The Immune system The Immune system is the body’s defense system • Against: – – – – – – – Bacteria Viruses Protists Other living invaders Toxins Foreign debris Cancerous cells • The immune system is complex • Defends against threats known and unknown Elements of the Immune system • Many lines of defense, for many kinds of threats • Skin • Blood • Thymus • Spleen • Lymphatic system • Mucous membranes • Bone marrow Innate vs. Adaptive immunity Innate Immunity • Non-specific • Defends against known invaders • Skin, lysozyme • Pre-existing • Cannot adapt to changing threats Adaptive Immunity • Mechanisms which fight specific invaders • For unknown threats • Responsive • Requires time to build defense (days) • Cannot anticipate threats • Remembers previous threats Humoral vs. Cell-mediated Immunity Cell- Mediated Immunity • Live cells kill invaders • Innate: Phagocytic cells (e.g. macrophages, neutrophils) • Adaptive: B lymphocytes and T lymphocytes create specific responses to unique invaders Humoral immunity • Proteins in blood (“humors”) • Innate- complement system, clotting factors, cytokines, etc. • Adaptive: Antibodies Blood is a mixture of cells and plasma Human Blood after centrifugation • ~55% Plasma • ~45% Red blood cells • <1% White blood cells and platelets (“buffy coat”) Blood plasma • Water • Nutrients • Solutes- Na+, Cl-, wastes, CO2, etc. • Contains humoral immune elements • Some innate immunity All blood cells are part of the hematopoetic stem cell lineage Hematopoetic stem cells differentiate into all blood cells • Pluripotent- able to become any one of many cell types • Includes T cells, B cells, macrophages, etc. Red blood cells carry oxygen and CO2 • Lose nucleus in development • Short-lived, no repair • Packed solid with hemoglobin • Membranes designed to maximize surface area • Facilitate gas transfer Hemoglobin • The oxygen-carrying protein • Heterotetrameric protein • 2 alpha subunits, 2 beta • Each subunit holds a Heme group • Each heme holds an Fe++ ion • Each Fe++ can bind an O2 Hemoglobin binding curve • In areas of High O2 (e.g., lungs)- binds O2 very well (picks up O2) • In areas of Low O2 (e.g., muscles) binds O2 poorly (drops off O2) • Myoglobin binds O2 in muscle & organ tissues Platelets assist with blood clotting • Recruit plasma protein fibrinogen to a cut • They release clotting factors • Clotting factors convert fibrinogen to fibrin • Fibrin net prevents blood loss • • • • • • The liquid part of blood is called A) water. B) plasma. C) serum. D) extrastitial fluid. E) anionic fluid. White blood cells come in a great variety of types Elements of Innate Immunity Lysozyme- an innate enzymatic defense • Enzyme that cuts bacterial cell walls • Also cuts chitin, a constituent of fungal cell walls and arthropod exoskeleton • Found in mucous, tears, egg whites Complement- humoral defense against non-specific invaders • A biochemical cascade • Non-specific • Signalling pathway to cause cell lysis • Also Recruitable by adaptive immune system Interferons are nonspecific anti-viral signalling molecules Phagocytic white blood cells devour bacteria • Which of the following, produced by virusinfected cells, diffuses to neighboring cells to help them fight a viral infection? • A) lysozyme • B) interferon • C) histamine • D) antigen • E) interleukin-2 The Inflammatory response Keeping the body safe comes at a cost • Inflammation implicated in heart disease, etc. • Gum inflammation linked to heart attacks The lymphatic system collects lymph and houses white blood cells in nodes Adaptive Immunity contains humoral and cell-mediated components Adaptive Immunity is learned, and has memory Antibodies- the Key component of humoral adaptive immunity • Two light chains, two heavy chains • Each contains a variable region and a constant region Antigen- anything which can be bound by an antibody B Cells- the source of antibodies Clonal selection musters B-cell defense forces against specific antigens Adaptive Immunity is learned, and has memory Immune cells are the only cells with different DNA • VDJ recombination of light and heavy chains generate antibody diversity • Change is permanent • A form of Russian Roulette for the cell • Successful recombination creates a binding antibodycell survives • Unsuccessful- cell is destroyed • Finding a good cell takes time Bound antibodies are the mark of death for invaders Breast milk contains maternal antibodies • Infants have no acquired immunity • Mother’s acquired immunity is transferred to the baby through nursing • Passive immunity • Is not retained by the baby Vaccination gives the body active immunity • An antigen sample is given to a person • Person’s immune system mounts a response to the antigen • Antigen can be deactivated/destroyed virus particles, etc. • No waiting time for body to develop 2o immune response Antibodies can be used as therapy • Some growth factors are overactive in certain cancers • Antibody binds to growth factors, or their receptors Polyclonal Antibodies • From multiple B cells • Bind to different epitopes of an antigen Monoclonal antibodies • Obtained from a single B cell • Bind to a single epitope • A single B cell is fused to a myeloma cell • Myeloma cells are immortal Mouse antibodies can be humanized • Constant regions of mouse antibody are gradually replaced with human sequences Fluorescent antibodies can be used in scientific experiments • Fluorescent molecules can be linked to antibodies • Antibodies show us where proteins exist in vivo In an ELISA, Horseradish Peroxidase is linked to a 2o antibody Indirect ELISA To detect the presence of an antibody Primary Antibody Secondary Antibody Wash Block Wash Substrate Home pregnancy tests utilize antibodies • The transfer of antibodies from breast milk to an infant is an example of __________ immunity. • A) nonspecific • B) passive • C) humoral • D) active • E) cell-mediated T cells are the primary cell-mediated adaptive immune response Major Histocompatibility Complex (MHC or HLA) • MHCI Found on all cells, recognized by TC cells • MHCII Found on B cells and Macrophages recognized by TH cells When presented with antigen, Helper T cells recruit other immune cells • The basic function of T cells is to identify and destroy invaders in our • A) blood or lymph. • B) interstitial fluid. • C) cells. • D) immune system. • E) brain. CD4 on the surface of TH cells is the site of HIV binding Any known stage of the HIV life cycle is a potential point for therapy Protease inhibitors prevent formation of HIV capsids AZT is a nucleoside analog reverse transcriptase inhibitor AZT Thymine Cytotoxic T cells destroy infected body cells In Autoimmune disease, the immune system attacks the self Allergies are immune responses to harmless antigens • A substance that can elicit an immune response is called a(n) • A) complement. • B) interferon. • C) histamine. • D) antibody. • E) antigen. • Which one of the following statements about HIV is false? • A) The genome of HIV consists of RNA. • B) HIV attacks helper T cells. • C) New HIV are produced inside helper T cells. • D) HIV is transmitted by body fluids transporting infected cells. • E) Some antibiotics have proven effective in combating the spread of AIDS. • Which type of immune response is always disadvantageous to a person? • A) cell-mediated • B) inflammatory • C) humoral-mediated • D) autoimmune • E) All immune responses are advantageous.