immunology

• Pathogenic


  An organism that causes a disease, damaging its host
• Infectious


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


  A person who shows no symptoms when infected by the disease organism but can pass the disease to another individual
• 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 that is always present in an area, but at low levels
• Epidemic


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


  An epidemic occurring worldwide or in multiple countries, usually affecting a large number of people
• Vaccine


  Uses non-pathogenic forms, products or antigens of microorganisms 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
• 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 types/serotypes


  Organisms with the same or very similar antigens on the surface. Such types are sub-groups or strains of a microbial species which may be used to trace infections. They are usually identified by using antibodies
• The human body is a host for a wide variety of microorganisms. This is termed the microflora of the body
• Many of the species of bacteria and fungi are in a symbiotic relationship with the human body. In return for a habitat and food, they provide a number of different services
• Some species are pathogenic or parasitic; they have the potential to cause disease if they secrete toxins or if their numbers increase too much
• Cholera


  Caused by a Gram negative bacterium (Vibrio cholerae), which is endemic in some areas of the world. Its toxins affect the gut lining, causing watery diarrhoea that leads to severe dehydration and, frequently, death. Humans act as reservoirs or carriers and contaminate water supplies in which the organism is transmitted, although it only multiplies in the human host
• Cholera prevention


  1. Treatment of contaminated or dirty water

  2. Good hygiene

  3. Provision of clean drinking water

  4. Antibiotic treatment

  5. Rehydration through a mixture of salt and sugar in water

  6. Vaccine (made from killed or possibly genetically engineered organism) may provide temporary protection
• Outbreaks of cholera are not uncommon where earthquakes have disrupted sewage pipes and water treatment. Refugee camps with little sanitation and clean water can also suffer from outbreaks
• Tuberculosis (TB)


  A bacterial disease that is again on the rise, partly due to the link with the HIV epidemic. It is caused by Mycobacterium tuberculosis. It can be spread rapidly in overcrowded conditions and is transmitted in airborne droplets when infected people cough, sneeze and spit. The most common form of TB attacks the lungs and neck lymph nodes. Symptoms include coughing, chest pain and coughing up blood. Areas of dead and damaged cells in the lungs show up clearly on x-rays. Without treatment TB is fatal, in 2019 1.4 million people died of TB. 208,000 of those also had HIV. Treatment involves a long course of antibiotics, but multidrug resistance is a big issue
• Tuberculosis is prevented by a BCG vaccination programme for children
• Smallpox


  The only organism that humans have intentionally made extinct (outside specialist laboratories). It is caused by the virus Variola major and can have a 30 to 60% fatality rate. A successful immunisation program was based on the virus's low rate of antigenic variation/mutation and the highly immunogenic nature of its component antigens. This meant that the vaccine was highly effective. In addition, there was no animal reservoir and people were keen to be immunised because of the devastating effects of the disease. The virus was inhaled or transmitted by saliva or from close contact with infected people. The symptoms were fever and fluid-filled blisters all over the body. There was no effective treatment, just fluids and drugs to reduce fever
• Influenza


  Caused by a virus that has three main sub-groups. Within each sub-group, there are many different antigenic types. When a new strain appears, there is no immunity in the population and epidemics and, sometimes, pandemics occur. Influenza infects cells lining the upper respiratory tract causing sore throat, coughing and fever. Sufferers spread the disease by droplet infection. Prevention includes quarantine and hygiene, but influenza's mode of spread is difficult to control. Hygiene methods include: washing hands frequently, sterilising surfaces, using tissues and disposing of them immediately, sneezing into the elbow. There is no treatment for influenza as it is a virus, except to keep fluid intake up and use drugs to reduce fever. Antibiotics are ineffective against influenza and are only used to treat the symptoms of secondary bacterial infection. Annual vaccination programmes are available but due to the number of antigenic types, together with the emergence of new types, they are not always effective. Chickens and pigs are among the animal reservoirs of the virus, hence 'bird flu' and 'swine flu'
• Malaria


