BBI Introduction to the Immune System PDF

Introduction to the Immune System  The Immune System pathogens: foreign bodies (bacteria, viruses, fungi, parasites) that pose threat of illness or harm Erythrocyte: red blood cell Starts in yolk sac All other cells are white b...

Introduction to the Immune System  The Immune System pathogens: foreign bodies (bacteria, viruses, fungi, parasites) that pose threat of illness or harm Erythrocyte: red blood cell Starts in yolk sac All other cells are white blood cells (leukocytes) Move to embryonic liver Dendritic Cell Migrate/mature in various tissues Dendritic Cell  The Immune System pathogens: foreign bodies (bacteria, viruses, fungi, parasites) that pose threat of illness or harm Innate Immune System: Non-specific defense against pathogens phagocytes: have receptors for chemicals on or released by pathogens macrophages → ingest pathogen via intracellular lysosomes → present pathogen antigens on cell surface as signals → releases cytokines: general term for proteins secreted by immune cells that signal to other immune cells → some cytokines released create a scaffold for other immune cells and regulate blood vessel widening and constriction dendritic cells → ingest pathogen via intracellular lysosomes → present pathogen antigens on cell surface as signals → releases cytokines: general term for proteins secreted by immune cells that signal to other immune cells  The Immune System pathogens: foreign bodies (bacteria, viruses, fungi, parasites) that pose threat of illness or harm Innate Immune System: Non-specific defense against pathogens phagocytes: have receptors for chemicals on or released by pathogens macrophages → ingest pathogen via intracellular lysosomes → present pathogen antigens on cell surface as signals → releases cytokines → chemicals released create a scaffold for migrating immune cells and regulate blood vessel widening and constriction neutrophils →cluster at area of infection (attracted by cytokines) →apoptosis—release lysosomes →pus  The Immune System pathogens: foreign bodies (bacteria, viruses, fungi, parasites) that pose threat of illness or harm Innate Immune System: Non-specific defense against pathogens A different kind of cell of the innate immune response: Natural Killer Cells (NK) NK are lymphocytes that play a role in innate immune response— → cause cytotoxicity (cell death) in VIRAL-INFECTED CELLS or TUMOR CELLS. → bore holes in pathogen intruders using perforins in response to signals of cell stress (when a cell is virus-infected), or pathogen signals  The Immune System Innate Immune System: Non-specific defense against pathogens White blood cells circulate and monitor the bloodstream for chemoattractants signaling injury or pathogens Also called: extravasation Running alongside vasculature (in next slide): Lymph vessels--tubes that carry lymph through the body to lymph nodes and back to veins. Primary and Secondary Lymphoid Organs Primary and Secondary Lymphoid Organs Primary Lymphoid Secondary Lymphoid Organs Organs Also called “central lymphoid It is where antigen is localized so organs” that it can be effectively exposed where immature lymphocytes to mature lymphocytes. develop initiate adaptive immune response. Organs where differentiation, proliferation and maturation of stem cells into immuno- Includes: competent cells take place. Spleen Lymph Nodes Includes: Tonsils Appendix Thymus Peyer’s patches Bone Marrow  The Immune System Acquired/Adaptive immunity: “variable chain” A way to patrol the body for new specific pathogens , like “light chain” infectious bacteria or viruses, to have a memory B cells: originate from stem cells in the bone marrow -develop antibodies (immunoglobins) antibodies: small proteins that circulate in the blood following invasion of a foreign substance— search for pathogens to destroy Rearrangement of B-cell DNA allows for a limitless variety of antibodies that can target any antigen. This occurs in the secondary lymphoid organs, through encounters with trapped pathogens and effector cells “constant region” “heavy chain”  The Immune System Acquired/Adaptive immunity: A way to patrol the body for specific pathogens , like infectious bacteria or viruses Antigen-driven activation of naïve B cells leads to generation of plasma cells and memory B cells—each one produces and secretes antibodies with one particular light chain In the absence of antigen-induced activation, naïve B cells in the periphery die within a few