immunologic tolerance, it's various types and how a breakdown of tolerance contributes to the pathogenesis of autoimmune diseases. Additionally a small quiz at the end to gauge the students' learning.
Hyper IgM syndrome is caused by defects in class switch recombination that result in low IgG, IgA, and IgE levels but normal or elevated IgM. The main types are X-linked CD40 ligand deficiency and autosomal recessive deficiencies in CD40, activation-induced cytidine deaminase, and uracil-N-glycosylase. These defects impair antibody-mediated immunity and predispose patients to recurrent bacterial infections as well as opportunistic infections. Patients may also experience autoimmunity, lymphoid hyperplasia, and other complications. Definitive diagnosis involves genetic and immunological testing.
This document outlines the molecular basis and clinical manifestations of different types of hyper-IgM syndrome. It discusses 6 types of HIGM defined by genetic defects such as CD40L, AICDA, CD40, and UNG deficiencies. The clinical features include recurrent infections, enlarged lymph nodes, impaired class switch recombination, and variable defects in somatic hypermutation. Diagnosis involves assessing serum immunoglobulin levels and identifying genetic mutations associated with each type.
This document discusses immunological tolerance and regulatory T cells. It defines tolerance as unresponsiveness to antigen induced by previous exposure. Central tolerance occurs in the thymus through deletion of self-reactive T cells. Peripheral tolerance occurs through several mechanisms in tissues, including regulatory T cells that suppress immune responses. The key transcription factor controlling regulatory T cells is FOXP3. Mutations in FOXP3 can lead to immune dysregulation diseases like IPEX syndrome.
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
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.
Immune tolerance is induced through central and peripheral mechanisms that eliminate or suppress self-reactive immune cells. Central tolerance occurs in the thymus and bone marrow where high-affinity self-reactive T and B cells undergo apoptosis or receptor editing. Peripheral tolerance includes anergy induction, suppression by regulatory T cells (Tregs), and inhibition by receptors like CTLA-4 and PD-1. Tregs expressing the transcription factor FoxP3 are critical for maintaining tolerance and preventing autoimmunity. Failure of these tolerance mechanisms can lead to autoimmune disease.
The document summarizes the major histocompatibility complex (MHC). It discusses how the MHC was discovered through studies of tissue transplantation in mice. The MHC locus contains genes that encode MHC class I and class II molecules that present antigens to T cells and play a key role in immune responses. MHC molecules are expressed on nearly all nucleated cells for class I and specifically on antigen presenting cells for class II. The genomic organization and structures of MHC class I and II molecules allow them to present peptides to CD8+ or CD4+ T cells, respectively.
An undergraduate lecture on immunologic tolerance, it's various types and how a breakdown of tolerance contributes to the pathogenesis of autoimmune diseases. Additionally a small quiz at the end to gauge the students' learning.
Hyper IgM syndrome is caused by defects in class switch recombination that result in low IgG, IgA, and IgE levels but normal or elevated IgM. The main types are X-linked CD40 ligand deficiency and autosomal recessive deficiencies in CD40, activation-induced cytidine deaminase, and uracil-N-glycosylase. These defects impair antibody-mediated immunity and predispose patients to recurrent bacterial infections as well as opportunistic infections. Patients may also experience autoimmunity, lymphoid hyperplasia, and other complications. Definitive diagnosis involves genetic and immunological testing.
This document outlines the molecular basis and clinical manifestations of different types of hyper-IgM syndrome. It discusses 6 types of HIGM defined by genetic defects such as CD40L, AICDA, CD40, and UNG deficiencies. The clinical features include recurrent infections, enlarged lymph nodes, impaired class switch recombination, and variable defects in somatic hypermutation. Diagnosis involves assessing serum immunoglobulin levels and identifying genetic mutations associated with each type.
This document discusses immunological tolerance and regulatory T cells. It defines tolerance as unresponsiveness to antigen induced by previous exposure. Central tolerance occurs in the thymus through deletion of self-reactive T cells. Peripheral tolerance occurs through several mechanisms in tissues, including regulatory T cells that suppress immune responses. The key transcription factor controlling regulatory T cells is FOXP3. Mutations in FOXP3 can lead to immune dysregulation diseases like IPEX syndrome.
The immune system plays an important role in tumor immunity by recognizing and destroying tumor cells. However, tumors have developed several mechanisms to evade the immune system. Tumors express a variety of tumor antigens that can elicit an immune response, but they often downregulate antigen expression or lose antigenicity over time. Additionally, tumors employ immunosuppressive strategies like increasing immunosuppressive cytokines or reducing co-stimulatory molecules to avoid immune detection and destruction. While immune surveillance exists, tumors have found ways to circumvent it through immune escape mechanisms.
1. Hematopoietic stem cells give rise to common lymphoid progenitors which differentiate into pro-B and pro-T cells.
2. Commitment to the B or T cell lineage is regulated by distinct transcription factors and cytokines direct proliferation of early lymphocytes.
3. Positive and negative selection during maturation ensure lymphocytes express functional receptors with low self-reactivity.
This document provides an overview of cells of the immune system. It discusses the origins of immune cells in the bone marrow and their classification into myeloid and lymphoid lineages. Key immune cells are described, including B cells, T cells, NK cells, macrophages, neutrophils, eosinophils, basophils, monocytes, dendritic cells and their roles in adaptive and innate immunity. The adaptive immune response is mediated by lymphocytes, specifically B and T cells, while the innate response involves phagocytic cells and NK cells.
This document summarizes various conditions that can cause secondary immunodeficiencies. It discusses how extreme ages like prematurity can impact immune system development. Conditions that cause protein or lymphatic losses like nephrotic syndrome and intestinal lymphangiectasia are described. Syndromes like Down syndrome that are associated with immune abnormalities are outlined. The document also reviews how undernutrition, overnutrition, and metabolic diseases like diabetes can negatively influence immunity.
The presentation outlines aspects of immunity against cancer, evasion strategies by cells, immunotherapy in cancer, cancer vaccines etc. Download and view the slideshow for better experience.
Prepared in Sept 2014
The document discusses immuno-oncology and the relationship between cancer and the immune system. It provides an overview of topics that will be covered in an upcoming webinar, including advances in immuno-oncology for different cancer types and combination immunotherapy approaches. The document then reviews key topics in more depth, including how immuno-oncology focuses on improving the body's immune response against cancer and recent immunotherapy approvals. It also discusses how cancer can evade the immune system and strategies for cancer immunotherapy, such as manipulating co-stimulatory signals, enhancing antigen presenting cells, and using cytokines, monoclonal antibodies, and cancer vaccines.
