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The Immune System: How does it work and were does it fail? Einar K. Kristoffersen Department of Immunology and Transfusion Medicine The Gade Institute Haukeland University Hospital University of Bergen Immune System & defects EiKKr Know Thy Enemy Immune System & defects Downloaded from: StudentConsult (on 7 June 2005 08:08 PM) © 2005 Elsevier EiKKr The Immune System • The seventh sense • Desentralized • Immun cells • Lymphocytes, phagocytes, dendritic, etc • Immune tissues • Bonemarrow • Thymus • Lymphatic system • Immunoproteins • Antibody, complement, CRP, etc Immune System & defects EiKKr Organsystemer Immune System & defects EiKKr Bone marrow • Where immune cells are made Immune System & defects EiKKr What are our weapons? • Phagocytes • Bacteria and fungi • Lymphocytes • B cells • Antibody: bacteria, toxins, virus • T cytotoxic og Natural killers(NK) • Virus • T helper cells • Bacteria, virus, antibody, etc. Immune System & defects EiKKr Immune System & defects Downloaded from: StudentConsult (on 7 June 2005 08:08 PM) © 2005 Elsevier EiKKr What are our weapons? • Phagocytes • Bacteria and fungi Immune System & defects EiKKr Natural cellular immunity • The Phagocytes • In blood: granulocytes • ~ 1011/d • Short-lived • Eat and kill Immune System & defects EiKKr Natural cellular immunity • The Phagocytes • In blood: granulocytes • ~ 1011/d • Short-lived • Eat and kill • In tissues: macrophages Immune System & defects EiKKr Macrophages Immune System & defects EiKKr Natural cellular immunity • Phagocytes • Granulocytes • Eat and kill • In tissues: macrophages • In all tissues • ”Housecleaning”, eat, kill, activation and regulation Immune System & defects EiKKr Phagocytosis •Binding til receptor •Cytokinfrigjøring •Inflammasjon •Aktivering Immune System & defects •Lysosomal nedbrytning •Fagocytose EiKKr Phagocyte hunting: Immune System & defects EiKKr Immunological proteins • Complement • • • • Network of serumproteins Induced by immune stimuli Binds and perforates Extracellular bacteria Immune System & defects EiKKr Phagocytosis •Binding til receptor •Cytokinfrigjøring •Inflammasjon •Aktivering Immune System & defects •Lysosomal nedbrytning •Fagocytose EiKKr Immunological proteins • Complement • Cytokines • The ”hormones” of immune cells Immune System & defects EiKKr Immunological proteins • Complement • Cytokines • The ”hormones” of immune cells • Acute phase proteines • CRP etc Immune System & defects EiKKr Immune System & defects EiKKr Natural cellular immunity • Phagocytes • Granulocytes • Eat and kill • In tissues: macrophages • In all tissues • ”Housecleaning”, eat, kill, activation and regulation • Natural killer cells: NK • Kill virusinfected cells Immune System & defects EiKKr NK cells Killing virus infected cells Stimulerer makrofager Immune System & defects EiKKr Natural cellular immunity • Phagocytes • Granulocytes • Eat and kill • In tissues: macrophages • In all tissues • ”Housecleaning”, eat, kill, activation and regulation • Natural killer • Kills virusinfected cells • Dendritic cells • Activation and regulation Immune System & defects EiKKr Immune System & defects EiKKr Adaptive cellular immunity • T cells from bone marrow: naïve • Matures in thymus • Most die there • Enormous potential specificities: ~1018 Immune System & defects EiKKr Lymphatic system Immune System & defects EiKKr Lymphoid circulation Immune System & defects EiKKr Immune System & defects EiKKr Adaptive cellular immunity • T helper CD4 activated • Activates B cells, macrophages, NK, T-cytotoxic • T cytotoxic: virus infected cells Immune System & defects EiKKr T cytotoxic cells Immune System & defects EiKKr Adaptive humoral immunity • B cells made and matured