BIOMED SCIE Lecture 12 The Immune System

• Immunity


  Ability to ward off disease
• Susceptibility


  Lack of resistance to a disease
• Innate immunity


  • Nonspecific defense mechanisms that provide immediate defense against infection
  • Come into play immediately or within hours of an infectious agent's appearance in the body
  • Include physical barriers such as skin, proteins in the blood, and immune system cells
  • Does not confer long-lasting or protective immunity to the host
  • Include both humoral immunity components and cell-mediated immunity components
  • Remember the microbiome plays a role too
• Adaptive immunity


  • Adaptive resistance to a specific pathogen
• Immunization and Vaccination provide active immunity
• Physical Barriers


  First line of defense against pathogens
• Inflammation


  • First response of the immune system to infection
  • Stimulated by chemical factors released by injured cells
  • Initiated by cells already present in all tissues
• Pattern recognition receptors (PRRs)


  Recognize pathogen associated molecular patterns (PAMPs)
• Toll-like Receptors (TLRs)

  • Germline-encoded pattern recognition receptors (PRRs)
  • Primarily found on macrophages, mast cells and dendritic cells
• Nod-like receptors (NLRs)


  Cytosolic receptors that sense infection and stress through the recognition of cytoplasmic PAMPs
• Other Innate Immune Receptors


  • RIG-I-Like Receptors (RLRs) and Cytosolic DNA Sensors (CDS) for host antiviral responses
  • C-Type Lectin Receptors (CLRs) for anti-fungal responses
• Cells of the Innate Immune Response


  • Phagocytes: Macrophages, Neutrophils, Dendritic cells
  • Mast cells, Basophils, Eosinophils
  • Natural Killer Cells
  • γδ T-cells
• Complement System


  • Complements the ability of antibodies and phagocytic cells to clear pathogens from an organism
  • Proteins (~30) found in the blood synthesized by the liver, circulate as inactive precursors
• Antigens


  • Substances that can elicit a response from a B or T cell
  • Exposure to the pathogen activates B and T cells with antigen receptors specific for parts of that pathogen
  • The small accessible part of an antigen that binds to an antigen receptor is called an epitope
• Antigen Presentation


  • Class I: Intracellular antigens presented by MHC Class I
  • Class II: Extracellular antigens presented by MHC Class II
  • Dendritic cells, activated macrophages, and B cells present antigen to B and T cells in lymph nodes
• Cells of the Adaptive Immune Response


  • T-cells mature in the thymus, B-cells mature in spleen and secondary lymphoid organs
• Humoral Adaptive Immunity


  • Aspects of the immune system conferred by the presence of macromolecules in the liquid part of the blood
  • Includes antibody production, pathogen and toxin neutralisation, classical complement activation, and opsonophagocytosis
• 1. Cell Receptor


  • Binding of a B cell antigen receptor to an antigen is an early step in B cell activation
  • Secreted antibodies are similar to B cell receptors but lack transmembrane regions that anchor receptors in the plasma membrane
• Antibody Function


  • Antibodies do not kill pathogens; instead they mark pathogens for destruction
  • Neutralisation: Antibodies bind to viral surface proteins preventing infection of a host cell
  • Antibodies may bind to toxins in body fluids and prevent them entering cells
• Immunoglobulin Classes


  • IgD, IgM, IgG, IgA, IgE
• Cell Mediated Adaptive Immunity


  • T-cells: αβ T-cell receptor
  • Cytotoxic T-cells: CD8, Perforin, Granulysin, Granzyme (apoptosis)
  • Helper or Regulatory T-cells: CD4, Th-1 (intracellular), Th-2 (extracellular)
  • γδ T-cells: Alternative T-cell receptor
• Immunological Memory


  • Memory B-cells and Memory T-cells
  • Active immunity develops naturally or through immunization
  • Passive immunity provides immediate, short-term protection
• Jenner and Smallpox: Variolation, Sarah Nelmes, Blossom, James Phipps
• The immune system is made up from an innate and adaptive immune response
• The innate immune response is fast if not immediate, the adaptive is slow but more specific to the pathogen
• Understanding the Immune system allows us to vaccinate - Entering the age of the vaccine
• Upon activation these cells release inflammatory mediators– Histamine, leukotrienes, bradykinin, prostaglandins, serotonin• Inflammation– Redness, swelling, heat, pain, mucus• Attract phagocytes