The innate immune response is the first line of defense against infection and predates the adaptive immune response. It uses germline-encoded pattern recognition receptors (PRRs) to recognize pathogen-associated molecular patterns (PAMPs) and initiate a proinflammatory response. The major PRR families are Toll-like receptors (TLRs), RIG-I-like receptors (RLRs), NOD-like receptors (NLRs), and C-type lectin receptors (CLRs). TLRs recognize bacteria and viruses at the cell surface and within endosomes, and signal through either the MyD88 or TRIF adaptor pathways to induce inflammatory cytokines and type I interferons. NLRs and RLRs function
The document summarizes key principles of the adaptive immune response. It describes how adaptive immunity arose due to limitations of innate immunity, including lack of specificity and memory. The adaptive response involves T and B lymphocytes that recognize specific antigens through cell surface receptors. Activation of T and B cells requires recognition of antigen along with costimulatory signals. This leads to clonal expansion and generation of effector cells and immunological memory. Adaptive immunity allows for tailored, amplified responses with self/non-self discrimination and immunological memory.
Secondary Immunodeficiency
By Dr. Usama Ragab Youssif
Reference: Included in Slides
Include causes of secondary immunodeficiency including AIDS and other viral infections
This lecture discusses how the immune system responds to tumors and how tumors evade the immune system. It covers various types of tumor antigens recognized by the immune system, including products of mutated genes, overexpressed proteins, and oncofetal antigens. The immune system mounts cellular and humoral responses against tumors through cytotoxic T cells, NK cells, macrophages, and antibodies. However, tumors have developed mechanisms to evade the immune system, such as antigen loss, lack of costimulation, immunosuppression, and inducing T cell apoptosis. Understanding the immune response and evasion is crucial for developing immunotherapies against cancer.
Central tolerance refers to deletion of self-reactive T and B cells in the thymus and bone marrow during maturation. T cells that recognize self antigens undergo apoptosis in the thymus. Peripheral tolerance uses backup mechanisms like clonal deletion through activation-induced cell death, clonal anergy from lack of co-stimulation, and suppression by regulatory T cells. These mechanisms help prevent autoimmune disease by silencing self-reactive cells that escape central tolerance.
This document provides an overview of principles of cancer immunotherapy. It discusses anti-cancer immunity mechanisms like antigen presentation and T cell activation. It also examines how cancers can evade the immune system through strategies like low MHC expression and immunosuppressive factors. The document then reviews clinical applications of immunotherapy including cytokines, monoclonal antibodies, adoptive cell transfer, vaccines, and checkpoint inhibitors. Combination therapies are showing promise for enhancing anti-tumor responses.
IMMUNE RESPONSE TO TUMORS-Humoral immunity
-Cellular Immunity- Failure of Host Defenses
- Evasion of Immune Responses by Tumors
- Cancer Immunosurveillance vs Immunoediting- Immunotherapy
This document summarizes various cytokine mediators and their functions. It discusses how cytokines are produced by different cell types and mediate effects through autocrine, paracrine and endocrine signaling. Specific cytokines discussed include interleukins (IL), interferons, tumor necrosis factor (TNF), and colony stimulating factors (CSFs). The roles of various cytokines in innate immunity, lymphocyte differentiation, and inflammation are described. Clinical uses of certain cytokines like IL-2, IL-11, anti-TNF antibodies, and GM-CSF are also mentioned.
Regulatory T cells (Tregs) play an important role in maintaining immune tolerance and suppressing excessive immune responses. Tregs can develop naturally in the thymus or be induced in the periphery. They express the transcription factor FoxP3 and surface markers CD4 and CD25. Tregs suppress the activation and functions of other immune cells and help prevent autoimmunity, control infections, allow transplantation tolerance, and support fetal-maternal tolerance in pregnancy. Dysregulation of Tregs has been linked to immunological diseases. Therapeutic use of Tregs may help treat diseases driven by excessive immune responses like autoimmunity.
Cytokines are low molecular weight proteins or peptides that are important signaling molecules that regulate immunity and inflammation. They act as intercellular messengers to regulate the intensity and duration of immune responses by binding to receptors on target cells. There are four main structural families of cytokines - hematopoietin receptor family, interferon receptor family, TNF receptor family, and chemokine receptor family. Cytokines can act through autocrine, paracrine, or endocrine signaling and activate signaling pathways like JAK-STAT. An imbalance in the levels of cytokines produced by TH1 and TH2 cells can lead to different disease outcomes. Cytokine-related diseases include septic shock, toxic shock syndrome, and some cancers and infections.
The document discusses adaptive immunity and the specific immune response. It describes how adaptive immunity provides lifelong protective immunity through antigen-specific responses that are mediated by lymphocytes, including B cells, T cells, helper T cells, and killer T cells. Lymphocytes have antigen receptors like the B cell receptor and T cell receptor that provide specificity. The adaptive immune response develops over a person's lifetime through somatic recombination and clonal selection that generates a diverse repertoire of lymphocytes each with a unique receptor.
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. Cytotoxic T-cells target many HIV proteins but often cannot eliminate the virus due to epitope escape, exhaustion, or suboptimal responses. Antibody responses have difficulty neutralizing HIV due to properties of the gp120 and gp41 envelope proteins. The immune response ultimately fails to clear HIV because the virus can integrate into genes, mutate, and impair antigen presenting cell function.
1) Antigen presenting cells (APCs) such as dendritic cells, macrophages, and B cells present antigen peptides on their surfaces to activate T cells.
2) APCs capture antigens through phagocytosis, pinocytosis, or receptor-mediated endocytosis and process the antigens into peptides.
3) The peptides are then presented on either MHC class I or MHC class II molecules for recognition by CD8+ or CD4+ T cells respectively, initiating an adaptive immune response.
The document summarizes the structure and function of the immune system. It describes the cells involved including lymphocytes, macrophages, dendritic cells, granulocytes, and plasma cells. It discusses the development and maturation of lymphocytes in primary and secondary lymphoid organs like the bone marrow, thymus, and lymph nodes. It also describes the activation of T cells and B cells, antigen presentation, and the roles of cytokines in immune responses.
1) Antigen processing and presentation involves extracellular and intracellular proteins being degraded into peptides and bound to MHC class I or II molecules. These peptide-MHC complexes are expressed on antigen presenting cells and recognized by T cells to initiate an immune response.
2) T cells are activated through recognition of peptide-MHC complexes by their T cell receptors along with co-stimulatory signals. Activated T cells proliferate and differentiate into effector and memory T cells.
3) Effector T cells stimulate immune responses like activating macrophages to kill intracellular pathogens, leading to delayed type hypersensitivity reactions which can cause tissue damage if infection is not resolved.
The immune system plays an important role in tumor immunity by recognizing and destroying tumor cells. However, tumors have developed several mechanisms to evade the immune system. Tumors express a variety of tumor antigens that can elicit an immune response, but they often downregulate antigen expression or lose antigenicity over time. Additionally, tumors employ immunosuppressive strategies like increasing immunosuppressive cytokines or reducing co-stimulatory molecules to avoid immune detection and destruction. While immune surveillance exists, tumors have found ways to circumvent it through immune escape mechanisms.
1. Hematopoietic stem cells give rise to common lymphoid progenitors which differentiate into pro-B and pro-T cells.
2. Commitment to the B or T cell lineage is regulated by distinct transcription factors and cytokines direct proliferation of early lymphocytes.
