HUBS M5 Immunology

• Immunology


  The study of an organism's defense system (immune system) in health and disease
• Immune system


  An organised system of organs, cells and molecules that interact together to defend the body against disease (eg pathogenic microorganisms and cancer)
• Microbes include viruses, bacteria, fungi, and protozoa. Some microbes are pathogens (disease-causing)
• Organs of the immune system

  • Spleen
  • Thymus
  • Bone marrow
  • Lymph nodes
  • Tonsils
• Primary lymphoid organs


  Production of white blood cells (lymphocytes)

  
• Secondary lymphoid organs


  Sites where immune responses are initiated
• Skin


  • Epidermis: Dead cells, keratin and phagocytic immune cells
  • Dermis: Thick layer of connective tissue, collagen and blood vessels and phagocytic immune cells
• Chemical defenses of the skin

  • Antimicrobial peptides, Lysozyme, Sebum, Salt
• Mucous Membranes


  • 1-2 layers, Epithelium: tightly packed live cells, constantly renewed, mucus-producing goblet cells
• Mucosal Membranes


  • Line parts of the body that lead to the outside and are exposed to air
• Mucociliary escalator


  • Cilia move mucus up to the pharynx
• Chemical defenses of mucosal surfaces

  • Stomach - low pH, Gall bladder - bile, Intestine - digestive enzymes, Mucus, Defensins, Lysozyme
• Innate immunity


  Already in place, Rapid (hours), Fixed, Limited specificities, Has no specific memory
• Adaptive immunity


  Improves during the response, Slow (days → weeks), Variable, Highly specific, Has long-term specific memory
• Blood


  Composed of plasma and cells
• Formed elements of blood

  • Platelets
  • White blood cells (leukocytes)
  • Red blood cells
• Bone marrow


  Source of blood cells (hematopoiesis)
• Blood cell lineages


  • Myeloid (red blood cells, granulocytes, monocytes, dendritic cells, platelets)
  • Lymphoid (B and T lymphocytes)
• Granulocytes


  Neutrophils - 75% of all leukocytes, highly phagocytic "eat and kill" - numbers in blood increase during infection
• Mast cells


  Line mucosal surfaces (not found in blood), release granules that attract white blood cells to areas of tissue damage
• Monocytes


  Present in blood, low phagocytosis
• Macrophages


  Develop from monocytes in tissues, high phagocytosis, release chemical messengers, show information about pathogens to T cells
• Dendritic cells


  Link innate and adaptive immune responses, phagocytic, most important to trigger adaptive immune responses
• How immune cells move around the body

  Carried in blood and lymph, can leave blood to enter tissues, lymph in tissues collects into lymphatic vessels which drain into lymph nodes
• Pathogen-associated molecular patterns (PAMPS)

  Common building blocks of bacteria (cell wall, flagella, nucleic acid) and viruses (nucleic acid)
• Pattern recognition receptors


  Detect PAMPS, located on cell membrane, in cytoplasm, and in phagolysosomes of phagocytic cells
• Fever/pyrexia


  Abnormally high temperature >37˚C, re-setting of thermostat (hypothalamus), pyrogens released by immune cells (e.g. IL-1 from phagocytes)
• 3 layers of immune defense

  • Physical & Chemical Barriers (skin, mucosal membranes)
  • The Innate Immune System
  • The Adaptive Immune System
• The inflammatory response


  1. Chemical signals from tissue-resident cells act to attract more cells to the site of injury or infection

  2. Neutrophils enter blood from the bone marrow

  3. Neutrophils cling to the capillary wall

  4. Chemical signals from tissue-resident cells dilate blood vessels and make capillaries 'leakier'

  5. Neutrophils squeeze through the 'leaky' capillary wall and follow the chemical trail to the injury site
• Phagocytosis


  The process of a cell engulfing and digesting a particle
• Events of phagocytosis


  1. Phagocyte forms pseudopods that eventually engulf the particles, forming a phagosome

  2. Phagocyte adheres to pathogens or debris

  3. Lysosome fuses with the phagocytic vesicle, forming a phagolysosome

  4. Toxic compounds and lysosomal enzymes destroy pathogens

  5. Sometimes exocytosis of the vesicle removes indigestible and residual material
• Killing and digestion of phagocytosed microbes

  • Low pH - acid environment
  • Reactive oxygen (hydrogen peroxide) and reactive nitrogen intermediates (nitric oxide)
  • Enzymes (Proteases, Lipases, Nucleases)
• Complement


  9 major proteins/protein complexes (C1-9) that act in sequence to clear pathogens from blood and tissues
• 3 Complement Pathways


  • CLASSICAL
  • ALTERNATIVE
  • LECTIN
• Complement pathways converge


  1. Triggers

  2. Amplification

  3. Outcomes
• 3 outcomes from the complement cascade

  • LABEL (Opsonisation)
  • DESTROY (Membrane Attack Complex formation)
  • RECRUIT (Complement proteins act as peptide mediators of inflammation and recruit phagocytes)
• Opsonisation


  Coating of a microbe with antibody and/or complement fragment C3b
• • Phagocytes attracted into site
  • Mast cells degranulated by C3a and C5a
  • Inflammatory mediators released including proteins that attract phagocytes
• • Microbes coated with C3b are phagocytosed
  • Assembly of the MAC causes lysis
• Soluble molecules


  Cytokines or chemokines binding to receptors on a cell membrane