Optional Module: Immunology and Disease

• Disease


  • Cholera
  • Tuberculosis
  • Smallpox
  • Influenza
  • Malaria
• Causative agent


  • Gram-negative bacterium
  • Bacteria
  • The Variola major virus
  • Virus- 3 sub-groups with many antigenic types
  • Protoctistan parasite
• Tissue affected


  • Toxins affect the gut lining causing watery diarrhoea
  • Lungs, neck and lymph nodes
  • Mouth, throat, lymph nodes, blood stream
  • Lining of the upper respiratory tract
  • Liver and red blood cells
• Mode of transmission


  • Water borne
  • Airborne droplets through coughs and sneezes
  • Contact person to person or from contaminated objects
  • Airborne droplet infection
  • Vector, passed to humans by the female mosquito when taking a blood meal
• Control methods and treatment

  • Treatment of water
  • Rehydration therapy
  • Antibiotics
  • Vaccine
  • Antibiotics
  • BCG vaccination
  • Low antigenic variation of the virus led to a highly effective vaccine. This, along with there being no animal reservoir, led to the eradication of smallpox in 1980
  • Quarantine and hygiene
  • Annual vaccination- not always effective
  • Stop the vector- Nets, clothing, insect repellent, fish to eat larvae, drain breeding grounds, spray water surfaces with oil. Use insecticides, bacterial infections of mosquitos, or sterilisation of mosquitos
  • Kill the parasite- drugs affect the parasite outside of blood cells but resistance is increasing. Vaccine difficult as the parasite mutates, and antibodies only help when the parasite is outside of blood cells

  
• Pathogenic


  An organism that causes damage to its host
• Infectious


  A disease that may be transmitted from one individual to another
• Carrier


  Shows no symptoms when infected but can pass the disease on to another
• Disease reservoir


  Where a pathogen is normally found; this may be in humans or another animal and may be a source of infection
• Endemic


  A disease, which is always present at low levels in an area
• Epidemic


  Where there is a significant increase in the usual number of cases of a disease, often associated with a rapid spread
• Pandemic


  A global epidemic
• Vaccine


  Uses non-pathogenic forms, products or antigens of micro-organisms to stimulate an immune response, which confers protection against subsequent infection

  
• Antibiotic


  Substances produced by microorganisms that affect the growth of other microorganisms
• Antibiotic resistance


  Where a microorganism, which should be affected by an antibiotic, is no longer susceptible to it

  
• Antigen


  A molecule that causes an immune response

  
• Antibody


  A protein produced by the immune system to recognise and destroy antigens

  
• Vector


  A living organism which transfers a disease from one individual to another
• Toxin


  A chemical produced by a microorganism, which causes damage to its host
• Antigenic type


  Organisms with the same or very similar antigens on the surface. Such types are subgroups or strains of a microbial species, which may be used to trace infections. They are usually identified by using antibodies from serum

  
• Viral diseases


  1. Viral DNA/RNA instructs the cell to make virus particles, when full cell lysis occurs, and the virus escapes the cells to infect other cells/organisms (shedding)

  2. Production of toxic substances

  3. Viral cell transformation, where they can trigger cells to become cancerous

  4. Viruses infecting white blood cells suppress the immune system (e.g. HIV)

  
• Gram negative bacteria


  Have a thin peptidoglycan cell wall with a layer of lipopolysaccharide. Gram negative bacteria stain red using Gram staining technique. The additional layer of lipopolysaccharide protects the bacterial cells from lysozyme and from penicillin type antibiotics
• Gram positive bacteria


  Have a thick peptidoglycan cell wall and no lipopolysaccharide layer. Gram positive bacteria stain purple using Gram staining technique. Gram positive bacteria are susceptible to lysozyme and penicillin
• Body defences


  • Skin
  • Lysozyme
  • Ciliated mucous membranes
  • Blood clotting
  • Inflammation
  • Blood - white blood cells called phagocytes kill invading microbes in a process called phagocytosis
  • Antibodies