3. Positive and negative selection during maturation ensure lymphocytes express functional receptors with low self-reactivity.
This document provides an overview of cells of the immune system. It discusses the origins of immune cells in the bone marrow and their classification into myeloid and lymphoid lineages. Key immune cells are described, including B cells, T cells, NK cells, macrophages, neutrophils, eosinophils, basophils, monocytes, dendritic cells and their roles in adaptive and innate immunity. The adaptive immune response is mediated by lymphocytes, specifically B and T cells, while the innate response involves phagocytic cells and NK cells.
This document summarizes various conditions that can cause secondary immunodeficiencies. It discusses how extreme ages like prematurity can impact immune system development. Conditions that cause protein or lymphatic losses like nephrotic syndrome and intestinal lymphangiectasia are described. Syndromes like Down syndrome that are associated with immune abnormalities are outlined. The document also reviews how undernutrition, overnutrition, and metabolic diseases like diabetes can negatively influence immunity.
The presentation outlines aspects of immunity against cancer, evasion strategies by cells, immunotherapy in cancer, cancer vaccines etc. Download and view the slideshow for better experience.
Prepared in Sept 2014
The document discusses immuno-oncology and the relationship between cancer and the immune system. It provides an overview of topics that will be covered in an upcoming webinar, including advances in immuno-oncology for different cancer types and combination immunotherapy approaches. The document then reviews key topics in more depth, including how immuno-oncology focuses on improving the body's immune response against cancer and recent immunotherapy approvals. It also discusses how cancer can evade the immune system and strategies for cancer immunotherapy, such as manipulating co-stimulatory signals, enhancing antigen presenting cells, and using cytokines, monoclonal antibodies, and cancer vaccines.
The innate immune response is the first line of defense against infection and predates the adaptive immune response. It uses germline-encoded pattern recognition receptors (PRRs) to recognize pathogen-associated molecular patterns (PAMPs) and initiate a proinflammatory response. The major PRR families are Toll-like receptors (TLRs), RIG-I-like receptors (RLRs), NOD-like receptors (NLRs), and C-type lectin receptors (CLRs). TLRs recognize bacteria and viruses at the cell surface and within endosomes, and signal through either the MyD88 or TRIF adaptor pathways to induce inflammatory cytokines and type I interferons. NLRs and RLRs function
The document summarizes key principles of the adaptive immune response. It describes how adaptive immunity arose due to limitations of innate immunity, including lack of specificity and memory. The adaptive response involves T and B lymphocytes that recognize specific antigens through cell surface receptors. Activation of T and B cells requires recognition of antigen along with costimulatory signals. This leads to clonal expansion and generation of effector cells and immunological memory. Adaptive immunity allows for tailored, amplified responses with self/non-self discrimination and immunological memory.
Secondary Immunodeficiency
By Dr. Usama Ragab Youssif
Reference: Included in Slides
Include causes of secondary immunodeficiency including AIDS and other viral infections
This lecture discusses how the immune system responds to tumors and how tumors evade the immune system. It covers various types of tumor antigens recognized by the immune system, including products of mutated genes, overexpressed proteins, and oncofetal antigens. The immune system mounts cellular and humoral responses against tumors through cytotoxic T cells, NK cells, macrophages, and antibodies. However, tumors have developed mechanisms to evade the immune system, such as antigen loss, lack of costimulation, immunosuppression, and inducing T cell apoptosis. Understanding the immune response and evasion is crucial for developing immunotherapies against cancer.
Central tolerance refers to deletion of self-reactive T and B cells in the thymus and bone marrow during maturation. T cells that recognize self antigens undergo apoptosis in the thymus. Peripheral tolerance uses backup mechanisms like clonal deletion through activation-induced cell death, clonal anergy from lack of co-stimulation, and suppression by regulatory T cells. These mechanisms help prevent autoimmune disease by silencing self-reactive cells that escape central tolerance.
This document provides an overview of principles of cancer immunotherapy. It discusses anti-cancer immunity mechanisms like antigen presentation and T cell activation. It also examines how cancers can evade the immune system through strategies like low MHC expression and immunosuppressive factors. The document then reviews clinical applications of immunotherapy including cytokines, monoclonal antibodies, adoptive cell transfer, vaccines, and checkpoint inhibitors. Combination therapies are showing promise for enhancing anti-tumor responses.
IMMUNE RESPONSE TO TUMORS-Humoral immunity
-Cellular Immunity- Failure of Host Defenses
- Evasion of Immune Responses by Tumors
- Cancer Immunosurveillance vs Immunoediting- Immunotherapy
This document summarizes various cytokine mediators and their functions. It discusses how cytokines are produced by different cell types and mediate effects through autocrine, paracrine and endocrine signaling. Specific cytokines discussed include interleukins (IL), interferons, tumor necrosis factor (TNF), and colony stimulating factors (CSFs). The roles of various cytokines in innate immunity, lymphocyte differentiation, and inflammation are described. Clinical uses of certain cytokines like IL-2, IL-11, anti-TNF antibodies, and GM-CSF are also mentioned.
Regulatory T cells (Tregs) play an important role in maintaining immune tolerance and suppressing excessive immune responses. Tregs can develop naturally in the thymus or be induced in the periphery. They express the transcription factor FoxP3 and surface markers CD4 and CD25. Tregs suppress the activation and functions of other immune cells and help prevent autoimmunity, control infections, allow transplantation tolerance, and support fetal-maternal tolerance in pregnancy. Dysregulation of Tregs has been linked to immunological diseases. Therapeutic use of Tregs may help treat diseases driven by excessive immune responses like autoimmunity.
Cytokines are low molecular weight proteins or peptides that are important signaling molecules that regulate immunity and inflammation. They act as intercellular messengers to regulate the intensity and duration of immune responses by binding to receptors on target cells. There are four main structural families of cytokines - hematopoietin receptor family, interferon receptor family, TNF receptor family, and chemokine receptor family. Cytokines can act through autocrine, paracrine, or endocrine signaling and activate signaling pathways like JAK-STAT. An imbalance in the levels of cytokines produced by TH1 and TH2 cells can lead to different disease outcomes. Cytokine-related diseases include septic shock, toxic shock syndrome, and some cancers and infections.
The document discusses adaptive immunity and the specific immune response. It describes how adaptive immunity provides lifelong protective immunity through antigen-specific responses that are mediated by lymphocytes, including B cells, T cells, helper T cells, and killer T cells. Lymphocytes have antigen receptors like the B cell receptor and T cell receptor that provide specificity. The adaptive immune response develops over a person's lifetime through somatic recombination and clonal selection that generates a diverse repertoire of lymphocytes each with a unique receptor.
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. Cytotoxic T-cells target many HIV proteins but often cannot eliminate the virus due to epitope escape, exhaustion, or suboptimal responses. Antibody responses have difficulty neutralizing HIV due to properties of the gp120 and gp41 envelope proteins. The immune response ultimately fails to clear HIV because the virus can integrate into genes, mutate, and impair antigen presenting cell function.
