Immune system

• Phagocytes


  White blood cells that are produced continuously in the bone marrow and are responsible for removing dead cells and invasive microorganisms
• Phagocytes


  • They carry out a non-specific immune response
  • There are two main types: neutrophils and macrophages
• Levels of defences


  • Physical (Skin)
  • Cellular (Signalling)
  • Chemical (Toxin storage)
  • Harmless bacteria/fungi
• Phagocytosis


  Recognising and engulfing a pathogen
• Neutrophils


  Phagocytes that travel throughout the body and often leave the blood to 'patrol' the body tissues
• Neutrophil mode of action


  1. Chemicals attract neutrophils to site of pathogens

  2. Neutrophils move towards pathogens

  3. Neutrophils engulf and digest pathogens

  4. Neutrophils die after killing pathogens
• Macrophages


  Larger and longer-lived phagocytes that move into organs including lungs, liver, spleen, kidney and lymph nodes
• Macrophage mode of action


  1. Macrophages carry out phagocytosis but do not completely destroy pathogens

  2. They cut up pathogens and display their antigens on their surface to initiate an immune response
• Antigens


  Markers that allow cell-to-cell recognition, found on cell surfaces, bacterial cell walls, and virus surfaces
• Self antigens


  Antigens produced by the organism's own body cells that the immune system does not recognise as foreign
• Non-self antigens


  Antigens not produced by the organism's own body cells that the immune system recognises as foreign, such as those found on pathogenic bacteria and viruses
• Lymphocytes


  White blood cells that play an important part in the specific immune response, including B-lymphocytes and T-lymphocytes
• 1. lymphocyte role in primary immune response
  2. cells with receptors for the antigen are stimulated to divide and form plasma cells that secrete antibodies and memory cells
• 1. lymphocyte role in primary immune response


  1. T-cells are activated when they encounter their specific antigen presented by host cells

  2. Activated T-cells divide and differentiate into helper T-cells and killer T-cells

  3. Helper T-cells stimulate B-cells and macrophages

  4. Killer T-cells destroy infected host cells
• Primary immune response


  The initial slow response to a newly encountered antigen
• Secondary immune response


  The faster response to a previously encountered antigen
• Memory cells


  Lymphocytes that can last for many years or a lifetime and provide the basis for immunological memory
• Types of immune response


  • Primary immune response (responding to a newly encountered antigen)
  • Secondary immune response (responding to a previously encountered antigen)
• Primary immune response


  1. When a pathogen first enters the body, there will be only a few lymphocytes with receptors that fit into its antigens

  2. It takes time for these lymphocytes to encounter and bind with these pathogens

  3. It takes more time for them to divide to form clones, and for the B lymphocytes to secrete enough antibodies to destroy the pathogens, or for enough T lymphocytes to be produced to be able to destroy all the cells that are infected by them

  4. During this delay, the pathogens have the opportunity to divide repeatedly, forming large populations in the body tissues

  5. The damage that they cause, and toxins that they may release, can make the person ill

  6. It may be several days, or even weeks, before the lymphocytes get on top of the pathogen population and destroy it
• Secondary immune response


  1. If the body survives this initial attack by the pathogen, memory cells will remain in the blood long after the pathogen has been destroyed

  2. If the same pathogen invades again, these memory cells can mount a much faster and more effective response

  3. More antibodies can be produced more quickly, usually destroying the pathogen before it has caused any illness

  4. The secondary response happens more quickly, and produces many more antibodies
• This is why we usually become immune to a disease if we have had it once
• 1. lymphocytes


  • They also play a part in the secondary immune response
  • They differentiate into memory cells, producing two main types: Memory helper T cells and Memory killer T cells
• 75% of immune cells are destroyed by HIV
• HIV destroys helper-T cells
• With less helper-T cells


  There is less stimulation for phagocytes and lymphocytes, leading to reduced immunity
• Antibody production

  1. Only one of the B cells has an antibody receptor that is specific to the shape of the antigen that has entered the body

  2. The selected B cell divides by mitosis. Some of the daughter cells develop into plasma cells, others into memory cells

  3. Plasma cells secrete antibodies that specifically combine with the antigen that has entered the body

  4. When the antigen enters the body for a second time, the memory cells produced during the first response respond and divide to form more plasma cells, which secrete antibodies

  5. The response in the second stage is much faster than the first because there are many memory cells in the body
• Immunological memory (made possible by memory cells) is the reason why catching certain diseases twice is so unlikely
• There is only one strain of the virus that causes measles, and each time someone is re-infected with this virus, there is a very fast secondary immune response so they do not get ill
• Some infections such as the common cold and influenza are caused by viruses that are constantly developing into new strains
• As each strain has different antigens, the primary immune response (during which we often become ill) must be carried out each time before immunity can be achieved
• Antibodies

  Globular glycoproteins called immunoglobulins
• Antibody structure


  • They have a quaternary structure (represented as Y-shaped), with two 'heavy' (long) polypeptide chains bonded by disulfide bonds to two 'light' (short) polypeptide chains
  • Each polypeptide chain has a constant region and variable region
  • The constant regions do not vary within a class (isotype) of antibodies but do vary between the classes. The constant region determines the mechanism used to destroy the antigens
  • There are 5 classes of mammalian antibodies each with different roles
• Variable regions of antibodies


  The amino acid sequence in the variable regions (the tips of the "Y") are different for each antibody. The variable region is where the antibody attaches to the antigen to form an antigen-antibody complex
• Antigen-binding site


  • At the end of the variable region, the antigen-binding site is generally composed of 110 to 130 amino acids and includes both the ends of the light and heavy chains
  • The antigen-binding sites vary greatly giving the antibody its specificity for binding to antigens. The sites are specific to the epitope (the part of the antigen that binds to the antibody)
• A pathogen or virus may present multiple antigens, so different antibodies need to be produced
• Hinge region


  • The 'hinge' region (where the disulfide bonds join the heavy chains) gives flexibility to the antibody molecule which allows the antigen-binding site to be placed at different angles when binding to antigens
  • This region is not present in all classes of antibodies
• Antibody functions


  • Antibodies can combine with viruses and toxins of pathogens to block them from entering or damaging cells
  • Antibodies can act as anti-toxins by binding to toxins produced by pathogens, which neutralises them making them harmless (immobilisation)
  • Antibodies can attach to bacteria making them readily identifiable to phagocytes, this is called opsonisation
  • Antibodies can attach to the flagella of bacteria making them less active, which makes it easier for phagocytes to do phagocytosis
  • Antibodies act as agglutinins causing pathogens carrying antigen-antibody complexes to clump together (agglutination)
  • Antibodies (together with other molecules) can create holes in the cell walls of pathogens causing them to burst (lysis) when water is absorbed by osmosis
• Monoclonal antibodies


  Artificially produced antibodies produced from a single B cell clone
• Hybridoma method for producing monoclonal antibodies


  1. Mice are injected with an antigen that stimulates the production of antibody-producing plasma cells

  2. Isolated plasma cells from the mice are fused with immortal tumour cells which result in hybridoma cells

  3. These hybrid cells are grown in a selective growth medium and screened for the production of the desired antibody

  4. They are then cultured to produce large numbers of monoclonal antibodies
• Diagnostic uses of monoclonal antibodies

  • Pregnancy tests
  • Diagnosing HIV
  • Detecting the presence of pathogens such as Streptococcus bacteria
  • Distinguishing between Herpes I and Herpes II
  • Blood typing before transfusions and tissue typing before transplants
  • Detecting the presence of antibiotics in milk
  • Detecting cancer cells