  Caused by Plasmodium spp., a protoctist parasite, which is an endemic in some sub-tropical regions. The disease is caused mainly by two species that have many antigenic types. The organism initially invades liver cells (hepatocytes). It then multiplies in red blood cells that burst, releasing more parasites (Plasmodium) into the blood and causing severe bouts of fever. Female Anopheles mosquitoes, through feeding on blood, act as vectors to transmit the parasite to new victims. The prevention of malaria relies on knowledge of the life cycle of both the vector and the parasite in order to exploit their weak points. A variety of methods are used either to prevent transmission (prevent biting by use of nets, clothing, insect repellent) or destroy populations of the vector. Mosquito larvae are aquatic and can be eaten by introduced fish, killed by draining the breeding sites or spraying oil on the water's surface. The adults are killed with insecticides, bacterial infections or by sterilisation. Each of these control measures has advantages and disadvantages. Treatment targets the parasite while it is in the blood rather than in the cells. Quinine has been used but it is now less effective as the Plasmodium has developed resistance. Artermisinin is also used, often combined with other drugs to reduce the possibility of resistance. A vaccine has been difficult to develop because of the many antigenic types
• Viruses


  Have a relatively simple structure. A core of nucleic acid (either DNA or RNA) is surrounded by a protein coat or capsid. The capsid is made of repeating subunits of protein called capsomeres. Some viruses are surrounded by a lipid coating, often derived from the cell membrane of the host. This can contain antigens, e.g. the flu virus has haemagglutinin (H) antigens and neuraminidase (N) antigens. The different types of antigen in combination give a number of different strains. Viruses are not capable of reproducing without a host cell, this is because they have no "cellular machinery" organelles or cytoplasm. The first step in a virus life cycle is to gain entry to a host cell, the virus attaches to receptors on the host cell membrane and enters the cell often by phagocytosis. Once inside the cell, the viral DNA inserts itself into the host DNA and instructs the cell to make new virus particles. If the virus nucleic acid is RNA, reverse transcription takes place to make a DNA copy of the virus genome; RNA viruses are often called retroviruses as a result. When the host cell fills up with virus particles it ruptures. The cell dies and the new virus can infect new cells. The cell bursting is called lysis, and this life cycle is a lytic cycle. Some viruses are lysogenic; the same things happen in terms of entry and modification of DNA of the host. The virus genome remains dormant until an environmental or cellular trigger results in a lytic phase, which causes the symptoms. Other ways in which viruses can be pathogenic are: By releasing toxins, some viral components are toxic. Viral DNA can activate oncogenes which can subsequently lead to cancer formation. If the virus is specific to an immune cell, like HIV infects T-helper cells, then the immune response to other diseases is compromised. Viral diseases are difficult to treat because the virus is inside the host cells. Any treatment would damage host cells as well as the virus
• Antibiotic


  A chemical produced by a microorganism that kills or inhibits the replication/growth of bacteria. In the natural world, antibiotics help fungi reduce competition from bacteria when food is scarce. They are produced after the growth phase of the fungus as a secondary metabolite. Antibiotics do not affect eukaryotic cells and are safe to use to treat bacterial infections
• Broad spectrum antibiotics


  Affect both Gram positive and Gram negative bacteria
• Narrow spectrum antibiotics


  Only act on certain bacteria
• Bactericidal antibiotics


  Antibiotics that kill bacteria. If bacteria are grown on a plate containing the antibiotic, they are killed. This means that if a swab of the plate is taken and transferred to an antibiotic-free plate, the bacteria are killed, so they cannot replicate and form colonies
• Bacteriostatic antibiotics


  Inhibit bacterial replication/growth. If the bacteria are grown on a plate containing the antibiotic, colonies will not form. If a swab of the plate is taken and transferred to an antibiotic-free plate, the bacteria can resume replication as they are not dead, and colonies can form
• Assessing the effectiveness of different strengths/types of antibiotic against a species of bacteria