1) Antigen presenting cells (APCs) such as dendritic cells, macrophages, and B cells present antigen peptides on their surfaces to activate T cells.
2) APCs capture antigens through phagocytosis, pinocytosis, or receptor-mediated endocytosis and process the antigens into peptides.
3) The peptides are then presented on either MHC class I or MHC class II molecules for recognition by CD8+ or CD4+ T cells respectively, initiating an adaptive immune response.
The document summarizes the structure and function of the immune system. It describes the cells involved including lymphocytes, macrophages, dendritic cells, granulocytes, and plasma cells. It discusses the development and maturation of lymphocytes in primary and secondary lymphoid organs like the bone marrow, thymus, and lymph nodes. It also describes the activation of T cells and B cells, antigen presentation, and the roles of cytokines in immune responses.
1) Antigen processing and presentation involves extracellular and intracellular proteins being degraded into peptides and bound to MHC class I or II molecules. These peptide-MHC complexes are expressed on antigen presenting cells and recognized by T cells to initiate an immune response.
2) T cells are activated through recognition of peptide-MHC complexes by their T cell receptors along with co-stimulatory signals. Activated T cells proliferate and differentiate into effector and memory T cells.
3) Effector T cells stimulate immune responses like activating macrophages to kill intracellular pathogens, leading to delayed type hypersensitivity reactions which can cause tissue damage if infection is not resolved.
Cell mediated immunity- a part of general immunology.pptxBlackSheep31
Cell mediated immunity is mediated by effector T cells such as cytotoxic T lymphocytes and helper T cells. It provides protection against intracellular pathogens and tumor cells. Antigen presentation to T cells is required for CMI responses, which involves processing antigens into peptides that are presented by MHC class I or II molecules. Activated helper T cells secrete cytokines that stimulate and regulate CMI and humoral immunity responses.
The document discusses an anti-radiation vaccine technology involving Dmitri Popov, Maliev Slava, and Jeffrey Jones. It summarizes the roles of white blood cells (leukocytes) and their organelles (lysosomes) in presenting antigen peptides through MHC class I and II molecules to activate immune responses. Specifically, it describes how lysosome-associated membrane proteins (LAMPs) are involved in antigen processing and presentation to T cells to stimulate immune defenses against radiation and infectious agents.
IMMUNITY.pptx pathology point of view taken from roobinstejaswi71117
Immunity can be beneficial for defending the body but can also cause harm in some cases. The immune system has two types of immunity - innate (natural) and adaptive (specific). While immunity normally protects the body, problems can arise if it fails or becomes imbalanced, leading to immune disorders. The four main types of immune disorders are immunodeficiencies, hypersensitivities, autoimmune diseases, and idiopathic immune disorders.
This document provides an overview of the immune system. It begins with definitions of immunity and the historical views of disease. It then describes the innate and adaptive immune systems in detail. The innate system includes physical barriers and the complement system. Adaptive immunity involves both humoral immunity through B cells and antibodies, and cell-mediated immunity through T cell subsets. Key immune cells like macrophages and neutrophils are also summarized in terms of their functions, including phagocytosis, antigen presentation, and cytokine secretion. The document provides an extensive but concise review of immune system components and their roles in protection from pathogens.
cellular and humoral components of immune System.vinu.pptxGokulVV3
This document summarizes the cellular and humoral components of the immune system. It discusses the primary and secondary lymphoid organs where immune cells develop and interact with antigens. The key immune cells discussed are T cells, B cells, natural killer cells, macrophages, and phagocytes. T cells recognize antigens through T cell receptors and can be helper, cytotoxic or memory cells. B cells mature in the bone marrow and produce antibodies when activated. The humoral and cellular immune responses mediated by B and T cells respectively provide adaptive immunity against pathogens.
This document provides an overview of antigen processing and presentation. It discusses that antigen processing is needed to generate peptide fragments from proteins that can bind MHC molecules and be recognized by T cells. It describes the separate pathways for endogenous and exogenous antigen processing, which involve the cytosolic and endocytic pathways, respectively. The key steps in each pathway include protein degradation, peptide transport, and loading onto MHC class I or II molecules. The pathways ensure that intracellular and extracellular antigens are presented through distinct MHC complexes to CD8+ or CD4+ T cells to initiate appropriate immune responses.
The document summarizes immune responses and the processes involved. It discusses:
1) The two types of immune responses - humoral/antibody-mediated (AMI) and cell-mediated (CMI) responses. AMI responds to extracellular pathogens using antibodies while CMI responds to intracellular pathogens using T cells.
2) Helper T cell activation is central to both responses. Naive T cells are activated by antigen presentation and costimulatory signals, then differentiate into TH1 and TH2 subsets to stimulate CMI and AMI, respectively.
3) CMI involves cytotoxic T cells directly killing infected cells by releasing perforins and granzymes. Natural killer cells are also involved in CMI through nonspecific
Histology of group of immune cells that mediate the cellular immune response by processing and presenting antigens for recognition by certain lymphocytes such as T cells.
The document discusses key aspects of the immune system, including:
1) Lymphocytes like T cells, B cells, and NK cells exist with diverse antigen receptors before exposure to allow recognition of a wide range of foreign antigens.
2) Antigens trigger proliferation and differentiation of antigen-specific lymphocytes.
3) Primary lymphoid organs like the bone marrow and thymus support lymphocyte development while secondary organs like lymph nodes, spleen, and mucosa-associated lymphoid tissue induce immune responses.
introduction of adaptive immunity. classification of adaptive immunity, factor affecting it and mechanism of adaptive immunity comparison between adaptive immunity and innate immunity. characteristic of adaptive immunity . cell mediated immune responses immunoglobulins
types of immunoglobulins. functions of immunoglobulins, hypersensitivity reactions
1. The document presents information about T cells and B cells, including their development, activation, and functions.
2. T cells develop in the thymus gland and have roles in direct killing of infected cells and regulating the immune response. B cells mature in the bone marrow and produce antibodies to help fight pathogens.
3. Activation of both T and B cells involves interaction with antigen-presenting cells and costimulatory signals, leading to cell proliferation and differentiation into effector and memory cells.
The document discusses adaptive immunity and the immune response. It describes the four phases of the adaptive immune response as encounter, activation, attack, and memory. Acquired immunity develops over one's lifetime from vaccines, infections, or antibodies from others. The adaptive immune response involves B cells, helper T cells and cytotoxic T cells. It also discusses the specificity, adaptiveness, discrimination between self and non-self, and memory properties of the adaptive immune response. The major cell types involved are T helper cells, cytotoxic T cells, T memory cells, and regulatory T cells. The roles and mechanisms of these cell types are described in detail.
The document discusses adaptive immunity and the immune response. It describes the four phases of the adaptive immune response as encounter, activation, attack, and memory. Acquired immunity develops over one's lifetime from vaccines, infections, or antibodies from others. The adaptive immune response involves B cells, helper T cells and cytotoxic T cells. It also discusses the specificity, adaptiveness, discrimination between self and non-self, and memory properties of the adaptive immune response. The major cell types involved are T helper cells, cytotoxic T cells, T memory cells, and regulatory T cells. The roles and mechanisms of these cell types are described in detail.
