ch7. immune system

• Ways we protect ourselves from attack by foreign invaders

  • Passive (physical barriers)
  • Active (immune system)
• Passive (physical barriers)

  • Behaviour – personal hygiene, cook food, safe water
  • Skin – upper layer of cells dead, sweat and oils contain anti-microbial chemicals – e.g., antibiotics
  • Mucus membranes -mucus coats and immobilises pathogens. Cilia move mucus out of lungs. Mucus contains lysozyme, which destroys bacterial cell walls
  • Saliva- contains anti-bacterial and anti-viral agents
• Active (immune system)

  • Innate immunity
  • Adaptive (acquired) immunity
• Innate immunity response (non-specific response)


  1. Damaged tissue and mast cells release histamine

  2. Histamine causes blood capillaries to dilate

  3. Pathogens recognised and phagocytosed by macrophages and dendritic cells

  4. Neutrophils and monocytes migrate to damaged tissue and engulf pathogens

  5. Blood clotting occurs to repair damaged blood vessels
• Natural killer cells

  • Destroy virus-infected cells and cancer cells by identifying cells that lack a cell surface receptor called major histocompatibility complex class | (MHC-I)
• Complement


  • Blood plasma proteins that amplify some immune responses
  • Trigger release of histamine from mast cells
  • Attract phagocytes
  • Form membrane attack complex that makes holes in bacterial cell walls
• Cells of the immune system

  
  

  Multipotent stem cells in red bone marrow divide to form 2 types of cells

  • Myeloid stem cells/progenitors
  • Lymphatic stem cells/lymphoid progenitors
• Myeloid stem cells/progenitors

  • Erythrocytes (red blood cells)
  • Megakaryoblasts, which produce thrombocytes (platelets)
  • Mast cells
  • Myeloblasts, which give rise to eosinophils, basophils, neutrophils, and monocytes
  • Monocytes give rise to macrophages and dendritic cells
• Lymphatic stem cells/lymphoid progenitors

  • Small lymphocytes which give rise to T-lymphocytes (or T-cells) and B-lymphocytes (or B-cells)
  • B-lymphocytes give rise to plasma cells
  • Large lymphocytes called natural killer cells
• Adaptive (acquired) immunity (specific response)


  Slower to respond first time, recognizes specific parts of pathogens, responsible for immune system memory, involves B-cells and T-cells
• 1. B-cells

  • Make antibodies
  • Activated in lymph nodes and spleen
  • B-cell receptors (BCR) bind to antigens on invading bacteria/virus (each B-cell have a different BCR)
  • Activated B-cells undergo clonal expansion
  • Most become plasma cells that secrete antibodies
  • Some become memory B-cells
• Antibody

  Soluble proteins engineered to bind to one antigen, inactivate pathogens by coating them or blocking receptors
• Antibody structure

  • Y-shaped, made up of heavy and light chains
  • variable regions form antigen binding sites
  • VDJ recombination creates unique variable regions
• 1. T-cells

  • Don't produce antibodies, attack pathogens directly
  • mature in thymus, because they can't recognise antigens without help
  • Require antigen presentation by antigen-presenting cells (APCs) to be activated (APC have MHC on surface ; APCs (eg. dendritic cells, macrophages, B-cells))
  • Two types: helper T-cells and cytotoxic T-cells
• Cytotoxic T-cells


  • Attack and destroy infected cells and cancer cells
  • Require MHC-I presentation of antigen to be activated
• Helper T-cells


  • Generate cytokines that stimulate cytotoxic T-cells and B-cells
  • Require MHC-II presentation of antigen to be activated
• How cytotoxic T-cells kill invaders