  1. Making a lawn plate of the bacteria

  2. Placing discs of different strengths of one antibiotic or different antibiotics on the surface

  3. Measuring the clear zone where the bacteria have not grown or have been killed. The larger the area of the clear zone, the more bacteria have been killed, so the more effective the antibiotic is
• Gram positive bacteria


  Have a thick peptidoglycan (also known as murein) layer, which retains a crystal violet stain. After Gram staining, they appear purple down the microscope
• Gram negative bacteria


  Have a thin peptidoglycan layer, so alcohol used in the procedure washes the crystal violet out. The counterstaining with safranin stains the cells red. Gram negative bacteria have extra layers of lipopolysaccharide which protects the cells from lysozyme and the action of penicillin
• Penicillin


  Affects the formation of cross linkages in the peptidoglycan of the cell wall during the growth and division of bacterial cells. It does this by binding to and inhibiting the enzyme responsible for the formation of cross-links between the molecules of peptidoglycan. The wall is weakened, so when osmotic changes occur and water enters the cells, the cells lyse. Consequently, penicillin is more effective against Gram positive bacteria than Gram negative, due to the difference in the structure of the cell wall. Once the cell has lysed it is dead, so penicillin is a bactericidal antibiotic
• Tetracycline


  An antibiotic that affects protein synthesis, a metabolic process common to all bacteria, and is effective against a broader range of bacteria. It is a broad spectrum antibiotic. It acts as a competitive inhibitor of the second anticodon-binding site on the 30S subunit of bacterial ribosomes, and prevents the binding of a tRNA molecule to its complementary codon. In this way, tetracycline inhibits the translation stage of protein synthesis. As the binding of tetracycline is reversible, it is a bacteriostatic antibiotic
• Viruses are unaffected by antibiotics as they have no cellular mechanisms or cell walls to be affected
• Antibiotic resistance


  Bacteria divide rapidly under optimum conditions and have a high mutation rate. Naturally occurring mutations that confer resistance to antibiotics have given these bacteria a selective advantage in the presence of antibiotics. When antibiotics are used, the resistant bacteria survive and replicate, so the resistance passes to the next generation. This is vertical transmission. Horizontal transmission of resistance happens when bacteria transfer plasmids between each other. This can happen between bacteria of the same or different species. Overuse of antibiotics by doctors and in agriculture, has resulted in the accidental selection of bacterial strains that are completely unaffected by some antibiotics. In agriculture, antibiotics are used as a preventative to keep livestock healthy. In the absence of antibiotics, resistant strains no longer have an advantage over non-mutated forms, but if they cause an infection the bacteria are becoming increasingly difficult to control with antibiotics. Through mutation and natural selection, bacteria can be resistant to many different antibiotics. This is called multidrug resistance. You may have come across the example of multidrug resistant TB. There is also increasing evidence that gonorrhoea is becoming resistant to many antibiotics. The concern is that in the future, antibiotics will be unable to treat infections
• Natural barriers in the body that reduce the risk of infection

  • Skin as a tough barrier
  • Skin microflora offering protection
  • Blood clotting to seal wounds
  • Inflammation to localise breaks in the barrier
  • Phagocytosis to destroy invading microbes
  • Ciliated epithelia/mucous membranes that trap microbes
  • Lysozyme in tears and saliva
  • Stomach acid killing ingested bacteria
• Adaptive immune response


  Specific to the pathogen and involves recognising antigens being "foreign" to the body. The immune system has two strands of action: the humoral and cell mediated responses
• Humoral response


  1. B lymphocytes originate from stem cells in the bone marrow and mature in the spleen and lymph nodes

  2. There are many different B lymphocytes and each B lymphocyte has receptors for the detection of its specific antigen. When a B lymphocyte with a specific receptor binds to the specific antigen it is activated. This is called clonal selection

  3. Activation stimulates the proliferation of B lymphocytes by repeated mitotic divisions, known as clonal expansion. These B lymphocytes differentiate to form antibody-secreting cells called plasma cells and memory cells

  4. Memory cells remain in the circulation, ready to divide quickly if the same antigen is encountered again

  5. Antibodies are proteins (globulins) wh