The adaptive immune system is composed of lymphocytes that generate a diverse repertoire of antigen receptors. T cells develop in the thymus through positive and negative selection to remove self-reactive cells. CD4+ T cells help B cells and CD8+ T cells perform cytotoxic functions by killing infected, tumor, or allograft cells via perforin/granzyme release or Fas/FasL interaction. Adaptive immunity provides tailored immune responses and immunological memory.
The document summarizes key concepts of immunity, including:
1. Innate immunity provides immediate defenses through physical barriers and cells like phagocytes, while adaptive immunity provides specific responses through antibodies and T cells.
2. The immune system is composed of circulating leukocytes and lymphoid organs that bring together antigens and immune cells.
3. Adaptive immunity involves antigen presentation, lymphocyte activation, proliferation into effector and memory cells, and specialized functions of B cells, cytotoxic T cells, and helper T cells.
An integrated and brief overview of the function of human immune systemHasan Al Banna
Pathogens first must cross physical and chemical barriers before potentially infecting cells. Microbial pathogens express PAMPs that are recognized by PRRs on sentinel cells like macrophages and dendritic cells. Macrophages become activated and have two subtypes - M1 which are killer cells and M2 which aid tissue repair. Antigen presenting cells display antigens using MHC molecules and travel to lymph nodes to activate T cells. Activated T cells differentiate into effector T cells that coordinate the immune response and memory T cells that remain inactive until future infection. B cells encounter antigens, become activated and undergo proliferation and somatic hypermutation in germinal centers, then differentiate into memory B cells or plasma cells that secrete antibodies.
Recent Modalities of Neuro-imaging discusses various imaging techniques used to image the brain and spinal cord, including:
- Computed tomography perfusion which uses contrast to generate maps of cerebral blood flow, volume, and transit time to identify ischemic tissue.
- Myelography which uses intrathecal contrast for spinal imaging.
- Magnetic resonance techniques like quantitative MRI, diffusion tensor imaging, and MR spectroscopy which provide microstructural data on tissues.
- Perfusion imaging uses ultrasound contrast to assess cerebral blood flow.
Imaging findings are discussed for conditions like multiple sclerosis, epilepsy, and stroke.
This document summarizes higher cortical functions including language, calculations, spatial awareness, memory, executive function, music and creativity. It discusses the cerebral cortex and different types of association cortices. It then examines various neurological functions like sensory processing, attention, motor programming, language, memory, agnosias, apraxia, aphasia and alexia. Key areas discussed include the visual and auditory systems, object recognition networks, spatial attention, praxis, types of agnosia and aphasia, and the neuroanatomy underlying different language functions.
The document discusses the importance of carefully considering alternative diagnoses to multiple sclerosis (MS) when evaluating patients. Common causes of MS misdiagnosis include nonspecific white matter abnormalities on brain MRI and vague neurological symptoms. Other disorders like neuromyelitis optica spectrum disorders, acute disseminated encephalomyelitis, and inherited disorders can mimic MS clinically and radiologically. A thorough evaluation of demographic, clinical, laboratory, and imaging factors is necessary to avoid misdiagnosis, as an MS diagnosis has significant implications for treatment.
This document discusses remyelinating therapies for multiple sclerosis (MS). It begins by explaining how MS results in demyelination and how remyelination can restore neuronal function. Several potential remyelinating therapies currently in preclinical or clinical trials are described, including clobetasol, opicinumab, guanabenz, and olesoxime. Biomarkers for measuring remyelination like diffusion tensor imaging, magnetization transfer imaging, and positron emission tomography are also summarized. The document concludes that while challenges remain, promising remyelinating strategies exist to provide benefit throughout the entire course of MS.
approach to Dystonia and myoclonus movement disordersOsama Ragab
This document provides an overview of the clinical approach to diagnosing dystonia and myoclonus. It discusses classifying dystonia based on characteristics like distribution, temporal pattern, age of onset, and etiology. Common causes of dystonia include inherited genetic forms, acquired causes like brain injuries, and idiopathic cases. The document also outlines an 8-step approach to diagnosing myoclonus that involves determining if symptoms are truly myoclonus, identifying anatomical substrates, defining the etiology, checking for medication involvement, running routine labs and imaging, considering mitochondrial or neurodegenerative causes, and potentially using next-generation sequencing.
Alzheimer disease , is there any hope for cureOsama Ragab
- Alzheimer's disease affects over 100 million people worldwide and is projected to increase significantly by 2050. While much research has focused on amyloid plaques and tau tangles as potential causes, treatments targeting these pathways have yet to successfully slow or stop the progression of the disease.
- Alternative hypotheses for Alzheimer's causation include neuroinflammation, oxidative stress, metabolic dysfunction, and aging. Strategies targeting these pathways also have not resulted in effective treatments.
- The exact causes and mechanisms of Alzheimer's remain unclear as amyloid and tau are normal brain proteins and their roles are still being understood. Further research is still needed to determine the root causes and identify effective treatments for this devastating disease.
Systemic infections may increase the risk of stroke through several mechanisms. Bacterial infections like infective endocarditis and meningitis have been linked to strokes, often due to inflammation and endothelial injury. Viruses such as HSV, VZV, HCV and HIV can cause vasculitis and coagulopathies leading to hemorrhagic or ischemic strokes. Fungi sometimes form cerebral abscesses or invade arteries, predisposing to aneurysms and thrombosis. Parasitic infections including Chagas disease are also associated with cardioembolic strokes. Overall, infections may exacerbate traditional stroke risk factors or directly cause strokes through inflammatory and thrombotic pathways.
This document provides an overview of ischaemic stroke, including its definition, risk factors, pathophysiology, clinical presentation, diagnosis and management. Key points include:
- Ischaemic stroke accounts for 80% of strokes and results from focal brain infarction due to obstruction of cerebral blood flow.
- Major risk factors include hypertension, atrial fibrillation, diabetes, hyperlipidemia and previous stroke or TIA.
- Clinical syndromes depend on the location of brain infarction and can include motor/sensory deficits, aphasia and visual field cuts.
- Diagnosis involves neuroimaging such as CT, MRI and vascular imaging to identify the cause.
- Acute
This document summarizes recent investigations in epilepsy, including various imaging and functional techniques. Neuroimaging techniques like fMRI, DTI, and PET can help localize epileptogenic foci and assess language dominance, memory function, and metabolic changes. SPECT and ictal-interictal subtraction can identify regions of hyperperfusion during seizures. MEG can localize irritative zones from magnetic fields generated by epileptic activity. Combined with MRI, these functional techniques provide valuable information to plan management of epilepsy.