in bone marrow • B cells activated divides in lymph nodes • Plasma cells: specific antibody: ~5 x 1013 • Memory B cells Immune System & defects EiKKr Immune System & defects EiKKr Antibody Fab-del Fc-del Immune System & defects EiKKr Antibody isotypes Immune System & defects EiKKr IgA and IgM Immune System & defects EiKKr Immune System & defects EiKKr Antibody: Immune-glue Immune System & defects EiKKr Immune System & defects EiKKr Adaptive cellular immunity • T lymphocytes in marrow matures • Potentially endless specificities: ~1018 • T lymphocytes activates: • B cells, macrophages, NK, T-cytotoxic • Memory T cells • Regulatory T cells Immune System & defects EiKKr Lymphocytes B cells T helper cells T cytotoxic NK cells Immune System & defects Antibody Activates phagocytes T cells B cells Memory T cell Regulatory T Direct killing EiKKr Specific immune response • Activated specific T cells • Cytotoxic specific T cells • Hyperactivated macrophages • Activated specific B cells • Specific antibody Immune System & defects EiKKr Immune System & defects EiKKr Inflammasjon Immune System & defects EiKKr Immune System & defects EiKKr The Lymphnode Immune System & defects EiKKr Immune System & defects EiKKr Immune response Stamceller Komplement m.m. Tymus Fagocytter NK celler Cellular responses Immune System & defects T celler B celler Humoral responses EiKKr Antobody production • B cells become plasma cells • ”Short-cut”: IgM producing in lymphnode • Longlived: IgG producing in bonemarrow Immune System & defects EiKKr Immune response Stamceller Komplement m.m. Tymus Fagocytter NK celler Cellular responses Immune System & defects T celler B celler Humoral responses EiKKr Immune response Immune System & defects EiKKr Immune System & defects EiKKr Immune System Stemcells Komplement Cytokiner Tymus Spiseceller NK celler Cellular responses Immune System & defects T celler B celler Humoral Protein responses EiKKr Immune responses Stamceller T helper cells B cells Komplement m.m. T cytotoxic Tymus Fagocytter NK celler T celler B celler Phagocytes Cellular responses Immune System & defects Antibody responses EiKKr Immunodefects vs. microbes Immune System & defects EiKKr Stem cells Phagocytes NK cells Cellular responses Immune System & defects • Severe combined Tymus immunodeficiency SCID Komplement m.m. T cells B cells Antibody responses EiKKr Stem cells • DiGeorge • T Komplement cell def m.m. Tymus Phagocytes NK cells Cellular responses Immune System & defects T cells B cells Antibody responses EiKKr Stem cells • Agammaglobulinemia NK • Common variable Fagocytter celler immunodeficiency Cellemediert responser Immune System & defects Complement Cytokines Tymus T cells B cells Antibody responses EiKKr • Chronic granulomatous disease Stamceller • leukocyte adhesion deficiency Komplement m.m. Tymus Phagocytes NK cells Celular responses Immune System & defects T cells B cells Antibody responses EiKKr Phagocyte hunting: Immune System & defects EiKKr • C2 deficiency Stamceller • Interferon gamma receptor Tymus Fagocytter NK celler Cellular responses Immune System & defects T celler Complement Cytokines B celler Antibody responses EiKKr Immune System Stem cells Complement Cytokines Tymus Phagocytes NK cells Cellular responses Immune System & defects T cells B cells Antibody responses EiKKr Primary immunodeficiencies 1. 2. 3. 4. 5. 6. 7. 8. Combined T&B Well-defined syndromes Predominantly antibody deficiencies Immune dysregulation Phagocytes Innate disorders Auto-inflammatory disorders Complement deficiencies Immune System & defects EiKKr Immune System & defects EiKKr CD4 T helper cells Th1 T memory Th2 T memory Treg T memory? Th1 7 TFH Immune System & defects EiKKr
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