weeks by apoptosis (programmed cell death)  The Immune System Acquired (adaptive) immunity: T Cells: Born in the bone marrow (like all blood cells), but mature in the thymus Helper T-cells: secrete cytokines to stimulate other immune mechanism; can tell B-cells to start producing antibodies Killer T cells: secrete perforins, or deliver enzyme packages to infected cells to induce apoptosis T cells require antigen presenting cells (APCs) in order to identify infected cells and get activated Antigen-presenting cells (examples): -dendritic cells -macrophages  The Immune System Acquired (adaptive) immunity: T Cells: Born in the bone marrow (like all blood cells), but mature in the thymus Helper T-cells: secrete cytokines to stimulate other immune mechanism; can tell B-cells to start producing antibodies Killer T cells: secrete perforins, or deliver enzyme packages to infected cells to induce apoptosis T cells require antigen presenting cells (APCs) in order to identify infected cells and get activated Antigen-presenting cells (examples): -dendritic cells -macrophages Our self-cells can also be antigen-presenting cells!  The Immune System Acquired immunity: Figure 13.5 Covert operations of the dendritic cells. Lambert and Kinsley: Clinical Neuroscience, Second Edition Copyright © 2011 by Oxford University Press, Inc.  The Immune System MHC I molecules bind peptides derived from endogenous antigens that have been processed within the cytoplasm of the cell—marker of SELF cells MHC II molecules bind peptides derived from exogenous antigens that are internalized by phagocytosis or endocytosis and processed MHC: Major Histocompatability Complex  The Immune System Self-cells that are infected will express their foreign antigen on their MHC I “Professional” antigen presenting cells express MHC II -Helper T cells recognize antigens bound to MHC II -Killer T cells recognize antigens bound to MHC I Tcell becomes becomes  Psychoneuroimmunology Immune-CNS interactions Backfire: Autoimmune diseases are disorders where the immune system attacks otherwise- healthy self-tissues Autoimmune diseases affecting the CNS: -Multiple Sclerosis (MS) -Paraneoplastic syndrome -PANDAS (Pediatric Autoimmune Neuropsychiatric Disease Associated with Streptococcus) -Myasthenea gravis  Psychoneuroimmunology Immune-CNS interactions Sickness Behavior: Anhedonia, lethargy, social withdrawal…. What disorder does that sound like? Components of sickness behavior: Fever: enhances the immunologic response, pathogens are weakened cytokines signal the hypothalamus to reset the body’s set point Anorexia: decreases iron, on which pathogens thrive Social withdrawal/anhedonia: encourages isolation in order not to infect others; Reserves energy  Psychoneuroimmunology Immune-CNS interactions Sickness Behavior: Anhedonia, loss of energy, cognitive dampening…. IL-1 is one of the cytokines produced by T cells and macrophages Cytokines are also produced by IL-6 resident immune cells in the brain Microglia IL-6 Astrocytes & T Cells… Figure 13.7 Inducing a sick response. Lambert and Kinsley: Clinical Neuroscience, Second Edition Copyright © 2011 by Oxford University Press, Inc.  Psychoneuroimmunology Immune-CNS interactions How do the immune and nervous systems talk to each other? 1. Through direct activation of cytokine receptors on neurons  Psychoneuroimmunology Immune-CNS interactions How do the immune and nervous systems talk to each other? 2. Through direct activation of neurotransmitter receptors  Psychoneuroimmunology Immune-CNS interactions How do the immune and nervous systems talk to each other? 3. Indirectly through microglia and astrocytes Microglia and astrocytes: When activated, can show macrophage and dendritic cell properties (i.e., antigen-presenting on MHC-II, phagocytosis) In fact, microglia are really macrophages that have colonized the brain during development!  Psychoneuroimmunology Immune-CNS interactions Cytokines activate microglia to secrete IDO, taken up by neurons Indoleamine Pro-inflammatory cytokine Kynurenine Quinolinic acid  Psychoneuroimmunology Immune-CNS interactions How do the immune and nervous systems talk to each other? 3. Indirectly through microglia and astrocytes Leah McNally, BS, Zubin Bhagwagar, MD, PhD, and Jonas Hannestad, MD, PhD Psychoneuroimmunology Immune-CNS interactions  Psychoneuroimmunology Immune-CNS interactions Psychiatric disorders that involve neuroinflammation Depression: Schizophrenia Bipolar Disorder Drug Addiction