Skeletal muscle disorders can be classified as either primary muscle diseases or secondary disorders caused by other conditions like inflammation, metabolic abnormalities, or drugs. Progressive muscle dystrophies are a primary cause and include Duchenne muscular dystrophy and Becker muscular dystrophy, which are caused by mutations in the dystrophin gene. Symptoms include weakness, wasting, and pseudohypertrophy. Management focuses on rehabilitation, steroids, respiratory support, and future gene therapies. Myasthenia gravis is an autoimmune disorder where antibodies target acetylcholine receptors, causing fluctuating weakness. Diagnosis involves the Tensilon test and repetitive nerve stimulation with treatment consisting of cholinesterase inhibitors, steroids, plasma exchange,
Approach to disturbance of consciousnessOsama Ragab
This document provides an overview of consciousness and approaches to disturbances of consciousness such as coma. It defines key terms like coma, stupor, and delirium. Coma can be caused by structural brain insults, metabolic derangements, infections, drugs or toxins. The clinical approach involves stabilizing vital functions, assessing severity using scales like Glasgow Coma Scale, and evaluating for immediate life-threatening causes through diagnostic tests and empirical treatment when needed to prevent further brain damage. A thorough neurological exam evaluates factors like consciousness level, pupil size and reactivity, ocular motility, motor responses and more to localize the cause. Distinguishing features between toxic/metabolic vs. structural comas are discussed.
Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system characterized by breakdown of the myelin sheath covering nerve axons. It affects over 400,000 people in the US and more than 2.1 million worldwide. Genetic factors, autoimmunity, infection, vitamin D levels, and loss of protective childhood infections may play a role in MS etiology. Clinically, MS presents with a variety of neurological symptoms depending on the location of lesions in the brain and spinal cord, including visual, motor, sensory and cognitive impairments. Disease courses include relapsing-remitting MS, secondary progressive MS, primary progressive MS and progressive-relapsing MS.
This document discusses viral encephalitis and provides examples of imaging findings. It begins with an overview of virus structure and taxonomy. It then focuses on specific neurotropic viruses like herpesviruses. For HSV-1, imaging may show temporal and frontal lobe lesions and hemorrhage. HSV-2 commonly causes neonatal encephalitis seen as white matter abnormalities. VZV can cause meningoencephalitis, vasculitis, and leukoencephalopathy. EBV occasionally causes non-specific cortical or deep nuclei abnormalities. Overall, the document examines viral encephalitis from multiple angles including virus properties, neuroanatomy, and characteristic imaging patterns.
non motor manifestation of parkinson diseaseOsama Ragab
This document discusses non-motor symptoms of Parkinson's disease. It begins by providing background on the original description of Parkinson's disease in 1817 and defines it as primarily affecting motor functions. However, it notes that nearly 90% of Parkinson's patients experience non-motor manifestations as well, including neuropsychiatric symptoms, sleep disorders, autonomic dysfunction, sensory symptoms, and other issues. The document then examines the roles of different neurotransmitter systems including dopamine, serotonin, norepinephrine, glutamate, and GABA in both motor and non-motor features of the disease.
This document discusses the effects of epilepsy and anti-epileptic drug (AED) use on reproductive health and pregnancy outcomes. It notes that women with epilepsy have an increased risk of gestational hypertension, preterm delivery, fetal malformations, and low birthweight infants. During pregnancy, AED levels may decrease due to changes in metabolism and clearance, increasing seizure risk. Close monitoring of drug levels and seizures is recommended during pregnancy to adjust dosages as needed. Folic acid supplementation is also advised to reduce the risk of neural tube defects.
This document discusses higher cortical functions and the neuroanatomy that supports them. It describes how different areas of the cerebral cortex are involved in functions like memory, language, reasoning and more. It discusses the primary and association areas, and how they communicate to allow for complex functions. It also summarizes different types of agnosias that can occur from damage to various cortical areas, disrupting abilities like object recognition, face recognition, and spatial attention.
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Overall life span (LS) was 1671.7±1721.6 days and cumulative 5YS reached 62.4%, 10 years – 50.4%, 20 years – 44.6%. 94 LCP lived more than 5 years without cancer (LS=2958.6±1723.6 days), 22 – more than 10 years (LS=5571±1841.8 days). 67 LCP died because of LC (LS=471.9±344 days). AT significantly improved 5YS (68% vs. 53.7%) (P=0.028 by log-rank test). Cox modeling displayed that 5YS of LCP significantly depended on: N0-N12, T3-4, blood cell circuit, cell ratio factors (ratio between cancer cells-CC and blood cells subpopulations), LC cell dynamics, recalcification time, heparin tolerance, prothrombin index, protein, AT, procedure type (P=0.000-0.031). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and N0-12 (rank=1), thrombocytes/CC (rank=2), segmented neutrophils/CC (3), eosinophils/CC (4), erythrocytes/CC (5), healthy cells/CC (6), lymphocytes/CC (7), stick neutrophils/CC (8), leucocytes/CC (9), monocytes/CC (10). Correct prediction of 5YS was 100% by neural networks computing (error=0.000; area under ROC curve=1.0).
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One health condition that is becoming more common day by day is diabetes.
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2. Immune System
• Normal Functions
Immunity against micro-organisms and pathogens
Wound healing
Tumor surveillance
• Disorders Resulting from Immune System Dysfunction
Autoimmunity
Immune-mediated disorders
Graft rejection
3. Adaptive and Innate Immunity
The immune system has two functional divisions:
• The innate immune system
• The adaptive immune system.
4. Adaptive and Innate Immunity
• The innate immune system consists :
Skin: The exterior surface of the body, primarily the skin, is the body's primary defense against
foreign pathogens.
Phagocytes are cells capable of phagocytosing foreign pathogens. They include
polymorphonuclear cells, monocytes, and macrophages.
Natural killer (NK) cells—NK cells recognize cell surface molecules on virally infected or
tumor cells.
Complement system ??
5. Complement system
• They are protein synthesized in the liver.
• They are inactivated proteolysis enzymes.
• Numbered from [1- 9 ] according cascade of activation.
• When activated complement occurs it breaks down into portion eg: C5a and
C5b.
• The b segment is the large one and in turn will activate the next step in the
cascade.
7. Adaptive and Innate Immunity
The immune system has two functional divisions:
• The innate immune system
• The adaptive immune system.
8. Immunoglobulins
1. Antibodies (Igs), antibodies are able to specifically recognize a
variety of free antigens.
2. Igs are produced by B cells and are present on their cell surface.
3. Antibodies recognize specific microbial and other antigens through
their antigen-binding sites and bind to cells via their Fc receptors.
9. Immunoglobulins
4. Each molecule consists of two identical polypeptide light chains
(kappa [κ] or lambda [λ]) linked to two identical heavy chains.
6. According to the biochemical nature of the heavy chain, Igs are
divided into five main classes: IgM, IgD, IgG, IgA, and IgE. These may
be further divided into subclasses depending on differences in the heavy
chain.
12. B cells
B cells: The primary function of B cells is to produce antibody.
Antigen binding to B cells stimulates proliferation and maturation of that
particular B cell, with subsequent enhancement of antigen-specific antibody
production, resulting in the development of antibody-secreting plasma cells.