  
• Antibodies


  These are produced by white blood cells called lymphocytes. Antibodies are proteins (globulins). They are Y shaped and formed from four polypeptide chains with two binding sites. They are specific to the antigen and they bind to form an antigen-antibody complex. This renders the antigen inactive by agglutination or marking for phagocytosis

  
• Antibiotic resistance


  1. Bacteria divide rapidly and have a high mutation rate. Bacteria can also obtain plasmids that carry antibiotic resistance genes from other resistant bacteria by conjugation

  2. Some mutations confer resistance to antibiotics. Overuse of these antibiotics gives the resistant strain a selective advantage

  3. Numbers of the resistant strain increase, making infections more difficult to treat with the usual antibiotics

  
• Penicillin


  Peptidoglycan bacterial cell walls are strengthened by polysaccharide cross-linked by amino acids. This stops osmotic lysis. Penicillin affects the formation of the cross links by inhibiting the enzyme that makes them. The wall is weakened and osmotic changes can cause cells to burst. Gram negative bacteria have an outer lipopolysaccharide layer that protects the cells from penicillin
• Tetracycline


  Tetracycline acts as a competitive inhibitor of the second anticodon-binding site on the 30S subunit of bacterial ribosomes. It prevents the binding of a tRNA molecule to its complementary codon. This prevents protein synthesis common to all bacteria
• Humoral immune response


  1. Stem cells in the bone marrow make B lymphocytes that mature in the spleen and lymph nodes and have receptors for the detection of specific antigens on the surface of foreign cells

  2. When the B lymphocytes are activated by a corresponding antigen, they divide rapidly forming antibody secreting plasma cells. This clonal expansion is increased by the cytokines from the cell mediated response

  3. B lymphocytes also make memory cells that remain in the bloodstream and divide rapidly if the antigen is encountered again

  
• Primary immune response


  1. On first exposure to the antigen, there is a latent period when antigen presenting cells (including macrophages) carry out phagocytosis and incorporate foreign antigen into their cell membranes (antigen presentation)

  2. T helper cells detect these antigens and secrete cytokines that stimulate B cells to undergo clonal expansion and stimulate macrophages to carry out phagocytosis

  3. Some B cells then differentiate to become antibody-secreting plasma cells with short lives. Others become long-lived memory cells that retain the ability to undergo mitosis in case of secondary infection

  
• Secondary immune response


  1. Following re-exposure to the same antigen, there is a very short latent period due to the presence of memory cells

  2. Only a very small amount of antigen is required to stimulate rapid production of plasma cells

  3. Antibody levels increase to between 10 and 100 times greater than the initial response in a very short time frame. Antibody levels stay high for longer and no symptoms develop

  
• Vaccinations


  • A vaccination stimulates artificial active immunity in an individual
  • A vaccine must contain an immunogenic antigen that stimulates a strong immune response
  • Vaccinations for pathogens that exhibit low levels of antigenic variation can protect an organism after one immunisation, e.g. Rubella
  • Some pathogens have many antigenic types and mutate frequently. These require seasonally repeated immunisations

  
• Immunisation programmes considerations


  • Cost vs effectiveness of the vaccine
  • Protection of the individual compared to protection of the community
  • The rights of the individual when considering mandatory or voluntary programmes
  • Side effects
• Active immunity


  Individual produces antibodies. Protection is long lasting due to production of antigen specific memory cells

  
• Passive immunity


  Individual receives antibodies from someone else. Protection is short lived as no memory cells are produced and the antibodies themselves identified as foreign and destroyed

  
• Cell mediated immune response

  1. Stem cells in the bone marrow make T lymphocytes, which are activated in the thymus gland

  2. Detecting a foreign antigen causes proliferation of T lymphocytes as: T killer cells cause lysis of target cells, T memory cells remain in bloodstream, T helper cells release cytokines

  3. Cytokines stimulate the clonal expansion of B cells and to produce antibodies. Cytokines activate phagocytes to engulf and digest the foreign cells

  
• Primary response


  Low level of antibody is secreted, which clears the infection and symptoms over a period of 2 – 3 weeks

  
• Secondary response


  Antibody levels increase to between 10 and 100 times greater than the initial response in a very short time frame. Antibody levels stay high for longer and no symptoms develop