  1. Expanded clone of T-cells dock on target cell

  2. Vesicles in cytotoxic T-cells fuse with target cell membrane and transfer perforins

  3. Perforins make holes in target cell membrane

  4. Cytotoxic T-cells also contain granzymes that trigger apoptosis in target cells
• Phagocytosis


  Pathogens (virus or bacteria) are phagocytosed
• Phagocytosis of pathogens

  Activates MHC-I which activates cytotoxic T-cells
• MHC-I


  Activates cytotoxic T-cells
• MHC-II

  Only found on specialised APCs such as dendritic cells
• Cytotoxic T-cells

  • Directly kill invading pathogens, infected cells, and cancer cells
  • Recognise MHC-I on all cells of the body
• Helper T-cells


  • Generate cytokines which help stimulate cytotoxic T-cells and B-cells to expand
  • Recognise MHC-II on APCs
• How cytotoxic T-cells kill invaders

  1. Expanded clone of T-cells in blood

  2. Dock on target cell

  3. Vesicles in cytotoxic T-cells fuse with target cell membrane and transfer perforins to the membrane

  4. Perforins make holes in the target cell membrane, changing the usual balance of ions and ATP

  5. Cytotoxic T-cells also contain enzymes called granzymes which trigger apoptosis in the target cells
• Cytotoxic T-cells and helper T-cells

  • Undergo clonal expansion and maintain memory cells in circulation
  • This allows rapid activation and expansion to mount a new defence upon recurrence of a viral infection or tumor
• Immune memory

  The basis of vaccination, where the immune system is primed by injecting dead viruses or bacteria to establish a memory of a specific antigen
• Passive immunity


  Temporary immunity received from another person, e.g. during development, childbirth, breastfeeding, or in the form of anti-venom
• Lymphatic system

  • Linked to circulatory system and immune system
  • Returns excess fluid from tissues to blood stream
  • Absorbs fats from digestive tract and transports them to bloodstream
  • Defends the body against disease
  • Contains T-cells and B-cells (lymphocytes)
  • Consists of vessels of varying sizes
• Lymphatic capillaries

  • Dead end vessels with one-way flap-like valves
  • Allow water and proteins into the lymphatic system, forming lymph
• Excess water in tissues

  Comes from blood capillaries due to higher hydrostatic pressure at the arteriole end pushing more water out into the tissues
• Lymph nodes

  • Located along lymphatic vessels
  • Packed full of lymphocytes (B-cells and T-cells) and macrophages
  • Lymph (water, proteins + garbage [bacteria and viruses]) passes through and interacts with lymphocytes
• Spleen

  • Consists of outer capsule, and inner red and white pulp
  • Red pulp contains macrophages that ingest old red blood cells
  • White pulp contains T-cells and B-cells exposed to foreign invaders
• Allergic reactions


  Caused by substances (allergens) that don't normally harm the body, triggering mast cells to release histamine
• Histamine


  Causes blood capillaries to dilate and become leaky, leading to edema and symptoms like a runny nose
• Incompatible blood types

  Occur when the recipient's antibodies bind to the donor's blood group antigens, leading to red cell clumping and potential complications
• Tissue rejection


  Occurs when the recipient's immune system recognizes the transplanted organ as foreign and attacks it
• Autoimmune disease

  Occurs when cytotoxic T-cells or antibodies attack the person's own cells, e.g. myasthenia gravis, multiple sclerosis, lupus, rheumatoid arthritis
• memory B-cells 


  After the first attack, memory B-cells won't die easily and will hang around in blood. If there is a subsequent attack, memory B-cells will recognise the same type of antigen and will stimulate B-cells to differentiate into plasma cells to produce antibodies at a faster rate.
• Antibody structure

  • light chain --> V, J regions ; heavy chains --> V, D, J regions
  • during B-cell maturation, the double-stranded bond breaks --> number of V, D, J regions varies a lot --> variable region of antibody varies slightly --> B-cell recognises a different antigen
  • NOTE: VDJ recombination occurs before B-cell activation and expansion <-- all B-cells are genetically the same before it
• Similarities and differences between T-cells and B-cells

  Similarities

  • ability to recognise antigens is due to VDJ recombination
  • both undergo colonial expansion once they are activated

  Differences

  • T-cells are activated ONLY if the antigen is presented via an MHC protein on another cell