Most B cells express class II major histocompatibility complex (MHC)??
antigens and have the ability to function as APCs??
14. Major histocompatibility complex
Major histocompatibility complex gene products or the human leukocyte antigens
(HLAs) serve to distinguish self from nonself.
They serve the important function of presenting antigen to the appropriate cells.
They are classified into MHC I and II.
Class I antigens are expressed on all nucleated cells, whereas class II antigens are
constitutively expressed only on dendritic cells, macrophages, and B cells
,endothelial cells, and astrocytes.
15. Major histocompatibility complex
In humans, class I molecules are HLA-A, B, and C, whereas the class II
molecules are HLA-DP, DQ, and DR.
Each one of these subclasses has wide range of alleles.
Class I antigens regulate the specificity of cytotoxic CD8 + T cells, which
are responsible for killing cells bearing viral antigens .
The function of class II MHC gene products appears to be to regulate the
specificity of T-helper cells.
18. Toll like receptors [ TLR]
TLR are pathogen recognition
receptors .
They recognize pathogen associated
molecular pattern.
They present on cell surface and
intracellular.
19. T Lymphocytes
Differentiation of T cells occurs in the thymus, and every T cell that
leaves the thymus is conferred with a unique specificity for recognizing
antigens.
T cells may be divided into two groups on the basis of expression of
either the CD4 + or CD8 + marker????.
The first step in activation is binding to APC by T cell receptor ( TCR).
20. T Lymphocytes
The TCR consists of two glycosylated polypeptide chains, alpha (α) and
beta (β), of 45,000 and 40,000 dalton molecular weight, respectively.
T cells can only recognize short peptides that are associated with MHC
molecules.
21. T Lymphocytes
Upon stimulation of their TcR in the presence of
co-stimulatory signals?? naïve T cells in the
peripheral immune compartment develop into
different subsets of effector T helper cells.
This differentiation process is directed by a
specific cytokine milieu as indicated leading to
the expression of transcription factors specific for
the respective lineages.
22. Cluster of differentiation [ CD]
They are group of proteins
presents on cell surface which are
expressed during different stages
of maturation and differentiation.
CD were numbered 1-340
according to discovery order.
25. Organization of the Immune Response
•Initiation of the Immune Response.
•Regulation of the Immune Response
•Termination of an Immune Response
26. Initiation of the Immune Response.
1- Antigen Presentation.
2- Accessory Molecules for T-Cell Activation
3- Co-stimulatory Molecules??
4- cell migration ??
5- Accessory Molecules for B-Cell Activation??
27. Co-stimulatory Molecules
Costimulatory molecules serve as a “second signal” to facilitate T-cell activation.
Members of the integrin families including vascular cell adhesion molecule 1
(VCAM-1), intercellular adhesion molecule (ICAM-1), and leukocyte function
antigen 3 (LFA-3) can provide costimulatory signals, but they also play critical roles
in T-cell adhesion, facilitate interaction with the APCs, mediate adhesion to
nonhematopoietic cells such as endothelial cells, and guide cell traffic
29. Cell migration
Molecules primarily involved in cell migration into tissues include
chemokines, integrins, selectins, and matrix metalloproteinases (MMPs).
Chemokines constitute a large family of chemoattractant peptides that
regulate the vast spectrum of leukocyte migration events through interactions
with chemokine receptors.
The integrin family includes VCAM-1, ICAM-1, LFA-3, CD45, and CD2 and
mediates adhesion to endothelial cells and guiding cell traffic.
30. Cell migration
Selectins facilitate the rolling of leukocytes along the surface of endothelial cells .
The MMPs are a family of proteinases secreted by inflammatory cells; MMPs
digest specific components of the extracellular matrix, thereby facilitating
lymphocyte entry through basement membranes including the blood–brain barrier
(BBB).
32. Accessory Molecules for B-Cell Activation
Like T cells, B cells require accessory molecules that supplement signals
mediated through cell-surface Igs.
B cells can respond to proteins, peptides, polysaccharides, nucleic acids,
lipids, and small chemicals.
B cells responding to peptide antigens are dependent on T-cell help for
proliferation and differentiation, and these antigens are termed thymus-
dependent (T-dependent).
35. Cytokines
Cytokines are broadly divided into the following categories:
(1) growth factors such as IL-1, IL-2, IL-3, and IL-4 and colony-stimulating factors.
(2) activation factors, such as interferons (α, β, and γ, which are also antiviral).
(3) regulatory or cytotoxic factors, including IL-10, IL-12, transforming growth
factor beta (TGF-β), lymphotoxins, and tumor necrosis factor alpha (TNF-α)
(4) chemokines that are chemotactic inflammatory factors, such as IL-8,
Macrophage Inflammatory Proteins(MIP-1α, and MIP-1β).
36. Cytokine Cell source Cells principally affected Major functions
IL-1 Most cells; macrophages, microglia Most cells; T cells, microglia,
astrocytes, macrophages
Costimulates T- and B-cell activation
Induces IL-6, promotes IL-2 and IL-2R
transcription
Endogenous pyrogen, induces sleep
IL-2 T cells T cells, NK cells, B cells Growth stimulation
IL-3 T cells Bone marrow precursors for all
cell lineages
Growth stimulation
IL-4 T cells B cells, T cells, macrophages MHC II upregulation
Isotype switching (IgG1, IgE)
IL-6 Macrophages, endothelial cells,
fibroblasts, T cells
Hepatocytes, B cells, T cells Inflammation, costimulates T-cell
activation
MHC I upregulation, increases vascular
permeability
Acute phase response (Schwartzman
reaction)
IL-10 Macrophages, T cells Macrophages, T cells Inhibition of IFN-γ, TNF-α, IL-6
production
37. Cytokine Cell source Cells principally affected Major functions
IL-12 Macrophages, dendritic cells T cells, NK cells Costimulates B-cell growth, CD4
+
T H 1
cell differentiation, IFN-γ synthesis,
cytolytic function
IL-17 T cells Neutrophils, T cells, epithelial
cells, fibroblasts
Host defense against gram-negative
bacteria, induction of neutrophilic
responses
Induction of proinflammatory cytokines
IFN-γ T cells, NK cells Astrocytes, macrophages,
endothelial cells, NK cells
MHC I and II expression
Induces TNF-α production, isotype
switching (IgG 2 )
Synergizes with TNF-α for many functions
TNF-α Macrophages, microglia (T cells) Most cells, including
oligodendrocytes
Cytotoxic (e.g., for oligodendrocytes),
lethal at high doses
Upregulates MHC, promotes leukocyte
extravasation
Induces IL-1, IL-6, cachexia; endogenous
pyrogen
Lymphotoxin
(TNF-β)
T cells Most cells (shares receptor with
TNF-α)
Cytotoxic (at short range or through
contact)
Promotes extravasation
TGF-β Most cells; macrophages, T cells,
neurons
Most cells Pleiotropic, antiproliferative, anticytokine
Promotes vascularization, healing
38. Cytokines
There are cytokines that can down regulate immune responses.
IFN-α and IFN-β, can modulate antibody response by their
antiproliferative properties.
TGF-β can also decrease cell proliferation.
IL-10, a growth factor for B cells, inhibits the production of IFN-γ and
thus may have anti-inflammatory effects.
39. Cytokines
Th 1 cells secrete IFN-γ, IL-2, and TNF-α. These cytokines exert
proinflammatory functions and, in T H 1-mediated diseases such as MS,
promote tissue injury.
In contrast, the Th 2 cytokines IL-4, IL-5, IL-6, IL-10, and IL-13
promote antibody production by B cells, enhance eosinophil functions,
and generally suppress cell-mediated immunity (CMI).
40. Chemokines
Chemokines are a group of molecules that aid in leukocyte mobility and directed
movement.
Chemokines may be grouped into two subfamilies based on the configuration and
binding of the two terminal cysteine residues,( C-C family and C-X-C family).
Chemokines are produced by a variety of immune and nonimmune cells.
42. Termination of an Immune Response
The primary goal of the immune response is to protect the organism
from infectious agents and generate memory T- and B-cell responses
that provide accelerated and high-avidity secondary responses on re-
encountering antigens.
It is desirable to terminate these responses once an antigen has been
cleared.
43. Termination of an Immune Response
• B-Cell Inhibition
• Immunoglobulin
• T Cells
44. B-Cell Inhibition
In most instances the formation of antigen–antibody
complexes can themselves result in the inhibition of B-
cell differentiation and proliferation through binding of
the Fc receptor to the CD32 (FcγRIIB) receptor on the
surface of the B cell.
45. Immunoglobulin
The variable regions of the Ig and the TCR molecule
represent novel proteins that can act as antigens. Antigenic
variable regions are called idiotopes , and responses against
such antigens are called anti-idiotypic.
this hypothesis still under research
46. T Cells Inhibition
Repeated stimulation of T cells may lead to activation-
induced cell death through apoptosis.
Regulatory cells generally inhibit the immune response
through secretion of cytokines.
48. Self-Tolerance
An organism's ability to maintain a state of
unresponsiveness to its own antigens is termed self-
tolerance .
Self-tolerance may be broadly categorized as either
central or peripheral tolerance.
49. Central Tolerance
Bone marrow stem cells migrate to the thymus, thereby
becoming T cells.
In the thymus medulla, thymocytes that display a high
affinity toward self-antigen are deleted by apoptosis, a
process called negative selection.
50. Peripheral Tolerance
Self-reactive lymphocytes may escape central tolerance;
therefore, peripheral mechanisms exist to maintain self-
tolerance.
Peripheral tolerance is maintained through clonal
anergy or clonal deletion.
52. Regulatory T Cells
Regulatory T cells (T reg ) function to down regulate CD4 and CD8 T-
cell responses.
Regulatory T cells suppress T-cell proliferation through a variety of
mechanisms, including the production of immunosuppressive cytokines
or through the expression of inhibitory molecules such cytotoxic T-
lymphocyte-associated protein 4 (CTLA-4).
54. Immune Privilege in the Central Nervous System
Important factors relevant to immunological responses in the CNS are:
(1) absence of lymphatic drainage.
(2) the blood–brain barrier.
(3) the low level of expression of MHC factors.
(4) low levels of potent APCs, such as dendritic or Langerhans cells.
(5) the presence of immunosuppressive factors such as TGF-β .
Normal function of neuromuscular junction, with major components implicated in MG shown. Action potential at the presynaptic nerve terminal causes opening of voltage-dependent Ca2+ channels, triggering release of acetylcholine and agrin into the synaptic cleft. Acetylcholine binds to acetylcholine receptors (AChRs), which promote sodium channel opening, which in turn triggers muscle contraction. Agrin binds to the complex formed by low-density lipoprotein receptor-related protein 4 (LRP4) and muscle-specific kinase (MuSK), causing acetylcholine receptor (AChR) clustering, which is required for maintenance of the postsynaptic structures of the neuromuscular junction.
b | Major pathogenic mechanisms of the AChR antibodies in MG include complement activation at the neuromuscular junction, which causes formation of membrane attack complexes (MACs) on the muscle membrane and destruction of the typical folds in the sarcolemma (1); antigenic modulation that results in internalization and degradation of surface AChRs (2); and binding of AChR antibodies at the AChR ligand binding site (3), which could directly block acetylcholine binding and, consequently, channel opening. Anti-MuSK and anti-LRP4 antibodies have been shown to block the intermolecular interactions of MuSK or LRP4 respectively, and could thus inhibit the normal mechanisms for maintenance of the organization of the neuromuscular junction (4). Antibodies with known pathogenic involvement in MG are shown in red
Both immune-mediated and non-immune-mediated pathways are implicated in the pathogenesis of idiopathic inflammatory myopathies (IIMs). a | Infiltrating immune cells within the skeletal muscle consist of macrophages (pro-inflammatory M1 and pro-resolution M2 macrophages); antigen-presenting cells (APCs; such as myeloid and plasmacytoid dendritic cells); T cells (including T helper (TH) TH1, TH2 and TH17 cells, regulatory T (Treg) cells, CD4+CD28null and CD8+CD28null cells, and cytotoxic T lymphocytes (CTLs)); B cells; and plasma cells. Treg cells influence both CD8+ T cells as well as TH cells. CTLs might engage MHC class I directly and contribute to muscle injury, but the extent of the contribution of CTL-mediated injury to muscle fibre death is currently unknown. B cells, with the help of TH1 cells, induce antibodies, including myositis-specific autoantibodies that are present in different forms of IIM. Infiltrating immune cells, as well as skeletal muscle cells, actively secrete a variety of pro-inflammatory cytokines and chemokines. b | Innate immune mechanisms include the binding of cytokines (such as TNF), TNF-related apoptosis-inducing ligand (TRAIL), and danger-associated molecular patterns (DAMPs) to receptors on skeletal muscle cells. Binding of these receptors and/or aberrant overexpression of MHC class I molecules can induce various signalling events including activation of the nuclear factor-κB (NF-κB) pathway and/or the endoplasmic reticulum (ER) stress response. These events can lead to proteasome activation and autophagy, which can result in dysregulated protein homeostasis, inflammasome activation, pro-inflammatory cytokine and chemokine production, and activation of cell death mechanisms (for example, pyroptosis or pyronecrosis) in skeletal muscle. Signalling through cytokine receptors (for example, the type I interferon receptor (IFNAR) and/or IL-1 receptor (IL-1R)) can cause dysfunction in mitochondrial metabolism and/or production of reactive oxygen species (ROS) and/or nitric oxide (NO), potentially leading to deficits in energy-generating metabolic pathways in skeletal muscle. These non-immune mechanisms (alone or in combination) contribute to muscle weakness and fatigue, common features of IIMs. TCR, T cell receptor; TLR, Toll-like receptor.